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Sample records for acid-catalyzed bamberger rearrangement

  1. Rearrangements of Cycloalkenyl Aryl Ethers.

    PubMed

    Törincsi, Mercedesz; Nagy, Melinda; Bihari, Tamás; Stirling, András; Kolonits, Pál; Novak, Lajos

    2016-01-01

    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. PMID:27104504

  2. 75 FR 65226 - Establishment of Class E Airspace; Bamberg, SC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ... Register a notice of proposed rulemaking to establish Class E airspace at Bamberg, SC (75 FR 52654) Docket... Federal Aviation Administration 14 CFR Part 71 Establishment of Class E Airspace; Bamberg, SC AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action establishes Class...

  3. Acid-Catalyzed Isomerization of Carvone to Carvacrol

    ERIC Educational Resources Information Center

    Kjonaas, Richard A.; Mattingly, Shawn P.

    2005-01-01

    The acid-catalyzed isomerization of carvone to carvacrol, first reported by Ritter and Ginsburg, is especially well suited with a permanent-magnet FT instrument. The acid-catalyzed isomerization of carvone to carvacrol produced a 61% yield after a three hour reflux with 30% aqueous sulfuric acid.

  4. The Optical Transient Search in the Bamberg Plate Archive

    NASA Astrophysics Data System (ADS)

    Hudec, René; Kopel, Fabian; Krapp, Pedro; Heber, Ulrich; Cayé, Walter

    2011-08-01

    A substantial fraction of gamma-ray bursts is related to objects emitting temporarily optical light, i.e. optical afterglows and optical transients. So far, these phenomena (optical transients) were detected only after related gamma-ray satellite detection. However, taking into account their optical magnitudes at maximum light, these objects should be detectable in various historical and recent optical surveys, including photographic sky patrol. Here we report on an extended study based on blink-comparison of 5004 Bamberg Observatory Southern Sky Patrol Plates performed within a student project (Jugend Forscht).

  5. [Medical history as an academic subject at the Bamberg University].

    PubMed

    Locher, W

    2000-01-01

    A full program of medicine was taught at the Catholic University of Bamberg (founded 1648 as the Academia Ottonia) from 1773 through 1803. Within this period of time, the History of Medicine was taught from 1790 through 1795 by Johann Baptist Dominicus Fin(c)k. This paper elucidates how in this instance protestant universities served as models for catholic universities. Interestingly, it was not the medical faculty itself which developed an interest in teaching medical history. Rather, it was Adalbert Friedrich Marcus (1753-1816), physician-in-waiting of the Prince-Bishop Franz Ludwig von Erthal and medical officer in the principality of Bamberg since June 22, 1790, who was charged by the Prince-Bishop with developing guidelines for medical education. The start of the History of Medicine lectures brought with it a heated dispute about an appropriate textbook. The discussion is evidence of a transition from historiography understood as an account of learned doctors of the past to a study of history in a modern sense. PMID:11068514

  6. Acid-catalyzed dehydrogenation of amine-boranes

    DOEpatents

    Stephens, Frances Helen; Baker, Ralph Thomas

    2010-01-12

    A method of dehydrogenating an amine-borane using an acid-catalyzed reaction. The method generates hydrogen and produces a solid polymeric [R.sup.1R.sup.2B--NR.sup.3R.sup.4].sub.n product. The method of dehydrogenating amine-boranes may be used to generate H.sub.2 for portable power sources.

  7. BAMBERGER REARRANGEMENT DURING TNT-METABOLISM BY CLOSTRIDIUM ACETORBUTYLICUM. (R825513C006)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  8. Methods of Comparative Androgogy: An International Expert Seminar (Bamberg, Germany, September 24-27, 1995).

    ERIC Educational Resources Information Center

    Charters, Margaret A.

    A seminar collected, shared, and discussed the consensus on definitions, standards, methods, and current problems in research methodology in comparative andragogy. Alfred Hierold opened the seminar with a brief history of the evolution of the University of Bamberg. The opening session focused on the importance of the researcher as a tool in…

  9. Solvent effects in acid-catalyzed biomass conversion reactions.

    PubMed

    Mellmer, Max A; Sener, Canan; Gallo, Jean Marcel R; Luterbacher, Jeremy S; Alonso, David Martin; Dumesic, James A

    2014-10-27

    Reaction kinetics were studied to quantify the effects of polar aprotic organic solvents on the acid-catalyzed conversion of xylose into furfural. A solvent of particular importance is γ-valerolactone (GVL), which leads to significant increases in reaction rates compared to water in addition to increased product selectivity. GVL has similar effects on the kinetics for the dehydration of 1,2-propanediol to propanal and for the hydrolysis of cellobiose to glucose. Based on results obtained for homogeneous Brønsted acid catalysts that span a range of pKa values, we suggest that an aprotic organic solvent affects the reaction kinetics by changing the stabilization of the acidic proton relative to the protonated transition state. This same behavior is displayed by strong solid Brønsted acid catalysts, such as H-mordenite and H-beta. PMID:25214063

  10. Acid-catalyzed Heterogeneous Reactions in SOA Formation

    NASA Astrophysics Data System (ADS)

    Ng, N.; Keywood, M.; Varutbangkul, V.; Gao, S.; Loewer, E.; Surratt, J.; Richard, F. C.; John, S. H.

    2003-12-01

    The importance of heterogeneous reactions in secondary organic aerosol (SOA) formation has recently excited a great deal of interest in the aerosol community. Jang and Kamens (2001) showed enhanced aerosol yield from aldehydes, which can be produced by atmospheric photochemical reactions, in the presence of acidic seed. They suggest that the carbonyl functional groups of the aldehydes further react in the aerosol phase via hydration, polymerization, and hemiacetal/acetal formation with alcohols at an accelerated rate in the presence of acid. Jang et al. (2003) demonstrated similar results using a flow reactor and Czoschke et al. (in press) qualitatively showed increased yields for isoprene and alpha-pinene ozonolysis in the presence of acidic seed. While these findings are intriguing and important, the conditions under which the experiments were carried out were atmospherically unrealistic. A series of SOA formation experiments have been carried out in the Caltech Indoor Chamber Facility, which is comprised of dual 28 m3 FEP Teflon chambers, with the flexibility to carry out both dark ozonolysis and photochemical OH oxidation reactions. Cycloheptene and alpha-pinene were oxidized in the presence of neutral seed under dry (<10% RH) and humid (50% RH) conditions and in the presence of acidic seed under humid (50% RH) conditions. The SOA yields for these experiments will be presented, and the extent of the influence of acid-catalyzed reactions on SOA yield will be discussed. Reference List 1. Cocker, D. R. III. and R. C. Flagan and J. H. Seinfeld, State-of-the-art chamber facility for studying atmospheric aerosol chemistry, Environmental Science and Technology, 35, 2594-2601, 2001. 2. Czoschke, N. M., M. Jang, and R. M. Kamens, Effect of acid seed on biogenic sceondary organic aerosol growth, Atmospheric Environment, In press. 3. Jang, M., S. Lee, and R. M. Kamens, Organic aerosol growth by acid-catalyzed heterogeneous reactions of octanal in a flow reactor

  11. Cooperative Catalysis: Calcium and Camphorsulfonic Acid Catalyzed Cycloisomerization of Diynols.

    PubMed

    Rauser, Marian; Schroeder, Sebastian; Niggemann, Meike

    2015-11-01

    The first transition metal-free cycloisomerization of easily accessible diynols is presented as a novel approach to bicyclic 2H-pyrans. As a one-step protocol, the reaction proceeds in a single reaction cascade by intertwining mechanistic fragments borrowed from transition metal-catalyzed Claisen rearrangment of vinyl ethers with our own work on allenyl/propargyl cation rearrangements and a 6π-oxo-electrocylization. It is enabled by a new cooperative catalytic system that combines a simple Ca(2+) catalyst with camphorsulfonic acid. PMID:26403228

  12. Photometric Study of the FU Orionis Object BBW 76 from the Bamberg Observatory Southern Sky Survey

    NASA Astrophysics Data System (ADS)

    Borisova, A.; Tsvetkova, K. P.; Tsvetkov, M. K.

    2006-04-01

    The Bamberg Observatory Southern Sky Survey provided 93 photographic plates with the FU Orionis object BBW 76, clearly detectable in the time interval 1963-1976. We perform aperture photometry of BBW 76 from the 2 x 2 degrees area near target star scanned with the Epson Expression 1640 XL flatbed scanner. For each plate a transformation of plate magnitude to the GSC 2.2 magnitudes in B photographic band was found out for selected reference stars, and used for deriving B magnitudes of BBW 76. The analysis of the photometric behaviour of BBW 76 is presented.

  13. Wagner–Meerwein-Type Rearrangements of Germapolysilanes - A Stable Ion Study

    PubMed Central

    2015-01-01

    The rearrangement of tris(trimethylsilyl)silyltrimethylgermane 1 to give tetrakis(trimethylsilyl)germane 2 was investigated as a typical example for Lewis acid catalyzed Wagner–Meerwein-type rearrangements of polysilanes and polygermasilanes. Direct 29Si NMR spectroscopic evidence is provided for several cationic intermediates during the reaction. The identity of these species was verified by independent synthesis and NMR characterization, and their transformation was followed by NMR spectroscopy. PMID:26294805

  14. Isoprene Epoxydiols as Precursors to Secondary Organic Aerosol Formation: Acid-Catalyzed Reactive Uptake Studies with Authentic Compounds

    PubMed Central

    Lin, Ying-Hsuan; Zhang, Zhenfa; Docherty, Kenneth S.; Zhang, Haofei; Budisulistiorini, Sri Hapsari; Rubitschun, Caitlin L.; Shaw, Stephanie L.; Knipping, Eladio M.; Edgerton, Eric S.; Kleindienst, Tadeusz E.; Gold, Avram; Surratt, Jason D.

    2011-01-01

    Isoprene epoxydiols (IEPOX), formed from the photooxidation of isoprene under low-NOx conditions, have recently been proposed as precursors of secondary organic aerosol (SOA) on the basis of mass spectrometric evidence. In the present study, IEPOX isomers were synthesized in high purity (> 99%) to investigate their potential to form SOA via reactive uptake in a series of controlled dark chamber studies followed by reaction product analyses. IEPOX-derived SOA was substantially observed only in the presence of acidic aerosols, with conservative lower-bound yields of 4.7–6.4% for β-IEPOX and 3.4–5.5% for δ-IEPOX, providing direct evidence for IEPOX isomers as precursors to isoprene SOA. These chamber studies demonstrate that IEPOX uptake explains the formation of known isoprene SOA tracers found in ambient aerosols, including 2-methyltetrols, C5-alkene triols, dimers, and IEPOX-derived organosulfates. Additionally, we show reactive uptake on the acidified sulfate aerosols supports a previously unreported acid-catalyzed intramolecular rearrangement of IEPOX to cis- and trans-3-methyltetrahydrofuran-3,4-diols (3-MeTHF-3,4-diols) in the particle phase. Analysis of these novel tracer compounds by aerosol mass spectrometry (AMS) suggests that they contribute to a unique factor resolved from positive matrix factorization (PMF) of AMS organic aerosol spectra collected from low-NOx, isoprene-dominated regions influenced by the presence of acidic aerosols. PMID:22103348

  15. Acid-Catalyzed Preparation of Biodiesel from Waste Vegetable Oil: An Experiment for the Undergraduate Organic Chemistry Laboratory

    ERIC Educational Resources Information Center

    Bladt, Don; Murray, Steve; Gitch, Brittany; Trout, Haylee; Liberko, Charles

    2011-01-01

    This undergraduate organic laboratory exercise involves the sulfuric acid-catalyzed conversion of waste vegetable oil into biodiesel. The acid-catalyzed method, although inherently slower than the base-catalyzed methods, does not suffer from the loss of product or the creation of emulsion producing soap that plagues the base-catalyzed methods when…

  16. Optimizing the Acid Catalyzed Synthesis of Hyperbranched Poly(Glycerol-diacids) Oligomers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oligomeric pre-polymers were synthesized by the acid-catalyzed condensation of glycerol with succinic acid, glutaric acid and azelaic acid in dimethylsulfoxide (DMSO) or dimethylformamide (DMF). The prepolymers were obtained, on average in 84% yield, and were characterized by proton NMR, MALDI-TOF ...

  17. 4-Dimenthylaminopyridine or Acid-Catalyzed Synthesis of Esters: A Comparison

    ERIC Educational Resources Information Center

    van den Berg, Annemieke W. C.; Hanefeld, Ulf

    2006-01-01

    A set of highly atom-economic experiments was developed to highlight the differences between acid- and base-catalyzed ester syntheses and to introduce the principles of atom economy. The hydrochloric acid-catalyzed formation of an ester was compared with the 4-dimethylaminopyradine-catalyzed ester synthesis.

  18. [The institutional care for incurable and dying patients in Bamberg around 1800].

    PubMed

    Langrieger, Hannes

    2010-01-01

    Opened in 1789, the Bamberg General Hospital has often been described as a mile stone on the road from the traditional hospital into an institution for the exclusive care of curable diseases. As this paper shows, however, the shift was much less clear-cut. Early plans for the hospital also envisaged several rooms for dying patients within the new building, and later its first medical director, Adalbert F. Marcus, explicitly demanded that also some incurable patients be admitted and assisted until their death. His demand was not heeded but eventually plans for a separate institution came up. In 1803, a nearby former seminary was turned into a hospital for incurables. This paper traces these developments and puts them into their context. PMID:21563370

  19. Synthesis and Preliminary Biological Study of Bisindolylmethanes Accessed by an Acid-Catalyzed Hydroarylation of Vinylindoles

    PubMed Central

    Pathak, Tejas P.; Osiak, Jaroslaw G.; Vaden, Rachel M.; Welm, Bryan E.; Sigman, Matthew S.

    2012-01-01

    An acid-catalyzed hydroarylation reaction of vinyl indoles is reported, which tolerates a wide range of heterocycles as the exogenous nucleophile such as indoles, pyrroles, and indolizines. The method rapidly accesses the biologically relevant bisindolylmethane scaffold in good to excellent yields. Evaluation of the biological activity of several synthesized analogues reveals cytotoxic activity against and selectivity for the MCF-7 breast cancer cell line. PMID:22778488

  20. A General Access to Propargylic Ethers through Brønsted Acid Catalyzed Alkynylation of Acetals and Ketals with Trifluoroborates .

    PubMed

    Baxter, Matthew; Bolshan, Yuri

    2015-09-21

    A general Brønsted acid catalyzed methodology for the alkynylation of acetals and ketals with alkynyltrifluoroborate salts has been developed. The reaction proceeds rapidly to afford valuable synthetic building block propargylic ethers in good to excellent yields. Unlike Lewis acid catalyzed transformations of trifluoroborates, this approach does not proceed via unstable organodifluoroborane intermediate. As a result, the developed methodology features excellent functional group tolerance and good atom economy. PMID:26248543

  1. Rearrangement/Fragmentation Reactions of Oligosilanes with Aluminum Chloride

    PubMed Central

    2011-01-01

    Reinvestigation of the Lewis acid catalyzed rearrangement of some open-chain permethyloligosilanes with the Al(Fe)Cl3 catalyst system exhibited several cases of additional reactivity: namely, a fragmentation/cyclization reaction. Introduction of (trimethylsilyl)methyl substituents into the oligosilane substrates strongly facilitated this reaction, yielding cyclic or bicyclic carbacyclosilanes. Investigations concerning the composition of the catalyst system indicated that the incorporation of about 0.1% FeCl3 into the AlCl3 lattice provided an effective catalyst. PMID:21818171

  2. Lewis Acid Catalyzed Selective Reactions of Donor-Acceptor Cyclopropanes with 2-Naphthols.

    PubMed

    Kaicharla, Trinadh; Roy, Tony; Thangaraj, Manikandan; Gonnade, Rajesh G; Biju, Akkattu T

    2016-08-16

    Lewis acid-catalyzed reactions of 2-substituted cyclopropane 1,1-dicarboxylates with 2-naphthols is reported. The reaction exhibits tunable selectivity depending on the nature of Lewis acid employed and proceed as a dearomatization/rearomatization sequence. With Bi(OTf)3 as the Lewis acid, a highly selective dehydrative [3+2] cyclopentannulation takes place leading to the formation of naphthalene-fused cyclopentanes. Interestingly, engaging Sc(OTf)3 as the Lewis acid, a Friedel-Crafts-type addition of 2-naphthols to cyclopropanes takes place, thus affording functionalized 2-naphthols. Both reactions furnished the target products in high regioselectivity and moderate to high yields. PMID:27391792

  3. Negative resists for electron-beam lithography utilizing acid-catalyzed intramolecular dehydration of phenylcarbinol

    NASA Astrophysics Data System (ADS)

    Migitaka, Sonoko; Uchino, Shou-ichi; Ueno, Takumi; Yamamoto, Jiro; Kojima, Kyoko; Hashimoto, Michiaki; Shiraishi, Hiroshi

    1996-06-01

    Acid-catalyzed intramolecular dehydration of phenylcarbinol is used to design highly sensitive negative resists for electron beam lithography. Of the phenylcarbinol resists evaluated in this study, the resist composed of 1,3-bis(alpha-hydroxyisopropyl)benzene (Diol-1), m/p-cresol novolak resin, and diphenyliodonium triflate (DIT) shows the best lithographic performance in terms of sensitivity and resolution. Fine 0.25-micrometer line-and-space patterns were formed by using the resist containing Diol-1 with a dose of 3.6 (mu) C/cm2 in conjunction with a 50 kV electron beam exposure system.

  4. Tunable and Diastereoselective Brønsted Acid Catalyzed Synthesis of β-Enaminones.

    PubMed

    Kang, Ye-Won; Cho, Yu Jin; Han, Seung Jin; Jang, Hye-Young

    2016-01-15

    The Brønsted acid catalyzed Meyer-Schuster reaction of hemiaminals was studied for the stereoselective synthesis of β-enaminones. Hemiaminals were formed from propargyl aldehydes (or the oxidation of propargyl alcohols) and amines in the presence of Brønsted acids. A critical step to control the stereochemistry of the products is the protonation of the corresponding allenol intermediate, which is dictated by the Brønsted acid used, the steric effect of the amine, and the electronic effect of the propargyl aldehyde. PMID:26741050

  5. Synthesis of phytuberin. 4-endo-tet acid-catalyzed cyclization of alpha-hydroxy epoxides.

    PubMed

    Prangé, Thierry; Rodríguez, María S; Suárez, Ernesto

    2003-05-30

    The total synthesis of phytuberin, a phytoalexin of the Solanum genus, from (-)-alpha-santonin is reported. The key steps include (a) reductive cleavage of the C-O bond of the gamma-lactone with concomitant protection of the C1 double bond, (b) Sharpless stereocontrolled hydroxy-assisted epoxidation of allylic alcohol 6 and simultaneous deprotection of the C1 double bond, (c) a rare 4-endo-tet acid-catalyzed cyclization of an alpha-hydroxy epoxide, and (d) an unprecedented 4-exo selenocyclization of a homoallylic alcohol. PMID:12762747

  6. Integrated Production of Xylonic Acid and Bioethanol from Acid-Catalyzed Steam-Exploded Corn Stover.

    PubMed

    Zhu, Junjun; Rong, Yayun; Yang, Jinlong; Zhou, Xin; Xu, Yong; Zhang, Lingling; Chen, Jiahui; Yong, Qiang; Yu, Shiyuan

    2015-07-01

    High-efficiency xylose utilization is one of the restrictive factors of bioethanol industrialization. However, xylonic acid (XA) as a new bio-based platform chemical can be produced by oxidation of xylose with microbial. So, an applicable technology of XA bioconversion was integrated into the process of bioethanol production. After corn stover was pretreated with acid-catalyzed steam-explosion, solid and liquid fractions were obtained. The liquid fraction, also named as acid-catalyzed steam-exploded corn stover (ASC) prehydrolyzate (mainly containing xylose), was catalyzed with Gluconobacter oxydans NL71 to prepare XA. After 72 h of bioconversion of concentrated ASC prehydrolyzate (containing 55.0 g/L of xylose), the XA concentration reached a peak value of 54.97 g/L, the sugar utilization ratio and XA yield were 94.08 and 95.45 %, respectively. The solid fraction was hydrolyzed to produce glucose with cellulase and then fermented with Saccharomyces cerevisiae NL22 to produce ethanol. After 18 h of fermentation of concentrated enzymatic hydrolyzate (containing 86.22 g/L of glucose), the ethanol concentration reached its highest value of 41.48 g/L, the sugar utilization ratio and ethanol yield were 98.72 and 95.25 %, respectively. The mass balance showed that 1 t ethanol and 1.3 t XA were produced from 7.8 t oven dry corn stover. PMID:25947618

  7. Kinetics of acid-catalyzed aldol condensation reactions of aliphatic aldehydes

    NASA Astrophysics Data System (ADS)

    Casale, Mia T.; Richman, Aviva R.; Elrod, Matthew J.; Garland, Rebecca M.; Beaver, Melinda R.; Tolbert, Margaret A.

    Field observations of atmospheric aerosols have established that organic compounds compose a large fraction of the atmospheric aerosol mass. However, the physical/chemical pathway by which organic compounds are incorporated into atmospheric aerosols remains unclear. The potential role of acid-catalyzed reactions of organic compounds on acidic aerosols has been explored as a possible chemical pathway for the incorporation of organic material into aerosols. In the present study, ultraviolet-visible (UV-vis) spectroscopy was used to monitor the kinetics of formation of the products of the acid-catalyzed aldol condensation reaction of a range of aliphatic aldehydes (C 2-C 8). The experiments were carried out at various sulfuric acid concentrations and a range of temperatures in order to estimate the rate constants of such reactions on sulfuric acid aerosols under tropospheric conditions. The rate constants were generally found to decrease as the chain length of the aliphatic aldehyde increased (except for acetaldehyde, which had an unusually small rate constant), increase as a function of sulfuric acid concentration as predicted by excess acidity theory, and showed normal Arrhenius behavior as a function of temperature. While the kinetic data are generally consistent with previous laboratory reports of aldehyde reactivity in various sulfuric acid media, the aldol condensation reactions involving aliphatic aldehydes do not appear fast enough to be responsible for significant transfer of organic material into atmospheric aerosols.

  8. Pitfalls in protein quantitation using acid-catalyzed O18 labeling: hydrolysis-driven deamidation

    PubMed Central

    Wang, Shunhai; Bobst, Cedric E.; Kaltashov, Igor A.

    2011-01-01

    Proteolysis combined with O18 labeling emerged recently as a powerful tool for quantitation of proteins for which suitable internal standards cannot be produced using molecular biology methods. Several recent reports suggested that acid-catalyzed O18 labeling may be superior to the commonly accepted enzymatic protocol, as it may allow more significant spacing between the isotopic clusters of labeled and unlabeled peptides, thereby eliminating signal interference and enhancing the quality of quantitation. However, careful examination of this procedure reveals that the results of protein quantitation assisted by acid-catalyzed O18 labeling are highly peptide-dependent. The inconsistency was found to be caused by deamidation of Asn, Gln and carbamidomethylated Cys residues during prolonged exposure of the proteolytic fragments to the acidic environment of the labeling reaction, which translates into a loss in signal for theses peptides. Taking deamidation into account leads to a significant improvement in the consistency of quantitation across a range of different proteolytic fragments. PMID:21819098

  9. Sulfuric, hydrochloric, and nitric acid-catalyzed triacetone triperoxide (TATP) reaction mixtures: an aging study.

    PubMed

    Fitzgerald, Mark; Bilusich, Daniel

    2011-09-01

    The organic peroxide explosive triacetone triperoxide (TATP) is regularly encountered by law enforcement agents in various stages of its production. This study utilizes solid-phase microextraction (SPME) and gas chromatography/mass spectrometry (GC/MS) to examine sulfuric acid-, hydrochloric acid-, and nitric acid-catalyzed TATP syntheses during the initial 24 h of these reactions at low temperatures (5-9°C). Additionally, aging of the reaction mixtures was examined at both low and ambient temperatures (19-21°C) for a further 9 days. For each experiment, TATP could be readily identified in the headspace above the reaction mixture 1 h subsequent to the combination of reagents; at 24 h, TATP and diacetone diperoxide (DADP) were prominent. TATP degraded more rapidly than DADP. Additionally, chlorinated acetones chloroacetone and 1,1,-dichloroacetone were identified in the headspace above the hydrochloric acid-catalyzed TATP reaction mixture. These were not present when the catalyst was sulfuric acid or nitric acid. PMID:21595692

  10. Mechanisms and energetics for acid catalyzed β-D-glucose conversion to 5-hydroxymethylfurfurl.

    PubMed

    Qian, Xianghong

    2011-10-27

    Car-Parrinello based ab initio molecular dynamics (CPMD) coupled with metadynamics (MTD) simulations were carried out to investigate the mechanism and energetics for acid-catalyzed β-d-glucose conversion to 5-hydroxymethylfurfurl (HMF) in water. HMF is a critical intermediate for biomass conversion to biofuels. It was found that protonation of the C2-OH on glucose, the breakage of the C2-O2 bond, and the formation of the C2-O5 bond is the critical rate-limiting step for the direct glucose conversion to HMF without converting to fructose first, contrary to the wide-spread assumption in literature that fructose is the main intermediate for glucose conversion to HMF. The calculated reaction barrier of 30-35 kcal/mol appears to be solvent-induced and is in excellent agreement with experimental observations. PMID:21916465

  11. Solid acid-catalyzed depolymerization of barley straw driven by ball milling.

    PubMed

    Schneider, Laura; Haverinen, Jasmiina; Jaakkola, Mari; Lassi, Ulla

    2016-04-01

    This study describes a time and energy saving, solvent-free procedure for the conversion of lignocellulosic barley straw into reducing sugars by mechanocatalytical pretreatment. The catalytic conversion efficiency of several solid acids was tested which revealed oxalic acid dihydrate as a potential catalyst with high conversion rate. Samples were mechanically treated by ball milling and subsequently hydrolyzed at different temperatures. The parameters of the mechanical treatment were optimized in order to obtain sufficient amount of total reducing sugar (TRS) which was determined following the DNS assay. Additionally, capillary electrophoresis (CE) and Fourier transform infrared spectrometry (FT-IR) were carried out. Under optimal conditions TRS 42% was released using oxalic acid dihydrate as a catalyst. This study revealed that the acid strength plays an important role in the depolymerization of barley straw and in addition, showed, that the oxalic acid-catalyzed reaction generates low level of the degradation product 5-hydroxymethylfurfural (HMF). PMID:26859328

  12. Efficient acid-catalyzed (18) F/(19) F fluoride exchange of BODIPY dyes.

    PubMed

    Keliher, Edmund J; Klubnick, Jenna A; Reiner, Thomas; Mazitschek, Ralph; Weissleder, Ralph

    2014-07-01

    Fluorine-containing fluorochromes are important validation agents for positron emission tomography imaging compounds, as they can be readily validated in cells by fluorescence imaging. In particular, the (18) F-labeled BODIPY-FL fluorophore has emerged as an important platform, but little is known about alternative (18) F-labeling strategies or labeling on red-shifted fluorophores. In this study we explore acid-catalyzed (18) F/(19) F exchange on a range of commercially available N-hydroxysuccinimidyl ester and maleimide BODIPY fluorophores. We show this method to be a simple and efficient (18) F-labeling strategy for a diverse span of fluorescent compounds, including a BODIPY-modified PARP-1 inhibitor, and amine- and thiol-reactive BODIPY fluorophores. PMID:24596307

  13. Acid-catalyzed reactions of hexanal on sulfuric acid particles: Identification of reaction products

    NASA Astrophysics Data System (ADS)

    Garland, Rebecca M.; Elrod, Matthew J.; Kincaid, Kristi; Beaver, Melinda R.; Jimenez, Jose L.; Tolbert, Margaret A.

    While it is well established that organics compose a large fraction of the atmospheric aerosol mass, the mechanisms through which organics are incorporated into atmospheric aerosols are not well understood. Acid-catalyzed reactions of compounds with carbonyl groups have recently been suggested as important pathways for transfer of volatile organics into acidic aerosols. In the present study, we use the aerodyne aerosol mass spectrometer (AMS) to probe the uptake of gas-phase hexanal into ammonium sulfate and sulfuric acid aerosols. While both deliquesced and dry non-acidic ammonium sulfate aerosols showed no organic uptake, the acidic aerosols took up substantial amounts of organic material when exposed to hexanal vapor. Further, we used 1H-NMR, Fourier transform infrared (FTIR) spectroscopy and GC-MS to identify the products of the acid-catalyzed reaction of hexanal in acidic aerosols. Both aldol condensation and hemiacetal products were identified, with the dominant reaction products dependent upon the initial acid concentration of the aerosol. The aldol condensation product was formed only at initial concentrations of 75-96 wt% sulfuric acid in water. The hemiacetal was produced at all sulfuric acid concentrations studied, 30-96 wt% sulfuric acid in water. Aerosols up to 88.4 wt% organic/11.1 wt% H 2SO 4/0.5 wt% water were produced via these two dimerization reaction pathways. The UV-VIS spectrum of the isolated aldol condensation product, 2-butyl 2-octenal, extends into the visible region, suggesting these reactions may impact aerosol optical properties as well as aerosol composition. In contrast to previous suggestions, no polymerization of hexanal or its products was observed at any sulfuric acid concentration studied, from 30 to 96 wt% in water.

  14. Lewis Acid Catalyzed Regiospecific Cross-Dehydrative Coupling Reaction of 2-Furylcarbinols with β-Keto Amides or 4-Hydroxycoumarins: A Route to Furyl Enols.

    PubMed

    Miao, Maozhong; Luo, Yi; Li, Hongli; Xu, Xin; Chen, Zhengkai; Xu, Jianfeng; Ren, Hongjun

    2016-06-17

    Lewis acid catalyzed directly dehydrative carbon-carbon bond formation reaction of 2-furylcarbinols with β-keto amides provides a straightforward method for regioselective synthesis of (Z)-furyl enols. Moreover, this Lewis acid catalyzed cross-coupling reaction can be extended to an interesting heterocyclic version featuring a functionalized 3-furyl-4-hydroxycoumarin synthesis. PMID:27224045

  15. Efficient Synthesis of 3,3'-Mixed Bisindoles via Lewis Acid Catalyzed Reaction of Spiro-epoxyoxindoles and Indoles.

    PubMed

    Hajra, Saumen; Maity, Subrata; Maity, Ramkrishna

    2015-07-17

    An efficient strategy for the synthesis of 3-(3-indolyl)-oxindole-3-methanol has been developed to achieve a Lewis acid catalyzed, highly regioselective ring opening of spiro-epoxyoxindoles with indoles. The method is used for the gram-scale formal total synthesis of (±)-gliocladin C. PMID:26158390

  16. Two-step one-pot synthesis of benzoannulated spiroacetals by Suzuki-Miyaura coupling/acid-catalyzed spiroacetalization.

    PubMed

    Butkevich, Alexey N; Corbu, Andrei; Meerpoel, Lieven; Stansfield, Ian; Angibaud, Patrick; Bonnet, Pascal; Cossy, Janine

    2012-10-01

    Substituted benzoannulated spiroacetals were prepared from (2-haloaryl)alkyl alcohols and dihydropyranyl or dihydrofuranyl pinacol boronates using a Suzuki-Miyaura coupling followed by an acid-catalyzed spirocyclization. Application of the reaction to a glycal boronate provides an approach to annulated spiroacetals in enantiopure form. PMID:22998767

  17. Origins of stereoselectivities in chiral phosphoric acid catalyzed allylborations and propargylations of aldehydes.

    PubMed

    Wang, Hao; Jain, Pankaj; Antilla, Jon C; Houk, K N

    2013-02-01

    The chiral BINOL-phosphoric acid catalyzed allylboration and propargylation reactions are studied with density functional theory (B3LYP and B3LYP-D3). Two different models were recently proposed for these reactions by Goodman and our group, respectively. In Goodman's model for allylborations, the catalyst interacts with the boronate pseudoaxial oxygen. By contrast, our model for propargylations predicts that the catalyst interacts with the boronate pseudoequatorial oxygen. In both models, the phosphoric acid stabilizes the transition state by forming a strong hydrogen bond with the oxygen of the boronate and is oriented by a formyl hydrogen bond (Goodman model) and by other electrostatic attractions in our model. Both of these models have now been reinvestigated for both allylborations and propargylations. For the most effective catalyst for these reactions, the lowest energy transition state corresponds to Goodman's axial model, while the best transition state leading to the minor enantiomer involves the equatorial model. The high enantioselectivity observed with only the bulkiest catalyst arises from the steric interactions between the substrates and the bulky groups on the catalyst, and the resulting necessity for distortion of the catalyst in the disfavored transition state. PMID:23298338

  18. Origins of Stereoselectivities in Chiral Phosphoric Acid-Catalyzed Allylborations and Propargylations of Aldehydes

    PubMed Central

    Wang, Hao; Jain, Pankaj; Antilla, Jon C.; Houk, K. N.

    2013-01-01

    The chiral BINOL-phosphoric acid catalyzed allylboration and propargylation reactions are studied with density functional theory (B3LYP and B3LYP-D3). Two different models were recently proposed for these reactions by Goodman and our group, respectively. In Goodman's model for allylborations, the catalyst interacts with the boronate pseudo-axial oxygen. By contrast, our model for propargylations predicts that the catalyst interacts with the boronate pseudo-equatorial oxygen. In both models, the phosphoric acid stabilizes the transition state by forming a strong hydrogen bond with the oxygen of the boronate, and is oriented by a formyl hydrogen bond (Goodman model), and by other electrostatic attractions in our model. Both of these models have now been reinvestigated for both allylborations and propargylations. For the most effective catalyst for these reactions, the lowest energy transition state corresponds to Goodman's axial model, while the best transition state leading to minor enantiomer involves the equatorial model. The high enantioselectivity observed with only the bulkiest catalyst arises from the steric interactions between the substrates and the bulky groups on the catalyst, and the resulting necessity for distortion of the catalyst in the disfavored transition state. PMID:23298338

  19. Computational Mechanistic Studies of Acid-Catalyzed Lignin Model Dimers for Lignin Depolymerization

    SciTech Connect

    Kim, S.; Sturgeon, M. R.; Chmely, S. C.; Paton, R. S.; Beckham, G. T.

    2013-01-01

    Lignin is a heterogeneous alkyl-aromatic polymer that constitutes up to 30% of plant cell walls, and is used for water transport, structure, and defense. The highly irregular and heterogeneous structure of lignin presents a major obstacle in the development of strategies for its deconstruction and upgrading. Here we present mechanistic studies of the acid-catalyzed cleavage of lignin aryl-ether linkages, combining both experimental studies and quantum chemical calculations. Quantum mechanical calculations provide a detailed interpretation of reaction mechanisms including possible intermediates and transition states. Solvent effects on the hydrolysis reactions were incorporated through the use of a conductor-like polarizable continuum model (CPCM) and with cluster models including explicit water molecules in the first solvation shell. Reaction pathways were computed for four lignin model dimers including 2-phenoxy-phenylethanol (PPE), 1-(para-hydroxyphenyl)-2-phenoxy-ethanol (HPPE), 2-phenoxy-phenyl-1,3-propanediol (PPPD), and 1-(para-hydroxyphenyl)-2-phenoxy-1,3-propanediol (HPPPD). Lignin model dimers with a para-hydroxyphenyl ether (HPPE and HPPPD) show substantial differences in reactivity relative to the phenyl ether compound (PPE and PPPD) which have been clarified theoretically and experimentally. The significance of these results for acid deconstruction of lignin in plant cell walls will be discussed.

  20. Acid-catalyzed conversion of xylose, xylan and straw into furfural by microwave-assisted reaction.

    PubMed

    Yemiş, Oktay; Mazza, Giuseppe

    2011-08-01

    Furfural is a biomass derived-chemical that can be used to replace petrochemicals. In this study, the acid-catalyzed conversion of xylose and xylan to furfural by microwave-assisted reaction was investigated at selected ranges of temperature (140-190°C), time (1-30 min), substrate concentration (1:5-1:200 solid:liquid ratio), and pH (2-0.13). We found that a temperature of 180°C, a solid:liquid ratio of 1:200, a residence time of 20 min, and a pH of 1.12 gave the best furfural yields. The effect of different Brønsted acids on the conversion efficiency of xylose and xylan was also evaluated, with hydrochloric acid being found to be the most effective catalyst. The microwave-assisted process provides highly efficient conversion: furfural yields obtained from wheat straw, triticale straw, and flax shives were 48.4%, 45.7%, and 72.1%, respectively. PMID:21620690

  1. Kinetics of Acid-Catalyzed Aldol Condensation Reactions of Aliphatic Aldehydes

    NASA Astrophysics Data System (ADS)

    Elrod, M. J.; Casale, M. T.; Richman, A. R.; Beaver, M. R.; Garland, R. M.; Tolbert, M. A.

    2006-12-01

    While it is well established that organic compounds compose a large fraction of the atmospheric aerosol mass, the mechanisms through which organics are incorporated into atmospheric aerosols are not well understood. Acid-catalyzed reactions of compounds with carbonyl groups have recently been suggested as important pathways for transfer of volatile organics into acidic aerosols. In the present study, ultraviolet-visible (UV-Vis) spectroscopy was used to monitor the kinetics of formation of the products of the aldol condensation reaction of a range of aliphatic aldehydes (C2-C8) The experiments were carried out at various sulfuric acid concentrations and a range of temperatures in order to estimate the rate constants of such reactions on sulfuric acid aerosols under tropospheric conditions. The rate constants were generally found to decrease as the chain length of the aliphatic aldehyde increased (except for acetaldehyde, which had an unusually small rate constant), increase as a function of sulfuric acid concentration as predicted by excess acidity theory, and showed normal Arrhenius behavior as a function of temperature.

  2. Investigation of the complex reaction coordinate of acid catalyzed amide hydrolysis from molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Zahn, Dirk

    2004-05-01

    The rate-determining step of acid catalyzed peptide hydrolysis is the nucleophilic attack of a water molecule to the carbon atom of the amide group. Therein the addition of the hydroxyl group to the amide carbon atom involves the association of a water molecule transferring one of its protons to an adjacent water molecule. The protonation of the amide nitrogen atom follows as a separate reaction step. Since the nucleophilic attack involves the breaking and formation of several bonds, the underlying reaction coordinate is rather complex. We investigate this reaction step from path sampling Car-Parrinello molecular dynamics simulations. This approach does not require the predefinition of reaction coordinates and is thus particularly suited for investigating reaction mechanisms. From our simulations the most relevant components of the reaction coordinate are elaborated. Though the C⋯O distance of the oxygen atom of the water molecule performing the nucleophilic attack and the corresponding amide carbon atom is a descriptor of the reaction progress, a complete picture of the reaction coordinate must include all three molecules taking part in the reaction. Moreover, the proton transfer is found to depend on favorable solvent configurations. Thus, also the arrangement of non-reacting, i.e. solvent water molecules needs to be considered in the reaction coordinate.

  3. PNPCB heterocycles via thermal and Lewis acid catalyzed trans-hydroborations.

    PubMed

    Fan, Louie; Stephan, Douglas W

    2016-05-31

    The compounds iPr2P(BH3)N3, tBu2PC[triple bond, length as m-dash]CR (R = Ph , tBu , Cy ) and Ph2PC[triple bond, length as m-dash]CR (R = Ph , tBu , Cy ) were reacted to give the products tBu2P(C[triple bond, length as m-dash]CR)NP(BH3)iPr2 (R = Ph , tBu , Cy ) and Ph2P(C[triple bond, length as m-dash]CR)NP(BH3)iPr2 (R = Ph , tBu , Cy ). Subsequent thermally induced or Lewis acid catalyzed intramolecular hydroboration of and afforded the PNPCB heterocyclic compounds Ph2P(C[double bond, length as m-dash]CHPh)NP(BH2)iPr2 and tBu2P(C[double bond, length as m-dash]CHPh)NP(BH2)iPr2, respectively. Compounds and were crystallographically characterized and the mechanisms and implications for the synthesis of inorganic heterocycles are considered. PMID:27177164

  4. A preliminary investigation of acid-catalyzed polymerization reactions of shale oil distillates

    SciTech Connect

    Netzel, D.A.

    1991-04-01

    Sinor (1989) reported that a major specialty market may exist for shale oil as an asphalt blending material. Shale oil can be converted to an asphalt blending material by acid catalyzed condensation and polymerization reactions of the many molecular species comprising the composition of shale oil. To simplify the investigation, crude shale oil was separated by distillation into three distillates of different hydrocarbon and heteroaromatic compositions. These distillates were then treated with two different types of acids to determine the effect of acid type on the end products. Three western shale oil distillates, a naphtha, a middle distillate, and an atmospheric gas oil, were reacted with anhydrous AlCl{sub 3} and 85% H{sub 2}SO{sub 4} under low-severity conditions. At relatively low temperatures, little change in the hydrocarbon composition was noted for the AlCl{sub 3} reactions. AlCl{sub 3}{center dot} (a polymerized product and/or complex) was formed. However, it is assumed that the sludge was mainly the result of heteroaromatic-AlCl{sub 3} reactions.

  5. A preliminary investigation of acid-catalyzed polymerization reactions of shale oil distillates

    SciTech Connect

    Netzel, D.A.

    1991-04-01

    Sinor (1989) reported that a major specialty market may exist for shale oil as an asphalt blending material. Shale oil can be converted to an asphalt blending material by acid catalyzed condensation and polymerization reactions of the many molecular species comprising the composition of shale oil. To simplify the investigation, crude shale oil was separated by distillation into three distillates of different hydrocarbon and heteroaromatic compositions. These distillates were then treated with two different types of acids to determine the effect of acid type on the end products. Three western shale oil distillates, a naphtha, a middle distillate, and an atmospheric gas oil, were reacted with anhydrous AlCl{sub 3} and 85% H{sub 2}SO{sub 4} under low-severity conditions. At relatively low temperatures, little change in the hydrocarbon composition was noted for the AlCl{sub 3} reactions. AlCl{sub 3}{center_dot} (a polymerized product and/or complex) was formed. However, it is assumed that the sludge was mainly the result of heteroaromatic-AlCl{sub 3} reactions.

  6. Potential of phosphoric acid-catalyzed pretreatment and subsequent enzymatic hydrolysis for biosugar production from Gracilaria verrucosa.

    PubMed

    Kwon, Oh-Min; Kim, Sung-Koo; Jeong, Gwi-Taek

    2016-07-01

    This study combined phosphoric acid-catalyzed pretreatment and enzymatic hydrolysis to produce biosugars from Gracilaria verrucosa as a potential renewable resource for bioenergy applications. We optimized phosphoric acid-catalyzed pretreatment conditions to 1:10 solid-to-liquid ratio, 1.5 % phosphoric acid, 140 °C, and 60 min reaction time, producing a 32.52 ± 0.06 % total reducing sugar (TRS) yield. By subsequent enzymatic hydrolysis, a 68.61 ± 0.90 % TRS yield was achieved. These results demonstrate the potential of phosphoric acid to produce biosugars for biofuel and biochemical production applications. PMID:27003825

  7. Molecular rearrangements of superelectrophiles

    PubMed Central

    2011-01-01

    Summary 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. PMID:21512598

  8. Kinetics and mechanism of the acid-catalyzed hydrolysis of a hypermodified nucleoside wyosine and its 5'-monophosphate.

    PubMed Central

    Golankiewicz, B; Zielonacka-Lis, E; Folkman, W

    1985-01-01

    The rates of acid-catalyzed hydrolysis of a hypermodified nucleoside, wyosine and its 5'-monophosphate were determined at various pH, temperature and buffer concentrations. The results show that despite distinct differences in structure and the glycosyl bond stability, the hydrolysis of wyosine proceeds via cleavage of the C-N bond by A-1 mechanism, analogously to simple nucleosides. Unlike majority of other monophosphates studied so far, wyosine 5'-monophosphate is not more stable than respective nucleoside. PMID:4000960

  9. Acid-Catalyzed Conversion of Furfuryl Alcohol to Ethyl Levulinate in Liquid Ethanol

    PubMed Central

    González Maldonado, Gretchen M.; Assary, Rajeev S.; Dumesic, James; Curtiss, Larry A.

    2014-01-01

    Reaction pathways for the acid-catalyzed conversion of furfuryl alcohol (FAL) to ethyl levulinate (EL) in ethanol were investigated using liquid chromatography-mass spectrometry (LC-MS), 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and ab initio high-level quantum chemical (G4MP2) calculations. Our combined studies show that the production of EL at high yields from FAL is not accompanied by stoichiometric production of diethyl either (DEE), indicating that ethoxymethyl furan (EMF) is not an intermediate in the major reaction pathway. Several intermediates were observed using an LC-MS system, and three of these intermediates were isolated and subjected to reaction conditions. The structures of two intermediates were elucidated using 1D and 2D NMR techniques. One of these intermediates is EMF, which forms EL and DEE in a secondary reaction pathway. The second intermediate identified is 4,5,5-triethoxypentan-2-one, which is analogous to one of the intermediates observed in the conversion of FAL to LA in water (i.e. 4,5,5-trihydroxypentan-2-one). Furthermore, conversion of this intermediate to EL again involves the formation of DEE, indicating that it is also part of a secondary pathway. The primary pathway for production of EL involves solvent-assisted transfer of a water molecule from the partially detached protonated hydroxyl group of FAL to a ring carbon, followed by intra-molecular hydrogen shift, where the apparent reaction barrier for the hydrogen shift is relatively smaller in ethanol (21.1 kcal/mol) than that in water (26.6 kcal/mol). PMID:25035710

  10. The Acid Catalyzed Nitration of Methanol: Formation of Methyl Nitrate via Aerosol Chemistry

    NASA Technical Reports Server (NTRS)

    Riffel, Brent G.; Michelsen, Rebecca R.; Iraci, Laura T.

    2004-01-01

    The liquid phase acid catalyzed reaction of methanol with nitric acid to yield methyl nitrate under atmospheric conditions has been investigated using gas phase infrared spectroscopy. This nitration reaction is expected to occur in acidic aerosol particles found in the upper troposphere/lower stratosphere as highly soluble methanol and nitric acid diffuse into these aerosols. Gaseous methyl nitrate is released upon formation, suggesting that some fraction of NO(x) may he liberated from nitric acid (methyl nitrate is later photolyzed to NO(x)) before it is removed from the atmosphere by wet deposition. Thus, this reaction may have important implications for the NO(x) budget. Reactions have been initiated in 45-62 wt% H2SO4 solutions at 10.0 C. Methyl nitrate production rates increased exponentially with acidity within the acidity regime studied. Preliminary calculations suggest that the nitronium ion (NO2(+) is the active nitrating agent under these conditions. The reaction order in methanol appears to depend on the water/methanol ratio and varies from first to zeroth order under conditions investigated. The nitration is first order in nitronium at all acidities investigated. A second order rate constant, kappa(sub 2), has been calculated to be 1 x 10(exp 8)/ M s when the reaction is first order in methanol. Calculations suggest the nitration is first order in methanol under tropospheric conditions. The infinitesimal percentage of nitric acid in the nitronium ion form in this acidity regime probably makes this reaction insignificant for the upper troposphere; however, this nitration may become significant in the mid stratosphere where colder temperatures increase nitric acid solubility and higher sulfuric acid content shifts nitric acid speciation toward the nitronium ion.

  11. Mechanistic Investigation of Acid-Catalyzed Cleavage of Aryl-Ether Linkages: Implications for Lignin Depolymerization

    SciTech Connect

    Sturgeon, M. R.; Kim, S.; Chmely, S. C.; Foust, T. D.; Beckham, G. T.

    2013-01-01

    Carbon-oxygen bonds are the primary inter-monomer linkages lignin polymers in plant cell walls, and as such, catalyst development to cleave these linkages is of paramount importance to deconstruct biomass to its constituent monomers for the production of renewable fuels and chemicals. For many decades, acid catalysis has been used to depolymerize lignin. Lignin is a primary component of plant cell walls, which is connected primarily by aryl-ether linkages, and the mechanism of its deconstruction by acid is not well understood, likely due to its heterogeneous and complex nature compared to cellulose. For effective biomass conversion strategies, utilization of lignin is of significant relevance and as such understanding the mechanisms of catalytic lignin deconstruction to constituent monomers and oligomers is of keen interest. Here, we present a comprehensive experimental and theoretical study of the acid catalysis of a range of dimeric species exhibiting the b-O-4 linkage, the most common inter-monomer linkage in lignin. We demonstrate that the presence of a phenolic species dramatically increases the rate of cleavage in acid at 150 degrees C. Quantum mechanical calculations on dimers with the para-hydroxyl group demonstrate that this acid-catalyzed pathway differs from the nonphenolic dimmers. Importantly, this result implies that depolymerization of native lignin in the plant cell wall will proceed via an unzipping mechanism wherein b-O-4 linkages will be cleaved from the ends of the branched, polymer chains inwards toward the center of the polymer. To test this hypothesis further, we synthesized a homopolymer of b-O-4 with a phenolic hydroxyl group, and demonstrate that it is cleaved in acid from the end containing the phenolic hydroxyl group. This result suggests that genetic modifications to lignin biosynthesis pathways in plants that will enable lower severity processes to fractionate lignin for upgrading and for easier access to the carbohydrate fraction of

  12. Tandem Suzuki-Miyaura coupling/acid-catalyzed cyclization between vinyl ether boronates and vinyl halides: a concise approach to polysubstituted furans.

    PubMed

    Butkevich, Alexey N; Meerpoel, Lieven; Stansfield, Ian; Angibaud, Patrick; Corbu, Andrei; Cossy, Janine

    2013-08-01

    Polysubstituted 2-(ω-hydroxyalkyl)furans were prepared by tandem Suzuki-Miyaura coupling/acid-catalyzed cyclization starting from appropriately substituted 3-haloallylic alcohols and dihydrofuran-, dihydropyran- or glycal-derived pinacol boronates. PMID:23855589

  13. A Practical Guide for Predicting the Stereochemistry of Bifunctional Phosphoric Acid Catalyzed Reactions of Imines.

    PubMed

    Reid, Jolene P; Simón, Luis; Goodman, Jonathan M

    2016-05-17

    Chiral phosphoric acids have become powerful catalysts for the stereocontrolled synthesis of a diverse array of organic compounds. Since the initial report, the development of phosphoric acids as catalysts has been rapid, demonstrating the tremendous generality of this catalyst system and advancing the use of phosphoric acids to catalyze a broad range of asymmetric transformations ranging from Mannich reactions to hydrogenations through complementary modes of activation. These powerful applications have been developed without a clear mechanistic understanding of the reasons for the high level of stereocontrol. This Account describes investigations into the mechanism of the phosphoric acid catalyzed addition of nucleophiles to imines, focusing on binaphthol-based systems. In many cases, the hydroxyl phosphoric acid can form a hydrogen bond to the imine while the P═O interacts with the nucleophile. The single catalyst, therefore, activates both the electrophile and the nucleophile, while holding both in the chiral pocket created by the binaphthol and constrained by substituents at the 3 and 3' positions. Detailed geometric and energetic information about the transition states can be gained from calculations using ONIOM methods that combine the advantages of DFT with some of the speed of force fields. These high-level calculations give a quantitative account of the selectivity in many cases, but require substantial computational resources. A simple qualitative model is a useful complement to this complex quantitative model. We summarize our calculations into a working model that can readily be sketched by hand and used to work out the likely sense of selectivity for each reaction. The steric demands of the different parts of the reactants determine how they fit into the chiral cavity and which of the competing pathways is favored. The preferred pathway can be found by considering the size of the substituents on the nitrogen and carbon atoms of the imine electrophile

  14. Acid-catalyzed isomerization of rhenium alkyne complexes to rhenium allene complexes via 1-metallacyclopropene intermediates

    SciTech Connect

    Casey, C.P.; Brady, J.T.

    1998-10-12

    The alkyne complexes C{sub 5}Me{sub 5}(CO){sub 2}Re({eta}{sup 2}-MeC{triple_bond}CMe) (1) and C{sub 5}H{sub 5}(CO){sub 2}Re({eta}{sup 2}-MeC{triple_bond}CMe) (6) underwent acid-catalyzed isomerization by way of 1-metallacyclopropene intermediates to form the allene complexes C{sub 5}Me{sub 5}(CO){sub 2}Re({eta}{sup 2}-2,3-MeHC{double_bond}C{double_bond}CH{sub 2}) (5) and C{sub 5}H{sub 5}(CO){sub 2}Re({eta}{sup 2}-2,3-MeHC{double_bond}C{double_bond}CH{sub 2}) (7). Stoichiometric reaction of 1 with CF{sub 3}CO{sub 2}H initially produced the kinetic addition product C{sub 5}Me{sub 5}(CO){sub 2}Re[{eta}{sup 2}-(Z)-MeHC{double_bond}CMeO{sub 2}CCF{sub 3}] (8-Z), which slowly isomerized to the thermodynamically more stable E isomer 8-E. The reaction of 6 with CF{sub 3}CO{sub 2}H at {minus}73 C produced only C{sub 5}H{sub 5}(CO){sub 2}Re[{eta}{sup 2}-(E)-MeHC{double_bond}CMeO{sub 2}CCF{sub 3}] (9-E), which isomerized at -60 C to a 80:20 equilibrium mixture of 9-E and 9-Z. Treatment of 9-E and 9-Z with base led to formation of allene complex 7. The rate of this elimination was independent of base concentration. Labeling studies showed that the 1-metallacyclopropene intermediate C{sub 5}H{sub 5}(CO){sub 2}({eta}{sup 2}-CMeCHMe){sup +}CF{sub 3}CO{sub 2}{sup {minus}} (12-CF{sub 3}CO{sub 2}) undergoes a number of important reactions which include, in order of decreasing relative rates: (1) addition of trifluoroacetate to give enol trifluoroacetate complexes, (2) deprotonation to give complexed allenes, (3) degenerate 1,2-hydride migrations, (4) hydride migrations to give {eta}{sup 3}-allyl complexes, and (5) deprotonation to give complexed alkynes.

  15. Degradations and Rearrangement Reactions

    NASA Astrophysics Data System (ADS)

    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.

  16. Brönsted Acid-Catalyzed One-Pot Synthesis of Indoles from o-Aminobenzyl Alcohols and Furans

    PubMed Central

    Kuznetsov, Alexey; Makarov, Anton; Rubtsov, Alexandr E.; Butin, Alexander V.; Gevorgyan, Vladimir

    2013-01-01

    Brönsted acid-catalyzed one-pot synthesis of indoles from o-aminobenzyl alcohols and furans has been developed. This method operates via the in situ formation of aminobenzylfuran, followed by its recyclization into the indole core. The method proved to be efficient for substrates possessing different functional groups, including -OMe, -CO2Cy, and -Br. The resulting indoles can easily be transformed into diverse scaffolds, including 2,3- and 1,2-fused indoles, and indole possessing an α,β-unsaturated ketone moiety at the C-2 position. PMID:24255969

  17. Enantiodivergent Atroposelective Synthesis of Chiral Biaryls by Asymmetric Transfer Hydrogenation: Chiral Phosphoric Acid Catalyzed Dynamic Kinetic Resolution.

    PubMed

    Mori, Keiji; Itakura, Tsubasa; Akiyama, Takahiko

    2016-09-12

    Reported herein is an enantiodivergent synthesis of chiral biaryls by a chiral phosphoric acid catalyzed asymmetric transfer hydrogenation reaction. Upon treatment of biaryl lactols with aromatic amines and a Hantzsch ester in the presence of chiral phosphoric acid, dynamic kinetic resolution (DKR) involving a reductive amination reaction proceeded smoothly to furnish both R and S isomers of chiral biaryls with excellent enantioselectivities by proper choice of hydroxyaniline derivative. This trend was observed in wide variety of substrates, and various chiral biphenyl and phenyl naphthyl adducts were synthesized with satisfactory enantioselectivities in enantiodivergent fashion. The enantiodivergent synthesis of synthetically challenging, chiral o-tetrasubstituted biaryls were also accomplished, and suggests high synthetic potential of the present method. PMID:27491630

  18. Acid-catalyzed conversion of mono- and poly-sugars into platform chemicals: effects of molecular structure of sugar substrate.

    PubMed

    Hu, Xun; Wu, Liping; Wang, Yi; Song, Yao; Mourant, Daniel; Gunawan, Richard; Gholizadeh, Mortaza; Li, Chun-Zhu

    2013-04-01

    Hydrolysis/pyrolysis of lignocellulosic biomass always produces a mixture of sugars with distinct structures as intermediates or products. This study tried to elucidate the effects of molecular structure of sugars on their acid-catalyzed conversions in ethanol/water. Location of carbonyl group in sugars (fructose versus glucose) and steric configuration of hydroxyl groups (glucose versus galactose) significantly affected yields of levulinic acid/ester (fructose>glucose>galactose). The dehydration of fructose to 5-(hydroxymethyl)furfural produces much less soluble polymer than that from glucose and galactose, which results in high yields of levulinic acid/ester from fructose. Anhydrate sugar such as levoglucosan tends to undergo the undesirable decomposition to form less levulinic acid/ester. Catalytic behaviors of the poly-sugars (sucrose, maltose, raffinose, β-cyclodextrins) were determined much by their basic units. However, their big molecular sizes create the steric hindrance that significantly affects their followed conversion over solid acid catalyst. PMID:23454803

  19. The cubyl cation rearrangements.

    PubMed

    Jalife, Said; Mondal, Sukanta; Cabellos, Jose Luis; Martinez-Guajardo, Gerardo; Fernandez-Herrera, Maria A; Merino, Gabriel

    2016-02-25

    Born-Oppenheimer molecular dynamics simulations and high-level ab initio computations predict that the cage-opening rearrangement of the cubyl cation to the 7H(+)-pentalenyl cation is feasible in the gas phase. The rate-determining step is the formation of the cuneyl cation with an activation barrier of 25.3 kcal mol(-1) at the CCSD(T)/def2-TZVP//MP2/def2-TZVP level. Thus, the cubyl cation is kinetically stable enough to be formed and trapped at moderate temperatures, but it may be rearranged at higher temperatures. PMID:26880646

  20. 3-Component synthesis of α-substituted sulfonamides via Brønsted acid-catalyzed C(sp(3))-H bond functionalization of 2-alkylazaarenes.

    PubMed

    Beisel, T; Kirchner, J; Kaehler, T; Knauer, J; Soltani, Y; Manolikakes, G

    2016-06-28

    A Brønsted acid-catalyzed addition of 2-alkylazaarenes to in situ generated N-sulfonylimines through selective C(sp(3))-H bond functionalization has been developed. This protocol provides an atom- and step-economic approach to α-substituted sulfonamides. PMID:26868020

  1. Phosphonate–phosphinate rearrangement.

    PubMed

    Qian, Renzhe; Roller, Alexander; Hammerschmidt, Friedrich

    2015-01-16

    LiTMP metalated dimethyl N-Boc-phosphoramidates derived from 1-phenylethylamine and 1,2,3,4-tetrahydronaphthalen-1-ylamine highly selectively at the CH3O group to generate short-lived oxymethyllithiums. These isomerized to diastereomeric hydroxymethylphosphonamidates (phosphate–phosphonate rearrangement). However, s-BuLi converted the dimethyl N-Boc-phosphoramidate derived from 1-phenylethylamine to the N-Boc α-aminophosphonate preferentially. Only s-BuLi deprotonated dimethyl hydroxymethylphosphonamidates at the benzylic position and dimethyl N-Boc α-aminophosphonates at the CH3O group to induce phosphonate–phosphinate rearrangements. In the former case, the migration of the phosphorus substituent from the nitrogen to the carbon atom followed a retentive course with some racemization because of the involvement of a benzyllithium as an intermediate. PMID:25525945

  2. Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

    PubMed Central

    Gulzar, Naeem; Klussmann, Martin

    2014-01-01

    The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order to streamline synthesis by saving steps, time and material compared to conventional methods that require the introduction and removal of activating or directing groups. Therefore, the functionalization of C-H bonds is also attractive for green chemistry. Under oxidative conditions, two C-H bonds or one C-H and one heteroatom-H bond can be transformed to C-C and C-heteroatom bonds, respectively. Often these oxidative coupling reactions require synthetic oxidants, expensive catalysts or high temperatures. Here, we describe a two-step procedure to functionalize indole derivatives, more specifically tetrahydrocarbazoles, by C-H amination using only elemental oxygen as oxidant. The reaction uses the principle of C-H functionalization via Intermediate PeroxideS (CHIPS). In the first step, a hydroperoxide is generated oxidatively using visible light, a photosensitizer and elemental oxygen. In the second step, the N-nucleophile, an aniline, is introduced by Brønsted-acid catalyzed activation of the hydroperoxide leaving group. The products of the first and second step often precipitate and can be conveniently filtered off. The synthesis of a biologically active compound is shown. PMID:24998636

  3. No evidence for acid-catalyzed secondary organic aerosol formation in power plant plumes over metropolitan Atlanta, Georgia

    NASA Astrophysics Data System (ADS)

    Peltier, R. E.; Sullivan, A. P.; Weber, R. J.; Wollny, A. G.; Holloway, J. S.; Brock, C. A.; de Gouw, J. A.; Atlas, E. L.

    2007-03-01

    Aircraft-based measurements of the water-soluble fraction of fine PM organic carbon (WSOC) and inorganic salt composition in the Atlanta, GA region were conducted in the summer of 2004. Five notable plumes of SO2, apparently from coal-fired power plants, were intercepted, and had NH4 +/SO4 2- molar ratios ranging from approximately 0.8 to 1.4 compared to molar ratios near 2 outside of the plumes. Sulfate aerosol concentrations increased from a regional background of 5-8 μg m-3 to as high as 19.5 μg m-3 within these plumes. No increase in WSOC concentrations was observed in plumes compared to out-of-plumes within a WSOC measurement uncertainty of 8%. These measurements suggest that secondary organic aerosol formation via heterogeneous acid-catalyzed reactions within power plant plumes are not likely a significant contributor to the ambient aerosol mass loading in Atlanta and the surrounding region. Because this region is rich in both biogenic and anthropogenic volatile organic carbon (VOC), the results may be widely applicable.

  4. Dietary phenolic acids and ascorbic acid: Influence on acid-catalyzed nitrosative chemistry in the presence and absence of lipids.

    PubMed

    Combet, Emilie; El Mesmari, Aziza; Preston, Tom; Crozier, Alan; McColl, Kenneth E L

    2010-03-15

    Acid-catalyzed nitrosation and production of potentially carcinogenic nitrosative species is focused at the gastroesophageal junction, where salivary nitrite, derived from dietary nitrate, encounters the gastric juice. Ascorbic acid provides protection by converting nitrosative species to nitric oxide (NO). However, NO may diffuse into adjacent lipid, where it reacts with O(2) to re-form nitrosative species and N-nitrosocompounds (NOC). In this way, ascorbic acid promotes acid nitrosation. Using a novel benchtop model representing the gastroesophageal junction, this study aimed to clarify the action of a range of water-soluble antioxidants on the nitrosative mechanisms in the presence or absence of lipids. Caffeic, ferulic, gallic, or chlorogenic and ascorbic acids were added individually to simulated gastric juice containing secondary amines, with or without lipid. NO and O(2) levels were monitored by electrochemical detection. NOC were measured in both aqueous and lipid phases by gas chromatography-tandem mass spectrometry. In the absence of lipids, all antioxidants tested inhibited nitrosation, ranging from 35.9 + or - 7.4% with gallic acid to 93 + or - 0.6% with ferulic acid. In the presence of lipids, the impact of each antioxidant on nitrosation was inversely correlated with the levels of NO they generated (R(2) = 0.95, p<0.01): gallic, chlorogenic, and ascorbic acid promoted nitrosation, whereas ferulic and caffeic acids markedly inhibited nitrosation. PMID:20026204

  5. Kinetics of Acid-Catalyzed Dehydration of Cyclic Hemiacetals in Organic Aerosol Particles in Equilibrium with Nitric Acid Vapor.

    PubMed

    Ranney, April P; Ziemann, Paul J

    2016-04-28

    Previous studies have shown that 1,4-hydroxycarbonyls, which are often major products of the atmospheric oxidation of hydrocarbons, can undergo acid-catalyzed cyclization and dehydration in aerosol particles to form highly reactive unsaturated dihydrofurans. In this study the kinetics of dehydration of cyclic hemiacetals, the rate-limiting step in this process, was investigated in a series of environmental chamber experiments in which secondary organic aerosol (SOA) containing cyclic hemiacetals was formed from the reaction of n-pentadecane with OH radicals in dry air in the presence of HNO3. A particle beam mass spectrometer was used to monitor the formation and dehydration of cyclic hemiacetals in real time, and SOA and HNO3 were quantified in filter samples by gravimetric analysis and ion chromatography. Measured dehydration rate constants increased linearly with increasing concentration of HNO3 in the gas phase and in SOA, corresponding to catalytic rate constants of 0.27 h(-1) ppmv(-1) and 7.0 h(-1) M(-1), respectively. The measured Henry's law constant for partitioning of HNO3 into SOA was 3.7 × 10(4) M atm(-1), ∼25% of the value for dissolution into water, and the acid dissociation constant was estimated to be <8 × 10(-4), at least a factor of 10(4) less than that for HNO3 in water. The results indicate that HNO3 was only weakly dissociated in the SOA and that dehydration of cyclic hemiacetals was catalyzed by molecular HNO3 rather than by H(+). The Henry's law constant and kinetics relationships measured here can be used to improve mechanisms and models of SOA formation from the oxidation of hydrocarbons in dry air in the presence of NOx, which are conditions commonly used in laboratory studies. The fate of cyclic hemiacetals in the atmosphere, where the effects of higher relative humidity, organic/aqueous phase separation, and acid catalysis by molecular H2SO4 and/or H(+) are likely to be important, is discussed. PMID:27043733

  6. {beta}-Secondary and solvent deuterium kinetic isotope effects and the mechanisms of base- and acid-catalyzed hydrolysis of penicillanic acid

    SciTech Connect

    Deraniyagala, S.A.; Adediran, S.A.; Pratt, R.F.

    1995-03-24

    {beta}-Secondary and solvent deuterium kinetic isotope effects have been determined at 25 {degrees}C for the alkaline and acid-catalyzed hydrolysis of penicillanic acid. In order to determine the former isotope effect, [6,6-{sup 2}H{sub 2}]dideuteriopenicillanic acid has been synthesized. In alkaline solution, the former isotope effect was found to be 0.95 {plus_minus} 0.01. These values support the B{sub AC}2 mechanism of hydrolysis with rate-determining formation of the tetrahedral intermediate that has been proposed for other {beta}-lactams. The measured {beta}-secondary kinetic isotope for the acid-catalyzed reaction was 1.00 {plus_minus} 0.01. The data indicates that a likely pathway of acid-catalyzed hydrolysis would be that of an A{sub AC}1 mechanism with an intermediate acylium ion. If this were so, the calculated {beta}-secondary isotope effect per hydrogen coplanar with the breaking C-N bond and corrected for the inductive effect of deuterium would be 1.06 {plus_minus} 0.01. This suggests an early A{sub AC}1 transition state, which would be reasonable in this case because of destabilization of the N-protonated amide with respect to the acylium ion because of ring strain. The absence of specific participation by solvent in the transition state, as would be expected of an A{sub AC}1 but not an associative mechanism, is supported by the strongly inverse solvent deuterium kinetic isotope effect of 0.25 {plus_minus} 0.00 in 1 M HCl and 0.22 {plus_minus} 0.01 in 33.3 wt % H{sub 2}SO{sub 4}. 1 fig., 3 tabs.

  7. Brønsted Acid-Catalyzed Transfer Hydrogenation of Imines and Alkenes Using Cyclohexa-1,4-dienes as Dihydrogen Surrogates.

    PubMed

    Chatterjee, Indranil; Oestreich, Martin

    2016-05-20

    Cyclohexa-1,4-dienes are introduced to Brønsted acid-catalyzed transfer hydrogenation as an alternative to the widely used Hantzsch dihydropyridines. While these hydrocarbon-based dihydrogen surrogates do offer little advantage over established protocols in imine reduction as well as reductive amination, their use enables the previously unprecedented transfer hydrogenation of structurally and electronically unbiased 1,1-di- and trisubstituted alkenes. The mild procedure requires 5.0 mol % of Tf2NH, but the less acidic sulfonic acids TfOH and TsOH work equally well. PMID:27181437

  8. Claisen thermally rearranged (CTR) polymers.

    PubMed

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

    2016-07-01

    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

  9. Claisen thermally rearranged (CTR) polymers

    PubMed Central

    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

  10. Radical Smiles Rearrangement: An Update.

    PubMed

    Allart-Simon, Ingrid; Gérard, Stéphane; Sapi, Janos

    2016-01-01

    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. PMID:27399654

  11. Immunoglobulin λ Gene Rearrangement Can Precede κ Gene Rearrangement

    DOE PAGESBeta

    Berg, Jörg; Mcdowell, Mindy; Jäck, Hans-Martin; Wabl, Matthias

    1990-01-01

    Imore » mmunoglobulin genes are generated during differentiation of B lymphocytes by joining gene segments. A mouse pre-B cell contains a functional immunoglobulin heavy-chain gene, but no light-chain gene. Although there is only one heavy-chain locus, there are two lightchain loci: κ and λ .It has been reported that κ loci in the germ-line configuration are never (in man) or very rarely (in the mouse) present in cells with functionally rearranged λ -chain genes. Two explanations have been proposed to explain this: (a) the ordered rearrangement theory, which postulates that light-chain gene rearrangement in the pre-B cell is first attempted at the κ locus, and that only upon failure to produce a functional κ chain is there an attempt to rearrange the λ locus; and (b) the stochastic theory, which postulates that rearrangement at the λ locus proceeds at a rate that is intrinsically much slower than that at the κ locus. We show here that λ -chain genes are generated whether or not the κ locus has lost its germ-line arrangement, a result that is compatible only with the stochastic theory.« less

  12. Hybrid Quantum Mechanics/Molecular Mechanics-Based Molecular Dynamics Simulation of Acid-Catalyzed Dehydration of Polyols in Liquid Water

    SciTech Connect

    Caratzoulas, Stavros; Courtney, Timothy; Vlachos, Dionisios G.

    2011-01-01

    We use the conversion of protonated glycerol to acrolein for a case study of the mechanism of acid-catalyzed dehydration of polyols in aqueous environments. We employ hybrid Quamtum Mechanics/Molecular Mechanics Molecular Dynamics (QM/MM MD) simulations with biased sampling and perform free energy calculations for the elementary steps of the reaction. We investigate the effects of solvent dynamics and in particular the role of quantum mechanical water in the dehydration mechanism. We present results supporting a mechanism that proceeds via water-mediated proton transfers and thus through an enol intermediate. We find that the first dehydration may take place by two, low-energy pathways requiring, respectively, 20.9 and 18.8 kcal/mol of activation free energy. The second dehydration requires 19.9 kcal/mol of activation free energy while for the overall reaction we compute a free energy change of -8 kcal/mol.

  13. Difference analysis of the enzymatic hydrolysis performance of acid-catalyzed steam-exploded corn stover before and after washing with water.

    PubMed

    Zhu, Junjun; Shi, Linli; Zhang, Lingling; Xu, Yong; Yong, Qiang; Ouyang, Jia; Yu, Shiyuan

    2016-10-01

    The difference in the enzymatic hydrolysis yield of acid-catalyzed steam-exploded corn stover (ASC) before and after washing with water reached approximately 15 % under the same conditions. The reasons for the difference in the yield between ASC and washed ASC (wASC) were determined through the analysis of the composition of ASC prehydrolyzate and sugar concentration of enzymatic hydrolyzate. Salts produced by neutralization (CaSO4, Na2SO4, K2SO4, and (NH4)2SO4), sugars (polysaccharides, oligosaccharides, and monosaccharides), sugar-degradation products (weak acids and furans), and lignin-degradation products (ethyl acetate extracts and nine main lignin-degradation products) were back-added to wASC. Results showed that these products, except furans, exerted negative effect on enzymatic hydrolysis. According to the characteristics of acid-catalyzed steam explosion pretreatment, the five sugar-degradation products' mixture and salts [Na2SO4, (NH4)2SO4] showed minimal negative inhibition effect on enzymatic hydrolysis. By contrast, furans demonstrated a promotion effect. Moreover, soluble sugars, such as 13 g/L xylose (decreased by 6.38 %), 5 g/L cellobiose (5.36 %), 10 g/L glucose (3.67 %), as well as lignin-degradation products, and ethyl acetate extracts (4.87 %), exhibited evident inhibition effect on enzymatic hydrolysis. Therefore, removal of soluble sugars and lignin-degradation products could effectively promote the enzymatic hydrolysis performance. PMID:27277746

  14. Biotransformation and Rearrangement of Laromustine.

    PubMed

    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. PMID:27278961

  15. Correction: Acid-catalyzed carboxylic acid esterification and ester hydrolysis mechanism: acylium ion as a sharing active intermediate via a spontaneous trimolecular reaction based on density functional theory calculation and supported by electrospray ionization-mass spectrometry.

    PubMed

    Shi, Hongchang; Wang, Yilei; Hua, Ruimao

    2015-12-28

    Correction for 'Acid-catalyzed carboxylic acid esterification and ester hydrolysis mechanism: acylium ion as a sharing active intermediate via a spontaneous trimolecular reaction based on density functional theory calculation and supported by electrospray ionization-mass spectrometry' by Hongchang Shi et al., Phys. Chem. Chem. Phys., 2015, DOI: 10.1039/c5cp02914g. PMID:26583937

  16. Real and Virtual Heritage Historical Astronomical Plate Archives in Sonneberg, Bamberg and Hamburg Observatories, the Evolution of Astrophysics and their Influence on Human Knowledge and Culture

    NASA Astrophysics Data System (ADS)

    Kunzmann, Björn

    The rise of astrophysics around 1860 introduced new instruments, methods and research areas. Of course, the increasing number of foundations of new observatories around the world starting at that time was forced by that new scientific discipline, too, but especially by the usage of photographic instruments. At the end of the 19th century the formation and development of photographic methods and techniques had reached a level of sufficient stability for productive usage in astronomy and astrophysics, their new instrumrents, methods and goals. The fundamental meaning of star light analysis for astrophysics by increasing discoveries of Variable Stars and the Systematic search for moving Solar System objects had basically driven the beginning of large photographic sky patrols at that time, using photographic glass plates as detectors and information storages. Sky Patrols, especially systematic long-term monitoring of the whole sky or of well defined selected areas and Sky Surveys were (and still are) an important key method that forced the evolution and progress of astrophysics. Important scientific results by famous astronomers, for example Walter Baade, Cuno Hoffmeister and Harlow Shapley depended on the analysis of photographic plates. Today, there are around 50 photographic plate archives world-wide. Most of them, unfortunately, are in a quite poor condition and not yet digitized. Following Harvard College Observatory with an estimated total of 600,000 plates, Sonneberg observatory harbours the second largest archive world-wide (around 300,000 plates) among other large ones in Germany like Bamberg (40,000 plates) and Hamburg (35,000 plates). These plate archives form an important heritage with a total of roughly two million direct plates and some ten or hundred thousands of spectroscopic plates. A lot of progress has been made by transforming this real heritage to a virtual one by systematic digitisation of the plates, but perhaps only 15% of them have been

  17. The cytogenetics of mammalian autosomal rearrangements

    SciTech Connect

    Daniel, A.

    1988-01-01

    Combining data from animal and clinical studies with classical cytogenetic observations, the volume provides information on various aspects of mammalian autosomal rearrangements. Topics range from the reproductive consequences to carriers of autosomal rearrangements to the application of structural rearrangements and DNA probes to gene mapping. In addition, the book presents an overview of new perspectives and future directions for research.

  18. The acid-catalyzed decompostion of phenacylcobalamin: evidence for the formation of an enol-Co(III) pi-complex intermediate.

    PubMed

    Brown, K L; Chu, M M; Ingraham, L L

    1976-04-01

    Phenacylcobalamin has been synthesized and characterized by thin-layer chromatography and uv-visible spectroscopy, as well as identification of the cobalt-containing and organic products of its cleavage in acid and base and by aerobic photolysis. The major organic product from all three cleavage reactions is acetophenone and the cobalt-containing product is aquacobalamin (or hydroxocobalamin, its conjugate base). In aqueous acidic solution (pH 0 to 7.3, ionic strength 1.0 M, and 25.0 degrees C), the kinetics of the formation of aquacobalamin are biphasic representing the linear sum of two exponential terms. The pH dependence of the first-order rate constant of both phases shows a first-order dependence on proton concentration but with an inflection point ot pH 3.55 for the faster phase and at pH 4.03 for the slower phase. This behavior is interpreted in terms of the specific acid catalyzed formation of an intermediate from both "base on" and "base off" phenacylcobalamin with different second-order rate constants for each form, followed by an intermediate decompotion step with a similar formal mechanism. The nature of the intermediate is discussed and it is concluded to be a pi-complex between cob(III)alamin and the enol of acetophenone. PMID:4086

  19. DFT Study of Solvent Effects in Acid-Catalyzed Diels-Alder Cycloadditions of 2,5-Dimethylfuran and Maleic Anhydride.

    PubMed

    Salavati-fard, Taha; Caratzoulas, Stavros; Doren, Douglas J

    2015-09-24

    Density functional theory electronic structure calculations were used to explore the mechanism for the Diels-Alder reaction between 2,5-dimethylfuran and maleic anhydride (MA). Reaction paths are reported for uncatalyzed and Lewis and Brønsted acid-catalyzed reactions in vacuum and in a broad range of solvents. The calculations show that, while the uncatalyzed Diels-Alder reaction is thermally feasible in vacuum, a Lewis acid (modeled as Na(+)) lowers the activation barrier by interacting with the dienophile (MA) and decreasing the HOMO-LUMO gap of the reactants. A Brønsted acid (modeled as a proton) can bind to a carbonyl oxygen in MA, changing the reaction mechanism from concerted to stepwise and eliminating the activation barrier. Solvation effects were studied with the SMD model. Electrostatic effects play the largest role in determining the solvation energy of the transition state, which tracks the net dipole moment at the transition state. For the uncatalyzed reaction, the dipole moment is largely determined by charge transfer between the reactants, but in the reactions with ionic catalysts, there is no simple relationship between solvation of the transition state and charge transfer between the reactants. Nonelectrostatic contributions to solvation of the reactants and transition state also make significant contributions to the activation energy. PMID:26331220

  20. No evidence for acid-catalyzed secondary organic aerosol formation in power plant plumes over metropolitan Atlanta, Georgia - article no. L06801

    SciTech Connect

    Peltier, R.E.; Sullivan, A.P.; Weber, R.J.; Wollny, A.G.; Holloway, J.S.; Brock, C.A.; de Gouw, J.A.; Atlas, E.L.

    2007-03-15

    Aircraft-based measurements of the water-soluble fraction of fine PM organic carbon (WSOC) and inorganic salt composition in the Atlanta, GA region were conducted in the summer of 2004. Five notable plumes of SO{sub 2}, apparently from coal-fired power plants, were intercepted, and had NH{sub 4}{sup +}/SO4{sup 2-} molar ratios ranging from approximately 0.8 to 1.4 compared to molar ratios near 2 outside of the plumes. Sulfate aerosol concentrations increased from a regional background of 5 - 8 {mu} g m{sup -3} to as high as 19.5 {mu} g m{sup -3} within these plumes. No increase in WSOC concentrations was observed in plumes compared to out-of-plumes within a WSOC measurement uncertainty of 8%. These measurements suggest that secondary organic aerosol formation via heterogeneous acid-catalyzed reactions within power plant plumes are not likely a significant contributor to the ambient aerosol mass loading in Atlanta and the surrounding region. Because this region is rich in both biogenic and anthropogenic volatile organic carbon (VOC), the results may be widely applicable.

  1. Programmed Rearrangement in Ciliates: Paramecium.

    PubMed

    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. PMID:26104450

  2. Transposable elements as catalysts for chromosome rearrangements.

    PubMed

    Zhang, Jianbo; Yu, Chuanhe; Krishnaswamy, Lakshminarasimhan; Peterson, Thomas

    2011-01-01

    Barbara McClintock first showed that transposable elements in maize can induce major chromosomal rearrangements, including duplications, deletions, inversions, and translocations. More recently, researchers have made significant progress in elucidating the mechanisms by which transposons can induce genome rearrangements. For the Ac/Ds transposable element system, rearrangements are generated when the termini of different elements are used as substrates for transposition. The resulting alternative transposition reaction directly generates a variety of rearrangements. The size and type of rearrangements produced depend on the location and orientation of transposon insertion. A single locus containing a pair of alternative transposition-competent elements can produce a virtually unlimited number of genome rearrangements. With a basic understanding of the mechanisms involved, researchers are beginning to utilize both naturally occurring and in vitro-generated configurations of transposable elements in order to manipulate chromosome structure. PMID:21181539

  3. Regulation of immunoglobulin gene rearrangement and expression.

    PubMed

    Taussig, M J; Sims, M J; Krawinkel, U

    1989-05-01

    The molecular genetic events leading to Ig expression and their control formed the topic of a recent EMBO workshop. This report by Michael Taussig, Martin Sims and Ulrich Krawinkel discusses contributions dealing with genes expressed in early pre-B cells, the mechanism of rearrangement, aberrant rearrangements seen in B cells of SCID mice, the feedback control of rearrangement as studied in transgenic mice, the control of Ig expression at the transcriptional and post-transcriptional levels, and class switching. PMID:2787158

  4. Metal- and Oxidant-Free Synthesis of Quinazolinones from β-Ketoesters with o-Aminobenzamides via Phosphorous Acid-Catalyzed Cyclocondensation and Selective C-C Bond Cleavage.

    PubMed

    Li, Zhongwen; Dong, Jianyu; Chen, Xiuling; Li, Qiang; Zhou, Yongbo; Yin, Shuang-Feng

    2015-10-01

    A general and efficient phosphorous acid-catalyzed cyclocondensation of β-ketoesters with o-aminobenzamides via selective C-C bond cleavage leading to quinazolinones is developed. This reaction proceeds smoothly under metal- and oxidant-free conditions, giving both 2-alkyl- and 2-aryl-substituted quinazolinones in excellent yields. This strategy can also be applied to the synthesis of other N-heterocycles, such as benzimidazoles and benzothiazoles. PMID:26339716

  5. Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

    PubMed Central

    Ravikumar, Ongolu; Majhi, Jadab

    2015-01-01

    Summary A tricyclic lactam is reported in a four step synthesis sequence via Beckmann rearrangement and ring-rearrangement metathesis as key steps. Here, we used a simple starting material such as dicyclopentadiene. PMID:26425207

  6. Fractionation, rearrangement and subgenome dominance

    PubMed Central

    Sankoff, David; Zheng, Chunfang

    2012-01-01

    Motivation: Fractionation is arguably the greatest cause of gene order disruption following whole genome duplication, causing severe biases in chromosome rearrangement-based estimates of evolutionary divergence. Results: We show how to correct for this bias almost entirely by means of a ‘consolidation’ algorithm for detecting and suitably transforming identifiable regions of fractionation. We characterize the process of fractionation and the performance of the algorithm through realistic simulations. We apply our method to a number of core eudicot genomes, we and by studying the fractionation regions detected, are able to address topical issues in polyploid evolution. Availability and implementation: Code for the consolidation algorithm, and sample data, is available at: http://137.122.149.195/Software/Fractionation/fractionation.html Contact: sankoff@uottawa.ca PMID:22962459

  7. Interpolation schemes for peptide rearrangements

    NASA Astrophysics Data System (ADS)

    Bauer, Marianne S.; Strodel, Birgit; Fejer, Szilard N.; Koslover, Elena F.; Wales, David J.

    2010-02-01

    A variety of methods (in total seven) comprising different combinations of internal and Cartesian coordinates are tested for interpolation and alignment in connection attempts for polypeptide rearrangements. We consider Cartesian coordinates, the internal coordinates used in CHARMM, and natural internal coordinates, each of which has been interfaced to the OPTIM code and compared with the corresponding results for united-atom force fields. We show that aligning the methylene hydrogens to preserve the sign of a local dihedral angle, rather than minimizing a distance metric, provides significant improvements with respect to connection times and failures. We also demonstrate the superiority of natural coordinate methods in conjunction with internal alignment. Checking the potential energy of the interpolated structures can act as a criterion for the choice of the interpolation coordinate system, which reduces failures and connection times significantly.

  8. Interpolation schemes for peptide rearrangements.

    PubMed

    Bauer, Marianne S; Strodel, Birgit; Fejer, Szilard N; Koslover, Elena F; Wales, David J

    2010-02-01

    A variety of methods (in total seven) comprising different combinations of internal and Cartesian coordinates are tested for interpolation and alignment in connection attempts for polypeptide rearrangements. We consider Cartesian coordinates, the internal coordinates used in CHARMM, and natural internal coordinates, each of which has been interfaced to the OPTIM code and compared with the corresponding results for united-atom force fields. We show that aligning the methylene hydrogens to preserve the sign of a local dihedral angle, rather than minimizing a distance metric, provides significant improvements with respect to connection times and failures. We also demonstrate the superiority of natural coordinate methods in conjunction with internal alignment. Checking the potential energy of the interpolated structures can act as a criterion for the choice of the interpolation coordinate system, which reduces failures and connection times significantly. PMID:20136299

  9. Rearrangement of sulfonamidyl radicals with hydrogen migration

    SciTech Connect

    Troyanskii, E.I.; Lazareva, M.I.; Nikishin, G.I.

    1987-01-20

    One-step outlying oxidative chlorination of alkanesulfonamides by the action of the Na/sub 2/S/sub 2/O/sub 8/-CuCl/sub 2/ system via intermediate sulfonamidyl radicals gives 3- and 4-chloroalkanesulfonamides. Rearrangements of sulfonamidyl radicals with H atom migration from the sulfonyl segment predominates over rearrangement with H atom migration from the amide segment.

  10. Inspiring Examples in Rearrangements of Infinite Products

    ERIC Educational Resources Information Center

    Ramasinghe, W.

    2007-01-01

    It is well known that simple examples are really encouraging in the understanding of rearrangements of infinite series. In this paper a similar role is played by simple examples in the case of infinite products. Iterated products of double products seem to have a similar spirit of rearrangements of products, although they are not the same.…

  11. Lack of feedback inhibition of V kappa gene rearrangement by productively rearranged alleles.

    PubMed

    Harada, K; Yamagishi, H

    1991-02-01

    Circular DNAs excised by immunoglobulin kappa chain gene rearrangements were cloned and characterized. 16 of 17 clones examined were double recombination products containing a V kappa-J kappa rearrangement (coding joint) as well as the reciprocal element (signal joint) of another V kappa-J kappa rearrangement. These products suggested multiple recombination, primary inversion, and secondary excision. In primary events, 5 of 16 translational reading frames were in-phase. Thus, V kappa gene rearrangement may not be inhibited by the presence of a productively rearranged allele. An unusually large trinucleotide (P) insertion forming a palindrome of 12 nucleotides was also observed in one of the coding joints. PMID:1988542

  12. Rearrangements of organic peroxides and related processes

    PubMed Central

    Yaremenko, Ivan A; Vil’, Vera A; Demchuk, Dmitry V

    2016-01-01

    Summary 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. PMID:27559418

  13. Chromosome rearrangements and transposable elements.

    PubMed

    Lonnig, Wolf-Ekkehard; Saedler, Heinz

    2002-01-01

    There has been limited corroboration to date for McClintock's vision of gene regulation by transposable elements (TEs), although her proposition on the origin of species by TE-induced complex chromosome reorganizations in combination with gene mutations, i.e., the involvement of both factors in relatively sudden formations of species in many plant and animal genera, has been more promising. Moreover, resolution is in sight for several seemingly contradictory phenomena such as the endless reshuffling of chromosome structures and gene sequences versus synteny and the constancy of living fossils (or stasis in general). Recent wide-ranging investigations have confirmed and enlarged the number of earlier cases of TE target site selection (hot spots for TE integration), implying preestablished rather than accidental chromosome rearrangements for nonhomologous recombination of host DNA. The possibility of a partly predetermined generation of biodiversity and new species is discussed. The views of several leading transposon experts on the rather abrupt origin of new species have not been synthesized into the macroevolutionary theory of the punctuated equilibrium school of paleontology inferred from thoroughly consistent features of the fossil record. PMID:12429698

  14. The speed of topological rearrangements in foam

    NASA Astrophysics Data System (ADS)

    Thoroddsen, S. T.; Tan, E.

    1999-11-01

    Coarsening of dry foam is characterized by a slow diffusion of gas across the fluid films separating adjacent foam cells, punctuated by rapid topological rearrangements of the polyhedral network. In this work we measure and model the speed of a typical rearrangement event, which has been reproduced on an adjustable metal frame. The interstitial liquid viscosity is varied by adding glycerin to the water/soap solution and is found to reduce the speed only at high viscosities. Marangoni effects play on the other hand a pivotal role for the lowest soap concentrations, greatly slowing down the rearrangements.

  15. Untangling Membrane Rearrangement in the Nidovirales

    PubMed Central

    Angelini, Megan Mary; Neuman, Benjamin William

    2014-01-01

    All known positive sense single-stranded RNA viruses induce host cell membrane rearrangement for purposes of aiding viral genome replication and transcription. Members of the Nidovirales order are no exception, inducing intricate regions of double membrane vesicles and convoluted membranes crucial for the production of viral progeny. Although these structures have been well studied for some members of this order, much remains unclear regarding the biogenesis of these rearranged membranes. Here, we discuss what is known about these structures and their formation, compare some of the driving viral proteins behind this process across the nidovirus order, and examine possible routes of mechanism by which membrane rearrangement may occur. PMID:24410069

  16. The cytogenetics of mammalian autosomal rearrangements

    SciTech Connect

    Daniel, A. )

    1988-01-01

    This book is covered under the following topics: Ascertainment and risks of recombinant progeny; Infertility, gametic selection, and fetal loss; origin of chromosome rearrangements; and Some implications of chromosome breakpoints.

  17. Glycolytic regulation of cell rearrangement in angiogenesis

    PubMed Central

    Cruys, Bert; Wong, Brian W.; Kuchnio, Anna; Verdegem, Dries; Cantelmo, Anna Rita; Conradi, Lena-Christin; Vandekeere, Saar; Bouché, Ann; Cornelissen, Ivo; Vinckier, Stefan; Merks, Roeland M. H.; Dejana, Elisabetta; Gerhardt, Holger; Dewerchin, Mieke; Bentley, Katie; Carmeliet, Peter

    2016-01-01

    During vessel sprouting, endothelial cells (ECs) dynamically rearrange positions in the sprout to compete for the tip position. We recently identified a key role for the glycolytic activator PFKFB3 in vessel sprouting by regulating cytoskeleton remodelling, migration and tip cell competitiveness. It is, however, unknown how glycolysis regulates EC rearrangement during vessel sprouting. Here we report that computational simulations, validated by experimentation, predict that glycolytic production of ATP drives EC rearrangement by promoting filopodia formation and reducing intercellular adhesion. Notably, the simulations correctly predicted that blocking PFKFB3 normalizes the disturbed EC rearrangement in high VEGF conditions, as occurs during pathological angiogenesis. This interdisciplinary study integrates EC metabolism in vessel sprouting, yielding mechanistic insight in the control of vessel sprouting by glycolysis, and suggesting anti-glycolytic therapy for vessel normalization in cancer and non-malignant diseases. PMID:27436424

  18. Glycolytic regulation of cell rearrangement in angiogenesis.

    PubMed

    Cruys, Bert; Wong, Brian W; Kuchnio, Anna; Verdegem, Dries; Cantelmo, Anna Rita; Conradi, Lena-Christin; Vandekeere, Saar; Bouché, Ann; Cornelissen, Ivo; Vinckier, Stefan; Merks, Roeland M H; Dejana, Elisabetta; Gerhardt, Holger; Dewerchin, Mieke; Bentley, Katie; Carmeliet, Peter

    2016-01-01

    During vessel sprouting, endothelial cells (ECs) dynamically rearrange positions in the sprout to compete for the tip position. We recently identified a key role for the glycolytic activator PFKFB3 in vessel sprouting by regulating cytoskeleton remodelling, migration and tip cell competitiveness. It is, however, unknown how glycolysis regulates EC rearrangement during vessel sprouting. Here we report that computational simulations, validated by experimentation, predict that glycolytic production of ATP drives EC rearrangement by promoting filopodia formation and reducing intercellular adhesion. Notably, the simulations correctly predicted that blocking PFKFB3 normalizes the disturbed EC rearrangement in high VEGF conditions, as occurs during pathological angiogenesis. This interdisciplinary study integrates EC metabolism in vessel sprouting, yielding mechanistic insight in the control of vessel sprouting by glycolysis, and suggesting anti-glycolytic therapy for vessel normalization in cancer and non-malignant diseases. PMID:27436424

  19. Thermal rearrangement of tert-butylsulfinamide

    PubMed Central

    Gorentla, Laxminarasimhulu; Dubey, Pramod Kumar

    2011-01-01

    Summary tert-Butylsulfinamides are unstable above room temperature, and in chlorinated solvents they undergo rearrangement to form the more stable N-(tert-butylthio)-tert-butylsulfonamide. PMID:21286388

  20. Brønsted Acid Catalyzed [3+2]-Cycloaddition of 2-Vinylindoles with In Situ Generated 2-Methide-2H-indoles: Highly Enantioselective Synthesis of Pyrrolo[1,2-a]indoles.

    PubMed

    Bera, Kalisankar; Schneider, Christoph

    2016-05-17

    Pyrrolo[1,2-a]indoles are privileged structural elements of many natural products and pharmaceuticals. An efficient one-step process for their highly diastereo- and enantioselective synthesis, comprising a direct [3+2]-cycloaddition, has been developed. A chiral BINOL-derived phosphoric acid catalyzes the reaction of in situ-generated 2-methide-2H-indoles with 2-vinylindoles, furnishing the target products incorporating three contiguous stereogenic centers as single diastereoisomers and with excellent yields and enantioselectivities. PMID:26991961

  1. Crystal structure of 2α-(1,1-di­phenyl­eth­yl)-4-methyl-4α,5α-diphenyl-1,3-dioxolane: the result of a non-acid pinacol rearrangement

    PubMed Central

    Kirchner, Richard M.; Corfield, Peter W. R.; Annabi, Michelle; Regan, John; Speina, Kevin; DiProperzio, Anthony; Ciaccio, James A.; Capitani, Joseph F.

    2015-01-01

    The title compound, C30H28O2, was obtained during recrystallization of (±)-1,2-diphenyl-1,2-propane­diol in 1-butanol, from an unexpected non-acid-catalyzed pinacol rearrangement followed by acetal formation of the newly formed aldehyde with the diol. The tri-substituted dioxolane ring has a twist conformation on the C—O bond opposite the methyl-substituted C atom. There is an intra­molecular C—H⋯π inter­action present involving one of the di­phenyl­ethyl rings and an H atom of the phenyl ring in position 4 of the dioxolane ring. In the crystal, mol­ecules are linked by weak C—H⋯O hydrogen bonds, forming chains along [001]. The chains are linked by a second C—H⋯π inter­action, forming sheets parallel to the bc plane. PMID:26594491

  2. [Development and synthetic application of epoxysilane rearrangement].

    PubMed

    Sasaki, Michiko

    2008-08-01

    O-Silyl cyanohydrins of beta-silyl-alpha,beta-epoxyaldehyde can function as a highly functionalized homoenolate equivalent via a tandem sequence involving base-promoted ring opening, Brook rearrangement, and alkylation at the allylic position. We named this rearrangement epoxysilane rearrangement. Based on results of mechanistic studies involving competitive experiments using diastereomeric cyanohydrins, we propose a reaction pathway involving a silicate intermediate formed by a concerted process via an anti-opening of the epoxide followed by the formation of an O-Si bond. Moreover, results of mechanistic studies on the rearrangement led to a conceptually novel approach to the chirality transfer in which epoxide chirality can be transferred into carbanion. We demonstrate the usefulness of the rearrangement through application to the following reactions: (1) reaction of gamma-p-toluenesulfonyl-alpha,beta-epoxysilane with alkyl halides and aldehydes followed by treatment with n-Bu4NF, which affords alpha,beta-unsaturated aldehydes (2) reaction of gamma-phosphonio-alpha,beta-epoxysilane with aldehydes, which affords dienol silyl ether derivatives (3) reaction of an enoate bearing an eposysilane moiety at the alpha-position with lithium enolate of 2-chloroacetamide, which affords highly functionalized cyclopropane derivatives. PMID:18670182

  3. FLNA genomic rearrangements cause periventricular nodular heterotopia

    PubMed Central

    Clapham, K.R.; Yu, T.W.; Ganesh, V.S.; Barry, B.; Chan, Y.; Mei, D.; Parrini, E.; Funalot, B.; Dupuis, L.; Nezarati, M.M.; du Souich, C.; van Karnebeek, C.

    2012-01-01

    Objective: To identify copy number variant (CNV) causes of periventricular nodular heterotopia (PNH) in patients for whom FLNA sequencing is negative. Methods: Screening of 35 patients from 33 pedigrees on an Affymetrix 6.0 microarray led to the identification of one individual bearing a CNV that disrupted FLNA. FLNA-disrupting CNVs were also isolated in 2 other individuals by multiplex ligation probe amplification. These 3 cases were further characterized by high-resolution oligo array comparative genomic hybridization (CGH), and the precise junctional breakpoints of the rearrangements were identified by PCR amplification and sequencing. Results: We report 3 cases of PNH caused by nonrecurrent genomic rearrangements that disrupt one copy of FLNA. The first individual carried a 113-kb deletion that removes all but the first exon of FLNA. A second patient harbored a complex rearrangement including a deletion of the 3′ end of FLNA accompanied by a partial duplication event. A third patient bore a 39-kb deletion encompassing all of FLNA and the neighboring gene EMD. High-resolution oligo array CGH of the FLNA locus suggests distinct molecular mechanisms for each of these rearrangements, and implicates nearby low copy repeats in their pathogenesis. Conclusions: These results demonstrate that FLNA is prone to pathogenic rearrangements, and highlight the importance of screening for CNVs in individuals with PNH lacking FLNA point mutations. Neurology® 2012;78:269–278 PMID:22238415

  4. Algorithm to search for genomic rearrangements

    NASA Astrophysics Data System (ADS)

    Nałecz-Charkiewicz, Katarzyna; Nowak, Robert

    2013-10-01

    The aim of this article is to discuss the issue of comparing nucleotide sequences in order to detect chromosomal rearrangements (for example, in the study of genomes of two cucumber varieties, Polish and Chinese). Two basic algorithms for detecting rearrangements has been described: Smith-Waterman algorithm, as well as a new method of searching genetic markers in combination with Knuth-Morris-Pratt algorithm. The computer program in client-server architecture was developed. The algorithms properties were examined on genomes Escherichia coli and Arabidopsis thaliana genomes, and are prepared to compare two cucumber varieties, Polish and Chinese. The results are promising and further works are planned.

  5. Tyrosine kinase gene rearrangements in epithelial malignancies

    PubMed Central

    Shaw, Alice T.; Hsu, Peggy P.; Awad, Mark M.; Engelman, Jeffrey A.

    2014-01-01

    Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as ‘druggable’ targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours. PMID:24132104

  6. Osteosarcoma With Apparent Ewing Sarcoma Gene Rearrangement.

    PubMed

    Mathias, Melissa D; Chou, Alexander J; Meyers, Paul; Shukla, Neerav; Hameed, Meera; Agaram, Narasimhan; Wang, Lu; Berger, Michael F; Walsh, Michael; Kentsis, Alex

    2016-07-01

    Poorly differentiated round cell sarcomas present diagnostic challenges because of their variable morphology and lack of specific immunophenotypic markers. We present a case of a 15-year-old female with a tibial tumor that exhibited features of Ewing-like sarcoma, including apparent rearrangement of the EWSR1 gene. Hybridization capture-based next-generation DNA sequencing showed evidence of complex genomic rearrangements, absence of known pathogenic Ewing-like chromosome translocations, and deletions RB1, PTCH1, and ATRX, supporting the diagnosis of osteosarcoma. This illustrates the potential of clinical genomic profiling to improve diagnosis and enable specifically targeted therapies for cancers with complex pathologies. PMID:27352193

  7. Thermal Claisen rearrangement of N-allylanilines

    SciTech Connect

    Abdrakhmanov, I.B.; Saraeva, Z.N.; Nigmatullin, N.G.; Tolstikov, G.A.

    1986-08-20

    Thermal Claisen rearrangement of N-allylanilines in undecane is accompanied by a parallel reaction involving elimination of the allyl fragment. The former reaction proceeds according to a (3,3)-sigmatropic mechanism with a varied structure of transition state, depending on the nature of the allyl substituent. The rearrangement of N-(2-chloro-1-methyl-2-butenyl)aniline has an autocatalytic nature on account of the HCl formed on elimination of the allyl fragment. The initial formation of an unreactive complex with composition (amine):(HCl) = 2:1, which decomposes by the action of a second HCl molecule, is postulated.

  8. Facility rearrangement scoping study: Draft letter report

    SciTech Connect

    Not Available

    1987-04-17

    We assessed the feasibility of designing the salt repository layouts so that shafts, surface structures and facilities would be totally within the north-east (NE) and center-east (CE) (one square mile) sections of the 9 square mile Deaf Smith site. With the latest version of the SCP-Conceptual Design as the basis, rearrangement analyses were conducted for the surface and subsurface layouts. For the rearranged layouts that were workable, impact assessments, relative to the SCP-Conceptual Design, were performed. This study concluded that, on a qualitative basis, the salt repository surface facilities can be relocated to within the north-east and center-east sections of the site. A suitable subsurface layout can be designed to accommodate this rearrangement. The resultant surface rearrangement is depicted. The two study sections (NE and CE) are emphasized on this figure. For reference, the location of the surface facilities in the SCP-Conceptual Design is also shown. 11 refs., 1 tab.

  9. Dynamics of Genome Rearrangement in Bacterial Populations

    PubMed Central

    Darling, Aaron E.; Miklós, István; Ragan, Mark A.

    2008-01-01

    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 represent the

  10. Deep cytoplasmic rearrangements in ventralized Xenopus embryos

    NASA Technical Reports Server (NTRS)

    Brown, E. E.; Denegre, J. M.; Danilchik, M. V.

    1993-01-01

    Following fertilization in Xenopus, dramatic rearrangements of the egg cytoplasm relocalize maternally synthesized egg components. During the first cell cycle the vegetal yolk mass rotates relative to the egg surface, toward the sperm entry point (SEP) (J. P. Vincent, G. F. Oster, and J. C. Gerhart, 1986, Dev. Biol. 113, 484-500), while concomitant deep cytoplasmic rearrangements occur in the animal hemisphere (M. V. Danilchik and J. M. Denegre, 1991, Development 111, 845-856). In this paper we examine the role of vegetal yolk mass rotation in producing the animal cytoplasmic rearrangements. We inhibited rotation by uv-irradiating embryos during the first cell cycle, a treatment that yields an extremely ventralized phenotype. Both uv-irradiated embryos and unirradiated control embryos show cytoplasmic rearrangements in the animal hemisphere during the first cell cycle. Cytoplasmic rearrangements on the SEP side of the embryo associated with the path of the sperm pronucleus, plus a swirl on the anti-SEP (dorsal) side, are seen, whether or not yolk mass rotation has occurred. This result suggests a role for the expanding sperm aster in directing animal hemisphere cytoplasmic movements. In unirradiated control embryos the anti-SEP (dorsal) swirl is larger than that in uv-irradiated embryos and often extends into the vegetal hemisphere, consistent with the animal cytoplasm having been pulled dorsally and vegetally by the sliding vegetal yolk mass. Thus the yolk mass rotation may normally enhance the dorsalward cytoplasmic movement, begun by the sperm aster, enough to induce normal axis formation. We extended our observations of unirradiated control and uv-irradiated embryos through early cleavages. The vegetal extent of the anti-SEP (dorsal) swirl pattern seen in control embryos persists through the early cleavage period, such that labeled animal cytoplasm extends deep into dorsal third-tier blastomeres at the 32-cell stage. Significantly, in uv-irradiated embryos

  11. Organometallic Enantiomeric Scaffolding: General Access to 2-Substituted Oxa- and Azabicyclo[3.2.1]octenes via a Brønsted Acid-catalyzed [5+2] Cycloaddition Reaction

    PubMed Central

    Garnier, Ethel C.; Liebeskind, Lanny S.

    2009-01-01

    6-Substituted TpMo(CO)2(η-2,3,4-pyranyl)- and TpMo(CO)2(η-2,3,4-pyridinyl) scaffolds (Tp = hydridotrispyrazolylborato) function as reaction partners in an efficient regio- and stereocontrolled synthesis of functionalized oxa- and azabicyclo[3.2.1]octenes through a novel Brønsted acid-catalyzed [5+2] cycloaddition reaction. Excellent exo-selectivities are obtained and the reaction gives products with complete retention of enantiomeric purity when carried out with chiral, non-racemic scaffolds. The substituent at C-6 of the η3-coordinated heterocyclic scaffold not only influences [5+2] reactivity but also plays a critical role in the demetalation step directing the reaction to only one of two possible products. PMID:18479131

  12. Methods for Detecting Chromosome Rearrangements in Gibberella Zeae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chromosome rearrangements between fungal strains may reduce fertility in sexual crosses through the production of genetically inviable recombinant progeny. As such, rearrangements can be important postzygotic reproductive barriers that contribute to the speciation process. The presence of chromosom...

  13. Sampling and counting genome rearrangement scenarios

    PubMed Central

    2015-01-01

    Background Even for moderate size inputs, there are a tremendous number of optimal rearrangement scenarios, regardless what the model is and which specific question is to be answered. Therefore giving one optimal solution might be misleading and cannot be used for statistical inferring. Statistically well funded methods are necessary to sample uniformly from the solution space and then a small number of samples are sufficient for statistical inferring. Contribution In this paper, we give a mini-review about the state-of-the-art of sampling and counting rearrangement scenarios, focusing on the reversal, DCJ and SCJ models. Above that, we also give a Gibbs sampler for sampling most parsimonious labeling of evolutionary trees under the SCJ model. The method has been implemented and tested on real life data. The software package together with example data can be downloaded from http://www.renyi.hu/~miklosi/SCJ-Gibbs/ PMID:26452124

  14. Rearrangements in 2-Dimensional Foam Simulations

    NASA Astrophysics Data System (ADS)

    Schiemann, Dylan; Tewari, Shubha; Liu, Andrea; Knobler, Charles; Durian, Douglas; Dennin, Michael; Langer, Stephen

    1998-03-01

    Foam is a collection of densely-packed polydisperse gas bubbles in liquid. Upon shear, the total interaction energy between bubbles fluctuates: it builds up and then is released via intermittent rearrangements of the bubbles. There is presently no effective experimental method for measuring these energy releases. However, it is possible to observe the relaxation of sheared foam through the analysis of topological rearrangements, or neighbor-switching events (T1 events) footnote A.D. Gopal and D.J. Durian, Phys. Rev. Lett. 75 2610 (1995) footnote M. Dennin and C.M. Knobler, Phys. Rev. Lett. 78 2485 (1997) We have used a simple two-dimensional model of foam proposed by Durian footnote D.J. Durian, Phys. Rev. Lett. 75 4780 (1995) to study rearrangements under steady-state shear flow. The aim is to study the connection between T1 events, which are typically measured experimentally, and the distribution of energy releases, which is typically measured from simulations. We find that T1 events tend to correspond to the largest energy releases. We present results as a function of strain rate and area fraction of bubbles.

  15. A new class of rearrangeable interconnection networks

    SciTech Connect

    Douglass, B.G.

    1989-01-01

    With the current interest in general purpose multiprocessing systems and distributed processing networks, a need exists for rearrangeable interconnection networks. These networks can simultaneously transmit information from all sources to all destinations, for all possible combinations of destinations. Such networks exist, and among these the Benes network is of asymptotically optimal hardware complexity. However, this network requires excessive time to recompute the switch settings each time a new set of transmissions is requested by the source processors. Some algorithms exist to reduce this time overhead but they require excessive hardware to compute the settings. This thesis introduces a new class of rearrangeable networks, called reduced networks, based on an extension of Clos three-stage networks. It is shown that the switches in the first and third stages of Clos networks can be constructed as unique path logarithmic networks. Only the center-stage switches must be rearrangeable. This fact is then used to develop a compact network structure. The routing properties of this structure are defined, and it is shown that there is a connectivity in the setting of the switches for any Clos network. An upper and lower bound on this connectivity are established, leading to a fast routing algorithm, with a trade off between the routing time and the network hardware complexity. This can be exploited by the network designer to achieve the best combination of hardware cost and data transfer rate for the particular application. For network sizes contemplated within the foreseeable future, the resulting design will in most cases be closer to the ideal combination than any other network.

  16. A general heuristic for genome rearrangement problems.

    PubMed

    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. PMID:24969750

  17. Nonclassical 21-Homododecahedryl Cation Rearrangement Revisited.

    PubMed

    Jalife, Said; Mondal, Sukanta; Osorio, Edison; Cabellos, José Luis; Martínez-Guajardo, Gerardo; Fernández-Herrera, María A; Merino, Gabriel

    2016-03-01

    The degenerate rearrangement in the 21-homododecahedryl cation (1) has been studied via density functional theory computations and Born-Oppenheimer Molecular Dynamics simulations. Compound 1 can be described as a highly fluxional hyperconjugated carbocation. Complete scrambling of 1 can be achieved by the combination of two unveiled barrierless processes. The first one is a "rotation" of one of the six-membered rings via a 0.8 kcal·mol(-1) barrier, and the second one is a slower interconvertion between two hyperconjomers via an out-of-plane methine bending (ΔG(⧧) = 4.0 kcal·mol(-1)). PMID:26862680

  18. Catalytic Environmentally Friendly Protocol for Achmatowicz Rearrangement.

    PubMed

    Li, Zhilong; Tong, Rongbiao

    2016-06-01

    The increasing interest in Achmatowicz rearrangement in organic synthesis calls for a more environmentally friendly protocol since the most popular oxidants m-CPBA and NBS produced stoichiometric organic side product (m-chlorobenzoic acid or succinimide). Mechanism-guided analysis enables us to develop a new catalytic method (Oxone/KBr) for AchR in excellent yield with K2SO4 as the only side product, which greatly facilitates the purification. This protocol was integrated with other transformations, leading to a rapid access to the highly functionalized dihydropyranones. PMID:27167167

  19. Structures of Local Rearrangements in Soft Colloidal Glasses

    NASA Astrophysics Data System (ADS)

    Yang, Xiunan; Liu, Rui; Yang, Mingcheng; Wang, Wei-Hua; Chen, Ke

    2016-06-01

    We image local structural rearrangements in soft colloidal glasses under small periodic perturbations induced by thermal cycling. Local structural entropy S2 positively correlates with observed rearrangements in colloidal glasses. The high S2 values of the rearranging clusters in glasses indicate that fragile regions in glasses are structurally less correlated, similar to structural defects in crystalline solids. Slow-evolving high S2 spots are capable of predicting local rearrangements long before the relaxations occur, while fluctuation-created high S2 spots best correlate with local deformations right before the rearrangement events. Local free volumes are also found to correlate with particle rearrangements at extreme values, although the ability to identify relaxation sites is substantially lower than S2. Our experiments provide an efficient structural identifier for the fragile regions in glasses and highlight the important role of structural correlations in the physics of glasses.

  20. Structures of Local Rearrangements in Soft Colloidal Glasses.

    PubMed

    Yang, Xiunan; Liu, Rui; Yang, Mingcheng; Wang, Wei-Hua; Chen, Ke

    2016-06-10

    We image local structural rearrangements in soft colloidal glasses under small periodic perturbations induced by thermal cycling. Local structural entropy S_{2} positively correlates with observed rearrangements in colloidal glasses. The high S_{2} values of the rearranging clusters in glasses indicate that fragile regions in glasses are structurally less correlated, similar to structural defects in crystalline solids. Slow-evolving high S_{2} spots are capable of predicting local rearrangements long before the relaxations occur, while fluctuation-created high S_{2} spots best correlate with local deformations right before the rearrangement events. Local free volumes are also found to correlate with particle rearrangements at extreme values, although the ability to identify relaxation sites is substantially lower than S_{2}. Our experiments provide an efficient structural identifier for the fragile regions in glasses and highlight the important role of structural correlations in the physics of glasses. PMID:27341261

  1. The Stereochemical Course of the α-Hydroxyphosphonate–Phosphate Rearrangement

    PubMed Central

    Pallitsch, Katharina; Roller, Alexander; Hammerschmidt, Friedrich

    2015-01-01

    The phosphonate–phosphate rearrangement is an isomerisation of α-hydroxyphosphonates bearing electron-withdrawing substituents at the α-carbon atom. We studied the stereochemical course of this rearrangement with respect to phosphorus. A set of four diastereomeric α-hydroxyphosphonates was prepared by a Pudovik reaction from two diastereomeric cyclic phosphites. The hydroxyphosphonates were separated and rearranged with Et3N as base. In analogy to trichlorphon, which was the first reported compound undergoing this rearrangement. All four hydroxyphosphonates could be rearranged to 2,2-dichlorovinyl phosphates. Single-crystal X-ray structure analyses of the α-hydroxyphosphonates and the corresponding phosphates allowed us to show that the rearrangement proceeds with retention of configuration on the phosphorus atom. PMID:26059025

  2. Programmed genome rearrangements in the ciliate Oxytricha

    PubMed Central

    Yerlici, V. Talya; Landweber, Laura F.

    2015-01-01

    The ciliate Oxytricha is a microbial eukaryote with two genomes, one of which experiences extensive genome remodeling during development. Each round of conjugation initiates a cascade of events that construct a transcriptionally active somatic genome from a scrambled germline genome, with considerable help from both long and small noncoding RNAs. This process of genome remodeling entails massive DNA deletion and reshuffling of remaining DNA segments to form functional genes from their interrupted and scrambled germline precursors. The use of Oxytricha as a model system provides an opportunity to study an exaggerated form of programmed genome rearrangement. Furthermore, studying the mechanisms that maintain nuclear dimorphism and mediate genome rearrangement has demonstrated a surprising plasticity and diversity of non-coding RNA pathways, with new roles that go beyond conventional gene silencing. Another aspect of ciliate genetics is their unorthodox patterns of RNA-mediated, epigenetic inheritance, that rival Mendelian inheritance. This review takes the reader through the key experiments in a model eukaryote that led to fundamental discoveries in RNA biology and pushes the biological limits of DNA processing. PMID:26104449

  3. Exceptional complex chromosomal rearrangements in three generations.

    PubMed

    Kartapradja, Hannie; Marzuki, Nanis Sacharina; Pertile, Mark D; Francis, David; Suciati, Lita Putri; Anggaratri, Helena Woro; Ambarwati, Debby Dwi; Idris, Firman Prathama; Lesmana, Harry; Trimarsanto, Hidayat; Paramayuda, Chrysantine; Harahap, Alida Roswita

    2015-01-01

    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. PMID:25722897

  4. Exceptional Complex Chromosomal Rearrangements in Three Generations

    PubMed Central

    Kartapradja, Hannie; Marzuki, Nanis Sacharina; Pertile, Mark D.; Francis, David; Suciati, Lita Putri; Anggaratri, Helena Woro; Ambarwati, Debby Dwi; Idris, Firman Prathama; Lesmana, Harry; Trimarsanto, Hidayat; Paramayuda, Chrysantine; Harahap, Alida Roswita

    2015-01-01

    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. PMID:25722897

  5. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors.

    PubMed

    Valentijn, Linda J; Koster, Jan; Zwijnenburg, Danny A; Hasselt, Nancy E; van Sluis, Peter; Volckmann, Richard; van Noesel, Max M; George, Rani E; Tytgat, Godelieve A M; Molenaar, Jan J; Versteeg, Rogier

    2015-12-01

    Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. PMID:26523776

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

    PubMed Central

    Hare, Stephanie R

    2016-01-01

    Summary 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. PMID:27340434

  7. Dispersion-Energy-Driven Wagner–Meerwein Rearrangements in Oligosilanes

    PubMed Central

    2016-01-01

    The installation of structural complex oligosilanes from linear starting materials by Lewis acid induced skeletal rearrangement reactions was studied under stable ion conditions. The produced cations were fully characterized by multinuclear NMR spectroscopy at low temperature, and the reaction course was studied by substitution experiments. The results of density functional theory calculations indicate the decisive role of attractive dispersion forces between neighboring trimethylsilyl groups for product formation in these rearrangement reactions. These attractive dispersion interactions control the course of Wagner–Meerwein rearrangements in oligosilanes, in contrast to the classical rearrangement in hydrocarbon systems, which are dominated by electronic substituent effects such as resonance and hyperconjugation. PMID:27195490

  8. Dispersion-Energy-Driven Wagner-Meerwein Rearrangements in Oligosilanes.

    PubMed

    Albers, Lena; Rathjen, Saskia; Baumgartner, Judith; Marschner, Christoph; Müller, Thomas

    2016-06-01

    The installation of structural complex oligosilanes from linear starting materials by Lewis acid induced skeletal rearrangement reactions was studied under stable ion conditions. The produced cations were fully characterized by multinuclear NMR spectroscopy at low temperature, and the reaction course was studied by substitution experiments. The results of density functional theory calculations indicate the decisive role of attractive dispersion forces between neighboring trimethylsilyl groups for product formation in these rearrangement reactions. These attractive dispersion interactions control the course of Wagner-Meerwein rearrangements in oligosilanes, in contrast to the classical rearrangement in hydrocarbon systems, which are dominated by electronic substituent effects such as resonance and hyperconjugation. PMID:27195490

  9. Acid-catalyzed carboxylic acid esterification and ester hydrolysis mechanism: acylium ion as a sharing active intermediate via a spontaneous trimolecular reaction based on density functional theory calculation and supported by electrospray ionization-mass spectrometry.

    PubMed

    Shi, Hongchang; Wang, Yilei; Hua, Ruimao

    2015-11-11

    By DFT calculation, we found that acid-catalyzed carboxylic acid esterification and ester hydrolysis are brief two-step reactions. First, the carboxylic acid hydroxyl-oxygen or ester alkyl-oxygen is protonated, which generates a highly active acylium ion. The protonation requires an activation energy (Ea) of 4-10 kcal mol(-1), and is the rate-controlling step of the esterification or hydrolysis. Sequentially, the acylium ion spontaneously reacts with two alcohol or two water molecules to form a neutral product molecule; this is a trimolecular reaction. The acylium ion is the highly active intermediate shared by esterification and hydrolysis. ESI-MS data for several typical carboxylic acids confirmed that their acylium ions are easily generated. For 2,4,6-trialkylbenzoic acid and its ester, the two unsubstituted carbons in the benzene ring are very easily protonated, and we have thus revealed the root of the success of Newman's method. Based on these results, the popular esterification and hydrolysis mechanism in organic chemistry textbooks is incorrect. PMID:26445892

  10. Common Gene Rearrangements in Prostate Cancer

    PubMed Central

    Rubin, Mark A.; Maher, Christopher A.; Chinnaiyan, Arul M.

    2011-01-01

    Prostate cancer is a common heterogeneous disease, and most patients diagnosed in the post prostate-specific antigen (PSA) era present with clinically localized disease, the majority of which do well regardless of treatment regimen undertaken. Overall, those with advanced prostate cancer at time of diagnosis do poorly after androgen withdrawal therapy. Understanding the biologic underpinning of prostate cancer is necessary to best determine the risk of disease progression and would be advantageous for the development of novel therapeutic approaches to impede or prevent disease. This review focuses on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer. Although multiple molecular alterations have been detected in prostate cancer, a detailed understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity, providing a rationale for a molecular subclassification of the disease. PMID:21859993

  11. New progress in snake mitochondrial gene rearrangement.

    PubMed

    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. PMID:19479623

  12. Cytoplasmic rearrangements associated with amphibian egg symmetrization

    NASA Technical Reports Server (NTRS)

    Malacinski, G. M.

    1984-01-01

    Cytoplasmic rearrangements which follow fertilization were mentioned in normal and inverted eggs. A set of yolk compartments was resolved by cytological analyses of both normally oriented and inverted eggs. Those compartments were characterized by their yolk platelet compositions and movement during egg inversion. It is found that during egg inversion the yolk compartments shift minor cytoplasmic compartments which line the egg cortex. Those yolk mass shifts occurred only after the inverted egg was activated. The direction of shift of the major yolk components, rather than the sperm entrance site, determines the dorsal/ventral polarity of the inverted egg. Among different spawnings the rate of shift varied. Eggs that displayed the fastest rate of shift exhibited the highest frequency of developmental abnormalities during organogenesis. Interpretation of novel observations on cytoplasmic organization provide criticism of some earlier models. A new density compartment model is presented as a coherent way to view the organization of the egg cytoplasm and the development of bilateral symmetry.

  13. Minimal distortion pathways in polyhedral rearrangements.

    PubMed

    Casanova, David; Cirera, Jordi; Llunell, Miquel; Alemany, Pere; Avnir, David; Alvarez, Santiago

    2004-02-18

    A definition of minimum distortion paths between two polyhedra in terms of continuous shape measures (CShM) is presented. A general analytical expression deduced for such pathways makes use of one parameter, the minimum distortion constant, that can be easily obtained through the CShM methodology and is herein tabulated for pairs of polyhedra having four to eight vertexes. The work presented here also allows us to obtain representative model molecular structures along the interconversion pathways. Several commonly used polytopal rearrangement pathways are shown to be in fact minimum distortion pathways: the spread path leading from the tetrahedron to the square, the Berry pseudorotation that interconverts a square pyramid and a trigonal bipyramid, and the Bailar twist for the interconversion of the octahedron and the trigonal prism. Examples of applications to the analysis of the stereochemistries of several families of metal complexes are presented. PMID:14871107

  14. Enantioselective Claisen rearrangements with a hydrogen-bond donor catalyst.

    PubMed

    Uyeda, Christopher; Jacobsen, Eric N

    2008-07-23

    N,N'-Diphenylguanidinium ion associated with the noncoordinating BArF counterion is shown to be an effective catalyst for the [3,3]-sigmatropic rearrangement of a variety of substituted allyl vinyl ethers. Highly enantioselective catalytic Claisen rearrangements of ester-substituted allyl vinyl ethers are then documented using a new C2-symmetric guanidinium ion derivative. PMID:18576616

  15. Uniparental disomy analysis in carriers of balanced chromosome rearrangements

    SciTech Connect

    May, K.M.; Pettay, D.; Muralidharan, K.

    1994-09-01

    Although most individuals who carry a balanced familial chromosome rearrangement are phenotypically normal, those who are clinically abnormal raise the question of whether or not the rearrangement plays a causative role. One possible mechanism involves meiotic segregation of a normal homolog along with the rearranged chromosome(s) such that a trisomic conception occurs. Subsequent loss by mitotic nondisjunction of the structurally normal chromosome contributed by the non-carrier parent would then result in uniparental disomy (UPD) in a conceptus carrying a balanced rearrangement. UPD for chromosomes 14 and 15 has been demonstrated in several clinically abnormal individuals who carry a familial Robertsonian translocation. We have extended this type of analysis to include other forms of balanced chromosome rearrangements. We report the results of UPD analysis of 14 families who have a phenotypically abnormal child with an apparently balanced rearrangement. The series includes 4 reciprocal translocations, 4 Robertsonian translocations, 2 X;autosome translocations, and 4 inversions. High resolution chromosomes were used to compare breakpoints between parent and offspring to exclude the possibility of further rearrangements. Parental origin of the chromosome(s) involved was determined by DNA polymorphism analysis using PCR or Southern blotting techniques. We found no evidence of UPD in any of the 14 cases. Our data suggest that UPD is not a common explanation for phenotypically abnormal carriers of balanced chromosome rearrangements.

  16. Ants cushion applied stress by active rearrangements

    NASA Astrophysics Data System (ADS)

    Liu, Zhongyang; Hyatt, John; Mlot, Nathan; Gerov, Michael; Fernandez-Nieves, Alberto; Hu, David

    2013-11-01

    Fire ants, Solenopsis invicta, link their bodies together to form waterproof rafts, which in turn drip, spread, and coagulate, demonstrating properties of an active material that can change state from a liquid to a solid. This soft-matter phase transition is important when the raft interacts with environmental forces such as raindrops and crashing waves. We study this active behavior through plate-on-plate rheology on the ants, extracting the active components by comparison with the rheological behavior of a collection of dead ants. In controlled shear tests, both and live and dead ants show properties of a non-Newtonian fluid, specifically, shear-thinning behavior. In oscillatory tests, live ants exhibit a rare behavior in which their storage modulus (G') and loss modulus (G'') have approximately the same value over three orders magnitudes of frequency and two orders of magnitude of strain, indicating the ants are neither fluid nor solid. In comparison, dead ants are more solid-like, with a storage modulus twice as large as their loss modulus. This striking active behavior arises from rearrangement of their bodies and storage and dissipation of energy with the ants' muscles.

  17. 2 CFR 200.462 - Rearrangement and reconversion costs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... rearrangement and alteration of facilities are allowable as indirect costs. Special arrangements and alterations... Agreements OFFICE OF MANAGEMENT AND BUDGET GUIDANCE Reserved UNIFORM ADMINISTRATIVE REQUIREMENTS, COST PRINCIPLES, AND AUDIT REQUIREMENTS FOR FEDERAL AWARDS Cost Principles General Provisions for Selected...

  18. Asymmetric Organocatalytic Wittig [2,3]-Rearrangement of Oxindoles.

    PubMed

    Ošeka, Maksim; Kimm, Mariliis; Kaabel, Sandra; Järving, Ivar; Rissanen, Kari; Kanger, Tõnis

    2016-03-18

    A highly enantioselective organocatalytic [2,3]-rearrangement of oxindole derivatives is presented. The reaction was catalyzed by squaramide, and this provides access to 3-hydroxy 3-substituted oxindoles in high enantiomeric purities. PMID:26937554

  19. : a database of ciliate genome rearrangements

    PubMed Central

    Burns, Jonathan; Kukushkin, Denys; Lindblad, Kelsi; Chen, Xiao; Jonoska, Nataša; Landweber, Laura F.

    2016-01-01

    Ciliated protists exhibit nuclear dimorphism through the presence of somatic macronuclei (MAC) and germline micronuclei (MIC). In some ciliates, DNA from precursor segments in the MIC genome rearranges to form transcriptionally active genes in the mature MAC genome, making these ciliates model organisms to study the process of somatic genome rearrangement. Similar broad scale, somatic rearrangement events occur in many eukaryotic cells and tumors. The (http://oxytricha.princeton.edu/mds_ies_db) is a database of genome recombination and rearrangement annotations, and it provides tools for visualization and comparative analysis of precursor and product genomes. The database currently contains annotations for two completely sequenced ciliate genomes: Oxytricha trifallax and Tetrahymena thermophila. PMID:26586804

  20. Ultrafast infrared studies of complex ligand rearrangements in solution

    SciTech Connect

    Payne, Christine K.

    2003-05-31

    The complete description of a chemical reaction in solution depends upon an understanding of the reactive molecule as well as its interactions with the surrounding solvent molecules. Using ultrafast infrared spectroscopy it is possible to observe both the solute-solvent interactions and the rearrangement steps which determine the overall course of a chemical reaction. The topics addressed in these studies focus on reaction mechanisms which require the rearrangement of complex ligands and the spectroscopic techniques necessary for the determination of these mechanisms. Ligand rearrangement is studied by considering two different reaction mechanisms for which the rearrangement of a complex ligand constitutes the most important step of the reaction. The first system concerns the rearrangement of a cyclopentadienyl ring as the response of an organometallic complex to a loss of electron density. This mechanism, commonly referred to as ''ring slip'', is frequently cited to explain reaction mechanisms. However, the ring slipped intermediate is too short-lived to be observed using conventional methods. Using a combination of ultrafast infrared spectroscopy and electronic structure calculations it has been shown that the intermediate exists, but does not form an eighteen-electron intermediate as suggested by traditional molecular orbital models. The second example examines the initial steps of alkyne polymerization. Group 6 (Cr, Mo, W) pentacarbonyl species are generated photolytically and used to catalyze the polymerization of unsaturated hydrocarbons through a series of coordination and rearrangement steps. Observing this reaction on the femto- to millisecond timescale indicates that the initial coordination of an alkyne solvent molecule to the metal center results in a stable intermediate that does not rearrange to form the polymer precursor. This suggests that polymerization requires the dissociation of additional carbonyl ligands before rearrangement can occur. Overall

  1. Fault tolerance analysis of the class of rearrangeable interconnection networks

    SciTech Connect

    Pakzad, S. . Dept. of Electrical Engineering)

    1989-08-01

    This paper analyzes the fault tolerance characteristics of a range or rearrangeable {beta}-networks based on the concepts and the framework developed by S. Pakzad and S. Lakshmivarahan. These rearrangeable {beta}-networks include the Benes network, the Waksman network, the Joel network, and the serial network. In addition, this paper presents a comparative analysis of the aforementioned networks according to their hardware cost, performance, and degree of fault tolerance.

  2. USP6 genetic rearrangements in cellular fibroma of tendon sheath.

    PubMed

    Carter, Jodi M; Wang, Xiaoke; Dong, Jie; Westendorf, Jennifer; Chou, Margaret M; Oliveira, Andre M

    2016-08-01

    Fibroma of tendon sheath is a benign (myo)fibroblastic neoplasm of the tenosynovial soft tissues, typically affecting the distal extremities. It is classically described as a paucicellular, densely collagenized tumor; however, cellular variants have been described. A subset of cellular fibromas of tendon sheath shares similar histological features with nodular fasciitis. As nodular fasciitis very frequently harbors rearrangement of ubiquitin-specific peptidase 6 (USP6), we hypothesized that cellular fibromas of tendon sheath with nodular fasciitis-like features may also contain USP6 rearrangements. Cases of fibroma of tendon sheath (n=19), including cellular (n=9) and classic (n=10) variants, were evaluated for USP6 rearrangement by fluorescence in situ hybridization studies. A subset of cases was tested for MYH9 rearrangements and MYH9-USP6 and CDH11-USP6 fusion products. Classic fibroma of tendon sheath occurred in 5 males and 5 females (median age 67 years, range 23-77 years) as soft tissue masses of the hand (n=4), finger (n=3), forearm (n=1) and foot (n=2). Cellular fibroma of tendon sheath occurred in 5 males and 4 females in a younger age group (median age 32 years, range 12-46 years) as small soft tissue masses of the finger (n=5), hand (n=3) and wrist (n=1). USP6 rearrangements were detected in 6/9 cellular fibromas of tendon sheath. Among cellular fibromas of tendon sheath with USP6 rearrangements, no MYH9 rearrangements were detected. By RT-PCR, neither the MYH9-USP6 or the CDH11-USP6 fusion products were detected in any case. Neither USP6 nor MYH9 rearrangement were detected in any classic fibroma of tendon sheath. We report for the first time the presence of USP6 rearrangements in a subset of cellular fibroma of tendon sheath. Based on the similar morphological and molecular genetic features, we suspect that a subset of cellular fibromas of tendon sheath are under-recognized examples of tenosynovial nodular fasciitis, driven by alternate USP6 fusion

  3. A versatile reporter system for CRISPR-mediated chromosomal rearrangements.

    PubMed

    Li, Yingxiang; Park, Angela I; Mou, Haiwei; Colpan, Cansu; Bizhanova, Aizhan; Akama-Garren, Elliot; Joshi, Nik; Hendrickson, Eric A; Feldser, David; Yin, Hao; Anderson, Daniel G; Jacks, Tyler; Weng, Zhiping; Xue, Wen

    2015-01-01

    Although chromosomal deletions and inversions are important in cancer, conventional methods for detecting DNA rearrangements require laborious indirect assays. Here we develop fluorescent reporters to rapidly quantify CRISPR/Cas9-mediated deletions and inversions. We find that inversion depends on the non-homologous end-joining enzyme LIG4. We also engineer deletions and inversions for a 50 kb Pten genomic region in mouse liver. We discover diverse yet sequence-specific indels at the rearrangement fusion sites. Moreover, we detect Cas9 cleavage at the fourth nucleotide on the non-complementary strand, leading to staggered instead of blunt DNA breaks. These reporters allow mechanisms of chromosomal rearrangements to be investigated. PMID:26018130

  4. Rearrangement Reactions Catalyzed by Cytochrome P450s

    PubMed Central

    Ortiz de Montellano, Paul R.; Nelson, Sidney D.

    2010-01-01

    Cytochrome P450s promote a variety of rearrangement reactions both as a consequence of the nature of the radical and other intermediates generated during catalysis, and of the neighboring structures in the substrate that can interact either with the initial radical intermediates or with further downstream products of the reactions. This article will review several kinds of previously published cytochrome P450-catalyzed rearrangement reactions, including changes in stereochemistry, radical clock reactions, allylic rearrangements, “NIH” and related shifts, ring contractions and expansions, and cyclizations that result from neighboring group interactions. Although most of these reactions can be carried out by many members of the cytochrome P450 superfamily, some have only been observed with select P450s, including some reactions that are catalyzed by specific endoperoxidases and cytochrome P450s found in plants. PMID:20971058

  5. Cell Division Drives Epithelial Cell Rearrangements during Gastrulation in Chick.

    PubMed

    Firmino, Joao; Rocancourt, Didier; Saadaoui, Mehdi; Moreau, Chloe; Gros, Jerome

    2016-02-01

    During early embryonic development, cells are organized as cohesive epithelial sheets that are continuously growing and remodeled without losing their integrity, giving rise to a wide array of tissue shapes. Here, using live imaging in chick embryo, we investigate how epithelial cells rearrange during gastrulation. We find that cell division is a major rearrangement driver that powers dramatic epithelial cell intercalation events. We show that these cell division-mediated intercalations, which represent the majority of epithelial rearrangements within the early embryo, are absolutely necessary for the spatial patterning of gastrulation movements. Furthermore, we demonstrate that these intercalation events result from overall low cortical actomyosin accumulation within the epithelial cells of the embryo, which enables dividing cells to remodel junctions in their vicinity. These findings uncover a role for cell division as coordinator of epithelial growth and remodeling that might underlie various developmental, homeostatic, or pathological processes in amniotes. PMID:26859350

  6. Low-Temperature Cationic Rearrangement in a Bulk Metal Oxide.

    PubMed

    Li, Man-Rong; Retuerto, Maria; Stephens, Peter W; Croft, Mark; Sheptyakov, Denis; Pomjakushin, Vladimir; Deng, Zheng; Akamatsu, Hirofumi; Gopalan, Venkatraman; Sánchez-Benítez, Javier; Saouma, Felix O; Jang, Joon I; Walker, David; Greenblatt, Martha

    2016-08-16

    Cationic rearrangement is a compelling strategy for producing desirable physical properties by atomic-scale manipulation. However, activating ionic diffusion typically requires high temperature, and in some cases also high pressure in bulk oxide materials. Herein, we present the cationic rearrangement in bulk Mn2 FeMoO6 at unparalleled low temperatures of 150-300 (o) C. The irreversible ionic motion at ambient pressure, as evidenced by real-time powder synchrotron X-ray and neutron diffraction, and second harmonic generation, leads to a transition from a Ni3 TeO6 -type to an ordered-ilmenite structure, and dramatic changes of the electrical and magnetic properties. This work demonstrates a remarkable cationic rearrangement, with corresponding large changes in the physical properties in a bulk oxide at unprecedented low temperatures. PMID:27203790

  7. Genome rearrangements caused by interstitial telomeric sequences in yeast

    PubMed Central

    Aksenova, Anna Y.; Greenwell, Patricia W.; Dominska, Margaret; Shishkin, Alexander A.; Kim, Jane C.; Petes, Thomas D.; Mirkin, Sergei M.

    2013-01-01

    Interstitial telomeric sequences (ITSs) are present in many eukaryotic genomes and are linked to genome instabilities and disease in humans. The mechanisms responsible for ITS-mediated genome instability are not understood in molecular detail. Here, we use a model Saccharomyces cerevisiae system to characterize genome instability mediated by yeast telomeric (Ytel) repeats embedded within an intron of a reporter gene inside a yeast chromosome. We observed a very high rate of small insertions and deletions within the repeats. We also found frequent gross chromosome rearrangements, including deletions, duplications, inversions, translocations, and formation of acentric minichromosomes. The inversions are a unique class of chromosome rearrangement involving an interaction between the ITS and the true telomere of the chromosome. Because we previously found that Ytel repeats cause strong replication fork stalling, we suggest that formation of double-stranded DNA breaks within the Ytel sequences might be responsible for these gross chromosome rearrangements. PMID:24191060

  8. DNA Oligonucleotide Fragment Ion Rearrangements Upon Collision-Induced Dissociation

    NASA Astrophysics Data System (ADS)

    Harper, Brett; Neumann, Elizabeth K.; Solouki, Touradj

    2015-08-01

    Collision-induced dissociation (CID) of m/z-isolated w type fragment ions and an intact 5' phosphorylated DNA oligonucleotide generated rearranged product ions. Of the 21 studied w ions of various nucleotide sequences, fragment ion sizes, and charge states, 18 (~86%) generated rearranged product ions upon CID in a Synapt G2-S HDMS (Waters Corporation, Manchester, England, UK) ion mobility-mass spectrometer. Mass spectrometry (MS), ion mobility spectrometry (IMS), and theoretical modeling data suggest that purine bases can attack the free 5' phosphate group in w type ions and 5' phosphorylated DNA to generate sequence permuted [phosphopurine]- fragment ions. We propose and discuss a potential mechanism for generation of rearranged [phosphopurine]- and complementary y-B type product ions.

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

    PubMed Central

    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

  10. Mycoreovirus genome rearrangements associated with RNA silencing deficiency

    PubMed Central

    Eusebio-Cope, Ana; Suzuki, Nobuhiro

    2015-01-01

    Mycoreovirus 1 (MyRV1) has 11 double-stranded RNA genome segments (S1 to S11) and confers hypovirulence to the chestnut blight fungus, Cryphonectria parasitica. MyRV1 genome rearrangements are frequently generated by a multifunctional protein, p29, encoded by a positive-strand RNA virus, Cryphonectria hypovirus 1. One of its functional roles is RNA silencing suppression. Here, we explored a possible link between MyRV1 genome rearrangements and the host RNA silencing pathway using wild-type (WT) and mutant strains of both MyRV1 and the host fungus. Host strains included deletion mutants of RNA silencing components such as dicer-like (dcl) and argonaute-like (agl) genes, while virus strains included an S4 internal deletion mutant MyRV1/S4ss. Consequently, intragenic rearrangements with nearly complete duplication of the three largest segments, i.e. S1, S2 and S3, were observed even more frequently in the RNA silencing-deficient strains Δdcl2 and Δagl2 infected with MyRV1/S4ss, but not with any other viral/host strain combinations. An interesting difference was noted between genome rearrangement events in the two host strains, i.e. generation of the rearrangement required prolonged culture for Δagl2 in comparison with Δdcl2. These results suggest a role for RNA silencing that suppresses genome rearrangements of a dsRNA virus. PMID:25800742

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

    PubMed

    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; Gloeckner, 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

    2015-10-29

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. 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 elusive. 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 type. 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

  12. Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy.

    PubMed

    Prier, Christopher K; Hyster, Todd K; Farwell, Christopher C; Huang, Audrey; Arnold, Frances H

    2016-04-01

    Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A "P411" serine-ligated variant of cytochrome P450BM3 has been engineered to initiate a sulfimidation/[2,3]-sigmatropic rearrangement sequence in whole E. coli cells, a non-natural function for any enzyme, providing access to enantioenriched, protected allylic amines. Five mutations in the enzyme substantially enhance its activity toward this new function, demonstrating the evolvability of the catalyst toward challenging nitrene transfer reactions. The evolved catalyst additionally performs the highly enantioselective imidation of non-allylic sulfides. PMID:26970325

  13. Rearrangement and evolution of mitochondrial genomes in parrots.

    PubMed

    Eberhard, Jessica R; Wright, Timothy F

    2016-01-01

    Mitochondrial genome rearrangements that result in control region duplication have been described for a variety of birds, but the mechanisms leading to their appearance and maintenance remain unclear, and their effect on sequence evolution has not been explored. A recent survey of mitochondrial genomes in the Psittaciformes (parrots) found that control region duplications have arisen independently at least six times across the order. We analyzed complete mitochondrial genome sequences from 20 parrot species, including representatives of each lineage with control region duplications, to document the gene order changes and to examine effects of genome rearrangements on patterns of sequence evolution. The gene order previously reported for Amazona parrots was found for four of the six independently derived genome rearrangements, and a previously undescribed gene order was found in Prioniturus luconensis, representing a fifth clade with rearranged genomes; the gene order resulting from the remaining rearrangement event could not be confirmed. In all rearranged genomes, two copies of the control region are present and are very similar at the sequence level, while duplicates of the other genes involved in the rearrangement show signs of degeneration or have been lost altogether. We compared rates of sequence evolution in genomes with and without control region duplications and did not find a consistent acceleration or deceleration associated with the duplications. This could be due to the fact that most of the genome rearrangement events in parrots are ancient, and additionally, to an effect of body size on evolutionary rate that we found for mitochondrial but not nuclear sequences. Base composition analyses found that relative to other birds, parrots have unusually strong compositional asymmetry (AT- and GC-skew) in their coding sequences, especially at fourfold degenerate sites. Furthermore, we found higher AT skew in species with control region duplications. One

  14. Submillisecond organic synthesis: Outpacing Fries rearrangement through microfluidic rapid mixing.

    PubMed

    Kim, Heejin; Min, Kyoung-Ik; Inoue, Keita; Im, Do Jin; Kim, Dong-Pyo; Yoshida, Jun-ichi

    2016-05-01

    In chemical synthesis, rapid intramolecular rearrangements often foil attempts at site-selective bimolecular functionalization. We developed a microfluidic technique that outpaces the very rapid anionic Fries rearrangement to chemoselectively functionalize iodophenyl carbamates at the ortho position. Central to the technique is a chip microreactor of our design, which can deliver a reaction time in the submillisecond range even at cryogenic temperatures. The microreactor was applied to the synthesis of afesal, a bioactive molecule exhibiting anthelmintic activity, to demonstrate its potential for practical synthesis and production. PMID:27151864

  15. Rearrangement of dypnones to 1,3,5-triarylbenzenes.

    PubMed

    Deng, Kai; Huai, Qi-Yong; Shen, Zhi-Lun; Li, Hui-Jing; Liu, Chen; Wu, Yan-Chao

    2015-03-20

    Rearrangement of dypnones to 1,3,5-triarylbenzenes is described. The reaction is proposed to involve an aldol-type self-condensation of dypnones, followed by an intramolecular [2 + 2] cycloaddition and a retro-[2 + 2] cycloaddition. The reaction goes smoothly under obviously milder conditions in comparison to the cyclotrimerization of acetophenones to 1,3,5-triarylbenzenes (10 mol % of TsOH, 80 °C versus 130-148 °C). This unexpected rearrangement would provide new possible considerations in dypnone-involved organic synthesis. PMID:25740008

  16. Oncogenic rearrangements driving ionizing radiation–associated human cancer

    PubMed Central

    Santoro, Massimo; Carlomagno, Francesca

    2013-01-01

    The Chernobyl nuclear disaster has caused a remarkable increase in radiation-induced papillary thyroid carcinoma in children and young adults. In this issue of the JCI, Ricarte-Filho and colleagues demonstrate that chromosomal rearrangements are the oncogenic “drivers” in most post-Chernobyl carcinomas and that they often lead to unscheduled activation of the MAPK signaling pathway. These findings represent a major step forward in our understanding of radiation-induced carcinogenesis and suggest various hypotheses about the mechanisms underlying the formation and selection of gene rearrangements during cancer cell evolution. PMID:24162670

  17. Enantioselective Oxidative Rearrangements with Chiral Hypervalent Iodine Reagents

    PubMed Central

    Brown, Michael; Kumar, Ravi; Rehbein, Julia

    2016-01-01

    Abstract A stereoselective hypervalent iodine‐promoted oxidative rearrangement of 1,1‐disubstituted alkenes has been developed. This practically simple protocol provides access to enantioenriched α‐arylated ketones without the use of transition metals from readily accessible alkenes. PMID:26800241

  18. The Basel Problem as a Rearrangement of Series

    ERIC Educational Resources Information Center

    Benko, David; Molokach, John

    2013-01-01

    We give an elementary solution to the famous Basel Problem, originally solved by Euler in 1735. We square the well-known series for arctan(1) due to Leibniz, and use a surprising relation among the re-arranged terms of this squared series.

  19. Computational Analysis of Stereospecificity in the Cope Rearrangement

    ERIC Educational Resources Information Center

    Glish, Laura; Hanks, Timothy W.

    2007-01-01

    The Cope rearrangement is a highly stereospecific, concerted reaction of considerable synthetic utility. Experimental product distributions from the reaction of disubstituted 1,5-hexadienes can be readily understood by computer modeling of the various possible transitions states. Semi-empirical methods give relative energies of transition states…

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

    PubMed Central

    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

  1. Enantioselective Oxidative Rearrangements with Chiral Hypervalent Iodine Reagents.

    PubMed

    Brown, Michael; Kumar, Ravi; Rehbein, Julia; Wirth, Thomas

    2016-03-14

    A stereoselective hypervalent iodine-promoted oxidative rearrangement of 1,1-disubstituted alkenes has been developed. This practically simple protocol provides access to enantioenriched α-arylated ketones without the use of transition metals from readily accessible alkenes. PMID:26800241

  2. The Manifestation of Chromosome Rearrangements in Unordered Asci of Neurospora

    PubMed Central

    Perkins, David D.

    1974-01-01

    Rapid, effective techniques have been developed for detecting and characterizing chromosome aberrations in Neurospora by visual inspection of ascospores and asci. Rearrangements that are detectable by the presence of deficient, nonblack ascospores in test crosses make up 5 to 10% of survivors after UV doses giving 10-55% survival. Over 135 rearrangements have been diagnosed by classifying unordered asci according to numbers of defective spores. (These include 15 originally identified or analyzed by other workers.) About 100 reciprocal translocations (RT's) have been confirmed and mapped genetically, involving all combinations of the seven chromosomes. Thirty-three other rearrangements generate viable nontandem duplications in meiosis. These consist of insertional translocations (IT's) (15 confirmed), and of rearrangements that involve a chromosome tip (10 translocations and 3 pericentric inversions). No inversion has been found that does not include the centromere. A reciprocal translocation was found within one population in nature. When pairs of RT's that involve the same two chromosome arms were intercrossed, viable duplications were produced if the breakpoints overlapped in such a way that pairing resembled that of insertional translocations (27 combinations).—The rapid analytical technique depends on the following. Deficiency ascospores are usually nonblack (W: "white") and inviable, while nondeficient ascospores, even those that include duplications, are black (B) and viable. Thus RT's typically produce 50% black spores, and IT's 75% black. Asci are shot spontaneously from ripe perithecia, and can be collected in large numbers as groups of eight ascospores representing unordered tetrads, which fall into five classes: 8B:0W; 6B:2W, 4B:4W, 2B:6B, 0B:8W. In isosequential crosses, 90-95% of tetrads are 8:0. When a rearrangement is heterozygous, the frequencies of tetrad classes are diagnostic of the type of rearrangement, and provide information also on the

  3. Models for antigen receptor gene rearrangement: CDR3 length.

    PubMed

    Saada, Ravit; Weinberger, Moran; Shahaf, Gitit; Mehr, Ramit

    2007-06-01

    Despite the various processing steps involved in V(D)J recombination, which could potentially introduce many biases in the length distribution of complementarity determining region 3 (CDR3) segments, the observed CDR3 length distributions for complete repertoires are very close to a normal-like distribution. This raises the question of whether this distribution is simply a result of the random steps included in the process of gene rearrangement, or has been optimized during evolution. We have addressed this issue by constructing a simulation of gene rearrangement, which takes into account the DNA modification steps included in the process, namely hairpin opening, nucleotide additions, and nucleotide deletions. We found that the near-Gaussian- shape of CDR3 length distribution can only be obtained under a relatively narrow set of parameter values, and thus our model suggests that specific biases govern the rearrangement process. In both B-cell receptor (BCR) heavy chain and T-cell receptor beta chain, we obtained a Gaussian distribution using identical parameters, despite the difference in the number and the lengths of the D segments. Hence our results suggest that these parameters most likely reflect the optimal conditions under which the rearrangement process occurs. We have subsequently used the insights gained in this study to estimate the probability of occurrence of two exactly identical BCRs over the course of a human lifetime. Whereas identical rearrangements of the heavy chain are highly unlikely to occur within one human lifetime, for the light chain we found that this probability is not negligible, and hence the light chain CDR3 alone cannot serve as an indicator of B-cell clonality. PMID:17404591

  4. The mechanism of a phosphazene-phosphazane rearrangement.

    PubMed

    Hayes, Robert F; Allen, Christopher W

    2016-02-01

    The phosphazene-phosphazane rearrangement of N3P3Cl5O(CH2)2OC(=O)CMe=CH2 (8) has been examined in detail using one and two dimensional NMR ((31)P, (1)H) spectroscopy and mass spectrometry. The mixed phosphazene-phosphazane [NPCl2]2[N((CH2)2OC(=O)CMe=CH2)P(O)Cl] (14), [NPCl2]2[NHP(O)Cl] (13) and a two ring assembly [NPCl2]2[NP(O{(NPCl2)2(N((CH2)2OC(=O)CMe=CH2)P(O)}] (15) have all been detected in the product mixture. The rate of the rearrangement has been measured at five temperatures by (31)P and (1)H NMR. The reaction is first order in 8 (T1/2 at 111° is 4.65 hours). The activation enthalpy is positive and the activation entropy is negative. A mechanism involving competing intra and inter molecular processes which fits the product distribution and kinetic data has been proposed. Several other methyacrylphosphazenes were examined under the same thermolysis conditions. The rearrangement was observed and the rates obtained in cases where the (CH2)2 spacer unit of the methacrylate was replaced by linear and branched propyl units. The rearrangement was not observed when the methacrylate was appended to a spirocyclic unit, the spacer unit was extended to the n-butyl group and when the methacrylate unit was replaced by a methoxy group. These results are all consistent with the proposed mechanism. This investigation resolves conflicting results previous reported for the rearrangement. PMID:26416486

  5. In vivo rearrangement of mitochondrial DNA in Saccharomyces cerevisiae.

    PubMed Central

    Clark-Walker, G D

    1989-01-01

    A revertant (SPR1) from a high-frequency petite strain of Saccharomyces cerevisiae has been shown by mapping and sequence analysis to have a rearranged mitochondrial genome. In vivo rearrangement has occurred through a subgenomic-recombination pathway involving the initial formation of subgenomic molecules in nascent petite mutants, recombination between these molecules to form an intermediate with direct repeats, and subsequent excision of the resident or symposed duplication to yield a molecule with three novel junctions and a changed gene order. Sequencing of the novel junctions shows that intramolecular recombination in each case occurs by means of G + C-rich short direct repeats of 40-51 base pairs. Mapping and sequence analysis also reveal that the SPR1 mitochondrial genome lacks three sectors of the wild-type molecule of 4.4, 1.7, and 0.5 kilobases. Each of these sectors occurs in nontemplate, base-biased DNA, that is over 90% A + T. Absence of these sectors together with a rearranged gene order does not appear to affect the phenotype of SPR1, as colony morphology and growth rate on a number of different substrates are not detectably different from the wild type. Lack of phenotypic change suggests that mitochondrial gene expression has not been noticeably disrupted in SPR1 despite deletion of the consensus nonomer promoter upstream from the glutamic acid tRNA gene. Dispensability of DNA sectors and the presence of recombinogenic short, direct repeats are mandatory features of the subgenomic-recombination pathway for creating rearrangements in baker's yeast mtDNA. It is proposed that, in other organisms, organelle genomes containing these elements may undergo rearrangement by the same steps. Images PMID:2682661

  6. A Rare Case of Pleomorphic Carcinoma of the Lung Harboring an Anaplastic Lymphoma Kinase (ALK) Rearrangement.

    PubMed

    Shiroyama, Takayuki; Tanaka, Ayako; Tamiya, Motohiro; Hamaguchi, Masanari; Osa, Akio; Takeoka, Sawa; Tani, Eriko; Azuma, Yuichiro; Morishita, Naoko; Suzuki, Hidekazu; Okamoto, Norio; Kimura, Kenji; Kadota, Yoshihisa; Kawahara, Kunimitsu; Hirashima, Tomonori; Kawase, Ichiro

    2015-01-01

    Molecular testing for anomalies, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangement, is part of the current standard of care for non-small cell lung cancer, particularly adenocarcinoma. ALK rearrangement occurs most frequently in adenocarcinoma cells and rarely in non-adenocarcinoma cells. We herein report a rare case of pleomorphic lung carcinoma with ALK rearrangement in both its adenocarcinoma and spindle cell components. This case suggests the possibility of ALK rearrangement in pleomorphic carcinoma. PMID:26521903

  7. Nucleotide resolution analysis of TMPRSS2 and ERG rearrangements in prostate cancer

    PubMed Central

    Weier, Christopher; Haffner, Michael C.; Mosbruger, Timothy; Esopi, David M.; Hicks, Jessica; Zheng, Qizhi; Fedor, Helen; Isaacs, William B.; De Marzo, Angelo M.; Nelson, William G.; Yegnasubramanian, Srinivasan

    2013-01-01

    TMPRSS2-ERG rearrangements occur in approximately 50% of prostate cancers and therefore represent one of the most frequently observed structural rearrangements in all cancers. However, little is known about the genomic architecture of such rearrangements. We therefore designed and optimized a pipeline involving target-capture of TMPRSS2 and ERG genomic sequences coupled with paired-end next generation sequencing to resolve genomic rearrangement breakpoints in TMPRSS2 and ERG at nucleotide resolution in a large series of primary prostate cancer specimens (n = 83). This strategy showed >90% sensitivity and specificity in identifying TMPRSS2-ERG rearrangements, and allowed identification of intra- and inter-chromosomal rearrangements involving TMPRSS2 and ERG with known and novel fusion partners. Our results indicate that rearrangement breakpoints show strong clustering in specific intronic regions of TMPRSS2 and ERG. The observed TMPRSS2-ERG rearrangements often exhibited complex chromosomal architecture associated with several intra- and inter-chromosomal rearrangements. Nucleotide resolution analysis of breakpoint junctions revealed that the majority of TMPRSS2 and ERG rearrangements (~88%) occurred at or near regions of microhomology or involved insertions of one or more base pairs. This architecture implicates nonhomologous end joining (NHEJ) and microhomology mediated end joining (MMEJ) pathways in the generation of such rearrangements. These analyses have provided important insights into the molecular mechanisms involved in generating prostate cancer-specific recurrent rearrangements. PMID:23447416

  8. One-Step Generation of Chromosomal Rearrangements in Rice.

    PubMed

    Murata, Minoru; Kanatani, Asaka; Kashihara, Kazunari

    2016-01-01

    The combination of the DNA sequence-specific recombination system Cre/LoxP and the DNA transposon system Activator (Ac)/Dissociation (Ds) has been used for insertional and deletional mutagenesis, as well as for the generation of artificial ring chromosomes in model plants such as Arabidopsis and tobacco. However, it takes a long time to complete this process, even in Arabidopsis. To overcome this issue, a new binary vector, pDLHC, has been developed to induce chromosomal rearrangements for a short time in rice. pDLHC has been found to be effective in the induction of deletions between two LoxPs in the T2 generation of "Nihon bare" expressing Ac TPase. pDLHC has potential for the efficient generation of various types of chromosomal rearrangements including deletions, inversions, translocations and artificial ring chromosomes in plants, and the detailed protocol for rice is described here. PMID:27557686

  9. Chromosome-specific staining to detect genetic rearrangements

    DOEpatents

    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.

  10. Multiple cellular mechanisms prevent chromosomal rearrangements involving repetitive DNA

    PubMed Central

    George, Carolyn M.; Alani, Eric

    2012-01-01

    Repetitive DNA is present in the eukaryotic genome in the form of segmental duplications, tandem and interspersed repeats, and satellites. Repetitive sequences can be beneficial by serving specific cellular functions (e.g. centromeric and telomeric DNA) and by providing a rapid means for adaptive evolution. However, such elements are also substrates for deleterious chromosomal rearrangements that affect fitness and promote human disease. Recent studies analyzing the role of nuclear organization in DNA repair and factors that suppress non-allelic homologous recombination have provided insights into how genome stability is maintained in eukaryotes. In this review we outline the types of repetitive sequences seen in eukaryotic genomes and how recombination mechanisms are regulated at the DNA sequence, cell organization, chromatin structure, and cell cycle control levels to prevent chromosomal rearrangements involving these sequences. PMID:22494239

  11. Thermal rearrangement of oxygen-containing {omicron}-allyltoluene derivatives

    SciTech Connect

    Li, F.

    1995-02-10

    For several years, workers in the Trahanovsky group have been studying the gas phase thermal reactions of simple organic molecules. The FVP of {Omicron}-allyltoluene involves a novel rearrangement that is proposed to involve a diradical produced by intramolecular hydrogen-atom transfer which undergoes intramolecular coupling to give 2-methylindan. Studies of this rearrangement have been extended to other systems. The two papers in this thesis describe studies of the flash vacuum pyrolysis (FVP) of oxygen-containing {omicron}-allyltoluene derivatives. In the first chapter of this thesis, the results from o-allylbenzaldehyde and related compounds are examined in terms of the intramolecular hydrogen-atom transfer diradical/coupling mechanism. A mechanism which involves an enol intermediate generated by an oxa-1,5 H shift is proposed for formation of naphthalene from the FVP of o-allylbenzaldehyde. In the second chapter more limitations of the formation of the diradicals is revealed.

  12. Competing sigmatropic shift rearrangements in excited allyl radicals

    SciTech Connect

    Stranges, D.; O'Keeffe, P.; Scotti, G.; Di Santo, R.; Houston, P. L.

    2008-04-21

    The competition between rearrangement of the excited allyl radical via a 1,3 sigmatropic shift versus sequential 1,2 shifts has been observed and characterized using isotopic substitution, laser excitation, and molecular beam techniques. Both rearrangements produce a 1-propenyl radical that subsequently dissociates to methyl plus acetylene. The 1,3 shift and 1,2 shift mechanisms are equally probable for CH{sub 2}CHCH{sub 2}, whereas the 1,3 shift is favored by a factor of 1.6 in CH{sub 2}CDCH{sub 2}. The translational energy distributions for the methyl and acetylene products of these two mechanisms are substantially different. Both of these allyl dissociation channels are minor pathways compared to hydrogen atom loss.

  13. RNA-Mediated Epigenetic Programming of Genome Rearrangements

    PubMed Central

    Nowacki, Mariusz; Shetty, Keerthi; Landweber, Laura F.

    2012-01-01

    RNA, normally thought of as a conduit in gene expression, has a novel mode of action in ciliated protozoa. Maternal RNA templates provide both an organizing guide for DNA rearrangements and a template that can transport somatic mutations to the next generation. This opportunity for RNA-mediated genome rearrangement and DNA repair is profound in the ciliate Oxytricha, which deletes 95% of its germline genome during development in a process that severely fragments its chromosomes and then sorts and reorders the hundreds of thousands of pieces remaining. Oxytricha’s somatic nuclear genome is therefore an epigenome formed through RNA templates and signals arising from the previous generation. Furthermore, this mechanism of RNA-mediated epigenetic inheritance can function across multiple generations, and the discovery of maternal template RNA molecules has revealed new biological roles for RNA and has hinted at the power of RNA molecules to sculpt genomic information in cells. PMID:21801022

  14. Rearrangements in Sheared Disordered Solids: Low and High Pressure Regimes

    NASA Astrophysics Data System (ADS)

    Wijtmans, Sven; van Deen, Merlijn; van Hecke, Martin; Manning, M. Lisa

    We study contact changes and rearrangements in quasistatic shear of disordered jammed packings at a range of pressures. We distinguish rearrangements where particle positions are discontinuous, leading to energy and stress discontinuities, from more frequent network events where contacts change but particle positions remain continuous. Moreover, we introduce two distinct protocols to unambiguously distinguish line reversible, loop reversible and irreversible events. The prevalence and spatial extension of five distinct event types (there are no loop reversible network events) evidence two distinct regimes: a low pressure regime dominated by irreversible extended events and a high pressure regime dominated by reversible localized ones. These trends indicate a crossover in the qualitative nature of plastic behavior in disordered solids near and far from jamming.

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

    PubMed

    Kotha, Sambasivarao; Meshram, Milind; Khedkar, Priti; Banerjee, Shaibal; Deodhar, Deepak

    2015-01-01

    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). PMID:26664603

  16. Rearranging the exponential wall for large N-body systems.

    PubMed

    Watson, Deborah K; Dunn, Martin

    2010-07-01

    The work required to solve for the fully interacting N boson wave function, which is widely believed to scale exponentially with N, is rearranged so the problem scales order by order in a perturbation series as N0. The exponential complexity reappears in an exponential scaling with the order of our perturbation series allowing exact analytical calculations for very large N systems through low order. PMID:20867687

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

    PubMed Central

    Meshram, Milind; Khedkar, Priti; Banerjee, Shaibal; Deodhar, Deepak

    2015-01-01

    Summary 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). PMID:26664603

  18. Comprehensive histologic analysis of ALK-rearranged lung carcinomas.

    PubMed

    Yoshida, Akihiko; Tsuta, Koji; Nakamura, Harumi; Kohno, Takashi; Takahashi, Fumiaki; Asamura, Hisao; Sekine, Ikuo; Fukayama, Masashi; Shibata, Tatsuhiro; Furuta, Koh; Tsuda, Hitoshi

    2011-08-01

    A subset (1% to 5%) of non-small-cell lung carcinomas harbors the EML4-ALK fusion gene. Data from previous studies on the histomorphology of ALK-rearranged lung cancer are inconsistent, and the specific histologic parameters that characterize this subset and how accurately such parameters predict underlying ALK abnormality remain uncertain. To answer these questions, we performed a comprehensive histologic analysis of 54 surgically resected, extensively sampled ALK-rearranged lung carcinomas and compared them with 100 consecutive resections of ALK-wild-type lung cancers. All 54 cases showed at least a focal adenocarcinoma component, and 3 and 2 cases had additional squamous and sarcomatoid differentiation, respectively. Solid or acinar growth pattern, cribriform structure, presence of mucous cells (signet-ring cells or goblet cells), abundant extracellular mucus, lack of lepidic growth, and lack of significant nuclear pleomorphism were more common in ALK-positive cancers. Two recognizable constellations of findings, a solid signet-ring cell pattern and a mucinous cribriform pattern, were present at least focally in the majority (78%) of ALK-positive tumors, but were rare (1%) in ALK-negative tumors. Multivariate analysis showed that a combination of these 2 patterns was the most powerful histologic indicator of ALK rearrangement. Characteristic histologies were present both in primary sites and in metastases. Thus, histologic findings may help to identify cases for ALK testing. However, none of the histologic parameters were completely sensitive or specific to ALK rearrangement, and histomorphology should not replace confirmatory molecular or immunohistochemical studies. ALK-positive cancers commonly showed coexpression of thyroid transcription factor-1 and p63, and its significance is currently unclear. PMID:21753699

  19. Rapid identification of chromosomal rearrangements by PRINS technique

    SciTech Connect

    Pellestor, F.; Giradet, A.; Andreo, B.

    1994-09-01

    Chromosomal rearrangements contribute significantly to human reproductive failure, malformation/mental retardation syndromes and carcinogenesis. The variety of structural rearrangements is almost infinite and an identification by conventional cytogenetics is often labor intensive and may remain doubtful. Recent advances in molecular cytogenetics have provided new tools for detecting chromosomal abnormalities. The fluorescence in situ hybridization (FISH) procedure is actually the most employed technique and has led to numerous clinical applications. However, techniques required to produce suitable probes are time consuming and not accessible to all cytogenetics laboratories. The PRimed In Situ labeling (PRINS) method provides an alternate way for in situ chromosome screening. In this procedure, the chromosomal detection is performed by in situ annealing of a specific primer and subsequent primer extension by a Taq DNA polymerase in the presence of labeled nucleotides. Application of PRINS in clinical diagnosis is still limited. We have developed a semi-automatic PRINS protocol and used it to identify the origin of several chromosomal abnormalities. We report here the results of studies of three structural rearrangements: a translocation t(21;21), a supernumerary ring marker chromosome 18 and a complex chromosome 13 mosaicism involving a 13;13 Robertsonian translocation and a ring chromosome 13.

  20. Frequent intragenic rearrangements of DPYD in colorectal tumours.

    PubMed

    van Kuilenburg, A B P; Etienne-Grimaldi, M-C; Mahamat, A; Meijer, J; Laurent-Puig, P; Olschwang, S; Gaub, M-P; Hennekam, R C M; Benchimol, D; Houry, S; Letoublon, C; Gilly, F-N; Pezet, D; Andre, T; Faucheron, J-L; Abderrahim-Ferkoune, A; Vijzelaar, R; Pradere, B; Milano, G

    2015-06-01

    Dihydropyrimidine dehydrogenase is a crucial enzyme for the degradation of 5-fluorouracil (5FU). DPYD, which encodes dihydropyrimidine dehydrogenase, is prone to acquire genomic rearrangements because of the presence of an intragenic fragile site FRA1E. We evaluated DPYD copy number variations (CNVs) in a prospective series of 242 stage I-III colorectal tumours (including 87 patients receiving 5FU-based treatment). CNVs in one or more exons of DPYD were detected in 27% of tumours (deletions or amplifications of one or more DPYD exons observed in 17% and 10% of cases, respectively). A significant relationship was observed between the DPYD intragenic rearrangement status and dihydropyrimidine dehydrogenase (DPD) mRNA levels (both at the tumour level). The presence of somatic DPYD aberrations was not associated with known prognostic or predictive biomarkers, except for LOH of chromosome 8p. No association was observed between DPYD aberrations and patient survival, suggesting that assessment of somatic DPYD intragenic rearrangement status is not a powerful biomarker to predict the outcome of 5FU-based chemotherapy in patients with colorectal cancer. PMID:25348620

  1. 4-Spiro[2.n]alkyl cations and their rearrangements.

    PubMed

    Prakash, G K; Fung, A P; Olah, G A; Rawdah, T N

    1987-08-01

    A series of 4-spiro[2.n]alkanols, where n = 3-7, were ionized in either FSO3H x SbF5/SO2ClF or SbF5/SO2ClF at -78 degrees C and -130 degrees C. The resulting solutions were studied by 13C NMR spectroscopy over the temperature range of -130 degrees C to -10 degrees C. The 4-spiro[2.5]octanol gave the expected static 4-spiro[2.5]octyl cation, which can be considered as a long-lived secondary cyclohexyl cation stabilized by an adjacent spirocyclopropane ring. The same spiro[2.5]octyl cation was also obtained by ionization of isomeric bicyclo[4.2.0]octan-1-ol and bicyclo[4.1.0]heptyl-1-methanol. The static spiro[2.5]-octyl cation was found to rearrange to the equilibrating 1-bicyclo[3.3.0]octyl cation above -10 degrees C. On the other hand, the 4-spiro[2.4]heptanol gave the rearranged 1-methylcyclohexenyl cation. The spiro[2.6]nonanol gave directly the equilibrating 1-bicyclo[4.3.0]nonyl cation. The other 4-spiro[2.n]-alkanols (n = 3 and 7) gave unidentifiable polymeric products. The ionization of 3-spirocyclopropyl-2-norbornanol yields only the rearranged 2-methylbicyclo[3.2.1]oct-3-ene-2-yl cation. PMID:3474642

  2. 4-Spiro[2.n]alkyl cations and their rearrangements.

    PubMed Central

    Prakash, G K; Fung, A P; Olah, G A; Rawdah, T N

    1987-01-01

    A series of 4-spiro[2.n]alkanols, where n = 3-7, were ionized in either FSO3H x SbF5/SO2ClF or SbF5/SO2ClF at -78 degrees C and -130 degrees C. The resulting solutions were studied by 13C NMR spectroscopy over the temperature range of -130 degrees C to -10 degrees C. The 4-spiro[2.5]octanol gave the expected static 4-spiro[2.5]octyl cation, which can be considered as a long-lived secondary cyclohexyl cation stabilized by an adjacent spirocyclopropane ring. The same spiro[2.5]octyl cation was also obtained by ionization of isomeric bicyclo[4.2.0]octan-1-ol and bicyclo[4.1.0]heptyl-1-methanol. The static spiro[2.5]-octyl cation was found to rearrange to the equilibrating 1-bicyclo[3.3.0]octyl cation above -10 degrees C. On the other hand, the 4-spiro[2.4]heptanol gave the rearranged 1-methylcyclohexenyl cation. The spiro[2.6]nonanol gave directly the equilibrating 1-bicyclo[4.3.0]nonyl cation. The other 4-spiro[2.n]-alkanols (n = 3 and 7) gave unidentifiable polymeric products. The ionization of 3-spirocyclopropyl-2-norbornanol yields only the rearranged 2-methylbicyclo[3.2.1]oct-3-ene-2-yl cation. PMID:3474642

  3. Engineering the Drosophila Genome: Chromosome Rearrangements by Design

    PubMed Central

    Golic, K. G.; Golic, M. M.

    1996-01-01

    We show that site-specific recombination can be used to engineer chromosome rearrangements in Drosophila melanogaster. The FLP site-specific recombinase acts on chromosomal target sites located within specially constructed P elements to provide an easy screen for the recovery of rearrangements with breakpoints that can be chosen in advance. Paracentric and pericentric inversions are easily recovered when two elements lie in the same chromosome in opposite orientation. These inversions are readily reversible. Duplications and deficiencies can be recovered by recombination between two elements that lie in the same orientation on the same chromosome or on homologues. We observe that the frequency of recombination between FRTs at ectopic locations decreases as the distance that separates those FRTs increases. We also describe methods to determine the absolute orientation of these P elements within the chromosome. The ability to produce chromosome rearrangements precisely between preselected sites provides a powerful new tool for investigations into the relationships between chromosome arrangement, structure, and function. PMID:8978056

  4. Native and rearranged ALK copy number and rearranged cell count in NSCLC: Implications for ALK inhibitor therapy

    PubMed Central

    Camidge, D. Ross; Skokan, Margaret; Kiatsimkul, Porntip; Helfrich, Barbara; Lu, Xian; Barón, Anna E.; Schulte, Nathan; Maxson, DeLee; Aisner, Dara L.; Franklin, Wilbur A.; Doebele, Robert C.; Varella-Garcia, Marileila

    2013-01-01

    Background Anaplastic Lymphoma Kinase positive (ALK+) non-small cell lung cancer (NSCLC) responds to ALK inhibitors. Clinically, ≥ 15% cells showing rearrangements by break-apart FISH classify tumors as positive. Increases in native and rearranged ALK copy number also occur. Methods 1426 NSCLC clinical specimens (174 ALK+ and 1252 ALK negative), and 24 ALK negative NSCLC cell lines were investigated. ALK copy number and genomic status were assessed by FISH. Results Clinical specimens with 0–9%, 10–15%, 16–30%, 31–50% and >50% of ALK+ cells were found in 79.3%, 8.5%, 1.4%, 2.7% and 8.1% of cases, respectively. Increased native ALK copy number (≥3 copies/cell in ≥40% cells) was detected in 19% of ALK+ and 62% of ALK negative tumors. In ALK negative tumors, abundant focal amplification of native ALK was rare (0.8%). Other atypical patterns occurred in ~6% of tumors. Mean native ALK copy number ranged from 2.1–6.9 in cell lines and was not correlated with crizotinib sensitivity (IC50s 0.34–2.8 uM) (r=0.279, p=0.1764). Neither native, nor rearranged ALK copy number, nor percentage cells positive correlated with extra-central nervous system progression free survivalin ALK+ patients on crizotinib. Conclusions 8.5% of cases are below the established positivity threshold by ≤5%. Further investigation of ALK by other diagnostic techniques in such cases may be warranted. Native ALK copy number increases alone are not associated with sensitivity to ALK inhibition in vitro. However, rare complex patterns of increased native ALK in patients should be studied further as atypical rearrangements contained within these may otherwise be missed. PMID:24022839

  5. Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases

    PubMed Central

    Chen, Yucai; Liu, Changsheng; Parker, William Davis; Chen, Hongyi; Beach, Thomas G.; Liu, Xinhua; Serrano, Geidy E.; Lu, Yanfen; Huang, Jianjun; Yang, Kunfang; Wang, Chunmei

    2016-01-01

    Background Mitochondrial dysfunction may play a central role in the pathologic process of Alzheimer’s disease (AD), but there is still a scarcity of data that directly links the pathology of AD with the alteration of mitochondrial DNA. This study aimed to provide a comprehensive assessment of mtDNA rearrangement events in AD brain tissue. Patients and Methods Postmortem frozen human brain cerebral cortex samples were obtained from the Banner Sun Health Research Institute Brain and Body Donation Program, Sun City, AZ. Mitochondria were isolated and direct sequence by using MiSeq®, and analyzed by relative software. Results Three types of mitochondrial DNA (mtDNA) rearrangements have been seen in post mortem human brain tissue from patients with AD and age matched control. These observed rearrangements include a deletion, F-type rearrangement, and R-type rearrangement. We detected a high level of mtDNA rearrangement in brain tissue from cognitively normal subjects, as well as the patients with Alzheimer's disease (AD). The rate of rearrangements was calculated by dividing the number of positive rearrangements by the coverage depth. The rearrangement rate was significantly higher in AD brain tissue than in control brain tissue (17.9%versus 6.7%; p = 0.0052). Of specific types of rearrangement, deletions were markedly increased in AD (9.2% versus 2.3%; p = 0.0005). Conclusions Our data showed that failure of mitochondrial DNA in AD brain might be important etiology of AD pathology. PMID:27299301

  6. Detection of Gene Rearrangements in Targeted Clinical Next-Generation Sequencing

    PubMed Central

    Abel, Haley J.; Al-Kateb, Hussam; Cottrell, Catherine E.; Bredemeyer, Andrew J.; Pritchard, Colin C.; Grossmann, Allie H.; Wallander, Michelle L.; Pfeifer, John D.; Lockwood, Christina M.; Duncavage, Eric J.

    2015-01-01

    The identification of recurrent gene rearrangements in the clinical laboratory is the cornerstone for risk stratification and treatment decisions in many malignant tumors. Studies have reported that targeted next-generation sequencing assays have the potential to identify such rearrangements; however, their utility in the clinical laboratory is unknown. We examine the sensitivity and specificity of ALK and KMT2A (MLL) rearrangement detection by next-generation sequencing in the clinical laboratory. We analyzed a series of seven ALK rearranged cancers, six KMT2A rearranged leukemias, and 77 ALK/KMT2A rearrangement–negative cancers, previously tested by fluorescence in situ hybridization (FISH). Rearrangement detection was tested using publicly available software tools, including Breakdancer, ClusterFAST, CREST, and Hydra. Using Breakdancer and ClusterFAST, we detected ALK rearrangements in seven of seven FISH-positive cases and KMT2A rearrangements in six of six FISH-positive cases. Among the 77 ALK/KMT2A FISH-negative cases, no false-positive identifications were made by Breakdancer or ClusterFAST. Further, we identified one ALK rearranged case with a noncanonical intron 16 breakpoint, which is likely to affect its response to targeted inhibitors. We report that clinically relevant chromosomal rearrangements can be detected from targeted gene panel–based next-generation sequencing with sensitivity and specificity equivalent to that of FISH while providing finer-scale information and increased efficiency for molecular oncology testing. PMID:24813172

  7. RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis

    PubMed Central

    Tsuta, K; Kohno, T; Yoshida, A; Shimada, Y; Asamura, H; Furuta, K; Kushima, R

    2014-01-01

    Background: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. Methods: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcription–PCR (RT–PCR) were performed to detect RET gene rearrangement. Results: In all, 22 cases (1.2%) showed RET rearrangements; all cases were of ADC histology. Of the 22 patients, 19 possessed KIF5B–RET fusion genes, whereas 3 possessed CCDC6–RET fusion genes. The RET-rearranged tumours were significantly more common in younger patients (P=0.038) and tended to occur in patients with no history of smoking (P=0.051). In addition, RET rearrangements were not associated with gender, occupational history (particularly radioactive exposure), tumour size, lymph node status, tumour stage, or patient survival. The predominant growth pattern in RET-rearranged ADCs was lepidic in 6 cases, papillary in 9 cases, acinar in 2 cases, micropapillary in 1 case, and solid in 4 cases. Cells with cytoplasmic mucin production were at least focally present in 12 of the 22 (54.5%) RET-rearranged ADC cases. Among the 21 analysed RET-rearranged tumours, RET immunopositivity was observed in 15 cases (71.4%), and was significantly associated with RET rearrangement (P<0.001). Conclusions: The RET rearrangements were observed in 1.2% of NSCLCs. All cases of RET rearrangement were ADCs. The RET rearrangements were more likely to be observed in younger patients. Although cytoplasmic mucin production was at least focally present in 54.5% of RET-rearranged ADCs, specific histological features were not detected. PMID:24504365

  8. Deep cytoplasmic rearrangements in axis-respecified Xenopus embryos

    NASA Technical Reports Server (NTRS)

    Denegre, J. M.; Danilchik, M. V.

    1993-01-01

    In fertilized eggs of the frog Xenopus, the vegetal yolk mass rotates away from the future dorsal side (J. P. Vincent and J. Gerhart, 1987, Dev. Biol. 123, 526-539), and a major rearrangement of the deep animal hemisphere cytoplasm produces a characteristic swirl in the prospective dorsal side (M. V. Danilchik and J. M. Denegre, 1991, Development 111, 845-856). The relationship between this swirl and determination of the dorsal-ventral axis was further investigated by attempting to experimentally separate the positions of the swirl and the dorsal-ventral axis. Eggs were obliquely oriented in the gravity field to respecify the direction of yolk mass rotation and the position of the dorsal-ventral axis. When yolk mass rotation occurred in the absence of a sperm, as in activated eggs, a swirl pattern formed on the side away from which the yolk mass had rotated. In fertilized eggs tipped with the sperm entry point (SEP) down or to the side, swirl patterns were always found to form on the side away from which the yolk mass was displaced. However, in eggs tipped SEP up, in which the yolk mass was forced to rotate away from the SEP, more complicated rearrangements were observed in addition to the rotation-oriented swirl. Because the direction of yolk mass rotation was found to be influenced by both gravity and the actual position of the SEP in obliquely oriented eggs (SEP to the side), such complicated rearrangement patterns may result from opposing forces generated by both yolk mass rotation and the expanding sperm aster. Thus, except in cases in which the influences of SEP position and unit gravity opposed each other, it was not possible to experimentally separate the position of the deep cytoplasmic swirl from the direction of yolk mass rotation, and therefore the position of the prospective dorsal side.

  9. Controlled order rearrangement encryption for quantum key distribution

    SciTech Connect

    Deng Fuguo; Long, G.L.

    2003-10-01

    A technique is devised to perform orthogonal state quantum key distribution. In this scheme, entangled parts of a quantum information carrier are sent from Alice to Bob through two quantum channels. However, before the transmission, the order of the quantum information carrier in one channel is reordered so that Eve cannot steal useful information. At the receiver's end, the order of the quantum information carrier is restored. The order rearrangement operation in both parties is controlled by a prior shared control key which is used repeatedly in a quantum key distribution session.

  10. Absence of heterozygosity due to template switching during replicative rearrangements.

    PubMed

    Carvalho, Claudia M B; Pfundt, Rolph; King, Daniel A; Lindsay, Sarah J; Zuccherato, Luciana W; Macville, Merryn V E; Liu, Pengfei; Johnson, Diana; Stankiewicz, Pawel; Brown, Chester W; Shaw, Chad A; Hurles, Matthew E; Ira, Grzegorz; Hastings, P J; Brunner, Han G; Lupski, James R

    2015-04-01

    We investigated complex genomic rearrangements (CGRs) consisting of triplication copy-number variants (CNVs) that were accompanied by extended regions of copy-number-neutral absence of heterozygosity (AOH) in subjects with multiple congenital abnormalities. Molecular analyses provided observational evidence that in humans, post-zygotically generated CGRs can lead to regional uniparental disomy (UPD) due to template switches between homologs versus sister chromatids by using microhomology to prime DNA replication-a prediction of the replicative repair model, MMBIR. Our findings suggest that replication-based mechanisms might underlie the formation of diverse types of genomic alterations (CGRs and AOH) implicated in constitutional disorders. PMID:25799105

  11. Multiparty semiquantum secret sharing based on rearranging orders of qubits

    NASA Astrophysics Data System (ADS)

    Gao, Gan; Wang, Yue; Wang, Dong

    2016-04-01

    Based on the assumption of a perfect qubit, Boyer et al. proposed a novel semiquantum key distribution protocol [Phys. Rev. Lett. 99 (2007) 140501], in which quantum Alice shares a secret key with classical Bob. In this paper, we use Bell states to propose a multiparty semiquantum secret sharing (MSQSS) protocol, in which only the boss is quantum and all agents are classical. Classical agents are restricted to performing measurements in a computational basis and rearranging orders of qubits. Unless all classical agents collaborate, no subset of them can obtain the secret of the quantum boss. Also, we show that this proposed protocol is secure against eavesdropping.

  12. Collective Epithelial Migration and Cell Rearrangements Drive Mammary Branching Morphogenesis

    PubMed Central

    Ewald, Andrew J.; Brenot, Audrey; Duong, Myhanh; Chan, Bianca S.; Werb, Zena

    2009-01-01

    Summary Epithelial organs are built through the movement of groups of interconnected cells. We observed cells in elongating mammary ducts reorganize into a multilayered epithelium, migrate collectively, and rearrange dynamically, all without forming leading cellular extensions. Duct initiation required proliferation, Rac, and myosin light-chain kinase, whereas repolarization to a bilayer depended on Rho kinase. We observed that branching morphogenesis results from the active motility of both luminal and myoepithelial cells. Luminal epithelial cells advanced collectively, whereas myoepithelial cells appeared to restrain elongating ducts. Significantly, we observed that normal epithelium and neoplastic hyperplasias are organized similarly during morphogenesis, suggesting common mechanisms of epithelial growth. PMID:18410732

  13. Confining bond rearrangement in the random center vortex model

    NASA Astrophysics Data System (ADS)

    Altarawneh, Derar; Höllwieser, Roman; Engelhardt, Michael

    2016-03-01

    We present static meson-meson and baryon-antibaryon potentials in Z (2 ) and Z (3 ) random center vortex models for the infrared sector of Yang-Mills theory, i.e., hypercubic lattice models of random vortex world surfaces. In particular, we calculate multiple Polyakov loop correlators corresponding to static meson-meson or baryon-antibaryon configurations in a center vortex background and observe that their expectation values follow the minimal area law, displaying bond rearrangement behavior, a characteristic expected for the confining dynamics of the strong interaction. The static meson-meson and baryon-antibaryon potentials are compared with theoretical predictions and lattice QCD simulations.

  14. Branched artificial nanofinger arrays by mesoporous interfacial atomic rearrangement.

    PubMed

    Kong, Biao; Tang, Jing; Zhang, Yueyu; Selomulya, Cordelia; Gong, Xingao; Liu, Yang; Zhang, Wei; Yang, Jianping; Wang, Wenshuo; Sun, Xiaotian; Wang, Yufei; Zheng, Gengfeng; Zhao, Dongyuan

    2015-04-01

    The direct production of branched semiconductor arrays with highly ordered orientation has proven to be a considerable challenge over the last two decades. Here we report a mesoporous interfacial atomic rearrangement (MIAR) method to directly produce highly crystalline, finger-like branched iron oxide nanoarrays from the mesoporous nanopyramids. This method has excellent versatility and flexibility for heteroatom doping of metallic elements, including Sn, Bi, Mn, Fe, Co, Ni, Cu, Zn, and W, in which the mesoporous nanopyramids first absorb guest-doping molecules into the mesoporous channels and then convert the mesoporous pyramids into branching artificial nanofingers. The crystalline structure can provide more optoelectronic active sites of the nanofingers by interfacial atomic rearrangements of doping molecules and mesopore channels at the porous solid-solid interface. As a proof-of-concept, the Sn-doped Fe2O3 artificial nanofingers (ANFs) exhibit a high photocurrent density of ∼1.26 mA/cm(2), ∼5.25-fold of the pristine mesoporous Fe2O3 nanopyramid arrays. Furthermore, with surface chemical functionalization, the Sn-doped ANF biointerfaces allow nanomolar level recognition of metabolism-related biomolecules (∼5 nm for glutathione). This MIAR method suggests a new growth means of branched mesostructures, with enhanced optoelectronic applications. PMID:25764364

  15. Compositions and methods for detecting gene rearrangements and translocations

    DOEpatents

    Rowley, Janet D.; Diaz, Manuel O.

    2000-01-01

    Disclosed is a series of nucleic acid probes for use in diagnosing and monitoring certain types of leukemia using, e.g., Southern and Northern blot analyses and fluorescence in situ hybridization (FISH). These probes detect rearrangements, such as translocations involving chromosome band 11q23 with other chromosomes bands, including 4q21, 6q27, 9p22, 19p13.3, in both dividing leukemic cells and interphase nuclei. The breakpoints in all such translocations are clustered within an 8.3 kb BamHI genomic region of the MLL gene. A novel 0.7 kb BamH1 cDNA fragment derived from this gene detects rearrangements on Southern blot analysis with a single BamHI restriction digest in all patients with the common 11q23 translocations and in patients with other 11q23 anomalies. Northern blot analyses are presented demonstrating that the MLL gene has multiple transcripts and that transcript size differentiates leukemic cells from normal cells. Also disclosed are MLL fusion proteins, MLL protein domains and anti-MLL antibodies.

  16. Rearrangement of layered double hydroxide nanoplatelets during hollow colloidosome preparation.

    PubMed

    Liu, Guopeng; Liu, Shangying; Dong, Xiaoqiang; Yang, Fei; Sun, Dejun

    2010-05-15

    Hollow colloidosomes consisting of plate-like Mg/Al layered double hydroxide (LDH) nanoparticles have been prepared by a facile route from a Pickering emulsion. The particles are first adsorbed onto the surface of paraffin oil-in-water emulsion droplets. After the core oil is dissolved in the surrounding bulk liquid, using solvents that are miscible with both the internal and external phases of the droplets, colloidosomes are formed. In this process, we find that the diameters of the colloidosomes are significantly reduced compared to those of the emulsion droplets. The reduction in the diameter is caused by rearrangement of the LDH platelets. That is, the platelets change their orientation from lying flat on the emulsion droplet surface to standing erect in a dense, face-to-face connecting pattern in the colloidosome shell. The main reason for the particle rearrangement is the increase of the attractive forces among the particles due to the reduced polarity of the solvents used during colloidosome preparation. PMID:20219203

  17. Rearranged mitochondrial genomes are present in human oocytes

    SciTech Connect

    Xi, Chen; Prosser, R.; Simonetti, S.

    1995-08-01

    Using quantitative PCR, we have determined that a human oocyte contains {approximately}100,000 mitochondrial genomes (mtDNAs). We have also found that some oocytes harbor measurable levels (up to 0.1%) of the so-called common deletion, an mtDNA molecule containing a 4,977-bp rearrangement that is present in high amounts in many patients with {open_quotes}sporadic{close_quotes} Kearns-Sayre syndrome (KSS) and progressive external ophthalmoplegia (PEO). This is the first demonstration that rearranged mtDNAs are present in human oocytes, and it provides experimental support for the supposition that pathogenic deletions associated with the ontogeny of sporadic KSS and PEO can be transmitted in the female germ line, from mother to child. The relevance of these findings to the accumulation of extremely low levels of deleted mtDNAs in both somatic and germ-line tissues during normal human aging is also discussed. 42 refs., 6 figs., 1 tab.

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

    SciTech Connect

    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.

  19. Mouse Model for ROS1-Rearranged Lung Cancer

    PubMed Central

    Takahashi, Hiroyuki; Nakamura, Hiromi; Hama, Natsuko; Kohno, Takashi; Tsuta, Koji; Yoshida, Akihiko; Asamura, Hisao; Mutoh, Michihiro; Hosoda, Fumie; Tsuda, Hitoshi; Shibata, Tatsuhiro

    2013-01-01

    Genetic rearrangement of the ROS1 receptor tyrosine kinase was recently identified as a distinct molecular signature for human non-small cell lung cancer (NSCLC). However, direct evidence of lung carcinogenesis induced by ROS1 fusion genes remains to be verified. The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene. EZR-ROS1 was identified in four female patients of lung adenocarcinoma. Three of them were never smokers. Interstitial deletion of 6q22–q25 resulted in gene fusion. Expression of the fusion kinase in NIH3T3 cells induced anchorage-independent growth in vitro, and subcutaneous tumors in nude mice. This transforming ability was attributable to its kinase activity. The ALK/MET/ROS1 kinase inhibitor, crizotinib, suppressed fusion-induced anchorage-independent growth of NIH3T3 cells. Most importantly, established transgenic mouse lines specifically expressing EZR-ROS1 in lung alveolar epithelial cells developed multiple adenocarcinoma nodules in both lungs at an early age. These data suggest that the EZR-ROS1 is a pivotal oncogene in human NSCLC, and that this animal model could be valuable for exploring therapeutic agents against ROS1-rearranged lung cancer. PMID:23418494

  20. Intramolecular Interactions That Induce Helical Rearrangement upon Rhodopsin Activation

    PubMed Central

    Yamazaki, Yoichi; Nagata, Tomoko; Terakita, Akihisa; Kandori, Hideki; Shichida, Yoshinori; Imamoto, Yasushi

    2014-01-01

    Rhodopsin undergoes rearrangements of its transmembrane helices after photon absorption to transfer a light signal to the G-protein transducin. To investigate the mechanism by which rhodopsin adopts the transducin-activating conformation, the local environmental changes in the transmembrane region were probed using the cysteine S-H group, whose stretching frequency is well isolated from the other protein vibrational modes. The S-H stretching modes of cysteine residues introduced into Helix III, which contains several key residues for the helical movements, and of native cysteine residues were measured by Fourier transform infrared spectroscopy. This method was applied to metarhodopsin IIa, a precursor of the transducin-activating state in which the intramolecular interactions are likely to produce a state ready for helical movements. No environmental change was observed near the ionic lock between Arg-135 in Helix III and Glu-247 in Helix VI that maintains the inactive conformation. Rather, the cysteine residues that showed environmental changes were located around the chromophore, Ala-164, His-211, and Phe-261. These findings imply that the hydrogen bond between Helix III and Helix V involving Glu-122 and His-211 and the hydrophobic packing between Helix III and Helix VI involving Gly-121, Leu-125, Phe-261, and Trp-265 are altered before the helical rearrangement leading toward the active conformation. PMID:24692562

  1. Calponin 3 regulates actin cytoskeleton rearrangement in trophoblastic cell fusion.

    PubMed

    Shibukawa, Yukinao; Yamazaki, Natsuko; Kumasawa, Keiichi; Daimon, Etsuko; Tajiri, Michiko; Okada, Yuka; Ikawa, Masahito; Wada, Yoshinao

    2010-11-15

    Cell-cell fusion is an intriguing differentiation process, essential for placental development and maturation. A proteomic approach identified a cytoplasmic protein, calponin 3 (CNN3), related to the fusion of BeWo choriocarcinoma cells. CNN3 was expressed in cytotrophoblasts in human placenta. CNN3 gene knockdown promoted actin cytoskeletal rearrangement and syncytium formation in BeWo cells, suggesting CNN3 to be a negative regulator of trophoblast fusion. Indeed, CNN3 depletion promoted BeWo cell fusion. CNN3 at the cytoplasmic face of cytoskeleton was dislocated from F-actin with forskolin treatment and diffused into the cytoplasm in a phosphorylation-dependent manner. Phosphorylation sites were located at Ser293/296 in the C-terminal region, and deletion of this region or site-specific disruption of Ser293/296 suppressed syncytium formation. These CNN3 mutants were colocalized with F-actin and remained there after forskolin treatment, suggesting that dissociation of CNN3 from F-actin is modulated by the phosphorylation status of the C-terminal region unique to CNN3 in the CNN family proteins. The mutant missing these phosphorylation sites displayed a dominant negative effect on cell fusion, while replacement of Ser293/296 with aspartic acid enhanced syncytium formation. These results indicated that CNN3 regulates actin cytoskeleton rearrangement which is required for the plasma membranes of trophoblasts to become fusion competent. PMID:20861310

  2. Synergistic Kinetic Resolution and Asymmetric Propargyl Claisen Rearrangement for the Synthesis of Chiral Allenes.

    PubMed

    Liu, Yangbin; Liu, Xiaohua; Hu, Haipeng; Guo, Jing; Xia, Yong; Lin, Lili; Feng, Xiaoming

    2016-03-14

    The asymmetric propargyl Claisen rearrangement provides a convenient entry to chiral allene motifs. Herein, we describe the development of a kinetic resolution and asymmetric rearrangement of racemic propargyl vinyl ethers. This transformation afforded chiral allene products along with the enantiomerically enriched substrate in good yields with excellent diastereo- and enantioselectivity. The complete chirality transfer and facially selective rearrangement enabled the simultaneous construction of an axially chiral allenic unit and a quaternary carbon stereocenter. PMID:26889758

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

    SciTech Connect

    Herman, V.; Drazin, N.Z.; Gonskey, R.; Melmed, S. )

    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.

  4. Large Chromosomal Rearrangements during a Long-Term Evolution Experiment with Escherichia coli

    PubMed Central

    Raeside, Colin; Gaffé, Joël; Deatherage, Daniel E.; Tenaillon, Olivier; Briska, Adam M.; Ptashkin, Ryan N.; Cruveiller, Stéphane; Médigue, Claudine; Lenski, Richard E.; Barrick, Jeffrey E.

    2014-01-01

    ABSTRACT Large-scale rearrangements may be important in evolution because they can alter chromosome organization and gene expression in ways not possible through point mutations. In a long-term evolution experiment, twelve Escherichia coli populations have been propagated in a glucose-limited environment for over 25 years. We used whole-genome mapping (optical mapping) combined with genome sequencing and PCR analysis to identify the large-scale chromosomal rearrangements in clones from each population after 40,000 generations. A total of 110 rearrangement events were detected, including 82 deletions, 19 inversions, and 9 duplications, with lineages having between 5 and 20 events. In three populations, successive rearrangements impacted particular regions. In five populations, rearrangements affected over a third of the chromosome. Most rearrangements involved recombination between insertion sequence (IS) elements, illustrating their importance in mediating genome plasticity. Two lines of evidence suggest that at least some of these rearrangements conferred higher fitness. First, parallel changes were observed across the independent populations, with ~65% of the rearrangements affecting the same loci in at least two populations. For example, the ribose-utilization operon and the manB-cpsG region were deleted in 12 and 10 populations, respectively, suggesting positive selection, and this inference was previously confirmed for the former case. Second, optical maps from clones sampled over time from one population showed that most rearrangements occurred early in the experiment, when fitness was increasing most rapidly. However, some rearrangements likely occur at high frequency and may have simply hitchhiked to fixation. In any case, large-scale rearrangements clearly influenced genomic evolution in these populations. PMID:25205090

  5. CIC-rearranged Sarcomas: A Study of 20 Cases and Comparisons With Ewing Sarcomas.

    PubMed

    Yoshida, Akihiko; Goto, Keisuke; Kodaira, Makoto; Kobayashi, Eisuke; Kawamoto, Hiroshi; Mori, Taisuke; Yoshimoto, Seiichi; Endo, Otone; Kodama, Narihito; Kushima, Ryoji; Hiraoka, Nobuyoshi; Motoi, Toru; Kawai, Akira

    2016-03-01

    The CIC gene rearrangement exists in a subset of small round cell sarcomas. As the nosologic relationship of these sarcomas to Ewing sarcomas remains undetermined, we examined 20 CIC-rearranged sarcomas to compare their clinicopathologic features with those of Ewing sarcomas. The CIC-rearranged sarcomas were from a group of 14 men and 6 women with a median age of 24.5 years. The primary tumor sites included the limbs, trunk wall, internal trunk, lung, cerebrum, and pharynx. A comparison of the demographic and clinical characteristics of the 20 patients with CIC-rearranged sarcomas with those of the 53 near-consecutive patients with EWSR1-rarranged Ewing sarcomas showed that there were no differences with respect to their ages and sexes. Although none of the CIC-rearranged sarcomas arose in the bone, 40% of the Ewing sarcomas primarily affected the skeleton. The overall survival of patients with Ewing sarcomas was significantly better than that for patients with CIC-rearranged sarcomas. A histologic comparison of the CIC-rearranged sarcomas with 20 EWSR1-rearranged Ewing sarcomas showed significantly higher degrees of lobulation, nuclear pleomorphism, the prominence of the nucleoli, spindle cell elements, and myxoid changes in the CIC-rearranged sarcomas. Distinguishing immunohistochemical features included heterogenous CD99 reactivity, nuclear WT1 expression, and calretinin expression in the CIC-rearranged sarcomas and NKX2.2 expression in the Ewing sarcomas. CIC-rearranged sarcomas are distinct from Ewing sarcomas clinically, morphologically, and immunohistochemically, and they should be considered a separate entity rather than being grouped within the same family of tumors. PMID:26685084

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

    PubMed

    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. PMID:27528689

  7. Charge carrier rearrangement in spinel crystals irradiated at low temperatures

    NASA Astrophysics Data System (ADS)

    Gritsyna, V. T.; Afanasyev-Charkin, I. V.; Kobyakov, V. A.; Voitsenya, T. I.; Sickafus, K. E.

    2000-05-01

    The results of an investigation of thermoluminescence (TL) in nominally pure MgAl2O4 spinel single crystals in the temperature range between 80-670 K are presented. For a heating rate of 0.21 K/s, TL spectra exhibit glow peaks in three distinct temperature ranges: 100-160, 270-370 and 470-670 K. The most prominent peaks are at 115, 140, 305, 335, 525, 570 and 605 K. The locations of the temperature maxima, as well as the intensity of the peaks, vary depending on the treatment of the crystals, the type of irradiation and the temperature of irradiation. Measurements of the glow peaks at different emission wavelengths and the use of partial bleaching and isothermal decay techniques for TL, allowed us to propose mechanisms for charge carrier rearrangement at lattice defects and impurity ions, during irradiation and subsequent heating.

  8. One-electron-mediated rearrangements of 2,3-disiladicarbene.

    PubMed

    Mondal, Kartik Chandra; Samuel, Prinson P; Roesky, Herbert W; Aysin, Rinat R; Leites, Larissa A; Neudeck, Sven; Lübben, Jens; Dittrich, Birger; Holzmann, Nicole; Hermann, Markus; Frenking, Gernot

    2014-06-25

    A disiladicarbene, (Cy-cAAC)2Si2 (2), was synthesized by reduction of Cy-cAAC:SiCl4 adduct with KC8. The dark-colored compound 2 is stable at room temperature for a year under an inert atmosphere. Moreover, it is stable up to 190 °C and also can be characterized by electron ionization mass spectrometry. Theoretical and Raman studies reveal the existence of a Si═Si double bond with a partial double bond between each carbene carbon atom and silicon atom. Cyclic voltammetry suggests that 2 can quasi-reversibly accept an electron to produce a very reactive radical anion, 2(•-), as an intermediate species. Thus, reduction of 2 with potassium metal at room temperature led to the isolation of an isomeric neutral rearranged product and an anionic dimer of a potassium salt via the formation of 2(•-). PMID:24911357

  9. On the Complexity of Rearrangement Problems under the Breakpoint Distance

    PubMed Central

    2014-01-01

    Abstract We study the complexity of rearrangement problems in the generalized breakpoint model of Tannier et al. and settle several open questions. We improve the algorithm for the median problem and show that it is equivalent to the problem of finding maximum cardinality nonbipartite matching (under linear reduction). On the other hand, we prove that the more general small phylogeny problem is NP-hard. Surprisingly, we show that it is already NP-hard (or even APX-hard) for a quartet phylogeny. We also show that in the unichromosomal and the multilinear breakpoint model the halving problem is NP-hard, refuting the conjecture of Tannier et al. Interestingly, this is the first problem that is harder in the breakpoint model than in the double cut and join or reversal models. PMID:24200391

  10. Independent functions in rearrangement invariant spaces and the Kruglov property

    NASA Astrophysics Data System (ADS)

    Astashkin, S. V.

    2008-08-01

    Let X be a separable or maximal rearrangement invariant space on [0,1]. It is shown that the inequality \\displaystyle \\biggl\\Vert\\,\\sum_{k=1}^\\infty f_k\\biggr\\Vert _{X}\\le C\\biggl\\Vert\\biggl(\\,\\sum_{k=1}^\\infty f_k^2\\biggl)^{1/2}\\biggr\\Vert _Xholds for an arbitrary sequence of independent functions \\{f_k\\}_{k=1}^\\infty\\subset X, \\displaystyle\\int_0^1f_k(t)\\,dt=0, k=1,2,\\dots, if and only if X has the Kruglov property. As a consequence, it is proved that the same property is necessary and sufficient for a version of Maurey's well-known inequality for vector-valued Rademacher series with independent coefficients to hold in X.Bibliography: 24 titles.

  11. Rapid cloning of any rearranged mouse immunoglobulin variable genes

    SciTech Connect

    Dattamajumdar, A.K.; Jacobson, D.P.; Hood, L.E.; Osman, G.E.

    1996-12-31

    Immunoglobulins (Ig) have been the focus of extensive study for several decades and have become an important research area for immunologists and molecular biologists. The use of polymerase chain reaction (PCR) technology has accelerated the cloning, sequencing, and characterization of genes of the immune system. However, cloning and sequencing the Ig variable (V) genes using the PCR technology has been a challenging task, primarily due to the very diverse nature of Ig V region genes. We have developed a simple, rapid, and reproducible PCR-based technique to clone any rearranged mouse Ig heavy or light chain genes. A close examination of all Ig heavy and light chain V gene families has resulted in the design of 5{prime} and 3{prime} universal primers from regions that are highly conserved across all heavy or light chain V gene families, and the joining or constant regions, respectively. We present our strategy for designing universal primers for Ig V gene families. These primers were able to rapidly amplify the rearranged Ig V genes, belonging to diverse Ig V gene families from very different cell lines, i.e., J558, MOPC-21, 36-60, and a chicken ovalbumin specific B-cell hybridoma. In addition, the present study provides the complete alignment of nucleotide sequences of all heavy and light chain variable gene families. This powerful method of cloning Ig V genes, therefore, allows rapid and precise analysis of B-cell hybridomas, B-cell repertoire, and B-cell ontogeny. 55 refs., 5 figs., 2 tabs.

  12. Synthesis and rearrangements of aminosubstituted ferra- and ruthenatricarbaboranes.

    PubMed

    Holub, Josef; Grüner, Bohumír; Perekalin, Dmitry S; Golovanov, Denis G; Lyssenko, Konstantin A; Petrovskii, Pavel V; Kudinov, Alexander R; Stíbr, Bohumil

    2005-03-21

    A room-temperature reaction between the [7-tBuNH-nido-7,8,9-C3B8H10]- anion (1a) and [Cp*RuCl]4 leads to the ruthenatricarbollide [1-Cp*-12-tBuNH-1,2,4,12-RuC3B8H10] (2) (yield 85%). Analogously, the room-temperature photochemical reaction of 1a with [CpFe(C6H6)]PF6 gives the previously reported iron complex [1-Cp-12-tBuNH-1,2,4,12-FeC3B8H10] (3) (yield 82%). Both reactions are associated with extensive polyhedral rearrangement, which occurs under very mild conditions and brings the carbon atoms to positions of maximum separation within the framework. Compounds 2 and 3 were also surprisingly obtained via complexation of the isomeric [8-tBuNH-nido-7,8,9-C3B8H10]- (1b) anion. Complex 2 rearranges further to [1-Cp*-10-tBuNH-1,2,4,10-RuC3B8H10] (4) upon refluxing in xylene (145 degrees C). Density functional theory calculations at the B3LYP/SDD level were used to estimate relative stabilities of these metallacarborane isomers. Compounds 2 and 4, along with the 11-vertex closo compounds [1-Cp*-1,2,3,10-RuC3B7H10] (5) and [1-Cp*-10-tBuNH-1,2,3,10-RuC3B7H9] (6), were also isolated from the reaction between [Cp*RuCl2]2 and 1a in boiling xylene. The structure of 2 was established by an X-ray diffraction study, and the constitution of all compounds was determined unambiguously by multinuclear NMR spectroscopy, mass spectrometry, and elemental analyses. PMID:15762692

  13. Chromosomal rearrangement in autotetraploid plants of Arabidopsis thaliana.

    PubMed

    Weiss, H; Maluszynska, J

    2000-01-01

    Recent development of cytogenetic techniques has facilitated significant progress in Arabidopsis thaliana karyotype studies. Double-target FISH with rRNA genes provides makers that allow individual chromosome in the genome to be distinguished. Those studies have revealed that the number and position of rDNA loci is ecotype-specific. Arabidopsis is believed to be a true diploid (x = 5) with numerous ecotypes (accessions) and only a very few natural polyploid populations reported. Few studies were undertaken to induce polyploidy in Arabidopsis, however none of those gave the cytogenetic characteristics of polyploid plants. Our analysis of chromosome pairing of colchicine-induced autotetraploid Arabidopsis (Wilna ecotype) revealed preferential bivalent pairing in PMCs (pollen mother cells). In order to attempt to explain this phenomenon, first of all more detailed cytogenetic studies of autopolyploid plants have been undertaken. The localization of 45S and 5S rDNA loci in the diploid and autotetraploid plants revealed that Wilna ecotypes belongs to the group of Arabidopsis accessions with only two 5S rDNA loci present in a genome. Furthermore, the rearrangement of 45S rDNA locus in autopolyploid, when compared to the diploid plants of the same ecotype, was revealed. These results are interesting also in the context of the recently emphasised role of polyploidy in plant evolution and speciation. Arabidopsis, despite having small chromosomes, is a good system to study chromosome behaviour in relation to diploidization of autopolyploids and to evaluate the degree of chromosomal rearrangements during this process. PMID:11433970

  14. Genome rearrangement affects RNA virus adaptability on prostate cancer cells.

    PubMed

    Pesko, Kendra; Voigt, Emily A; Swick, Adam; Morley, Valerie J; Timm, Collin; Yin, John; Turner, Paul E

    2015-01-01

    Gene order is often highly conserved within taxonomic groups, such that organisms with rearranged genomes tend to be less fit than wild type gene orders, and suggesting natural selection favors genome architectures that maximize fitness. But it is unclear whether rearranged genomes hinder adaptability: capacity to evolutionarily improve in a new environment. Negative-sense non-segmented RNA viruses (order Mononegavirales) have specific genome architecture: 3' UTR - core protein genes - envelope protein genes - RNA-dependent RNA-polymerase gene - 5' UTR. To test how genome architecture affects RNA virus evolution, we examined vesicular stomatitis virus (VSV) variants with the nucleocapsid (N) gene moved sequentially downstream in the genome. Because RNA polymerase stuttering in VSV replication causes greater mRNA production in upstream genes, N gene translocation toward the 5' end leads to stepwise decreases in N transcription, viral replication and progeny production, and also impacts the activation of type 1 interferon mediated antiviral responses. We evolved VSV gene-order variants in two prostate cancer cell lines: LNCap cells deficient in innate immune response to viral infection, and PC-3 cells that mount an IFN stimulated anti-viral response to infection. We observed that gene order affects phenotypic adaptability (reproductive growth; viral suppression of immune function), especially on PC-3 cells that strongly select against virus infection. Overall, populations derived from the least-fit ancestor (most-altered N position architecture) adapted fastest, consistent with theory predicting populations with low initial fitness should improve faster in evolutionary time. Also, we observed correlated responses to selection, where viruses improved across both hosts, rather than suffer fitness trade-offs on unselected hosts. Whole genomics revealed multiple mutations in evolved variants, some of which were conserved across selective environments for a given gene

  15. Solution (31)P NMR Study of the Acid-Catalyzed Formation of a Highly Charged {U24Pp12} Nanocluster, [(UO2)24(O2)24(P2O7)12](48-), and Its Structural Characterization in the Solid State Using Single-Crystal Neutron Diffraction.

    PubMed

    Dembowski, Mateusz; Olds, Travis A; Pellegrini, Kristi L; Hoffmann, Christina; Wang, Xiaoping; Hickam, Sarah; He, Junhong; Oliver, Allen G; Burns, Peter C

    2016-07-13

    The first neutron diffraction study of a single crystal containing uranyl peroxide nanoclusters is reported for pyrophosphate-functionalized Na44K6[(UO2)24(O2)24(P2O7)12][IO3]2·140H2O (1). Relative to earlier X-ray studies, neutron diffraction provides superior information concerning the positions of H atoms and lighter counterions. Hydrogen positions have been assigned and reveal an extensive network of H-bonds; notably, most O atoms present in the anionic cluster accept H-bonds from surrounding H2O molecules, and none of the surface-bound O atoms are protonated. The D4h symmetry of the cage is consistent with the presence of six encapsulated K cations, which appear to stabilize the lower symmetry variant of this cluster. (31)P NMR measurements demonstrate retention of this symmetry in solution, while in situ (31)P NMR studies suggest an acid-catalyzed mechanism for the assembly of 1 across a wide range of pH values. PMID:27322657

  16. Lecture Capture with Real-Time Rearrangement of Visual Elements: Impact on Student Performance

    ERIC Educational Resources Information Center

    Yu, P.-T.; Wang, B.-Y.; Su, M.-H.

    2015-01-01

    The primary goal of this study is to create and test a lecture-capture system that can rearrange visual elements while recording is still taking place, in such a way that student performance can be positively influenced. The system we have devised is capable of integrating and rearranging multimedia sources, including learning content, the…

  17. Inverted genomic segments and complex triplication rearrangements are mediated by inverted repeats in the human genome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We identified complex genomic rearrangements consisting of intermixed duplications and triplications of genomic segments at the MECP2 and PLP1 loci. These complex rearrangements were characterized by a triplicated segment embedded within a duplication in 11 unrelated subjects. Notably, only two brea...

  18. 10 CFR 110.124 - Rearrangement or suspension of a hearing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Rearrangement or suspension of a hearing. 110.124 Section 110.124 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Special Procedures for Classified Information in Hearings § 110.124 Rearrangement or suspension of a hearing. When a participant gives...

  19. On the association between chromosomal rearrangements and genic evolution in humans and chimpanzees

    PubMed Central

    Marques-Bonet, Tomàs; Sànchez-Ruiz, Jesús; Armengol, Lluís; Khaja, Razi; Bertranpetit, Jaume; Lopez-Bigas, Núria; Rocchi, Mariano; Gazave, Elodie; Navarro, Arcadi

    2007-01-01

    Background The role that chromosomal rearrangements might have played in the speciation processes that have separated the lineages of humans and chimpanzees has recently come into the spotlight. To date, however, results are contradictory. Here we revisit this issue by making use of the available human and chimpanzee genome sequence to study the relationship between chromosomal rearrangements and rates of DNA sequence evolution. Results Contrary to previous findings for this pair of species, we show that genes located in the rearranged chromosomes that differentiate the genomes of humans and chimpanzees, especially genes within rearrangements themselves, present lower divergence than genes elsewhere in the genome. Still, there are considerable differences between individual chromosomes. Chromosome 4, in particular, presents higher divergence in genes located within its rearrangement. Conclusion A first conclusion of our analysis is that divergence is lower for genes located in rearranged chromosomes than for those in colinear chromosomes. We also report that non-coding regions within rearranged regions tend to have lower divergence than non-coding regions outside them. These results suggest an association between chromosomal rearrangements and lower non-coding divergence that has not been reported before, even if some chromosomes do not follow this trend and could be potentially associated with a speciation episode. In summary, without excluding it, our results suggest that chromosomal speciation has not been common along the human and chimpanzee lineage. PMID:17971225

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

    PubMed Central

    Krüger, Sebastian

    2014-01-01

    Summary 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. PMID:24605138

  1. Rearrangement hotspots in the sex chromosome of the Palearctic black fly Simulium bergi (Diptera, Simuliidae)

    PubMed Central

    Adler, Peter H.; Yildirim, Alparslan; Onder, Zuhal; Tasci, G. Taskin; Duzlu, Onder; Arslan, M. Ozkan; Ciloglu, Arif; Sari, Baris; Parmaksizoglu, Nilgun; Inci, Abdullah

    2016-01-01

    Abstract An extreme example of nonrandom rearrangements, especially inversion breaks, is described in the polytene chromosomes of the black fly Simulium bergi Rubtsov, 1956 from Armenia and Turkey. A total of 48 rearrangements was discovered, relative to the standard banding sequence for the subgenus Simulium Latreille, 1802. One rearrangement, an inversion (IIS-C) in the short arm of the second chromosome, was fixed. Six (12.5%) of the rearrangements were autosomal polymorphisms, and the remaining 41 (85.4%) were sex linked. More than 40 X- and Y-linked rearrangements, predominantly inversions, were clustered in the long arm of the second chromosome (IIL), representing about 15% of the total complement. The pattern conforms to a nonrandom model of chromosome breakage, perhaps associated with an underlying molecular mechanism. PMID:27551350

  2. T cell receptor gamma and delta rearrangements in hematologic malignancies. Relationship to lymphoid differentiation.

    PubMed Central

    Griesinger, F; Greenberg, J M; Kersey, J H

    1989-01-01

    We have studied recombinatorial events of the T cell receptor delta and gamma chain genes in hematopoietic malignancies and related these to normal stages of lymphoid differentiation. T cell receptor delta gene recombinatorial events were found in 91% of acute T cell lymphoblastic leukemia, 68% of non-T, non-B lymphoid precursor acute lymphoblastic leukemia (ALL) and 80% of mixed lineage acute leukemias. Mature B-lineage leukemias and acute nonlymphocytic leukemias retained the T-cell receptor delta gene in the germline configuration. The incidence of T cell receptor gamma and delta was particularly high in CD10+CD19+ non-T, non-B lymphoid precursor ALL. In lymphoid precursor ALL, T cell receptor delta was frequently rearranged while T cell receptor gamma was in the germline configuration. This suggests that TCR delta rearrangements may precede TCR gamma rearrangements in lymphoid ontogeny. In T-ALL, only concordant T cell receptor delta and gamma rearrangements were observed. Several distinct rearrangements were defined using a panel of restriction enzymes. Most of the rearrangements observed in T-ALL represented joining events of J delta 1 to upstream regions. In contrast, the majority of rearrangements in lymphoid precursor ALL most likely represented D-D or V-D rearrangements, which have been found to be early recombinatorial events of the TCR delta locus. We next analyzed TCR delta rearrangements in five CD3+TCR gamma/delta+ ALL and cell lines. One T-ALL, which demonstrated a different staining pattern with monoclonal antibodies against the products of the TCR gamma/delta genes than the PEER cell line, rearranges J delta 1 to a currently unidentified variable region. Images PMID:2547833

  3. Bubble rearrangement dynamics and light transport in aqueous foams

    NASA Astrophysics Data System (ADS)

    Gittings, Alex St Clair

    The general scope of this work investigates two essential, yet surprisingly elusive, properties of aqueous foams. The first concerns how multiply scattered light is transported throughout the foam. The second concerns the dynamics of bubble rearrangement events for coarsening foams. The absorption of diffuse photons in aqueous foams is measured by adding a dye to the continuous liquid phase. For very wet and for dry foams, the absorption of the diffuse photons equals the absorption length of the liquid divided by the liquid volume fraction, indicating photons propagate by a random walk, sampling each phase in proportion to its volume. Foams of intermediate wetness, by contrast, absorb photons more strongly than expected, indicating photons have a higher probability for being transported in the network. This suggests novel transport effects such as photons that enter a border in a state that only allows internal reflection for the border length. We further investigate light transport in foams by considering a two-dimensional model foam with scattering described by geometric optics and the Fresnel equations. Here we develop theoretical results for bulk transport quantities, such as the scattering length, in terms of the basic microscopic structural elements of the foam. Results are compared with a computer simulation. Essential to this work is determining key quantities, such as the scattering length, for each phase separately. The transport quantity for the foam is then constructed from the phase dependant parts using probability weights. The probability weights represent the probability that a diffuse photon scatters at network and disperse incidence, and are determined simply in terms of the index of refraction for the liquid and gas. Study of bubble rearrangement dynamics for coarsening foams proceeds in two steps. First, simultaneous measurement of second and three-time temporal intensity correlations are performed to test the validity of Diffusing

  4. B lineage-restricted rearrangement of a human Ig kappa transgene.

    PubMed

    Cavelier, P; Nato, F; Coquilleau, I; Rolink, A; Rougeon, F; Goodhardt, M

    1997-07-01

    To study the control of immunoglobulin kappa light chain gene rearrangement, we generated transgenic mice carrying a germ-line human kappa minilocus (HK) containing the J kappa-proximal V gene, V kappa IV, the V-J intergenic region, the five J kappa segments and the C kappa gene. This construct includes the intronic, but not the 3' kappa enhancer. Rearrangement of the HK transgene was found to be lymphoid specific and restricted to the B cell lineage. Quantification of kappa gene rearrangement in pre-B cell lines established from HK transgenic mice showed that, like endogenous kappa genes, rearrangement of the transgene is repressed in mu-negative early B cell precursors. These results indicate that rearrangement of the HK transgene is subjected to the same B/T cell and developmental regulation as V kappa-J kappa rearrangement at the endogenous locus. Comparison with an unrearranged kappa transgenic construct lacking the V-J intergenic region, suggests that this region, or elements associated with the proximal V gene, may act to restrict kappa gene rearrangement to the B cell lineage. PMID:9247570

  5. PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas.

    PubMed

    Ozawa, Tatsuya; Brennan, Cameron W; Wang, Lu; Squatrito, Massimo; Sasayama, Takashi; Nakada, Mitsutoshi; Huse, Jason T; Pedraza, Alicia; Utsuki, Satoshi; Yasui, Yoshie; Tandon, Adesh; Fomchenko, Elena I; Oka, Hidehiro; Levine, Ross L; Fujii, Kiyotaka; Ladanyi, Marc; Holland, Eric C

    2010-10-01

    Gene rearrangement in the form of an intragenic deletion is the primary mechanism of oncogenic mutation of the epidermal growth factor receptor (EGFR) gene in gliomas. However, the incidence of platelet-derived growth factor receptor-α (PDGFRA) gene rearrangement in these tumors is unknown. We investigated the PDGFRA locus in PDGFRA-amplified gliomas and identified two rearrangements, including the first case of a gene fusion between kinase insert domain receptor (KDR) (VEGFRII) and the PDGFRA gene, and six cases of PDGFRA(Δ8, 9), an intragenic deletion rearrangement. The PDGFRA(Δ8, 9) mutant was common, being present in 40% of the glioblastoma multiformes (GBMs) with PDGFRA amplification. Tumors with these two types of PDGFRA rearrangement displayed histologic features of oligodendroglioma, and the gene products of both rearrangements showed constitutively elevated tyrosine kinase activity and transforming potential that was reversed by PDGFR blockade. These results suggest the possibility that these PDGFRA mutants behave as oncogenes in this subset of gliomas, and that the prevalence of such rearrangements may have been considerably underestimated. PMID:20889717

  6. BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome

    PubMed Central

    Ewald, Ingrid Petroni; Cossio, Silvia Liliana; Palmero, Edenir Inez; Pinheiro, Manuela; Nascimento, Ivana Lucia de Oliveira; Machado, Taisa Manuela Bonfim; Sandes, Kiyoko Abe; Toralles, Betânia; Garicochea, Bernardo; Izetti, Patricia; Pereira, Maria Luiza Saraiva; Bock, Hugo; Vargas, Fernando Regla; Moreira, Miguel Ângelo Martins; Peixoto, Ana; Teixeira, Manuel R.; Ashton-Prolla, Patricia

    2016-01-01

    Abstract Approximately 5-10% of breast cancers are caused by germline mutations in high penetrance predisposition genes. Among these, BRCA1 and BRCA2, which are associated with the Hereditary Breast and Ovarian Cancer (HBOC) syndrome, are the most frequently affected genes. Recent studies confirm that gene rearrangements, especially in BRCA1, are responsible for a significant proportion of mutations in certain populations. In this study we determined the prevalence of BRCA rearrangements in 145 unrelated Brazilian individuals at risk for HBOC syndrome who had not been previously tested for BRCA mutations. Using Multiplex Ligation-dependent Probe Amplification (MLPA) and a specific PCR-based protocol to identify a Portuguese founder BRCA2 mutation, we identified two (1,4%) individuals with germline BRCA1 rearrangements (c.547+240_5193+178del and c.4675+467_5075-990del) and three probands with the c.156_157insAlu founder BRCA2 rearrangement. Furthermore, two families with false positive MLPA results were shown to carry a deleterious point mutation at the probe binding site. This study comprises the largest Brazilian series of HBOC families tested for BRCA1 and BRCA2 rearrangements to date and includes patients from three regions of the country. The overall observed rearrangement frequency of 3.44% indicates that rearrangements are relatively uncommon in the admixed population of Brazil. PMID:27303907

  7. Chromosomal Rearrangements in Salmonella enterica Serovar Typhi Strains Isolated from Asymptomatic Human Carriers

    PubMed Central

    Matthews, T. David; Rabsch, Wolfgang; Maloy, Stanley

    2011-01-01

    ABSTRACT Host-specific serovars of Salmonella enterica often have large-scale chromosomal rearrangements that occur by recombination between rrn operons. Two hypotheses have been proposed to explain these rearrangements: (i) replichore imbalance from horizontal gene transfer drives the rearrangements to restore balance, or (ii) the rearrangements are a consequence of the host-specific lifestyle. Although recent evidence has refuted the replichore balance hypothesis, there has been no direct evidence for the lifestyle hypothesis. To test this hypothesis, we determined the rrn arrangement type for 20 Salmonella enterica serovar Typhi strains obtained from human carriers at periodic intervals over multiple years. These strains were also phage typed and analyzed for rearrangements that occurred over long-term storage versus routine culturing. Strains isolated from the same carrier at different time points often exhibited different arrangement types. Furthermore, colonies isolated directly from the Dorset egg slants used to store the strains also had different arrangement types. In contrast, colonies that were repeatedly cultured always had the same arrangement type. Estimated replichore balance of isolated strains did not improve over time, and some of the rearrangements resulted in decreased replicore balance. Our results support the hypothesis that the restricted lifestyle of host-specific Salmonella is responsible for the frequent chromosomal rearrangements in these serovars. PMID:21652779

  8. BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome.

    PubMed

    Ewald, Ingrid Petroni; Cossio, Silvia Liliana; Palmero, Edenir Inez; Pinheiro, Manuela; Nascimento, Ivana Lucia de Oliveira; Machado, Taisa Manuela Bonfim; Sandes, Kiyoko Abe; Toralles, Betânia; Garicochea, Bernardo; Izetti, Patricia; Pereira, Maria Luiza Saraiva; Bock, Hugo; Vargas, Fernando Regla; Moreira, Miguel Ângelo Martins; Peixoto, Ana; Teixeira, Manuel R; Ashton-Prolla, Patricia

    2016-01-01

    Approximately 5-10% of breast cancers are caused by germline mutations in high penetrance predisposition genes. Among these, BRCA1 and BRCA2, which are associated with the Hereditary Breast and Ovarian Cancer (HBOC) syndrome, are the most frequently affected genes. Recent studies confirm that gene rearrangements, especially in BRCA1, are responsible for a significant proportion of mutations in certain populations. In this study we determined the prevalence of BRCA rearrangements in 145 unrelated Brazilian individuals at risk for HBOC syndrome who had not been previously tested for BRCA mutations. Using Multiplex Ligation-dependent Probe Amplification (MLPA) and a specific PCR-based protocol to identify a Portuguese founder BRCA2 mutation, we identified two (1,4%) individuals with germline BRCA1 rearrangements (c.547+240_5193+178del and c.4675+467_5075-990del) and three probands with the c.156_157insAlu founder BRCA2 rearrangement. Furthermore, two families with false positive MLPA results were shown to carry a deleterious point mutation at the probe binding site. This study comprises the largest Brazilian series of HBOC families tested for BRCA1 and BRCA2 rearrangements to date and includes patients from three regions of the country. The overall observed rearrangement frequency of 3.44% indicates that rearrangements are relatively uncommon in the admixed population of Brazil. PMID:27303907

  9. Genome Rearrangements in Mammalian Evolution: Lessons From Human and Mouse Genomes

    PubMed Central

    Pevzner, Pavel; Tesler, Glenn

    2003-01-01

    Although analysis of genome rearrangements was pioneered by Dobzhansky and Sturtevant 65 years ago, we still know very little about the rearrangement events that produced the existing varieties of genomic architectures. The genomic sequences of human and mouse provide evidence for a larger number of rearrangements than previously thought and shed some light on previously unknown features of mammalian evolution. In particular, they reveal that a large number of microrearrangements is required to explain the differences in draft human and mouse sequences. Here we describe a new algorithm for constructing synteny blocks, study arrangements of synteny blocks in human and mouse, derive a most parsimonious human–mouse rearrangement scenario, and provide evidence that intrachromosomal rearrangements are more frequent than interchromosomal rearrangements. Our analysis is based on the human–mouse breakpoint graph, which reveals related breakpoints and allows one to find a most parsimonious scenario. Because these graphs provide important insights into rearrangement scenarios, we introduce a new visualization tool that allows one to view breakpoint graphs superimposed with genomic dot-plots. [Supplemental material is available online at www.genome.org.] PMID:12529304

  10. The potential of clofarabine in MLL-rearranged infant acute lymphoblastic leukaemia.

    PubMed

    Stumpel, Dominique J P M; Schneider, Pauline; Pieters, Rob; Stam, Ronald W

    2015-09-01

    MLL-rearranged acute lymphoblastic leukaemia (ALL) in infants is the most difficult-to-treat type of childhood ALL, displaying a chemotherapy-resistant phenotype, and unique histone modifications, gene expression signatures and DNA methylation patterns. MLL-rearranged infant ALL responds remarkably well to nucleoside analogue drugs in vitro, such as cytarabine and cladribine, and to the demethylating agents decitabine and zebularine as measured by cytotoxicity assays. These observations led to the inclusion of cytarabine into the treatment regimens currently used for infants with ALL. However, survival chances for infants with MLL-rearranged ALL do still not exceed 30-40%. Here we explored the in vitro potential of the novel nucleoside analogue clofarabine for MLL-rearranged infant ALL. Therefore we used both cell line models as well as primary patient cells. Compared with other nucleoside analogues, clofarabine effectively targeted primary MLL-rearranged infant ALL cells at the lowest concentrations, with median LC50 values of ∼25 nM. Interestingly, clofarabine displayed synergistic cytotoxic effects in combination with cytarabine. Furthermore, at concentrations of 5-10nM clofarabine induced demethylation of the promoter region of the tumour suppressor gene FHIT (Fragile Histidine Triad), a gene typically hypermethylated in MLL-rearranged ALL. Demethylation of the FHIT promoter region was accompanied by subtle re-expression of this gene both at the mRNA and protein level. We conclude that clofarabine is an interesting candidate for further studies in MLL-rearranged ALL in infants. PMID:26188848

  11. Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers.

    PubMed

    Yoshida, Akihiko; Tsuta, Koji; Wakai, Susumu; Arai, Yasuhito; Asamura, Hisao; Shibata, Tatsuhiro; Furuta, Koh; Kohno, Takashi; Kushima, Ryoji

    2014-05-01

    The recent discovery and characterization of an oncogenic ROS1 gene fusion in a subset of lung cancers has raised significant clinical interest because small molecule inhibitors may be effective to these tumors. As lung cancers with ROS1 rearrangements comprise only 1-3% of lung adenocarcinomas, patients with such tumors must be identified to gain optimal benefit from molecular therapy. Recently, immunohistochemical analyses using a novel anti-ROS1 rabbit monoclonal antibody (D4D6) have shown promise for accurate identification of ROS1-rearranged cancers. To validate this finding, we compared the immunostaining results of tissue microarrays (TMAs) containing 17 ROS1-rearranged and 253 ROS1-non-rearranged lung carcinomas. All 17 ROS1-rearranged cancers showed ROS1 immunoreactivity mostly in a diffuse and moderate-to-strong manner with an H-score range of 5-300 (median, 260). In contrast, 69% of ROS1-non-rearranged cancers lacked detectable immunoreactivity, whereas the remaining 31% showed reactivity mainly in a weak or focal manner. The H-score for the entire ROS1-non-rearranged group ranged from 0 to 240 (median, 0). The difference in H-score between the two cohorts was statistically significant, and the H-score cutoff (≥150) allowed optimal discrimination (94% sensitivity and 98% specificity). Similar but slightly less-specific performance was achieved using the extent of diffuse (≥75%) staining or ≥2+ staining intensity as cutoffs. CD74-ROS1 and EZR-ROS1 fusions were significantly associated with at least focal globular immunoreactivity and plasma membranous accentuation, respectively, and these patterns were specific to ROS1-rearranged cases. Although full-length ROS1 is expressed in some ROS1-non-rearranged cases, we showed that establishment of an optimal set of interpretative criteria makes ROS1 immunohistochemistry a valuable method to rapidly and accurately screen lung cancer patients for appropriate molecular therapy. PMID:24186139

  12. Order and disorder control the functional rearrangement of influenza hemagglutinin.

    PubMed

    Lin, Xingcheng; Eddy, Nathanial R; Noel, Jeffrey K; Whitford, Paul C; Wang, Qinghua; Ma, Jianpeng; Onuchic, José N

    2014-08-19

    Influenza hemagglutinin (HA), a homotrimeric glycoprotein crucial for membrane fusion, undergoes a large-scale structural rearrangement during viral invasion. X-ray crystallography has shown that the pre- and postfusion configurations of HA2, the membrane-fusion subunit of HA, have disparate secondary, tertiary, and quaternary structures, where some regions are displaced by more than 100 Å. To explore structural dynamics during the conformational transition, we studied simulations of a minimally frustrated model based on energy landscape theory. The model combines structural information from both the pre- and postfusion crystallographic configurations of HA2. Rather than a downhill drive toward formation of the central coiled-coil, we discovered an order-disorder transition early in the conformational change as the mechanism for the release of the fusion peptides from their burial sites in the prefusion crystal structure. This disorder quickly leads to a metastable intermediate with a broken threefold symmetry. Finally, kinetic competition between the formation of the extended coiled-coil and C-terminal melting results in two routes from this intermediate to the postfusion structure. Our study reiterates the roles that cracking and disorder can play in functional molecular motions, in contrast to the downhill mechanical interpretations of the "spring-loaded" model proposed for the HA2 conformational transition. PMID:25082896

  13. Effects of structural rearrangements on sorption capacity of coals

    SciTech Connect

    Romanov, Vyacheslav; Soong, Yee; Warzinski, R.P.; Lynn, R.J.

    2006-09-01

    Recently, the problems in practical application of experimental data and modeling to the sequestration of carbon dioxide in coal seams and the concurrent enhanced coalbed methane (ECBM) recovery have underscored the need for new approaches that take into account the ability of coal for structural rearrangements. Areas of interest include plasticization of coal due to CO2 dissolution, the effect of coal swelling on estimation of the capacity of a coal-seam to adsorb CO2 (adsorption isotherm), and the stability of the CO2 saturated phase once formed, especially with respect to how it might be affected by changes in the post-sequestration environment (environmental effects). Coals are organic macromolecular systems well known to imbibe organic liquids and carbon dioxide. CO2 dissolves in coals and swells them. The problems become more prominent in the region of supercritical CO2. We investigated the effects of moisture content and pressure cycling history on temporal changes in the coal sorptive capacity for a set of Argonne premium coals. The samples were tested as received, dried at 80oC for 36 hours, and moisture equilibrated at 96-97% RH and 30oC for 48 hours. The powders were compared to core samples. Additionally, plasticization of coal powders was studied by high pressure dilatometer.

  14. Model of the cooperative rearranging region for polyhydric alcohols

    NASA Astrophysics Data System (ADS)

    Nakanishi, Masahiro; Nozaki, Ryusuke

    2011-07-01

    A simplified model of a hydrogen-bonding network is proposed in order to clarify the microscopic structure of the cooperative rearranging region (CRR) in Adam-Gibbs theory [G. Adam and J. H. Gibbs, J. Chem. Phys.JCPSA60021-960610.1063/1.1696442 43, 139 (1965)]. Our model can be solved analytically, and it successfully explains the reported systematic features of the glass transition of polyhydric alcohols. In this model, hydrogen bonding is formulated based on binding free energy. Assuming a cluster of molecules connected by double hydrogen bonds is a CRR and approximating the hydrogen-bonding network as a Bethe lattice in percolation theory, the temperature dependence of the structural relaxation time can be obtained analytically. Reported data on relaxation times are well described by the obtained equation. By taking the lower limit of the binding free energy with this equation, the Vogel-Fulcher-Tammann equation can be derived. Consequently, the fragility index and glass transition temperature can be expressed as functions of the number of OH groups in a molecule, and this relation agrees well with the reported experimental data.

  15. Structural rearrangement through lanthanide contraction in dinuclear complexes.

    PubMed

    Hutchings, Amy-Jayne; Habib, Fatemah; Holmberg, Rebecca J; Korobkov, Ilia; Murugesu, Muralee

    2014-02-17

    A new series of lanthanide complexes was synthesized, and the geometry and preliminary magnetic measurements of the complexes were explored. The specific ligand used (N'-(2-hydroxy-3-methoxybenzylidene)benzhydrazide) (H2hmb) was synthesized using a Schiff-base approach and was employed due to the presence of a coordination pocket that is able to accommodate magnetically selective lanthanide ions. The series can be divided into two groups that are categorized by a drastic structural rearrangement. The first group, Type I, contains six analogous complexes with the formula [M(III)2(Hhmb)3(NCS)3]·2MeOH·py (M = Y 1, Eu 2, Gd 3, Tb 4, Dy 5, Ho 6), while the second group, Type II, contains two dinuclear complexes with formula [M(III)2(Hhmb)2(NCS)4(MeOH)2] (M = Er 7, and Yb 8). Single-crystal X-ray analysis revealed that all M(III) ions in Type I exhibit monocapped distorted square antiprismatic geometries, while those of Type II exhibit distorted dodecahedron geometry. The direct current and alternating current magnetic measurements were carried out on all complexes, with 5, 7, and 8 exhibiting slow relaxation of the magnetization under an applied optimum dc field. Furthermore, complex 8 is the first example of a dinuclear Yb-based single-molecule magnet showing field-dependent multiple relaxation processes. PMID:24499030

  16. Role of chromosomal rearrangement in N. gonorrhoeae pilus phase variation.

    PubMed

    Segal, E; Billyard, E; So, M; Storzbach, S; Meyer, T F

    1985-02-01

    N. gonorrhoeae undergoes pilus phase and antigenic variation. During phase variation, the pilin gene is turned on and off at high frequencies. Two loci on the gonococcal chromosome from strain MS11 function as expression sites for the pilin gene (pilE1 and pilE2); many other sites apparently contain silent variant pilin sequences. We reported previously that during pilus phase variation, when cells switch from the pilus expressing state (P+) to the nonexpressing state (P-), genome rearrangement occurs. We have examined phase variation in more detail, and we report that in most P+ to P- switches a deletion of pilin gene information occurs in one or both expression sites. This deletion is due to either a simple or a multiple-step recombination event involving directly repeated sequences in the expression loci. The deletion explains the state of some P- cells, but not all. In the latter cells pilin expression is probably controlled by an undefined regulator. PMID:2857113

  17. Distinct structural rearrangements of the VSV glycoprotein drive membrane fusion

    PubMed Central

    Libersou, Sonia; Albertini, Aurélie A.V.; Ouldali, Malika; Maury, Virginie; Maheu, Christine; Raux, Hélène; de Haas, Felix; Roche, Stéphane

    2010-01-01

    The entry of enveloped viruses into cells requires the fusion of viral and cellular membranes, driven by conformational changes in viral glycoproteins. Many studies have shown that fusion involves the cooperative action of a large number of these glycoproteins, but the underlying mechanisms are unknown. We used electron microscopy and tomography to study the low pH–induced fusion reaction catalyzed by vesicular stomatitis virus glycoprotein (G). Pre- and post-fusion crystal structures were observed on virions at high and low pH, respectively. Individual fusion events with liposomes were also visualized. Fusion appears to be driven by two successive structural rearrangements of G at different sites on the virion. Fusion is initiated at the flat base of the particle. Glycoproteins located outside the contact zone between virions and liposomes then reorganize into regular arrays. We suggest that the formation of these arrays, which have been shown to be an intrinsic property of the G ectodomain, induces membrane constraints, achieving the fusion reaction. PMID:20921141

  18. Oxidative dehydrogenation of ethane on dynamically rearranging supported chloride catalysts.

    PubMed

    Gärtner, Christian A; van Veen, André C; Lercher, Johannes A

    2014-09-10

    Ethane is oxidatively dehydrogenated with a selectivity up to 95% on catalysts comprising a mixed molten alkali chloride supported on a mildly redox-active Dy2O3-doped MgO. The reactive oxyanionic OCl(-) species acting as active sites are catalytically formed by oxidation of Cl(-) at the MgO surface. Under reaction conditions this site is regenerated by O2, dissolving first in the alkali chloride melt, and in the second step dissociating and replenishing the oxygen vacancies on MgO. The oxyanion reactively dehydrogenates ethane at the melt-gas phase interface with nearly ideal selectivity. Thus, the reaction is concluded to proceed via two coupled steps following a Mars-van-Krevelen-mechanism at the solid-liquid and gas-liquid interface. The dissociation of O2 and/or the oxidation of Cl(-) at the melt-solid interface is concluded to have the lowest forward rate constants. The compositions of the oxide core and the molten chloride shell control the catalytic activity via the redox potential of the metal oxide and of the OCl(-). Traces of water may be present in the molten chloride under reaction conditions, but the specific impact of this water is not obvious at present. The spatial separation of oxygen and ethane activation sites and the dynamic rearrangement of the surface anions and cations, preventing the exposure of coordinatively unsaturated cations, are concluded to be the origin of the surprisingly high olefin selectivity. PMID:25118821

  19. Lamellar rearrangement of internal lipids from human hair.

    PubMed

    Coderch, L; Méndez, S; Barba, C; Pons, R; Martí, M; Parra, J L

    2008-09-01

    The internal lipids were extracted from untreated hair without surface lipids. Liposomes were formed with the internal lipids at different hydration levels to determine the organization of these lipids and the influence of the water content on the lamellar structure of the hair fibres by X-ray Scattering (SAXS). Two structures of hair lipids were observed at 4.5 and approximately 9.0 nm with a different behaviour as a function of water content: the largest bilayer being the one that showed a capacity to retain water inside its structure. SAXS was also applied directly to three samples: a packed swatch of hair fibres at 60% RH, fibres soaked in water and delipidized fibres. Only the lamella at 9.0 nm was slightly affected by water content. Moreover, there was a small diminution in intensity probably due to a high permeability of wet fibres which could give rise to a disorder of the lipid structure. These two lamellar rearrangements are probably made up of lipids with a different and specific hydrophilic/hydrophobic balance. PMID:18619428

  20. Complex Chromosomal Rearrangements Induced in Vivo by Heavy Ions

    NASA Technical Reports Server (NTRS)

    Durante, M.; Ando, K.; Furusawa, G.; Obe, G.; George, K.; Cucinotta, F. A.

    2004-01-01

    It has been suggested that the ratio complex/simple exchanges can be used as a biomarker of exposure to high-LET radiation. We tested this hypothesis in vivo, by considering data from several studies that measured complex exchanges in peripheral blood from humans exposed to mixed fields of low- and high-LET radiation. In particular, we studied data from astronauts involved in long-term missions in low-Earth-orbit, and uterus cancer patients treated with accelerated carbon ions. Data from two studies of chromosomal aberrations in astronauts used blood samples obtained before and after space flight, and a third study used blood samples from patients before and after radiotherapy course. Similar methods were used in each study, where lymphocytes were stimulated to grow in vitro, and collected after incubation in either colcemid or calyculin A. Slides were painted with whole-chromosome DNA fluorescent probes (FISH), and complex and simple chromosome exchanges in the painted genome were classified separately. Complex-type exchanges were observed at low frequencies in control subjects, and in our test subjects before the treatment. No statistically significant increase in the yield of complex-type exchanges was induced by the space flight. Radiation therapy induced a high fraction of complex exchanges, but no significant differences could be detected between patients treated with accelerated carbon ions or X-rays. Complex chromosomal rearrangements do not represent a practical biomarker of radiation quality in our test subjects. Copyright 2003 S. Karger AG, Basel.

  1. Chromosome painting defines genomic rearrangements between red howler monkey subspecies.

    PubMed

    Consigliere, S; Stanyon, R; Koehler, U; Agoramoorthy, G; Wienberg, J

    1996-06-01

    We hybridized whole human chromosome-specific DNA libraries to chromosomes of two supposed subspecies of Alouatta seniculus: Alouatta seniculus sara and Alouatta seniculus arctoides. The number of hybridization signals per haploid set is 42 in A. s. sara and 43 in A. s. arctoidea; the two karyotypes differ by at least 16 chromosomal rearrangements, including numerous translocations. An unusual sex chromosome system is shared by both taxa. The sex chromosome system results from a Y translocation with a chromosome homologous to parts of human chromosome 3/15 and can be described as X1X2Y1Y2/X1X1X2X2 (male/female). Both red howlers also have microchromosomes, a highly unusual karyological trait not found in other higher primates. These microchromosomes are not hybridized by any human chromosome paint and therefore are probably composed of repetitive DNA. It is well known that New World monkeys have high karyological variability. It is probable that molecular cytogenetic analyses including chromosome painting will permit an accurate reconstruction of the phylogeny of these monkeys and help establish the ancestral karyotype for higher primates. PMID:8817065

  2. Coupled-rearrangement-channels calculation of the three-body system under the absorbing boundary condition

    NASA Astrophysics Data System (ADS)

    Iwasaki, M.; Otani, R.; Ito, M.; Kamimura, M.

    2016-05-01

    We formulate the method of the absorbing boundary condition (ABC) in the coupled-rearrangement-channels variational method (CRCMV) for the three-body problem. In the present study, we handle the simple three-boson system, and the absorbing potential is introduced in the Jacobi coordinate in the individual rearrangement channels. The resonance parameters and the strength of the monopole breakup are compared with the complex scaling method (CSM). We have found that the CRCVM + ABC method nicely works in the threebody problem with the rearrangement channels.

  3. Premature termination of variable gene rearrangement in B lymphocytes from X-linked agammaglobulinemia.

    PubMed Central

    Schwaber, J; Chen, R H

    1988-01-01

    X-linked agammaglobulinemia (XLA) results from failure of B lymphocyte development. Immature B cells from a patient with XLA were found to produce truncated mu and delta immunoglobulin H chains encoded by D-JH-C (mu delta). The 5' terminal sequence of cDNA encoding the H chains is composed of D-JH with the characteristic GGTTTGAAG/CACTGTG consensus sequence utilized for VH gene rearrangement upstream, and a leader sequence that serves for translation of this intermediate stage of rearrangement. Failure of variable region gene rearrangement may underlie the failure of B lymphoid development in XLA. Images PMID:2838527

  4. Transcriptome-guided characterization of genomic rearrangements in a breast cancer cell line

    PubMed Central

    Zhao, Qi; Caballero, Otavia L.; Levy, Samuel; Stevenson, Brian J.; Iseli, Christian; de Souza, Sandro J.; Galante, Pedro A.; Busam, Dana; Leversha, Margaret A.; Chadalavada, Kalyani; Rogers, Yu-Hui; Venter, J. Craig; Simpson, Andrew J. G.; Strausberg, Robert L.

    2009-01-01

    We have identified new genomic alterations in the breast cancer cell line HCC1954, using high-throughput transcriptome sequencing. With 120 Mb of cDNA sequences, we were able to identify genomic rearrangement events leading to fusions or truncations of genes including MRE11 and NSD1, genes already implicated in oncogenesis, and 7 rearrangements involving other additional genes. This approach demonstrates that high-throughput transcriptome sequencing is an effective strategy for the characterization of genomic rearrangements in cancers. PMID:19181860

  5. An efficient algorithm for the contig ordering problem under algebraic rearrangement distance.

    PubMed

    Lu, Chin Lung

    2015-11-01

    Assembling a genome from short reads currently obtained by next-generation sequencing techniques often results in a collection of contigs, whose relative position and orientation along the genome being sequenced are unknown. Given two sets of contigs, the contig ordering problem is to order and orient the contigs in each set such that the genome rearrangement distance between the resulting sets of ordered and oriented contigs is minimized. In this article, we utilize the permutation groups in algebra to propose a near-linear time algorithm for solving the contig ordering problem under algebraic rearrangement distance, where the algebraic rearrangement distance between two sets of ordered and oriented contigs is the minimum weight of applicable rearrangement operations required to transform one set into the other. PMID:26247343

  6. Imaging atomic rearrangements in two-dimensional silica glass: watching silica's dance.

    PubMed

    Huang, Pinshane Y; Kurasch, Simon; Alden, Jonathan S; Shekhawat, Ashivni; Alemi, Alexander A; McEuen, Paul L; Sethna, James P; Kaiser, Ute; Muller, David A

    2013-10-11

    Structural rearrangements control a wide range of behavior in amorphous materials, and visualizing these atomic-scale rearrangements is critical for developing and refining models for how glasses bend, break, and melt. It is difficult, however, to directly image atomic motion in disordered solids. We demonstrate that using aberration-corrected transmission electron microscopy, we can excite and image atomic rearrangements in a two-dimensional silica glass-revealing a complex dance of elastic and plastic deformations, phase transitions, and their interplay. We identified the strain associated with individual ring rearrangements, observed the role of vacancies in shear deformation, and quantified fluctuations at a glass/liquid interface. These examples illustrate the wide-ranging and fundamental materials physics that can now be studied at atomic-resolution via transmission electron microscopy of two-dimensional glasses. PMID:24115436

  7. One-pot oxidation and rearrangement of propargylamines and in situ pyrazole synthesis.

    PubMed

    Chen, Jinshan; Properzi, Roberta; Uccello, Daniel P; Young, Jennifer A; Dushin, Russell G; Starr, Jeremy T

    2014-08-15

    Reported here are procedures for a one-pot oxidation and rearrangement of propargylamines to synthesize enaminones, with supporting mechanistic studies. Also reported are the extended one-pot syntheses of pyrazoles, including celecoxib and various heterocyclic compounds. PMID:25069029

  8. The Architecture of a Scrambled Genome Reveals Massive Levels of Genomic Rearrangement during Development

    PubMed Central

    Chen, Xiao; Bracht, John R.; Goldman, Aaron David; Dolzhenko, Egor; Clay, Derek M.; Swart, Estienne C.; Perlman, David H.; Doak, Thomas G.; Stuart, Andrew; Amemiya, Chris T.; Sebra, Robert P.; Landweber, Laura F.

    2014-01-01

    SUMMARY Programmed DNA rearrangements in the single-celled eukaryote Oxytricha trifallax completely rewire its germline into a somatic nucleus during development. This elaborate, RNA-mediated pathway eliminates noncoding DNA sequences that interrupt gene loci and reorganizes the remaining fragments by inversions and permutations to produce functional genes. Here, we report the Oxytricha germline genome and compare it to the somatic genome to present a global view of its massive scale of genome rearrangements. The remarkably encrypted genome architecture contains >3,500 scrambled genes, as well as >800 predicted germline-limited genes expressed, and some posttranslationally modified, during genome rearrangements. Gene segments for different somatic loci often interweave with each other. Single gene segments can contribute to multiple, distinct somatic loci. Terminal precursor segments from neighboring somatic loci map extremely close to each other, often overlapping. This genome assembly provides a draft of a scrambled genome and a powerful model for studies of genome rearrangement. PMID:25171416

  9. Rearrangements of c-myc and c-abl genes in tumour cells in Burkitt's lymphoma.

    PubMed Central

    Casares, S; Rodríguez, J M; Martin, A; Parrado, A

    1993-01-01

    Rearrangements of oncogenes c-myc and c-abl were detected by non-radioactive hybridisation in a case of Burkitt's lymphoma/leukaemia. The surface phenotype of Burkitt's cells were positive for CD19, CD20, HLA-DR, CD14, CD33 and surface immunoglobulin markers. Although cytogenetic analysis was not performed, the c-myc and heavy immunoglobulin genes had the same 14.2 kilobase EcoRI molecular size fragment, suggesting a possible t(8;14) translocation which is a common marker of this malignancy. The c-abl oncogene was also rearranged in DNA digested BamHI and EcoRI. The physiopathological implications of the rearranged c-abl gene are unknown, this being the first case, as for as is known, of Burkitt's lymphoma/leukaemia with a rearranged c-abl gene. Images PMID:8408711

  10. Thermal rearrangements in 1,2-poly/1,4-hexadiene/s

    NASA Technical Reports Server (NTRS)

    Golub, M. A.

    1978-01-01

    The work described was carried out to study the thermal rearrangements of two unsaturated diene polymers - 1,2-poly(cis-1,4-hexadiene) (CHD) and 1,2-poly(trans-1.4-hexadiene) (THD). It is shown that both CHD and THD have a predominatly 1,8 diene structure and seem to cyclize mainly by the (2 + 2) thermal cycloaddition of double bonds, and to a small extent also by sigmatropic rearrangement with hydrogen shift.

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

    PubMed Central

    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

  12. ROS1 rearranged non-small cell lung cancer brain metastases respond to low dose radiotherapy.

    PubMed

    Lukas, Rimas V; Hasan, Yasmin; Nicholas, Martin K; Salgia, Ravi

    2015-12-01

    We present a young woman with ROS1 gene rearranged non-small cell lung cancer (NSCLC) with brain metastases. ROS is a proto-oncogene tyrosine protein kinase. The patient received a partial course of whole brain radiation therapy and experienced a sustained partial response in the brain. We hypothesize that ROS1 rearranged NSCLC brain metastases may be particularly sensitive to radiation therapy. PMID:26159887

  13. Mechanistic Studies on Au(I)-Catalyzed [3,3]-Sigmatropic Rearrangements using Cyclopropane Probes

    PubMed Central

    Mauleón, Pablo; Krinsky, Jamin L.

    2009-01-01

    A comparative study of the Au(I)-catalyzed [3,3]-sigmatropic rearrangement of propargylic esters and propargyl vinyl ethers is described. Stereochemically defined cyclopropanes are employed as mechanistic probes to provide new synthetic and theoretical data concerning the reversibility of this type of rearrangement. Factors controlling the structure-reactivity relationship of Au(I)-coordinated allenes have been examined, thereby allowing for controlled access to orthogonal reactivity. PMID:19275228

  14. Synthesis of novel boron chelate complexes and proposed mechanism of new rearrangement

    NASA Astrophysics Data System (ADS)

    Zhang, Rui-Zhe; Feng, Xiao; Liu, Ying; Wang, Sheng-Qing; Liu, Jin-Ting; Zhao, Bao-Xiang

    2015-03-01

    We synthesized novel boron chelate complexes by the reaction of pyrazoline derivatives and boron trifluoride diethyl etherate followed by a new rearrangement. The structures of the compounds were characterized by IR, NMR and HRMS, especially, a typical compound 3c was confirmed by X-ray single crystal analysis. We proposed a mechanism of the rearrangement. Moreover, the absorption and fluorescence spectroscopy of these compounds were measured.

  15. Rearrangement dynamics in colloidal particle packings identified through local structure and machine-learning

    NASA Astrophysics Data System (ADS)

    Davidson, Zoey S.; Still, Tim; Gratale, Matthew D.; Ma, Xiaoguang; Schoenholz, Samuel S.; Sussman, Daniel M.; Liu, A. J.; Yodh, A. G.

    We explore the connection between measures of local structure and particle rearrangements in soft thermal quasi-two-dimensional colloidal systems employing a machine learning approach. Local structure is characterized by two and three point structure functions that measure radial and angular distributions of particles, and rearrangements are identified by a measure of change in average colloidal particle position. By generating labeled training data, we can extract the features of these functions that contribute to the likelihood of a rearrangement. In particular, we use a machine-learning algorithm to construct a decision function in the form of a scalar field we call softness that with high accuracy labels regions of particles more likely to rearrange. Thus, we can predict dynamic rearrangements from the instantaneous local structure. The softness field remains a good predictor when we vary the packing fraction between training and test data sets. In glassy samples, the softness field can identify aging as particles become less likely to undergo cage rearrangements. We gratefully acknowledge financial support through NSF DMR12-05463, MRSEC DMR11-20901, NASA NNX08AO0G, and DE-FG02-05ER46199.

  16. Complex genomic rearrangements in the dystrophin gene due to replication-based mechanisms

    PubMed Central

    Baskin, Berivan; Stavropoulos, Dimitri J; Rebeiro, Paige A; Orr, Jennifer; Li, Martin; Steele, Leslie; Marshall, Christian R; Lemire, Edmond G; Boycott, Kym M; Gibson, William; Ray, Peter N

    2014-01-01

    Genomic rearrangements such as intragenic deletions and duplications are the most prevalent type of mutations in the dystrophin gene resulting in Duchenne and Becker muscular dystrophy (D/BMD). These copy number variations (CNVs) are nonrecurrent and can result from either nonhomologous end joining (NHEJ) or microhomology-mediated replication-dependent recombination (MMRDR). We characterized five DMD patients with complex genomic rearrangements using a combination of MLPA/mRNA transcript analysis/custom array comparative hybridization arrays (CGH) and breakpoint sequence analysis to investigate the mechanisms for these rearrangements. Two patients had complex rearrangements that involved microhomologies at breakpoints. One patient had a noncontiguous insertion of 89.7 kb chromosome 4 into intron 43 of DMD involving three breakpoints with 2–5 bp microhomology at the junctions. A second patient had an inversion of exon 44 flanked by intronic deletions with two breakpoint junctions each showing 2 bp microhomology. The third patient was a female with an inherited deletion of exon 47 in DMD on the maternal allele and a de novo noncontiguous duplication of exons 45–49 in DMD and MID1 on the paternal allele. The other two patients harbored complex noncontiguous duplications within the dystrophin gene. We propose a replication-based mechanisms for all five complex DMD rearrangements. This study identifies additional underlying mechanisms in DMD, and provides insight into the molecular bases of these genomic rearrangements. PMID:25614876

  17. Dynamic Large-Scale Chromosomal Rearrangements Fuel Rapid Adaptation in Yeast Populations

    PubMed Central

    Chang, Shang-Lin; Lai, Huei-Yi; Tung, Shu-Yun; Leu, Jun-Yi

    2013-01-01

    Large-scale genome rearrangements have been observed in cells adapting to various selective conditions during laboratory evolution experiments. However, it remains unclear whether these types of mutations can be stably maintained in populations and how they impact the evolutionary trajectories. Here we show that chromosomal rearrangements contribute to extremely high copper tolerance in a set of natural yeast strains isolated from Evolution Canyon (EC), Israel. The chromosomal rearrangements in EC strains result in segmental duplications in chromosomes 7 and 8, which increase the copy number of genes involved in copper regulation, including the crucial transcriptional activator CUP2 and the metallothionein CUP1. The copy number of CUP2 is correlated with the level of copper tolerance, indicating that increasing dosages of a single transcriptional activator by chromosomal rearrangements has a profound effect on a regulatory pathway. By gene expression analysis and functional assays, we identified three previously unknown downstream targets of CUP2: PHO84, SCM4, and CIN2, all of which contributed to copper tolerance in EC strains. Finally, we conducted an evolution experiment to examine how cells maintained these changes in a fluctuating environment. Interestingly, the rearranged chromosomes were reverted back to the wild-type configuration at a high frequency and the recovered chromosome became fixed in less selective conditions. Our results suggest that transposon-mediated chromosomal rearrangements can be highly dynamic and can serve as a reversible mechanism during early stages of adaptive evolution. PMID:23358723

  18. Breakpoint Features of Genomic Rearrangements in Neuroblastoma with Unbalanced Translocations and Chromothripsis

    PubMed Central

    Daveau, Romain; Combaret, Valérie; Pierre-Eugène, Cécile; Cazes, Alex; Louis-Brennetot, Caroline; Schleiermacher, Gudrun; Ferrand, Sandrine; Pierron, Gaëlle; Lermine, Alban; Frio, Thomas Rio; Raynal, Virginie; Vassal, Gilles; Barillot, Emmanuel; Delattre, Olivier; Janoueix-Lerosey, Isabelle

    2013-01-01

    Neuroblastoma is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we performed an in-depth analysis of somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequencing of mate-pair libraries and RNA-seq. The cell lines presented with typical genetic alterations of neuroblastoma and the two tumors belong to the group of neuroblastoma exhibiting a profile of chromothripsis. Inter and intra-chromosomal rearrangements were identified in the four samples, allowing in particular characterization of unbalanced translocations at high resolution. Using complementary experiments, we further characterized 51 rearrangements at the base pair resolution that revealed 59 DNA junctions. In a subset of cases, complex rearrangements were observed with templated insertion of fragments of nearby sequences. Although we did not identify known particular motifs in the local environment of the breakpoints, we documented frequent microhomologies at the junctions in both chromothripsis and non-chromothripsis associated breakpoints. RNA-seq experiments confirmed expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4. Our study therefore indicates that both non-homologous end joining-mediated repair and replicative processes may account for genomic rearrangements in neuroblastoma. RNA-seq analysis allows the identification of the subset of abnormal transcripts expressed from genomic rearrangements that may be involved in neuroblastoma oncogenesis. PMID:23991058

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

    PubMed Central

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

    2000-01-01

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

  20. Detection of Enhancer-Associated Rearrangements Reveals Mechanisms of Oncogene Dysregulation in B-cell Lymphoma

    PubMed Central

    Ryan, Russell J.H.; Drier, Yotam; Whitton, Holly; Cotton, M. Joel; Kaur, Jasleen; Issner, Robbyn; Gillespie, Shawn; Epstein, Charles B.; Nardi, Valentina; Sohani, Aliyah R.; Hochberg, Ephraim P.; Bernstein, Bradley E.

    2015-01-01

    B-cell lymphomas frequently contain genomic rearrangements that lead to oncogene activation by heterologous distal regulatory elements. We utilized a novel approach, termed ‘Pinpointing Enhancer-Associated Rearrangements by Chromatin Immunoprecipitation’ or PEAR-ChIP, to simultaneously map enhancer activity and proximal rearrangements in lymphoma cell lines and patient biopsies. This method detects rearrangements involving known cancer genes, including CCND1, BCL2, MYC, PDCD1LG2, NOTCH1, CIITA, and SGK1, as well as novel enhancer duplication events of likely oncogenic significance. We identify lymphoma subtype-specific enhancers in the MYC locus that are silenced in lymphomas with MYC-activating rearrangements and are associated with germline polymorphisms that alter lymphoma risk. We show that BCL6-locus enhancers are acetylated by the BCL6-activating transcription factor MEF2B, and can undergo genomic duplication, or target the MYC promoter for activation in the context of a “pseudo-double-hit” t(3;8)(q27;q24) rearrangement linking the BCL6 and MYC loci. Our work provides novel insights regarding enhancer-driven oncogene activation in lymphoma. PMID:26229090

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

    SciTech Connect

    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.

  2. Inorganic acid-catalyzed tautomerization of vinyl alcohol to acetaldehyde

    NASA Astrophysics Data System (ADS)

    Karton, Amir

    2014-01-01

    The vinyl alcohol-acetaldehyde tautomerization reaction has recently received considerable attention as a potential route for the formation of organic acids in the troposphere (Andrews et al., 2012 [7]). We examine the catalytic effect of inorganic acids in the troposphere (e.g. HNO3, H2SO4 and HClO4) on the vinyl alcohol-acetaldehyde tautomerization reaction, by means high-level thermochemical procedures. We show that H2SO4 and HClO4 catalysts lead to near-zero reaction barrier heights for the vinyl alcohol → acetaldehyde reaction, and to low reaction barrier heights in the reverse direction (ΔH298‡=40.6 and 39.5 kJ mol, respectively).

  3. LEWIS ACID CATALYZED FORMATION OF TETRAHYDROPYRANS IN IONIC LIQUID

    EPA Science Inventory

    Tetrahydropyrans are integral moieties in innumerable natural products and have inspired the development of a variety of different methodologies. A Prins-type cyclization involving the coupling of a homoallylic alcohol and an aldehyde in the presence of catalytic scandium triflat...

  4. Decomposition of peracetic acid catalyzed by vanadium complexes

    SciTech Connect

    Makarov, A.P.; Gekhman, A.E.; Moiseev, I.I.; Polotryuk, O.Y.

    1986-02-01

    This paper studies the decomposition of peracetic acid (AcOOH) in acetic acid (AcOH) catalyzed by vanadium complexes. It is shown that peractic acid in acetic acid solutions of ammonium anadate decomposes with the predominant formation of 0/sub 2/ and small amounts of CO/sub 2/, the yield of which increases with increasing temperature and peracetic acid concentration. Both reactions proceed without the formation of free radicals in amounts detectable by ESR spectroscopy. The rate of oxygen release under conditions in which the formation of CO/sub 2/ is insignificant obeys a kinetic equation indicating the intermediate formation of a complex between V/sup 5 +/ ions and peracetic acid and the slow conversion of this complex into the observed products.

  5. Acid-Catalyzed Reaction of Epoxides on Atmospheric Nanoparticles

    NASA Astrophysics Data System (ADS)

    Xu, W.; Gomez-Hernandez, M.; Lal, V.; Qiu, C.; Khalizov, A. F.; Wang, L.; Zhang, R.

    2013-12-01

    Aerosol plays an important role in affecting the earth climate and harming human health. Atmospheric aerosols can be formed from either primary emissions or gas-to-particle conversion process. Numerous studies, including both experimental and theoretical, have been carried out to elucidate the mechanism of gas-to-particle conversion process (a.k.a. nucleation) and the later growth stage of newly formed nanoparticles. However, a complete list of species involving in the nucleation and growth processes of nanoparticles is still poorly understood. The growth of newly formed sulfuric acid - water nanoparticles has been suggested to involve several potential organic vapors, such as amines, glyoxal, 2-4 hexadienal, and epoxides. In the present study, new formed sulfuric acid -water nanoparticles were size selected by a differential mobility analyzer and exposed to epoxide vapors. The size-change after exposure was detected using the second differential mobility analyzer. The size-enlarged particles were then collected by an electrostatic precipitator, thermal vaporized, and analyzed by an ion drift chemical ionization mass spectrometer. Our results show that the sizes of nanoparticles are increased considerably and the magnitude of the increment in size is size-dependent. Mass spectrometry analysis of the nanoparticles after exposure demonstrates that low volatile organosulfate and oligomers are formed in nanoparticles upon their exposure to epoxide vapors.

  6. Acid-Catalyzed Enolization of [beta]-Tetralone

    ERIC Educational Resources Information Center

    Dewprashad, Brahmadeo; Nesturi, Anthony; Urena, Joel

    2008-01-01

    This experiment allows students to use [to the first power]H NMR to directly compare the relative initial rates of substitution of the benzylic and non-benzylic [alpha] hydrogens of [beta]-tetralone and correlate their findings with the predictions made by resonance theory. The experiment demonstrates that the benzylic hydrogens undergo [alpha]…

  7. A Lewis Acid Catalyzed Annulation to 2,1-Benzisoxazoles

    PubMed Central

    2015-01-01

    We report here a new, atom economical annulation to 2,1-benzisoxazole scaffolds via the BF3·Et2O-catalyzed reaction of glyoxylate esters and nitrosoarenes. The developed method represents a convergent route to this compound class from previously unexplored inputs and provides a range of 2,1-benzisoxazoles in moderate to high yields under convenient conditions. Along with exploration of substrate scope, initial mechanistic investigation through 18O labeling and the synthesis of a reaction intermediate provides evidence for an unusual umpolung addition of glyoxylates to nitrosobenzenes with high O-selectivity, followed by a new type of Friedel–Crafts cyclization. PMID:25157596

  8. Evaluating the thermal vinylcyclopropane rearrangement (VCPR) as a practical method for the synthesis of difluorinated cyclopentenes: experimental and computational studies of rearrangement stereospecificity.

    PubMed

    Orr, David; Percy, Jonathan M; Tuttle, Tell; Kennedy, Alan R; Harrison, Zoë A

    2014-10-27

    Vinyl cyclopropane rearrangement (VCPR) has been utilised to synthesise a difluorinated cyclopentene stereospecifically and under mild thermal conditions. Difluorocyclopropanation chemistry afforded ethyl 3-(1'(2'2'-difluoro-3'-phenyl)cyclopropyl) propenoate as all four stereoisomers (18a, 18b, 22a, 22b) (all racemic). The trans-E isomer (18a), prepared in 70 % yield over three steps, underwent near quantitative VCPR to difluorocyclopentene 23 (99 %). Rearrangements were monitored by (19) F NMR (100-180 °C). While cis/trans cyclopropane stereoisomerisation was facile, favouring trans-isomers by a modest margin, no E/Z alkene isomerisation was observed even at higher temperatures. Neither cis nor trans Z-alkenoates underwent VCPR, even up to much higher temperatures (180 °C). The cis-cyclopropanes underwent [3,3]-rearrangement to afford benzocycloheptadiene species. The reaction stereospecificity was explored by using electronic structure calculations, and UB3LYP/6-31G* methodology allowed the energy barriers for cyclopropane stereoisomerisation, diastereoisomeric VCPR and [3,3]-rearrangement to be ranked in agreement with experiment. PMID:25212120

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. Arenavirus Genome Rearrangement for the Development of Live Attenuated Vaccines

    PubMed Central

    Cheng, Benson Yee Hin; Ortiz-Riaño, Emilio

    2015-01-01

    ABSTRACT Several members of the Arenaviridae family cause hemorrhagic fever disease in humans and pose serious public health problems in their geographic regions of endemicity as well as a credible biodefense threat. To date, there have been no FDA-approved arenavirus vaccines, and current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. Arenaviruses are enveloped viruses with a bisegmented negative-stranded RNA genome. Each genome segment uses an ambisense coding strategy to direct the synthesis of two viral polypeptides in opposite orientations, separated by a noncoding intergenic region. Here we have used minigenome-based approaches to evaluate expression levels of reporter genes from the nucleoprotein (NP) and glycoprotein precursor (GPC) loci within the S segment of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). We found that reporter genes are expressed to higher levels from the NP than from the GPC locus. Differences in reporter gene expression levels from the NP and GPC loci were confirmed with recombinant trisegmented LCM viruses. We then used reverse genetics to rescue a recombinant LCMV (rLCMV) containing a translocated viral S segment (rLCMV/TransS), where the viral NP and GPC open reading frames replaced one another. The rLCMV/TransS showed slower growth kinetics in cultured cells and was highly attenuated in vivo in a mouse model of lethal LCMV infection, but immunization with rLCMV/TransS conferred complete protection against a lethal challenge with wild-type LCMV. Attenuation of rLCMV/TransS was associated with reduced NP expression levels. These results open a new avenue for the development of arenavirus live attenuated vaccines based on rearrangement of their viral genome. IMPORTANCE Several arenaviruses cause severe hemorrhagic fever in humans and also pose a credible bioterrorism threat. Currently, no FDA-licensed vaccines are available to combat arenavirus infections and

  11. T cell receptor alpha-chain gene rearrangements in B-precursor leukemia are in contrast to the findings in T cell acute lymphoblastic leukemia. Comparative study of T cell receptor gene rearrangement in childhood leukemia.

    PubMed Central

    Hara, J; Benedict, S H; Mak, T W; Gelfand, E W

    1987-01-01

    We have analyzed T cell receptor alpha-chain gene configuration using three genomic joining (J) region probes in 64 children with acute lymphoblastic leukemia (ALL). 11 out of 18 T-ALLs were T3 positive; alpha-chain gene rearrangements were demonstrated in only two of 18, indicating that the majority of T-ALLs would have rearrangements involving J alpha segments located upstream of these probes. In contrast, 15 out of 46 B-precursor ALLs showed rearrangements of the alpha-chain gene and J alpha segments located approximately 20-30 kb upstream of the constant region were involved in 13 of these patients. Nine of 15 B-precursor ALLs with rearranged alpha-chain genes had rearrangements of both gamma- and beta-chain genes, whereas the remaining six had no rearrangements of gamma- and beta-chain genes. These findings indicated that alpha-chain gene rearrangement is not specific for T lineage cells and gamma- and/or beta-chain gene rearrangement does not appear essential for alpha-chain gene rearrangement, at least in B-precursor leukemic cells. Images PMID:3500187

  12. Analysis of Micro-Rearrangements in 25 Eukaryotic Species Pairs by SyntenyMapper

    PubMed Central

    Kaufmann, Stefanie; Frishman, Dmitrij

    2014-01-01

    High-quality mapping of genomic regions and genes between two organisms is an indispensable prerequisite for evolutionary analyses and comparative genomics. Existing approaches to this problem focus on either delineating orthologs or finding extended sequence regions of common evolutionary origin (syntenic blocks). We propose SyntenyMapper, a novel tool for refining predefined syntenic regions. SyntenyMapper creates a set of blocks with conserved gene order between two genomes and finds all minor rearrangements that occurred since the evolutionary split of the two species considered. We also present TrackMapper, a SyntenyMapper-based tool that allows users to directly compare genome features, such as histone modifications, between two organisms, and identify genes with highly conserved features. We demonstrate SyntenyMapper's advantages by conducting a large-scale analysis of micro-rearrangements within syntenic regions of 25 eukaryotic species. Unsurprisingly, the number and length of syntenic regions is correlated with evolutionary distance, while the number of micro-rearrangements depends only on the size of the harboring region. On the other hand, the size of rearranged regions remains relatively constant regardless of the evolutionary distance between the organisms, implying a length constraint in the rearrangement process. SyntenyMapper is a useful software tool for both large-scale and gene-centric genome comparisons. PMID:25375783

  13. Characterization of Apparently Balanced Chromosomal Rearrangements from the Developmental Genome Anatomy Project

    PubMed Central

    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.

    2008-01-01

    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. PMID:18319076

  14. DNA Rearrangement in Orthologous Orp Regions of the Maize, Rice and Sorghum Genomes

    PubMed Central

    Ma, Jianxin; SanMiguel, Phillip; Lai, Jinsheng; Messing, Joachim; Bennetzen, Jeffrey L.

    2005-01-01

    The homeologous Orp1 and Orp2 regions of maize and the orthologous regions in sorghum and rice were compared by generating sequence data for >486 kb of genomic DNA. At least three genic rearrangements differentiate the maize Orp1 and Orp2 segments, including an insertion of a single gene and two deletions that removed one gene each, while no genic rearrangements were detected in the maize Orp2 region relative to sorghum. Extended comparison of the orthologous Orp regions of sorghum and japonica rice uncovered numerous genic rearrangements and the presence of a transposon-rich region in rice. Only 11 of 27 genes (40%) are arranged in the same order and orientation between sorghum and rice. Of the 8 genes that are uniquely present in the sorghum region, 4 were found to have single-copy homologs in both rice and Arabidopsis, but none of these genes are located near each other, indicating frequent gene movement. Further comparison of the Orp segments from two rice subspecies, japonica and indica, revealed that the transposon-rich region is both an ancient and current hotspot for retrotransposon accumulation and genic rearrangement. We also identify unequal gene conversion as a mechanism for maize retrotransposon rearrangement.

  15. Rearrangement of mitochondrial tRNA genes in flat bugs (Hemiptera: Aradidae).

    PubMed

    Song, Fan; Li, Hu; Shao, Renfu; Shi, Aimin; Bai, Xiaoshuan; Zheng, Xiaorong; Heiss, Ernst; Cai, Wanzhi

    2016-01-01

    The typical insect mitochondrial (mt) genome organization, which contains a single chromosome with 37 genes, was found in the infraorder Pentatomomorpha (suborder Heteroptera). The arrangement of mt genes in these true bugs is usually the same as the ancestral mt gene arrangement of insects. Rearrangement of transfer RNA (tRNA) genes, however, has been found in two subfamilies of flat bugs (Mezirinae and Calisiinae, family Aradidae). In this study, we sequenced the complete mt genomes of four species from three other subfamilies (Aradinae, Carventinae and Aneurinae). We found tRNA gene rearrangement in all of these four species. All of the rearranged tRNA genes are located between the mitochondrial control region and cox1, indicating this region as a hotspot for gene rearrangement in flat bugs; the rearrangement is likely caused by events of tandem duplication and random deletion of genes. Furthermore, our phylogenetic and dating analyses indicated that the swap of positions between trnQ and trnI occurred ~162 million years ago (MYA) in the most recent common ancestor of the five subfamilies of flat bugs investigated to date, whereas the swap of positions between trnC and trnW occurred later in the lineage leading to Calisiinae, and the translocation of trnC and trnY occurred later than 134 MYA in the lineage leading to Aradinae. PMID:27180804

  16. Copy number variation, chromosome rearrangement, and their association with recombination during avian evolution

    PubMed Central

    Völker, Martin; Backström, Niclas; Skinner, Benjamin M.; Langley, Elizabeth J.; Bunzey, Sydney K.; Ellegren, Hans; Griffin, Darren K.

    2010-01-01

    Chromosomal rearrangements and copy number variants (CNVs) play key roles in genome evolution and genetic disease; however, the molecular mechanisms underlying these types of structural genomic variation are not fully understood. The availability of complete genome sequences for two bird species, the chicken and the zebra finch, provides, for the first time, an ideal opportunity to analyze the relationship between structural genomic variation (chromosomal and CNV) and recombination on a genome-wide level. The aims of this study were therefore threefold: (1) to combine bioinformatics, physical mapping to produce comprehensive comparative maps of the genomes of chicken and zebra finch. In so doing, this allowed the identification of evolutionary chromosomal rearrangements distinguishing them. The previously reported interchromosomal conservation of synteny was confirmed, but a larger than expected number of intrachromosomal rearrangements were reported; (2) to hybridize zebra finch genomic DNA to a chicken tiling path microarray and identify CNVs in the zebra finch genome relative to chicken; 32 interspecific CNVs were identified; and (3) to test the hypothesis that there is an association between CNV, chromosomal rearrangements, and recombination by correlating data from (1) and (2) with recombination rate data from a high-resolution genetic linkage map of the zebra finch. We found a highly significant association of both chromosomal rearrangements and CNVs with elevated recombination rates. The results thus provide support for the notion of recombination-based processes playing a major role in avian genome evolution. PMID:20357050

  17. Complex mitochondrial DNA rearrangements in individual cells from patients with sporadic inclusion body myositis.

    PubMed

    Rygiel, Karolina A; Tuppen, Helen A; Grady, John P; Vincent, Amy; Blakely, Emma L; Reeve, Amy K; Taylor, Robert W; Picard, Martin; Miller, James; Turnbull, Doug M

    2016-06-20

    Mitochondrial DNA (mtDNA) rearrangements are an important cause of mitochondrial disease and age related mitochondrial dysfunction in tissues including brain and skeletal muscle. It is known that different mtDNA deletions accumulate in single cells, but the detailed nature of these rearrangements is still unknown. To evaluate this we used a complementary set of sensitive assays to explore the mtDNA rearrangements in individual cells from patients with sporadic inclusion body myositis, a late-onset inflammatory myopathy with prominent mitochondrial changes. We identified large-scale mtDNA deletions in individual muscle fibres with 20% of cytochrome c oxidase-deficient myofibres accumulating two or more mtDNA deletions. The majority of deletions removed only the major arc but ∼10% of all deletions extended into the minor arc removing the origin of light strand replication (OL) and a variable number of genes. Some mtDNA molecules contained two deletion sites. Additionally, we found evidence of mitochondrial genome duplications allowing replication and clonal expansion of these complex rearranged molecules. The extended spectrum of mtDNA rearrangements in single cells provides insight into the process of clonal expansion which is fundamental to our understanding of the role of mtDNA mutations in ageing and disease. PMID:27131788

  18. Genome Rearrangements in Maize Induced by Alternative Transposition of Reversed Ac/Ds Termini

    PubMed Central

    Yu, Chuanhe; Zhang, Jianbo; Peterson, Thomas

    2011-01-01

    Alternative transposition can induce genome rearrangements, including deletions, inverted duplications, inversions, and translocations. To investigate the types and frequency of the rearrangements elicited by a pair of reversed Ac/Ds termini, we isolated and analyzed 100 new mutant alleles derived from two parental alleles that both contain an intact Ac and a fractured Ac (fAc) structure at the maize p1 locus. Mutants were characterized by PCR and sequencing; the results show that nearly 90% (89/100) of the mutant alleles represent structural rearrangements including deletions, inversions, translocations, or rearrangement of the intertransposon sequence (ITS). Among 37 deletions obtained, 20 extend into the external flanking sequences, while 17 delete portions of the intertransposon sequence. Interestingly, one deletion allele that contains only a single nucleotide between the retained Ac and fAc termini is not competent for further alternative transposition events. We propose a new model for the formation of intertransposon deletions through insertion of reversed transposon termini into sister-chromatid sequences. These results document the types and frequencies of genome rearrangements induced by alternative transposition of reversed Ac/Ds termini in maize. PMID:21339479

  19. Rearrangement of mitochondrial tRNA genes in flat bugs (Hemiptera: Aradidae)

    PubMed Central

    Song, Fan; Li, Hu; Shao, Renfu; Shi, Aimin; Bai, Xiaoshuan; Zheng, Xiaorong; Heiss, Ernst; Cai, Wanzhi

    2016-01-01

    The typical insect mitochondrial (mt) genome organization, which contains a single chromosome with 37 genes, was found in the infraorder Pentatomomorpha (suborder Heteroptera). The arrangement of mt genes in these true bugs is usually the same as the ancestral mt gene arrangement of insects. Rearrangement of transfer RNA (tRNA) genes, however, has been found in two subfamilies of flat bugs (Mezirinae and Calisiinae, family Aradidae). In this study, we sequenced the complete mt genomes of four species from three other subfamilies (Aradinae, Carventinae and Aneurinae). We found tRNA gene rearrangement in all of these four species. All of the rearranged tRNA genes are located between the mitochondrial control region and cox1, indicating this region as a hotspot for gene rearrangement in flat bugs; the rearrangement is likely caused by events of tandem duplication and random deletion of genes. Furthermore, our phylogenetic and dating analyses indicated that the swap of positions between trnQ and trnI occurred ~162 million years ago (MYA) in the most recent common ancestor of the five subfamilies of flat bugs investigated to date, whereas the swap of positions between trnC and trnW occurred later in the lineage leading to Calisiinae, and the translocation of trnC and trnY occurred later than 134 MYA in the lineage leading to Aradinae. PMID:27180804

  20. Complex mitochondrial DNA rearrangements in individual cells from patients with sporadic inclusion body myositis

    PubMed Central

    Rygiel, Karolina A.; Tuppen, Helen A.; Grady, John P.; Vincent, Amy; Blakely, Emma L.; Reeve, Amy K.; Taylor, Robert W.; Picard, Martin; Miller, James; Turnbull, Doug M.

    2016-01-01

    Mitochondrial DNA (mtDNA) rearrangements are an important cause of mitochondrial disease and age related mitochondrial dysfunction in tissues including brain and skeletal muscle. It is known that different mtDNA deletions accumulate in single cells, but the detailed nature of these rearrangements is still unknown. To evaluate this we used a complementary set of sensitive assays to explore the mtDNA rearrangements in individual cells from patients with sporadic inclusion body myositis, a late-onset inflammatory myopathy with prominent mitochondrial changes. We identified large-scale mtDNA deletions in individual muscle fibres with 20% of cytochrome c oxidase-deficient myofibres accumulating two or more mtDNA deletions. The majority of deletions removed only the major arc but ∼10% of all deletions extended into the minor arc removing the origin of light strand replication (OL) and a variable number of genes. Some mtDNA molecules contained two deletion sites. Additionally, we found evidence of mitochondrial genome duplications allowing replication and clonal expansion of these complex rearranged molecules. The extended spectrum of mtDNA rearrangements in single cells provides insight into the process of clonal expansion which is fundamental to our understanding of the role of mtDNA mutations in ageing and disease. PMID:27131788

  1. BCL-1 Gene Rearrangements in Iranian Non-Hodgkin Lymphoma Patients

    PubMed Central

    Tohidirad, Manoush; Estiar, Mehrdad Asghari; Rezamand, Azim; Ghorbian, Saeid; Andalib, Sasan; Jahanzad, Issa; Bahrami, Tayyeb; Sakhinia, Ebrahim

    2016-01-01

    In the present study, our aim was to assess the incidence of BCL-1 gene rearrangements in formalin-fixed paraffin embedded (FFPE) tissue in patients with non-Hodgkin lymphomas (NHL). The BIOMED-2 protocol was applied to assess the BCL-1 gene rearrangements in NHL patients. PCR amplification was carried out on FFPE in 100 patients with B-cell lymphoma including 89 cases with diffused large B-cell lymphoma (DLBCL) (15 cases under 18 years old) and 11 cases with mantle cell lymphoma (MCL). Out of the 100 patients, 19 cases (19%) were identified to have concurrent translocation involving BCL-1. The significant association was seen between BCL-1 gene rearrangements and the lymphomas in patients older than 55 years (P<0.05). Out of 100 cases, 80 cases were positive and 20 cases were negative regarding CD20. No significant association was found between DLBCL lymphoma in patients under 18 years old and BCL-1 gene rearrangements (P>0.05). In addition, the positive and negative expressions of LCA/CD45 marker were 76% (76/100) and 26% (26/100), respectively. Our findings revealed that BCL-1 gene rearrangement assays using BIOMED-2 protocol can be considered as a valuable approach in detection of the lymphomas. PMID:27045402

  2. Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies.

    PubMed

    Shaver, Timothy M; Lehmann, Brian D; Beeler, J Scott; Li, Chung-I; Li, Zhu; Jin, Hailing; Stricker, Thomas P; Shyr, Yu; Pietenpol, Jennifer A

    2016-08-15

    Triple-negative breast cancer (TNBC) and other molecularly heterogeneous malignancies present a significant clinical challenge due to a lack of high-frequency "driver" alterations amenable to therapeutic intervention. These cancers often exhibit genomic instability, resulting in chromosomal rearrangements that affect the structure and expression of protein-coding genes. However, identification of these rearrangements remains technically challenging. Using a newly developed approach that quantitatively predicts gene rearrangements in tumor-derived genetic material, we identified and characterized a novel oncogenic fusion involving the MER proto-oncogene tyrosine kinase (MERTK) and discovered a clinical occurrence and cell line model of the targetable FGFR3-TACC3 fusion in TNBC. Expanding our analysis to other malignancies, we identified a diverse array of novel and known hybrid transcripts, including rearrangements between noncoding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1 The over 1,000 genetic alterations we identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. Cancer Res; 76(16); 4850-60. ©2016 AACR. PMID:27231203

  3. Breaking Good: Accounting for Fragility of Genomic Regions in Rearrangement Distance Estimation

    PubMed Central

    Biller, Priscila; Guéguen, Laurent; Knibbe, Carole; Tannier, Eric

    2016-01-01

    Models of evolution by genome rearrangements are prone to two types of flaws: One is to ignore the diversity of susceptibility to breakage across genomic regions, and the other is to suppose that susceptibility values are given. Without necessarily supposing their precise localization, we call “solid” the regions that are improbably broken by rearrangements and “fragile” the regions outside solid ones. We propose a model of evolution by inversions where breakage probabilities vary across fragile regions and over time. It contains as a particular case the uniform breakage model on the nucleotidic sequence, where breakage probabilities are proportional to fragile region lengths. This is very different from the frequently used pseudouniform model where all fragile regions have the same probability to break. Estimations of rearrangement distances based on the pseudouniform model completely fail on simulations with the truly uniform model. On pairs of amniote genomes, we show that identifying coding genes with solid regions yields incoherent distance estimations, especially with the pseudouniform model, and to a lesser extent with the truly uniform model. This incoherence is solved when we coestimate the number of fragile regions with the rearrangement distance. The estimated number of fragile regions is surprisingly small, suggesting that a minority of regions are recurrently used by rearrangements. Estimations for several pairs of genomes at different divergence times are in agreement with a slowly evolvable colocalization of active genomic regions in the cell. PMID:27190002

  4. Scoliosis and vertebral anomalies: additional abnormal phenotypes associated with chromosome 16p11.2 rearrangement.

    PubMed

    Al-Kateb, Hussam; Khanna, Geetika; Filges, Isabel; Hauser, Natalie; Grange, Dorothy K; Shen, Joseph; Smyser, Christopher D; Kulkarni, Shashikant; Shinawi, Marwan

    2014-05-01

    The typical chromosome 16p11.2 rearrangements are estimated to occur at a frequency of approximately 0.6% of all samples tested clinically and have been identified as a major cause of autism spectrum disorders, developmental delay, behavioral abnormalities, and seizures. Careful examination of patients with these rearrangements revealed association with abnormal head size, obesity, dysmorphism, and congenital abnormalities. In this report, we extend this list of phenotypic abnormalities to include scoliosis and vertebral anomalies. We present detailed characterization of phenotypic and radiological data of 10 new patients, nine with the 16p11.2 deletion and one with the duplication within the coordinates chr16:29,366,195 and 30,306,956 (hg19) with a minimal size of 555 kb. We discuss the phenotypical and radiological findings in our patients and review 5 previously reported patients with 16p11.2 rearrangement and similar skeletal abnormalities. Our data suggest that patients with the recurrent 16p11.2 rearrangement have increased incidence of scoliosis and vertebral anomalies. However, additional studies are required to confirm this observation and to establish the incidence of these anomalies. We discuss the potential implications of our findings on the diagnosis, surveillance and genetic counseling of patients with 16p11.2 rearrangement. PMID:24458548

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

    PubMed Central

    Nanya, Mai; Sato, Masaki; Tanimoto, Kousuke; Tozuka, Minoru; Mizutani, Shuki; Takagi, Masatoshi

    2015-01-01

    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. PMID:26657054

  6. Generation and Analysis of Transposon Ac/Ds-Induced Chromosomal Rearrangements in Rice Plants.

    PubMed

    Xuan, Yuan Hu; Peterson, Thomas; Han, Chang-Deok

    2016-01-01

    Closely-located transposable elements (TEs) have been known to induce chromosomal breakage and rearrangements via alternative transposition. To study genome rearrangements in rice, an Ac/Ds system has been employed. This system comprises an immobile Ac element expressed under the control of CaMV 35S promoter, and a modified Ds element. A starter line carried Ac and a single copy of Ds at the OsRLG5 (Oryza sativa receptor-like gene 5). To enhance the transpositional activity, seed-derived calli were cultured and regenerated into plants. Among 270 lines regenerated from the starter, one line was selected that contained a pair of inversely-oriented Ds elements at the OsRLG5 (Oryza sativa receptor-like gene 5). The selected line was again subjected to tissue culture to obtain a regenerant population. Among 300 regenerated plants, 107 (36 %) contained chromosomal rearrangements including deletions, duplications, and inversions of various sizes. From 34 plants, transposition mechanisms leading to such genomic rearrangements were analyzed. The rearrangements were induced by sister chromatid transposition (SCT), homologous recombination (HR), and single chromatid transposition (SLCT). Among them, 22 events (65 %) were found to be transmitted to the next generation. These results demonstrate a great potential of tissue culture regeneration and the Ac/Ds system in understanding alternative transposition mechanisms and in developing chromosome engineering in plants. PMID:27557685

  7. Integrated Genomic Analysis of Pancreatic Ductal Adenocarcinomas Reveals Genomic Rearrangement Events as Significant Drivers of Disease.

    PubMed

    Murphy, Stephen J; Hart, Steven N; Halling, Geoffrey C; Johnson, Sarah H; Smadbeck, James B; Drucker, Travis; Lima, Joema Felipe; Rohakhtar, Fariborz Rakhshan; Harris, Faye R; Kosari, Farhad; Subramanian, Subbaya; Petersen, Gloria M; Wiltshire, Timothy D; Kipp, Benjamin R; Truty, Mark J; McWilliams, Robert R; Couch, Fergus J; Vasmatzis, George

    2016-02-01

    Many somatic mutations have been detected in pancreatic ductal adenocarcinoma (PDAC), leading to the identification of some key drivers of disease progression, but the involvement of large genomic rearrangements has often been overlooked. In this study, we performed mate pair sequencing (MPseq) on genomic DNA from 24 PDAC tumors, including 15 laser-captured microdissected PDAC and 9 patient-derived xenografts, to identify genome-wide rearrangements. Large genomic rearrangements with intragenic breakpoints altering key regulatory genes involved in PDAC progression were detected in all tumors. SMAD4, ZNF521, and FHIT were among the most frequently hit genes. Conversely, commonly reported genes with copy number gains, including MYC and GATA6, were frequently observed in the absence of direct intragenic breakpoints, suggesting a requirement for sustaining oncogenic function during PDAC progression. Integration of data from MPseq, exome sequencing, and transcriptome analysis of primary PDAC cases identified limited overlap in genes affected by both rearrangements and point mutations. However, significant overlap was observed in major PDAC-associated signaling pathways, with all PDAC exhibiting reduced SMAD4 expression, reduced SMAD-dependent TGFβ signaling, and increased WNT and Hedgehog signaling. The frequent loss of SMAD4 and FHIT due to genomic rearrangements strongly implicates these genes as key drivers of PDAC, thus highlighting the strengths of an integrated genomic and transcriptomic approach for identifying mechanisms underlying disease initiation and progression. PMID:26676757

  8. A new approach to the elucidation of complex chromosome rearrangements illustrated by a case of Rieger syndrome.

    PubMed Central

    Ogilvie, C M; Raymond, F L; Harrison, R H; Scriven, P N; Docherty, Z

    1998-01-01

    A patient with a complex chromosome rearrangement and unilateral Rieger syndrome is presented. This rearrangement involves four chromosomes and six breakpoints, one of which is at 4q25, the candidate region for Rieger syndrome. We discuss a novel approach to the elucidation of this case using a multiprobe fluorescence in situ hybridisation method to show rearrangements unpredictable from G banded analysis, and the clear and unambiguous presentation of the karyotype using computer generated colour ideograms. Images PMID:9541109

  9. Regulation of T cell receptor beta gene rearrangements and allelic exclusion by the helix-loop-helix protein, E47.

    PubMed

    Agata, Yasutoshi; Tamaki, Nobuyuki; Sakamoto, Shuji; Ikawa, Tomokatsu; Masuda, Kyoko; Kawamoto, Hiroshi; Murre, Cornelis

    2007-12-01

    Allelic exclusion of antigen-receptor genes is ensured primarily by monoallelic locus activation upon rearrangement and subsequently by feedback inhibition of continued rearrangement. Here, we demonstrated that the basic helix-loop-helix protein, E47, promoted T cell receptor beta (TCRbeta) gene rearrangement by directly binding to target gene segments to increase chromatin accessibility in a dosage-sensitive manner. Feedback signaling abrogated E47 binding, leading to a decline in accessibility. Conversely, enforced expression of E47 induced TCRbeta gene rearrangement by antagonizing feedback inhibition. Thus, the abundance of E47 is rate limiting in locus activation, and feedback signaling downregulates E47 activity to ensure allelic exclusion. PMID:18093539

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

    SciTech Connect

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

    1988-02-01

    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.

  11. An elongation factor G-induced ribosome rearrangement precedes tRNA-mRNA translocation.

    PubMed

    Savelsbergh, Andreas; Katunin, Vladimir I; Mohr, Dagmar; Peske, Frank; Rodnina, Marina V; Wintermeyer, Wolfgang

    2003-06-01

    The elongation cycle of protein synthesis is completed by translocation, a rearrangement during which two tRNAs bound to the mRNA move on the ribosome. The reaction is promoted by elongation factor G (EF-G) and accelerated by GTP hydrolysis. Here we report a pre-steady-state kinetic analysis of translocation. The kinetic model suggests that GTP hydrolysis drives a conformational rearrangement of the ribosome that precedes and limits the rates of tRNA-mRNA translocation and Pi release from EF-G.GDP.Pi. The latter two steps are intrinsically rapid and take place at random. These results indicate that the energy of GTP hydrolysis is utilized to promote the ribosome rearrangement and to bias spontaneous fluctuations within the ribosome-EF-G complex toward unidirectional movement of mRNA and tRNA. PMID:12820965

  12. The systematic approach to describing conformational rearrangements in G-quadruplexes.

    PubMed

    Tsvetkov, Vladimir; Pozmogova, Galina; Varizhuk, Anna

    2016-04-01

    Conformational changes in DNA G-quadruplex (GQ)-forming regions affect genome function and, thus, compose an interesting research topic. Computer modelling may yield insight into quadruplex folding and rearrangement, particularly molecular dynamics simulations. Here, we show that specific parameters, which are distinct from those commonly used in DNA conformational analyses, must be introduced for adequate interpretation and, most importantly, convenient visual representation of the quadruplex modelling results. We report a set of parameters that comprehensively and systematically describe GQ geometry in dynamics. The parameters include those related to quartet planarity, quadruplex twist, and quartet stacking; they are used to quantitatively characterise various types of quadruplexes and rearrangements, such as quartet distortion/disruption or deviation/bulging of a single nucleotide from the quartet plane. Our approach to describing conformational changes in quadruplexes using the new parameters is exemplified by telomeric quadruplex rearrangement, and the benefits of applying this approach to analyse other structures are discussed. PMID:26017012

  13. The systematic approach to describing conformational rearrangements in G-quadruplexes

    PubMed Central

    Tsvetkov, Vladimir; Pozmogova, Galina; Varizhuk, Anna

    2016-01-01

    Conformational changes in DNA G-quadruplex (GQ)-forming regions affect genome function and, thus, compose an interesting research topic. Computer modelling may yield insight into quadruplex folding and rearrangement, particularly molecular dynamics simulations. Here, we show that specific parameters, which are distinct from those commonly used in DNA conformational analyses, must be introduced for adequate interpretation and, most importantly, convenient visual representation of the quadruplex modelling results. We report a set of parameters that comprehensively and systematically describe GQ geometry in dynamics. The parameters include those related to quartet planarity, quadruplex twist, and quartet stacking; they are used to quantitatively characterise various types of quadruplexes and rearrangements, such as quartet distortion/disruption or deviation/bulging of a single nucleotide from the quartet plane. Our approach to describing conformational changes in quadruplexes using the new parameters is exemplified by telomeric quadruplex rearrangement, and the benefits of applying this approach to analyse other structures are discussed. PMID:26017012

  14. Theoretical study on cycloaddition of singlet dichlorocarbene with formaldehyde, acetaldehyde and benzaldehyde and subsequent rearrangement reactions

    NASA Astrophysics Data System (ADS)

    Peng, L.; Li, Q. S.; Fang, W. H.; Fu, C. J.; Zhang, J.

    2003-11-01

    Cycloaddition reactions of the singlet CCl 2 carbene with H 2CO, CH 3CHO and C 6H 5CHO and the subsequent rearrangement processes have been investigated with density functional theory. It was found that the interaction between the σ orbital of CCl 2 and the CO π* orbital plays an important role in the cycloaddition reactions. The addition reaction of CCl 2 with H 2CO proceeds very easily, which is slightly influenced by the methyl and phenyl substitutions. However, the substitutions significantly reduce the barrier to the rearrangement reactions. The interaction between solvent and solute has a little influence on the structures of the stationary points, but has a noticeable influence on the barrier heights of the rearrangement reactions.

  15. Synergistic Ion-Binding Catalysis Demonstrated via an Enantioselective, Catalytic [2,3]-Wittig Rearrangement

    PubMed Central

    2016-01-01

    Sigmatropic rearrangements number among the most powerful complexity-building transformations in organic synthesis but have remained largely insensitive to enantioselective catalysis due to the diffuse nature of their transition structures. Here, we describe a synergistic ion-binding strategy for asymmetric catalysis of anionic sigmatropic rearrangements. This approach is demonstrated with the enantioselective [2,3]-Wittig rearrangement of α-allyloxy carbonyl compounds to afford highly enantioenriched homoallylic alcohol products. Chiral thiourea catalysts are shown to engage reactive anions and their countercations through a cooperative set of attractive, noncovalent interactions. Catalyst structure–reactivity–selectivity relationship studies and computational analyses provide insight into catalyst–substrate interactions responsible for enantioinduction and allude to the potential generality of this catalytic strategy. PMID:27413786

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

    PubMed Central

    2012-01-01

    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. PMID:22260333

  17. Molecular analysis of DNA rearrangements in leukemias and non-Hodgkin's lymphomas.

    PubMed

    Longtine, J; Fox, E; Reynolds, C; Sklar, J

    2001-05-01

    Genetic markers for leukemias and lymphomas include chromosomal translocations and antigen-receptor gene rearrangements. Clonal rearrangements of immunoglobulin or T cell receptor (TCR) genes reflect clonal proliferations of lymphocytes, a characteristic feature of lymphoid neoplasia. These rearrangements can be detected as described in this unit by Southern blot hybridization or, in many instances, the polymerase chain reaction (PCR). Specific chromosomal translocations can also serve as markers for clonality, for malignant transformation, and for various defined subtypes of hematopoietic cancers. PCR protocols are described for detection of the two most commonly assayed translocations, t(9;22) of chronic myelogenous leukemia or acute lymphoblastic leukemia, and t(14;18) of follicular lymphomas. PMID:18428241

  18. Molecular genetics of childhood papillary thyroid carcinomas after irradiation: high prevalence of RET rearrangement.

    PubMed

    Rabes, H M; Klugbauer, S

    1998-01-01

    Epidemiological studies have revealed a connection between thyroid carcinogenesis and a history of radiation. The molecular mechanisms involved are not well understood. It has been claimed that RAS, p53 or GSP mutations and RET or TRK rearrangements might play a role in adult thyroid tumors. In childhood, the thyroid gland is particularly sensitive to ionizing radiation. The reactor accident in Chernobyl provided a unique chance to study molecular genetic aberrations in a cohort of children who developed papillary thyroid carcinomas after a short latency time after exposure to high doses of radioactive iodine isotopes. According to the concepts of molecular genetic epidemiology, exposure to a specific type of irradiation might result in a typical molecular lesion. Childhood papillary thyroid tumors after Chernobyl exhibit a high prevalence of RET rearrangement as almost the only molecular alteration. The majority showed RET/PTC3 (i.e., ELE/RET rearrangements), including several subtypes. Less frequently, RET/PTC1 (i.e., H4/RET rearrangements), and a novel type (RET/PTC5, i.e., RFG5/RET) were observed. Proof of reciprocal transcripts suggests that a balanced intrachromosomal inversion leads to this rearrangement. Breakpoint analyses revealed short homologous nucleotide stretches at the fusion points. In all types of rearrangement, the RET tyrosine kinase domain becomes controlled by 5' fused regulatory sequences of ubiquitously expressed genes that display coiled-coil regions with dimerization potential. Oncogenic activation of RET is apparently due to ligand-independent constitutive ectopic RET tyrosine kinase activity. The analysis of this cohort of children with radiation-induced thyroid tumors after Chernobyl provides insights into typical molecular aberrations in relation to a specific mode of environmental exposure and may serve as a paradigm for molecular genetic epidemiology. PMID:10027005

  19. Durable Clinical Response to Entrectinib in NTRK1-Rearranged Non-Small Cell Lung Cancer

    PubMed Central

    Le, Long P.; Zheng, Zongli; Muzikansky, Alona; Drilon, Alexander; Patel, Manish; Bauer, Todd M.; Liu, Stephen V.; Ou, Sai-Hong I.; Jackman, David; Costa, Daniel B.; Multani, Pratik S.; Li, Gary G.; Hornby, Zachary; Chow-Maneval, Edna; Luo, David; Lim, Jonathan E.; Iafrate, Anthony J.; Shaw, Alice T.

    2015-01-01

    Introduction: Chromosomal rearrangements involving neurotrophic tyrosine kinase 1 (NTRK1) occur in a subset of non-small cell lung cancers (NSCLCs) and other solid tumor malignancies, leading to expression of an oncogenic TrkA fusion protein. Entrectinib (RXDX-101) is an orally available tyrosine kinase inhibitor, including TrkA. We sought to determine the frequency of NTRK1 rearrangements in NSCLC and to assess the clinical activity of entrectinib. Methods: We screened 1378 cases of NSCLC using anchored multiplex polymerase chain reaction (AMP). A patient with an NTRK1 gene rearrangement was enrolled onto a Phase 1 dose escalation study of entrectinib in adult patients with locally advanced or metastatic tumors (NCT02097810). We assessed safety and response to treatment. Results: We identified NTRK1 gene rearrangements at a frequency of 0.1% in this cohort. A patient with stage IV lung adenocrcinoma with an SQSTM1-NTRK1 fusion transcript expression was treated with entrectinib. Entrectinib was well tolerated, with no grade 3–4 adverse events. Within three weeks of starting on treatment, the patient reported resolution of prior dyspnea and pain. Restaging CT scans demonstrated a RECIST partial response (PR) and complete resolution of all brain metastases. This patient has continued on treatment for over 6 months with an ongoing PR. Conclusions: Entrectinib demonstrated significant anti-tumor activity in a patient with NSCLC harboring an SQSTM1-NTRK1 gene rearrangement, indicating that entrectinib may be an effective therapy for tumors with NTRK gene rearrangements, including those with central nervous system metastases. PMID:26565381

  20. Intratumor Heterogeneity of ALK-Rearrangements and Homogeneity of EGFR-Mutations in Mixed Lung Adenocarcinoma

    PubMed Central

    Marino, Federica Zito; Liguori, Giuseppina; Aquino, Gabriella; La Mantia, Elvira; Bosari, Silvano; Ferrero, Stefano; Rosso, Lorenzo; Gaudioso, Gabriella; De Rosa, Nicla; Scrima, Marianna; Martucci, Nicola; La Rocca, Antonello; Normanno, Nicola; Morabito, Alessandro; Rocco, Gaetano; Botti, Gerardo; Franco, Renato

    2015-01-01

    Background Non Small Cell Lung Cancer is a highly heterogeneous tumor. Histologic intratumor heterogeneity could be ‘major’, characterized by a single tumor showing two different histologic types, and ‘minor’, due to at least 2 different growth patterns in the same tumor. Therefore, a morphological heterogeneity could reflect an intratumor molecular heterogeneity. To date, few data are reported in literature about molecular features of the mixed adenocarcinoma. The aim of our study was to assess EGFR-mutations and ALK-rearrangements in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas and adenosquamous carcinomas. Methods 590 Non Small Cell Lung Carcinomas tumor samples were revised in order to select mixed adenocarcinomas with available tumor components. Finally, only 105 mixed adenocarcinomas and 17 adenosquamous carcinomas were included in the study for further analyses. Two TMAs were built selecting the different intratumor histotypes. ALK-rearrangements were detected through FISH and IHC, and EGFR-mutations were detected through IHC and confirmed by RT-PCR. Results 10/122 cases were ALK-rearranged and 7 from those 10 showing an intratumor heterogeneity of the rearrangements. 12/122 cases were EGFR-mutated, uniformly expressing the EGFR-mutated protein in all histologic components. Conclusion Our data suggests that EGFR-mutations is generally homogeneously expressed. On the contrary, ALK-rearrangement showed an intratumor heterogeneity in both mixed adenocarcinomas and adenosquamous carcinomas. The intratumor heterogeneity of ALK-rearrangements could lead to a possible impact on the therapeutic responses and the disease outcomes. PMID:26422230

  1. ROS1-rearranged lung cancer: a clinicopathologic and molecular study of 15 surgical cases.

    PubMed

    Yoshida, Akihiko; Kohno, Takashi; Tsuta, Koji; Wakai, Susumu; Arai, Yasuhito; Shimada, Yoko; Asamura, Hisao; Furuta, Koh; Shibata, Tatsuhiro; Tsuda, Hitoshi

    2013-04-01

    Recent discovery of ROS1 gene fusion in a subset of lung cancers has raised clinical interest, because ROS1 fusion-positive cancers are reportedly sensitive to kinase inhibitors. To better understand these tumors, we examined 799 surgically resected non-small cell lung cancers by reverse transcriptase polymerase chain reaction and identified 15 tumors harboring ROS1 fusion transcripts (2.5% of adenocarcinomas). The most frequent fusion partner was CD74 followed by EZR. The affected patients were often younger nonsmoking female individuals, and they had overall survival rates similar to those of the ROS1 fusion-negative cancer patients. All the ROS1 fusion-positive tumors were adenocarcinomas except 1, which was an adenosquamous carcinoma. Histologic examination identified an at least focal presence of either solid growth with signet-ring cells or cribriform architecture with abundant extracellular mucus in 53% of the cases. These 2 patterns are reportedly also characteristic of anaplastic lymphoma kinase (ALK)-rearranged lung cancers, and our data suggest a phenotypic resemblance between the ROS1-rearranged and ALK-rearranged tumors. All tumors except 1 were immunoreactive to thyroid transcription factor-1. Fluorescence in situ hybridization using ROS1 break-apart probes revealed positive rearrangement signals in 23% to 93% of the tumor cells in ROS1 fusion-positive cancers, which were readily distinguished using a 15% cutoff value from 50 ROS1 fusion-negative tumors tested, which showed 0% to 6% rearrangement signals. However, this perfect test performance was achieved only when isolated 3' signals were included along with classic split signals in the definition of rearrangement positivity. Fluorescence in situ hybridization signal patterns were unrelated to 5' fusion partner genes. All ROS1 fusion-positive tumors lacked alteration of EGFR, KRAS, HER2, ALK, and RET genes. PMID:23426121

  2. The clinical significance of 8q24/MYC rearrangement in chronic lymphocytic leukemia.

    PubMed

    Li, Yan; Hu, Shimin; Wang, Sa A; Li, Shaoying; Huh, Yang O; Tang, Zhenya; Medeiros, L Jeffrey; Tang, Guilin

    2016-05-01

    Chromosome 8q24/MYC rearrangement is associated with Burkitt lymphoma and some aggressive B-cell lymphomas, but is rare in chronic lymphocytic leukemia. We here report a cohort of 20 chronic lymphocytic leukemia patients with 8q24/MYC rearrangement, 3 detected at time of initial diagnosis and 17 acquired after a median interval of 48 months. At the time when 8q24/MYC arrangement was detected, 18 patients had B-symptoms, 17 had lymphadenopathy, and 17 had splenomegaly. Histologically, typical chronic lymphocytic leukemia morphology was seen in six patients, increased prolymphocytes in nine and Richter's transformation in five patients. Eighteen patients had karyotypic information available that showed t(8;v) in a complex karyotype in 12 patients and in a non-complex karyotype in 6 patients. Fluorescence in situ hybridization confirmed MYC rearrangement in 17/17 patients. All patients required therapy after 8q24/MYC rearrangement was detected. At last follow-up, five of six patients with a non-complex karyotype were alive after a median of 74 months (10~143 months) from the detection of 8q24/MYC rearrangement. In contrast, 10 of 12 patients with a complex karyotype died with a median survival of 5.5 months. We conclude that 8q24/MYC rearrangement in chronic lymphocytic leukemia is rare and often acquired during the course of disease. If it is presented in a complex karyotype, it is often associated with Richter's transformation, refractory to therapy and an aggressive clinical course; on the other hand, if it is present in a non-complex karyotype, patients often respond to risk-adapted therapies and achieve remission. PMID:26916070

  3. Chromosomal Rearrangements as Barriers to Genetic Homogenization between Archaic and Modern Humans.

    PubMed

    Rogers, Rebekah L

    2015-12-01

    Chromosomal rearrangements, which shuffle DNA throughout the genome, are an important source of divergence across taxa. Using a paired-end read approach with Illumina sequence data for archaic humans, I identify changes in genome structure that occurred recently in human evolution. Hundreds of rearrangements indicate genomic trafficking between the sex chromosomes and autosomes, raising the possibility of sex-specific changes. Additionally, genes adjacent to genome structure changes in Neanderthals are associated with testis-specific expression, consistent with evolutionary theory that new genes commonly form with expression in the testes. I identify one case of new-gene creation through transposition from the Y chromosome to chromosome 10 that combines the 5'-end of the testis-specific gene Fank1 with previously untranscribed sequence. This new transcript experienced copy number expansion in archaic genomes, indicating rapid genomic change. Among rearrangements identified in Neanderthals, 13% are transposition of selfish genetic elements, whereas 32% appear to be ectopic exchange between repeats. In Denisovan, the pattern is similar but numbers are significantly higher with 18% of rearrangements reflecting transposition and 40% ectopic exchange between distantly related repeats. There is an excess of divergent rearrangements relative to polymorphism in Denisovan, which might result from nonuniform rates of mutation, possibly reflecting a burst of transposable element activity in the lineage that led to Denisovan. Finally, loci containing genome structure changes show diminished rates of introgression from Neanderthals into modern humans, consistent with the hypothesis that rearrangements serve as barriers to gene flow during hybridization. Together, these results suggest that this previously unidentified source of genomic variation has important biological consequences in human evolution. PMID:26399483

  4. ‘Chromosomal Rainbows’ Detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

    PubMed Central

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

    2011-01-01

    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 megabasepair (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 techniques for fine

  5. A case report of CIC-rearranged undifferentiated small round cell sarcoma in the cerebrum.

    PubMed

    Ito, Mayumi; Ishikawa, Misawo; Kitajima, Masateru; Narita, Jun; Hattori, Shinya; Endo, Otone; Goto, Keisuke

    2016-10-01

    CIC-rearranged undifferentiated small round cell sarcoma (CIC-rearranged USRCS) is a recently established type of Ewing-like small round cell sarcomas, characterized by CIC gene rearrangement, most commonly CIC-DUX4 fusion. This report presents the second case of CIC-rearranged USRCS arising primarily in the cerebrum. A 64-year-old otherwise healthy woman presented with a 1 × 1 cm sized hemorrhagic subcortical tumor in the left temporo-parietal lobe. The tumor repeatedly recurred, and the patient underwent three surgeries, chemotherapy with doxorubicin and ifosfamide, and radiotherapy, as well as gamma knife surgery. Systemic examination revealed no other extracranial masses. Imprint cytology revealed small to moderate-sized round-to-ovoid tumor cells with mild pleomorphism and variations in size and shape. The nuclei contained finely granular chromatin, and some had easily-recognizable nucleoli. The tumor exhibited a mainly cytoplasmic pattern of CD99 immunostaining, rather than a diffuse membranous pattern. The tumor also exhibited diffuse positivity for calretinin and p16, as well as partial positivity for WT1 (nuclear and cytoplasmic staining pattern) and D2-40. FISH assessment showed CIC split signals. In conclusion, CIC-rearranged USRCSs can occur primarily in the cerebrum. It would be impossible to diagnose them through cytology alone, but cytology would be useful to rule out other small round cell brain tumors including gliomas, lymphomas, carcinomas, and germinoma. Immunohistochemical analysis including tests for CD99, calretinin, and WT1 would help to suggest CIC-rearranged USRCSs and distinguish them from Ewing sarcomas. Additionally, immunohistochemistry for p16 might be useful in the diagnosis. Diagn. Cytopathol. 2016;44:828-832. © 2016 Wiley Periodicals, Inc. PMID:27324529

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

    SciTech Connect

    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 techniques for fine mapping of

  7. 'Chromosomal Rainbows' Detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors.

    PubMed

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

    2010-01-01

    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 megabasepair (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 techniques for fine mapping of

  8. Deletion of the immunoglobulin kappa chain intron enhancer abolishes kappa chain gene rearrangement in cis but not lambda chain gene rearrangement in trans.

    PubMed Central

    Takeda, S; Zou, Y R; Bluethmann, H; Kitamura, D; Muller, U; Rajewsky, K

    1993-01-01

    Immunoglobulins (Ig) secreted from a plasma cell contain either kappa or lambda light chains, but not both. This phenomenon is termed isotypic kappa-lambda exclusion. While kappa-producing cells have their lambda chain genes in germline configuration, in most lambda-producing cells the kappa chain genes are either non-productively rearranged or deleted. To investigate the molecular mechanism for isotypic kappa-lambda exclusion, in particular the role of the Ig kappa intron enhancer, we replaced this enhancer by a neomycin resistance (neoR) gene in embryonic stem (ES) cells. B cells heterozygous for the mutation undergo V kappa-J kappa recombination exclusively in the intact Ig kappa locus but not in the mutated Ig kappa locus. Homozygous mutant mice exhibited no rearrangements in their Ig kappa loci. However, splenic B cell numbers were only slightly reduced as compared with the wild-type, and all B cells expressed lambda chain bearing surface Ig. These findings demonstrate that rearrangement in the Ig kappa locus is not essential for lambda gene rearrangement. We also generated homozygous mutant mice in which the neoR gene was inserted at the 3' end of the Ig kappa intron enhancer. Unexpectedly, mere insertion of the neoR gene showed some suppressive effect on V kappa-J kappa recombination. However, the much more pronounced inhibition of V kappa-J kappa recombination by the replacement of the Ig kappa intron enhancer suggests that this enhancer is essential for V kappa-J kappa recombination. Images PMID:8508766

  9. [3,3]-Sigmatropic rearrangements: recent applications in the total synthesis of natural products†

    PubMed Central

    Ilardi, Elizabeth A.; Stivala, Craig E.

    2014-01-01

    Among the fundamental chemical transformations in organic synthesis, the [3,3]-sigmatropic rearrangement occupies a unique position as a powerful, reliable, and well-defined method for the stereoselective construction of carbon–carbon or carbon–heteroatom bonds. While many other reactions can unite two subunits and create a new bond, the strengths of sigmatropic rearrangements derive from their ability to enable structural reorganization with unmatched build-up of complexity. Recent applications that illustrate [3,3]-sigmatropic processes as a key concept in the synthesis of complex natural products are described in this tutorial review, covering literature from about 2001 through early 2009. PMID:19847347

  10. Base-mediated cascade rearrangements of aryl-substituted diallyl ethers.

    PubMed

    Reid, Jolene P; McAdam, Catherine A; Johnston, Adam J S; Grayson, Matthew N; Goodman, Jonathan M; Cook, Matthew J

    2015-02-01

    Two base-mediated cascade rearrangement reactions of diallyl ethers were developed leading to selective [2,3]-Wittig-oxy-Cope and isomerization-Claisen rearrangements. Both diaryl and arylsilyl-substituted 1,3-substituted propenyl substrates were examined, and each exhibits unique reactivity and different reaction pathways. Detailed mechanistic and computational analysis was conducted, which demonstrated that the role of the base and solvent was key to the reactivity and selectivity observed. Crossover experiments also suggest that these reactions proceed with a certain degree of dissociation, and the mechanistic pathway is highly complex with multiple competing routes. PMID:25514457

  11. MYB-QKI rearrangements in Angiocentric Glioma drive tumorigenicity through a tripartite mechanism

    PubMed Central

    Bandopadhayay, Pratiti; Ramkissoon, Lori A.; Jain, Payal; Bergthold, Guillaume; Wala, Jeremiah; Zeid, Rhamy; Schumacher, Steven E.; Urbanski, Laura; O’Rourke, Ryan; Gibson, William J.; Pelton, Kristine; Ramkissoon, Shakti H.; Han, Harry J.; Zhu, Yuankun; Choudhari, Namrata; Silva, Amanda; Boucher, Katie; Henn, Rosemary E.; Kang, Yun Jee; Knoff, David; Paolella, Brenton R.; Gladden-Young, Adrianne; Varlet, Pascale; Pages, Melanie; Horowitz, Peleg M.; Federation, Alexander; Malkin, Hayley; Tracy, Adam; Seepo, Sara; Ducar, Matthew; Hummelen, Paul Van; Santi, Mariarita; Buccoliero, Anna Maria; Scagnet, Mirko; Bowers, Daniel C.; Giannini, Caterina; Puget, Stephanie; Hawkins, Cynthia; Tabori, Uri; Klekner, Almos; Bognar, Laszlo; Burger, Peter C.; Eberhart, Charles; Rodriguez, Fausto J.; Hill, D. Ashley; Mueller, Sabine; Haas-Kogan, Daphne A.; Phillips, Joanna J.; Santagata, Sandro; Stiles, Charles D.; Bradner, James E.; Jabado, Nada; Goren, Alon; Grill, Jacques; Ligon, Azra H.; Goumnerova, Liliana; Waanders, Angela J.; Storm, Phillip B.; Kieran, Mark W.; Ligon, Keith L.; Beroukhim, Rameen; Resnick, Adam C.

    2016-01-01

    Angiocentric gliomas are pediatric low-grade gliomas (PLGGs) without known recurrent genetic drivers. We performed genomic analysis of new and published data from 249 PLGGs including 19 Angiocentric Gliomas. We identified MYB-QKI fusions as a specific and single candidate driver event in Angiocentric Gliomas. In vitro and in vivo functional studies show MYB-QKI rearrangements promote tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression, and hemizygous loss of the tumor suppressor QKI. This represents the first example of a single driver rearrangement simultaneously transforming cells via three genetic and epigenetic mechanisms in a tumor. PMID:26829751

  12. Normal Expression of a Rearranged and Mutated c-myc Oncogene after Transfection into Fibroblasts

    NASA Astrophysics Data System (ADS)

    Richman, Adam; Hayday, Adrian

    1989-10-01

    Expression of the c-myc oncogene is deregulated in a variety of malignancies. Rearrangement and mutation of the c-myc locus is a characteristic feature of human Burkitt's lymphoma. Whether deregulation is solely a result of mutation of c-myc or whether it is influenced by the transformed B cell context has not been determined. A translocated and mutated allele of c-myc was stably transfected into fibroblasts. The rearranged allele was expressed indistinguishably from a normal c-myc gene: it had serum-regulated expression, was transcribed with normal promoter preference, and was strongly attenuated. Thus mutations by themselves are insufficient to deregulate c-myc transcription.

  13. Application of exterior complex scaling to positron-hydrogencollisions including rearrangement

    SciTech Connect

    Bartlett, Philip L.; Stelbovics, Andris T.; Rescigno, Thomas N.; McCurdy, C. William

    2007-12-06

    The first application of an exterior complex scaling method to an atomic scattering problem with distinct rearrangement channels is reported. Calculations are performed for positron-hydrogen collisions in an s-wave model employing an electron-positron potential of V{sub 12} = -(8+(r{sub 1}-r{sub 2}){sup 2}){sup 1/2}, using the time-independent propagating exterior complex scaling (PECS) method. This potential has the correct long-range Coulomb tail of the full problem and the results demonstrate that ECS-based methods can accurately calculate scattering, ionization and positronium formation cross sections in this three-body rearrangement collision.

  14. Application of exterior complex scaling to positron-hydrogen collisions including rearrangement

    NASA Astrophysics Data System (ADS)

    Bartlett, Philip L.; Stelbovics, Andris T.; Rescigno, T. N.; McCurdy, C. W.

    2008-03-01

    The application of an exterior complex scaling method to an atomic scattering problem with distinct rearrangement channels is reported. Calculations are performed for positron-hydrogen collisions in an s -wave model employing an electron-positron potential of V12=-[8+(r1-r2)2]-1/2 , using the time-independent propagating exterior complex scaling method. This potential has the correct long-range Coulomb tail of the full problem and the results demonstrate that exterior-complex-scaling-based methods can accurately calculate scattering, ionization,and positronium formation cross sections in this three-body rearrangement collision.

  15. Azulenylcarbenes: Rearrangements on the C11 H8 Potential Energy Surface.

    PubMed

    Henkel, Stefan; Pollok, Corina H; Schleif, Tim; Sander, Wolfram

    2016-08-22

    Four isomeric azulenylcarbenes were synthesized in argon matrices by photolysis of the corresponding diazo precursors, and the photochemistry of these carbenes was studied. The carbenes and their rearranged products were characterized by IR, UV/Vis, and EPR spectroscopy, and the experimental data were compared to results from DFT calculations. While 2-, 5- and 6-azulenylcarbene show triplet ground states, 1-azulenylcarbene exhibits a singlet ground state, in accord with theoretical predictions. The rearrangements of the azulenylcarbenes give access to a number of unusual C11 H8 isomers, such as other carbenes and strained allenes. PMID:27404847

  16. Experimental observation of local rearrangements in dense quasi-two-dimensional emulsion flow.

    PubMed

    Chen, Dandan; Desmond, Kenneth W; Weeks, Eric R

    2015-06-01

    We experimentally study rearranging regions in slow athermal flow by observing the flow of a concentrated oil-in-water emulsion in a thin chamber with a constricting hopper shape. The gap of the chamber is smaller than the droplet diameters, so that the droplets are compressed into quasi-two-dimensional pancakes. We focus on localized rearrangements known as "T1 events" where four droplets exchange neighbors. Flowing droplets are deformed due to forces from neighboring droplets, and these deformations are decreased by nearby T1 events, with a spatial dependence related to the local structure. We see a tendency of the T1 events to occur in small clusters. PMID:26172718

  17. MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.

    PubMed

    Bandopadhayay, Pratiti; Ramkissoon, Lori A; Jain, Payal; Bergthold, Guillaume; Wala, Jeremiah; Zeid, Rhamy; Schumacher, Steven E; Urbanski, Laura; O'Rourke, Ryan; Gibson, William J; Pelton, Kristine; Ramkissoon, Shakti H; Han, Harry J; Zhu, Yuankun; Choudhari, Namrata; Silva, Amanda; Boucher, Katie; Henn, Rosemary E; Kang, Yun Jee; Knoff, David; Paolella, Brenton R; Gladden-Young, Adrianne; Varlet, Pascale; Pages, Melanie; Horowitz, Peleg M; Federation, Alexander; Malkin, Hayley; Tracy, Adam A; Seepo, Sara; Ducar, Matthew; Van Hummelen, Paul; Santi, Mariarita; Buccoliero, Anna Maria; Scagnet, Mirko; Bowers, Daniel C; Giannini, Caterina; Puget, Stephanie; Hawkins, Cynthia; Tabori, Uri; Klekner, Almos; Bognar, Laszlo; Burger, Peter C; Eberhart, Charles; Rodriguez, Fausto J; Hill, D Ashley; Mueller, Sabine; Haas-Kogan, Daphne A; Phillips, Joanna J; Santagata, Sandro; Stiles, Charles D; Bradner, James E; Jabado, Nada; Goren, Alon; Grill, Jacques; Ligon, Azra H; Goumnerova, Liliana; Waanders, Angela J; Storm, Phillip B; Kieran, Mark W; Ligon, Keith L; Beroukhim, Rameen; Resnick, Adam C

    2016-03-01

    Angiocentric gliomas are pediatric low-grade gliomas (PLGGs) without known recurrent genetic drivers. We performed genomic analysis of new and published data from 249 PLGGs, including 19 angiocentric gliomas. We identified MYB-QKI fusions as a specific and single candidate driver event in angiocentric gliomas. In vitro and in vivo functional studies show that MYB-QKI rearrangements promote tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression and hemizygous loss of the tumor suppressor QKI. To our knowledge, this represents the first example of a single driver rearrangement simultaneously transforming cells via three genetic and epigenetic mechanisms in a tumor. PMID:26829751

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

    PubMed Central

    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.

    2015-01-01

    Background 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. Patients and methods 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. Results 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. Conclusion 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

  19. The analysis of ALK gene rearrangement by fluorescence in situ hybridization in non-small cell lung cancer patients

    PubMed Central

    Krawczyk, Paweł Adam; Ramlau, Rodryg Adam; Szumiło, Justyna; Kozielski, Jerzy; Kalinka-Warzocha, Ewa; Bryl, Maciej; Knopik-Dąbrowicz, Alina; Spychalski, Łukasz; Szczęsna, Aleksandra; Rydzik, Ewelina; Milanowski, Janusz

    2013-01-01

    Introduction ALK gene rearrangement is observed in a small subset (3–7%) of non-small cell lung cancer (NSCLC) patients. The efficacy of crizotinib was shown in lung cancer patients harbouring ALK rearrangement. Nowadays, the analysis of ALK gene rearrangement is added to molecular examination of predictive factors. Aim of the study The frequency of ALK gene rearrangement as well as the type of its irregularity was analysed by fluorescence in situ hybridisation (FISH) in tissue samples from NSCLC patients. Material and methods The ALK gene rearrangement was analysed in 71 samples including 53 histological and 18 cytological samples. The analysis could be performed in 56 cases (78.87%), significantly more frequently in histological than in cytological materials. The encountered problem with ALK rearrangement diagnosis resulted from the scarcity of tumour cells in cytological samples, high background fluorescence noises and fragmentation of cell nuclei. Results The normal ALK copy number without gene rearrangement was observed in 26 (36.62%) patients ALK gene polysomy without gene rearrangement was observed in 25 (35.21%) samples while in 3 (4.23%) samples ALK gene amplification was found. ALK gene rearrangement was observed in 2 (2.82%) samples from males, while in the first case the rearrangement coexisted with ALK amplification. In the second case, signet-ring tumour cells were found during histopathological examination and this patient was successfully treated with crizotinib with partial remission lasting 16 months. Conclusions FISH is a useful technique for ALK gene rearrangement analysis which allows us to specify the type of gene irregularities. ALK gene examination could be performed in histological as well as cytological (cellblocks) samples, but obtaining a reliable result in cytological samples depends on the cellularity of examined materials. PMID:24592134

  20. Analyzing Somatic Genome Rearrangements in Human Cancers by Using Whole-Exome Sequencing | Office of Cancer Genomics

    Cancer.gov

    Although exome sequencing data are generated primarily to detect single-nucleotide variants and indels, they can also be used to identify a subset of genomic rearrangements whose breakpoints are located in or near exons. Using >4,600 tumor and normal pairs across 15 cancer types, we identified over 9,000 high confidence somatic rearrangements, including a large number of gene fusions.

  1. A metal-free dyotropic-like rearrangement of 2-oxa allylic alcohols in the presence of organoboronic acids.

    PubMed

    Ye, Weimin; Li, Wenbo; Zhang, Junliang

    2014-09-01

    The first example of a dyotropic-like rearrangement of 2-oxa allylic alcohols in the presence of catalytic amounts of Selectfluor and DABCO was reported, which provides a facile access to organoboronates. This reaction represents an unprecedented dyotropic rearrangement consisting of cleavage of two vicinal bonds (one C-C bond and one C=C bond). PMID:25026497

  2. New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling

    PubMed Central

    Dik, Willem A.; Pike-Overzet, Karin; Weerkamp, Floor; de Ridder, Dick; de Haas, Edwin F.E.; Baert, Miranda R.M.; van der Spek, Peter; Koster, Esther E.L.; Reinders, Marcel J.T.; van Dongen, Jacques J.M.; Langerak, Anton W.; Staal, Frank J.T.

    2005-01-01

    To gain more insight into initiation and regulation of T cell receptor (TCR) gene rearrangement during human T cell development, we analyzed TCR gene rearrangements by quantitative PCR analysis in nine consecutive T cell developmental stages, including CD34+ lin− cord blood cells as a reference. The same stages were used for gene expression profiling using DNA microarrays. We show that TCR loci rearrange in a highly ordered way (TCRD-TCRG-TCRB-TCRA) and that the initiating Dδ2-Dδ3 rearrangement occurs at the most immature CD34+CD38−CD1a− stage. TCRB rearrangement starts at the CD34+CD38+CD1a− stage and complete in-frame TCRB rearrangements were first detected in the immature single positive stage. TCRB rearrangement data together with the PTCRA (pTα) expression pattern show that human TCRβ-selection occurs at the CD34+CD38+CD1a+ stage. By combining the TCR rearrangement data with gene expression data, we identified candidate factors for the initiation/regulation of TCR recombination. Our data demonstrate that a number of key events occur earlier than assumed previously; therefore, human T cell development is much more similar to murine T cell development than reported before. PMID:15928199

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

    ERIC Educational Resources Information Center

    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…

  4. Early vertebrate whole genome duplications were predated by a period of intense genome rearrangement

    PubMed Central

    Hufton, Andrew L.; Groth, Detlef; Vingron, Martin; Lehrach, Hans; Poustka, Albert J.; Panopoulou, Georgia

    2008-01-01

    Researchers, supported by data from polyploid plants, have suggested that whole genome duplication (WGD) may induce genomic instability and rearrangement, an idea which could have important implications for vertebrate evolution. Benefiting from the newly released amphioxus genome sequence (Branchiostoma floridae), an invertebrate that researchers have hoped is representative of the ancestral chordate genome, we have used gene proximity conservation to estimate rates of genome rearrangement throughout vertebrates and some of their invertebrate ancestors. We find that, while amphioxus remains the best single source of invertebrate information about the early chordate genome, its genome structure is not particularly well conserved and it cannot be considered a fossilization of the vertebrate preduplication genome. In agreement with previous reports, we identify two WGD events in early vertebrates and another in teleost fish. However, we find that the early vertebrate WGD events were not followed by increased rates of genome rearrangement. Indeed, we measure massive genome rearrangement prior to these WGD events. We propose that the vertebrate WGD events may have been symptoms of a preexisting predisposition toward genomic structural change. PMID:18625908

  5. Oxidative radical skeletal rearrangement induced by molecular oxygen: synthesis of quinazolinones.

    PubMed

    Wang, Yi-Feng; Zhang, Feng-Lian; Chiba, Shunsuke

    2013-06-01

    Oxidative skeletal rearrangement of 5-aryl-4,5-dihydro-1,2,4-oxadiazoles into quinazolinones is induced by molecular oxygen (under a dry air atmosphere) that likely proceeds via transient iminyl radical species. Concise syntheses of biologically active quinazolinone derivatives were demonstrated using the present strategy. PMID:23692460

  6. Asymmetric Total Synthesis of Kopsiyunnanine K, a Monoterpenoid Indole Alkaloid with a Rearranged Skeleton.

    PubMed

    Tokuda, Ryoko; Okamoto, Yoshiki; Koyama, Tetsuya; Kogure, Noriyuki; Kitajima, Mariko; Takayama, Hiromitsu

    2016-07-15

    A new monoterpenoid indole alkaloid, kopsiyunnanine K, was isolated from Kopsia arborea. Its intriguing rearranged structure and absolute configuration, which were inferred from spectral data and a possible biosynthetic pathway, were determined on the basis of a 13-step asymmetric total synthesis. PMID:27355591

  7. Transgenic induction of mitochondrial rearrangements for cytoplasmic male sterility in crop plants.

    PubMed

    Sandhu, Ajay Pal S; Abdelnoor, Ricardo V; Mackenzie, Sally A

    2007-02-01

    Stability of the mitochondrial genome is controlled by nuclear loci. In plants, nuclear genes suppress mitochondrial DNA rearrangements during development. One nuclear gene involved in this process is Msh1. Msh1 appears to be involved in the suppression of illegitimate recombination in plant mitochondria. To test the hypothesis that Msh1 disruption leads to the type of mitochondrial DNA rearrangements associated with naturally occurring cytoplasmic male sterility in plants, a transgenic approach for RNAi was used to modulate expression of Msh1 in tobacco and tomato. In both species, these experiments resulted in reproducible mitochondrial DNA rearrangements and a condition of male (pollen) sterility. The male sterility was, in each case, heritable, associated with normal female fertility, and apparently maternal in its inheritance. Segregation of the transgene did not reverse the male sterile phenotype, producing stable, nontransgenic male sterility. The reproducible transgenic induction of mitochondrial rearrangements in plants is unprecedented, providing a means to develop novel cytoplasmic male sterile lines for release as non-GMO or transgenic materials. PMID:17261806

  8. Synthetically useful Brønsted acid-promoted arylbenzyl ether --> o-benzylphenol rearrangements.

    PubMed

    Luzzio, Frederick A; Chen, Juan

    2009-08-01

    Camphorsulfonic acid in warm fluorobenzene facilitates the ortho rearrangement of (alkoxy-substituted) benzyl ethers of 1-(O-methyl)-2-nitroresorcinols to the corresponding o-(alkoxy-substituted) arylmethylnitrophenols. The substrate phenolic ethers are prepared by ultrasound-promoted arylmethylation of the appropriate 1-alkoxy-substituted 2-nitroresorcinol. PMID:19518072

  9. The Rearranged Workweek of Four Days, Forty Hours with a Treatment of Military Applications.

    ERIC Educational Resources Information Center

    Foster, William J.

    The primary purpose of the study was to develop a military reference on the rearranged workweek, especially the four-day, forty-hour arrangement. In the research an extensive review of pertinent literature was accomplished to provide the necessary background to properly evaluate the military four-day, forty-hour workweek experience at McGuire Air…

  10. Competition between Different Variegating Rearrangements for Limited Heterochromatic Factors in Drosophila Melanogaster

    PubMed Central

    Lloyd, V. K.; Sinclair, D. A.; Grigliatti, T. A.

    1997-01-01

    Position effect variegation (PEV) results from the juxtaposition of a euchromatic gene to heterochromatin. In its new position the gene is inactivated in some cells and not in others. This mosaic expression is consistent with variability in the spread of heterochromatin from cell to cell. As many components of heterochromatin are likely to be produced in limited amounts, the spread of heterochromatin into a normally euchromatic region should be accompanied by a concomitant loss or redistribution of the protein components from other heterochromatic regions. We have shown that this is the case by simultaneously monitoring variegation of a euchromatic and a heterochromatic gene associated with a single chromosome rearrangement. Secondly, if several heterochromatic regions of the genome share limited components of heterochromatin, then some variegating rearrangements should compete for these components. We have examined this hypothesis by testing flies with combinations of two or more different variegating rearrangements. Of the nine combinations of pairs of variegating rearrangements we studied, seven showed nonreciprocal interactions. These results imply that many components of heterochromatin are both shared and present in limited amounts and that they can transfer between chromosomal sites. Consequently, even nonvariegation portions of the genome will be disrupted by re-allocation of heterochromatic proteins associated with PEV. These results have implications for models of PEV. PMID:9093849

  11. Isolation of Betulin and Rearrangement to Allobetulin: A Biomimetic Natural Product Synthesis

    ERIC Educational Resources Information Center

    Green, Brian; Bentley, Michael D.; Chung, Bong Y.; Lynch, Nicholas G.; Jensen, Bruce L.

    2007-01-01

    The triterpenes are a diverse class of widely distributed natural products derived from squalene. Various cyclization and subsequent rearrangement reactions produce many complex structural types. These compounds frequently display a wide divergence of biological properties. For example the pentacyclic triterpene, betulin, is isolated from white…

  12. Complex Chromosomal Rearrangements in B-Cell Lymphoma: Evidence of Chromoanagenesis? A Case Report

    PubMed Central

    Ortega, Veronica; Chaubey, Alka; Mendiola, Christina; Ehman, William; Vadlamudi, Kumari; Dupont, Barbara; Velagaleti, Gopalrao

    2016-01-01

    Genomic instability is a well-known hallmark of cancer. Recent genome sequencing studies have led to the identification of novel phenomena called chromothripsis and chromoanasynthesis in which complex genomic rearrangements are thought to be derived from a single catastrophic event rather than by several incremental steps. A new term chromoanagenesis or chromosomal rebirth was coined recently to group these two one-step catastrophic events together. These phenomena suggest an evolutionary modality for cancer cells to circumvent individual mutational events with one simultaneous shattering of chromosomes resulting in the random reassembling of segmented genetic material to form complex derivative chromosomes. We report a case of possible chromoanagenesis in a patient with diffuse large B-cell lymphoma. Chromosome analysis from the biopsy showed a complex karyotype with multiple numerical and structural rearrangements including a translocation of chromosomes 3 and 7 involving the BCL6 gene region, with the derivative chromosome further rearranging with chromosomes 14, 7, and 22 with involvement of the IGH gene region. Fluorescence in situ hybridization studies confirmed these findings. Chromosomal microarray studies showed multiple complex copy number variations including a chromosome 12 abnormality, the complexity of which appears to suggest the phenomenon of chromoanagenesis. Our case further illustrates that lymphomagenesis can be complex and may arise from a catastrophic event resulting in multiple complex chromosome rearrangements. PMID:27108385

  13. Enantioselective total synthesis of (+)-Lingzhiol via tandem semipinacol rearrangement/Friedel-Crafts type cyclization.

    PubMed

    Chen, Dong; Xu, Wen-Dan; Liu, Hao-Miao; Li, Ming-Ming; Yan, Yong-Min; Li, Xiao-Nian; Li, Yan; Cheng, Yong-Xian; Qin, Hong-Bo

    2016-06-30

    Enantioselective total synthesis of (+)-Lingzhiol has been achieved. It is the first example of in tandem semipinacol rearrangement reactions, the migrated aryl group further reacting with the carbonyl oxonium electrophile to furnish a polycyclic skeleton. Our synthesis involves 13 steps and proceeds in 6% overall yield. PMID:27321202

  14. Complex Chromosomal Rearrangements in B-Cell Lymphoma: Evidence of Chromoanagenesis? A Case Report.

    PubMed

    Ortega, Veronica; Chaubey, Alka; Mendiola, Christina; Ehman, William; Vadlamudi, Kumari; Dupont, Barbara; Velagaleti, Gopalrao

    2016-04-01

    Genomic instability is a well-known hallmark of cancer. Recent genome sequencing studies have led to the identification of novel phenomena called chromothripsis and chromoanasynthesis in which complex genomic rearrangements are thought to be derived from a single catastrophic event rather than by several incremental steps. A new term chromoanagenesis or chromosomal rebirth was coined recently to group these two one-step catastrophic events together. These phenomena suggest an evolutionary modality for cancer cells to circumvent individual mutational events with one simultaneous shattering of chromosomes resulting in the random reassembling of segmented genetic material to form complex derivative chromosomes. We report a case of possible chromoanagenesis in a patient with diffuse large B-cell lymphoma. Chromosome analysis from the biopsy showed a complex karyotype with multiple numerical and structural rearrangements including a translocation of chromosomes 3 and 7 involving the BCL6 gene region, with the derivative chromosome further rearranging with chromosomes 14, 7, and 22 with involvement of the IGH gene region. Fluorescence in situ hybridization studies confirmed these findings. Chromosomal microarray studies showed multiple complex copy number variations including a chromosome 12 abnormality, the complexity of which appears to suggest the phenomenon of chromoanagenesis. Our case further illustrates that lymphomagenesis can be complex and may arise from a catastrophic event resulting in multiple complex chromosome rearrangements. PMID:27108385

  15. 18 CFR 157.208 - Construction, acquisition, operation, replacement, and miscellaneous rearrangement of facilities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Construction, acquisition, operation, replacement, and miscellaneous rearrangement of facilities. 157.208 Section 157.208 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS...

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

    SciTech Connect

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

    1987-11-15

    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, /sup 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.

  17. Cycloaddition-Rearrangement Sequence of 2-Amido Substituted Furans as a Method of Synthesizing Hexahydroindolinones.

    PubMed

    Padwa, Albert; Brodney, Michael A.; Satake, Kyosuke; Straub, Christopher S.

    1999-06-25

    A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels-Alder cycloaddition (IMDAF) reaction of 2-amido substituted furans. The initially formed [4 + 2] cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The reaction rate and product yield were found to be markedly dependent upon the electronic properties of the alkenyl pi-bond. 2-[2-(tert-Butoxycarbonylfuran-2-yl-amino)ethyl]acrylic acid methyl ester was synthesized from 3-chlorocarbonyl-but-3-enoic acid methyl ester. Thermolysis of the carbomethoxy activated furanamide occurred at 80 degrees C to produce a rearranged hexahydroindolinone. When Me(3)Al or (MeO)(3)Al was used as a Lewis acid to promote the cycloaddition, a rearranged alcohol was obtained. The initially formed [4 + 2] cycloadduct undergoes ring opening in the presence of the Lewis acid, and the resulting aluminum intermediate delivers the substituent group from the same face as the neighboring oxygen to ultimately furnish a rearranged cis-alcohol. In contrast to this result, a mixture of diastereomeric methoxy alcohols was isolated when the IMDAF cycloaddition was carried out in methanol. The major isomer corresponds to the trans-diastereomer that results from trapping of the iminium ion from the less crowded face of the pi-bond. PMID:11674531

  18. Novel Cryptic Rearrangements in Adult B-Cell Precursor Acute Lymphoblastic Leukemia Involving the MLL Gene.

    PubMed

    Othman, Moneeb A K; Grygalewicz, Beata; Pienkowska-Grela, Barbara; Rincic, Martina; Rittscher, Katharina; Melo, Joana B; Carreira, Isabel M; Meyer, Britta; Marzena, Watek; Liehr, Thomas

    2015-05-01

    MLL (mixed-lineage-leukemia) gene rearrangements are typical for acute leukemia and are associated with an aggressive course of disease, with a worse outcome than comparable case, and thus require intensified treatment. Here we describe a 69-year-old female with adult B cell precursor acute lymphoblastic leukemia (BCP-ALL) with hyperleukocytosis and immunophenotype CD10- and CD19+ with cryptic MLL rearrangements. G-banding at the time of diagnosis showed a normal karyotype: 46,XX. Molecular cytogenetics using multitude multicolor banding (mMCB) revealed a complex rearrangement of the two copies of chromosome 11. However, a locus-specific probe additionally identified that the MLL gene at 11q23.3 was disrupted, and that the 5' region was inserted into the chromosomal sub-band 4q21; thus the aberration involved three chromosomes and five break events. Unfortunately, the patient died six months after the initial diagnosis from serious infections and severe complications. Overall, the present findings confirm that, by far not all MLL aberrations are seen by routine chromosome banding techniques and that fluorescence in situ hybridization (FISH) should be regarded as standard tool to access MLL rearrangements in patients with BCP-ALL. PMID:25699572

  19. ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability

    PubMed Central

    Teixido, Cristina; Michels, Sebastian; Morales-Espinosa, Daniela; Viteri, Santiago; Hartmann, Wolfgang; Merkelbach-Bruse, Sabine; Fischer, Rieke; Schildhaus, Hans-Ulrich; Fassunke, Jana; Sebastian, Martin; Serke, Monika; Kaminsky, Britta; Randerath, Winfried; Gerigk, Ulrich; Ko, Yon-Dschun; Krüger, Stefan; Schnell, Roland; Rothe, Achim; Kropf-Sanchen, Cornelia; Heukamp, Lukas; Rosell, Rafael

    2015-01-01

    Background While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. Patients and Methods 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. Results 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations. Conclusion ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC. PMID:25868855

  20. Emerging Role of Genomic Rearrangements in Breast Cancer: Applying Knowledge from Other Cancers

    PubMed Central

    Paratala, Bhavna S.; Dolfi, Sonia C.; Khiabanian, Hossein; Rodriguez-Rodriguez, Lorna; Ganesan, Shridar; Hirshfield, Kim M.

    2016-01-01

    Significant advances in our knowledge of cancer genomes are rapidly changing the way we think about tumor biology and the heterogeneity of cancer. Recent successes in genomically-guided treatment approaches accompanied by more sophisticated sequencing techniques have paved the way for deeper investigation into the landscape of genomic rearrangements in cancer. While considerable research on solid tumors has focused on point mutations that directly alter the coding sequence of key genes, far less is known about the role of somatic rearrangements. With many recurring alterations observed across tumor types, there is an obvious need for functional characterization of these genomic biomarkers in order to understand their relevance to tumor biology, therapy, and prognosis. As personalized therapy approaches are turning toward genomic alterations for answers, these biomarkers will become increasingly relevant to the practice of precision medicine. This review discusses the emerging role of genomic rearrangements in breast cancer, with a particular focus on fusion genes. In addition, it raises several key questions on the therapeutic value of such rearrangements and provides a framework to evaluate their significance as predictive and prognostic biomarkers. PMID:26917980

  1. An unexpected rearrangement of pent-4-enofuranosides to cyclopentanones upon hydrogenolysis of the anomeric benzyl group.

    PubMed

    Nie, Shenyou; Chen, Xiaoping; Ma, Yuyong; Li, Wei; Yu, Biao

    2016-09-01

    During our synthesis toward the unique nucleoside antibiotic A201A, we were surprised to find that a benzyl arabino-pent-4-enofuranoside underwent a Ferrier II-like rearrangement readily to provide the corresponding cyclopentanone derivative in high yield and stereoselectivity upon hydrogenolysis of the anomeric benzyl group. PMID:27366975

  2. LONG-PCR AS A TOOL FOR DETECTING REARRANGEMENTS OF ARTHROPOD MTDNA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rearrangements of the mitochondrial DNA gene order have been used to help define the pattern of evolutionary divergence in arthropod taxa. We have employed a combination of highly conserved insect-based PCR primers with long-PCR to survey fourteen non-insect arthropods for mitochondrial gene rearra...

  3. Synthesis of Vitamin K and Related Naphthoquinones via Demethoxycarbonylative Annulations and a Retro-Wittig Rearrangement.

    PubMed

    Mal, Dipakranjan; Ghosh, Ketaki; Jana, Supriti

    2015-12-01

    Anionic annulations of 3-nucleofugal phthalides with α-alkyl(aryl)acrylates involving a demethoxycarbonylation provide a succinct synthesis of vitamin K and related naphthoquinones. Also reported is a new cascade reaction stemming from a Cope-retro-Wittig rearrangement. This cascade leads to direct formation of 1-hydroxy-4-prenyloxynaphthalene-2-carboxylates from the corresponding α-prenyl acrylate acceptors. PMID:26572315

  4. Enantioselective and collective syntheses of xanthanolides involving a controllable dyotropic rearrangement of cis-β-lactones.

    PubMed

    Ren, Weiwu; Bian, Yichao; Zhang, Ziyang; Shang, Hai; Zhang, Pengtao; Chen, Yuejie; Yang, Zhen; Luo, Tuoping; Tang, Yefeng

    2012-07-01

    Let's swap: a scalable, atom-economic, enantio-, and diastereoselective synthetic route to trisubstituted γ-butyrolactones based on a Wagner-Meerwein-type dyotropic rearrangement of cis-β-lactones is described. This methodology was applied in efficient and protecting-group-free formal syntheses and total syntheses of various xanthanolide natural products. PMID:22674838

  5. Malignant perivascular epithelioid cell tumor (PEComa) of cervix with TFE3 gene rearrangement: a case report

    PubMed Central

    Liu, Feifei; Zhang, Renya; Wang, Zi-Yu; Xia, Qiuyuan; Shen, Qin; Shi, Shanshan; Tu, Pin; Shi, Qunli; Zhou, Xiaojun; Rao, Qiu

    2014-01-01

    In this study, we reported the first PEComa arising within the cervix with TFE3 gene rearrangement and aggressive biological behavior. Morphologically, the tumor showed infiltrative growth into the surrounding parenchyma. The majority of tumor cells were arrayed in sheets, alveolar structures, or nests separated by delicate fibrovascular septa. There was marked intratumoral hemorrhage, necrosis, and stromal calcifications. The tumor cells had abundant clear cytoplasm, focally containing finely granular dark brown pigment, morphologically considered to be melanin. Immunohistochemically, the tumor cells demonstrated moderately (2+) or strongly (3+) positive staining for TFE3, HMB45, and Melan A but negative for CKpan, SMA, S100, PAX8, and PAX2. The presence of Ki-67 protein demonstrated a moderate proliferation rate, with a few Ki-67-positive nuclei. Using a recently developed TFE3 split FISH assay, the presence of TFE3 rearrangement was demonstrated. All these clinicopathologic features are suggestive of TFE3-rearranged PEComas of the cervix. Our results both expand the known characteristics of primary cervix PEComas and add to the data regarding TFE3 rearrangement-associated PEComas. PMID:25337301

  6. Acid-promoted bicyclization of arylacetylenes to benzobicyclo[3.2.1]octanes through cationic rearrangements.

    PubMed

    Su, Xiang; Sun, Yihua; Yao, Jiannian; Chen, Hui; Chen, Chao

    2016-03-15

    Acid-promoted efficient, site- and stereo-selective bicyclization of alkynes to polycyclic compounds (benzobicyclo[3.2.1]octanes) was realized with atom- and step-economy. The reaction proceeded through two C-C bonds formed on remote alkyl C-H bonds via twice long-distance cationic rearrangement. PMID:26935906

  7. Lager yeasts possess dynamic genomes that undergo rearrangements and gene amplification in response to stress.

    PubMed

    James, Tharappel C; Usher, Jane; Campbell, Susan; Bond, Ursula

    2008-03-01

    A long-term goal of the brewing industry is to identify yeast strains with increased tolerance to the stresses experienced during the brewing process. We have characterised the genomes of a number of stress-tolerant mutants, derived from the lager yeast strain CMBS-33, that were selected for tolerance to high temperatures and to growth in high specific gravity wort. Our results indicate that the heat-tolerant strains have undergone a number of gross chromosomal rearrangements when compared to the parental strain. To determine if such rearrangements can spontaneously arise in response to exposure to stress conditions experienced during the brewing process, we examined the chromosome integrity of both the stress-tolerant strains and their parent during a single round of fermentation under a variety of environmental stresses. Our results show that the lager yeast genome shows tremendous plasticity during fermentation, especially when fermentations are carried out in high specific gravity wort and at higher than normal temperatures. Many localised regions of gene amplification were observed especially at the telomeres and at the rRNA gene locus on chromosome XII, and general chromosomal instability was evident. However, gross chromosomal rearrangements were not detected, indicating that continued selection in the stress conditions are required to obtain clonal isolates with stable rearrangements. Taken together, the data suggest that lager yeasts display a high degree of genomic plasticity and undergo genomic changes in response to environmental stress. PMID:18183398

  8. A Girl with Pervasive Developmental Disorder and Complex Chromosome Rearrangement Involving 8p and 10p

    ERIC Educational Resources Information Center

    Zwaigenbaum, L; Sonnenberg, L. K.; Heshka, T.; Eastwood, S.; Xu, J.

    2005-01-01

    We report a 4-year-old girl with a "de novo", apparently balanced complex chromosome rearrangement. She initially presented for assessment of velopharyngeal insufficiency due to hypernasal speech. She has distinctive facial features (long face, broad nasal bridge, and protuberant ears with simplified helices), bifid uvula, strabismus, and joint…

  9. The Ireland-Claisen rearrangement strategy towards the synthesis of the schizophrenia drug, (+)-asenapine.

    PubMed

    Anugu, Raghunath Reddy; Mainkar, Prathama S; Sridhar, Balasubramanian; Chandrasekhar, Srivari

    2016-01-28

    (±)-Asenapine, sold in the market as Saphris/Sycrest for the treatment of bipolar disorders, is synthesized in an optically pure form involving an Ireland-Claisen rearrangement as the key step. This approach allows access to all diastereomers. PMID:26659332

  10. Submicrosecond rearrangeable nonblocking silicon-on-insulator thermo-optic 4x4 switch matrix.

    PubMed

    Li, Yuntao; Yu, Jinzhong; Chen, Shaowu; Li, Yanping; Chen, Yuanyuan

    2007-03-15

    A rearrangeable nonblocking silicon-on-insulator-based thermo-optic 4x4 switch matrix is designed and fabricated. A spot-size converter is integrated to reduce the insertion loss, and a new driving circuit is designed to improve the response speed. The insertion loss is less than 10 dB, and the response time is 950 ns. PMID:17308574

  11. Complex polycyclic scaffolds by metathesis rearrangement of Himbert arene/allene cycloadducts.

    PubMed

    Lam, Jonathan K; Schmidt, Yvonne; Vanderwal, Christopher D

    2012-11-01

    The intramolecular arene/allene cycloaddition first described 30 years ago by Himbert and Henn permits rapid access to strained polycyclic compounds. Alkene metathesis processes cleanly rearrange appropriately substituted cycloadducts into complex, functional-group-rich polycyclic lactams of potential utility for natural product synthesis and medicinal chemistry. PMID:23067058

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

    ERIC Educational Resources Information Center

    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…

  13. RUNX1-dependent RAG1 deposition instigates human TCR-δ locus rearrangement

    PubMed Central

    Cieslak, Agata; Le Noir, Sandrine; Trinquand, Amélie; Lhermitte, Ludovic; Franchini, Don-Marc; Villarese, Patrick; Gon, Stéphanie; Bond, Jonathan; Simonin, Mathieu; Vanhille, Laurent; Reimann, Christian; Verhoeyen, Els; Larghero, Jerome; Six, Emmanuelle; Spicuglia, Salvatore; André-Schmutz, Isabelle; Langerak, Anton; Nadel, Bertrand; Macintyre, Elizabeth

    2014-01-01

    V(D)J recombination of TCR loci is regulated by chromatin accessibility to RAG1/2 proteins, rendering RAG1/2 targeting a potentially important regulator of lymphoid differentiation. We show that within the human TCR-α/δ locus, Dδ2-Dδ3 rearrangements occur at a very immature thymic, CD34+/CD1a−/CD7+dim stage, before Dδ2(Dδ3)-Jδ1 rearrangements. These strictly ordered rearrangements are regulated by mechanisms acting beyond chromatin accessibility. Importantly, direct Dδ2-Jδ1 rearrangements are prohibited by a B12/23 restriction and ordered human TCR-δ gene assembly requires RUNX1 protein, which binds to the Dδ2-23RSS, interacts with RAG1, and enhances RAG1 deposition at this site. This RUNX1-mediated V(D)J recombinase targeting imposes the use of two Dδ gene segments in human TCR-δ chains. Absence of this RUNX1 binding site in the homologous mouse Dδ1-23RSS provides a molecular explanation for the lack of ordered TCR-δ gene assembly in mice and may underlie differences in early lymphoid differentiation between these species. PMID:25135298

  14. Preadaptation to the stimulus rearrangement of weightlessness: Preliminary studies and concepts for trainer designs

    NASA Technical Reports Server (NTRS)

    Parker, D. E.; Reschke, M. F.

    1988-01-01

    An effort to develop preflight adaptation training (PAT) apparatus and procedures to adapt astronauts to the stimulus rearrangement of weightless spaceflight is being pursued. Based on the otolith tilt-translation reinterpretation model of sensory adaptation to weightlessness, two prototype preflight adaptation trainers (PAT) have been developed. These trainers couple pitch movement of the subject with translation of the visual surround. Subjects were exposed to this stimulus rearrangement for periods of 30 m. The hypothesis is that exposure to the rearrangement would attenuate vertical eye movements was supported by two experiments using the Miami University Seesaw (MUS) PAT prototype. The Dynamic Environment Simulator (DES) prototype failed to support this hypothesis; this result is attributed to a pecularity of the DES apparatus. A final experiment demonstrated that changes in vertical eye movements were not a consequence of fixation on an external target during exposure to a control condition. Together these experiments support the view that preflight adaptation training can alter eye movements in a manner consistent with adaptation to weightlessness. Following these initial studies, concepts for development of operational preflight trainers were proposed. The trainers are intended to: demonstrate the stimulus rearrangement of weightlessness; allow astronauts to train in altered sensory environment; modify sensory motor reflexes; and reduce/eliminate space motion sickness symptoms.

  15. Analyzing the CDR3 Repertoire with respect to TCR—Beta Chain V-D-J and V-J Rearrangements in Peripheral T Cells using HTS

    PubMed Central

    Ma, Long; Yang, Liwen; Bin Shi; He, Xiaoyan; Peng, Aihua; Li, Yuehong; Zhang, Teng; Sun, Suhong; Ma, Rui; Yao, Xinsheng

    2016-01-01

    V-D-J rearrangement of the TCR—beta chain follows the 12/23 rule and the beyond 12/23 restriction. Currently, the proportion and characteristics of TCR—beta chain V—J rearrangement is unclear. We used high-throughput sequencing to compare and analyze TCR—beta chain V-J rearrangement and V-D-J rearrangement in the CDR3 repertoires of T cells from the PBMCs of six volunteers and six BALB/c mice. The results showed that the percentage of V-J rearrangement of the volunteers was approximately 0.7%, whereas that of the mice was 2.2%. The clonality of mice V-J rearrangement was significantly reduced compared with the V-D-J rearrangement, whereas the clonality of human V-J rearrangement was slightly reduced compared with the V-D-J rearrangement. V-J rearrangement in CDR3 involved the significant usage of N, S, F and L, whereas V-D-J rearrangement in CDR3 involved the significant usage of R and G. The levels of V deletion and J deletion in V-J rearrangement were significantly reduced compared with V-D-J rearrangement. TRBD and TRBJ usage in V-J rearrangement differed from that of V-D-J rearrangement, including dominant usage of TRBV and TRBJ and their pairing. Taken together, these results provide new ideas and technology for studies of V-D-J rearrangement and V-J rearrangement in the CDR3 repertoire. PMID:27404392

  16. Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration

    PubMed Central

    Chiang, Colby; Jacobsen, Jessie C.; Ernst, Carl; Hanscom, Carrie; Heilbut, Adrian; Blumenthal, Ian; Mills, Ryan E.; Kirby, Andrew; Lindgren, Amelia M.; Rudiger, Skye R.; McLaughlan, Clive J.; Bawden, C. Simon; Reid, Suzanne J.; Faull, Richard L. M.; Snell, Russell G.; Hall, Ira M.; Shen, Yiping; Ohsumi, Toshiro K.; Borowsky, Mark L.; Daly, Mark J.; Lee, Charles; Morton, Cynthia C.; MacDonald, Marcy E.; Gusella, James F.; Talkowski, Michael E.

    2012-01-01

    We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically-interpreted translocations and inversions. We confirm that the recently described phenomenon of “chromothripsis” (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline where it can resolve to a karyotypically balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign CNVs. We compared these results to experimentally-generated DNA breakage-repair by sequencing seven transgenic animals, and revealed extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion is the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations. PMID:22388000

  17. Frequent FOS Gene Rearrangements in Epithelioid Hemangioma: A Molecular Study of 58 Cases With Morphologic Reappraisal.

    PubMed

    Huang, Shih-Chiang; Zhang, Lei; Sung, Yun-Shao; Chen, Chun-Liang; Krausz, Thomas; Dickson, Brendan C; Kao, Yu-Chien; Agaram, Narasimhan P; Fletcher, Christopher D M; Antonescu, Cristina R

    2015-10-01

    Epithelioid hemangioma (EH) is a unique benign vasoformative tumor composed of epithelioid endothelial cells. Although a small subset of EHs with atypical features harbor ZFP36-FOSB fusions, no additional genetic abnormalities have been found to date in the remaining cases. On the basis of a novel FOS-LMNA gene fusion identified by RNA sequencing in an index case of a skeletal EH with typical morphology, we sought to investigate the prevalence of FOS rearrangement in a large cohort of EHs. Thus 57 additional EH cases lacking FOSB rearrangements were studied for FOS gene abnormalities by fluorescence in situ hybridization, and results were correlated with morphologic appearance and clinical presentation. The EHs were subclassified as typical (n=25), cellular (n=21), and angiolymphoid hyperplasia with eosinophilia (ALHE) (n=12) variants. The ALHE was defined as an EH with a vascular "blow-out" pattern associated with a variable degree of inflammation. There were 17 (29%) cases bearing FOS gene rearrangements among 58 cases tested, including 12 male and 5 female patients, with a mean age of 42 years. Most FOS-rearranged EHs occurred in the bone (10) and soft tissue (6), whereas only 1 case was cutaneous. The predominant anatomic site was the extremity (12), followed by trunk (3), head and neck (1), and penis (1). The incidence of FOS rearrangement was significantly higher in bone (59%, P=0.006) and lower in head and neck (5%, P=0.009). Twelve of the FOS-rearranged cases were cellular EH (P=0.001) associated with moderate mitotic activity (2 to 5/10 HPF) and milder inflammatory background. All 12 ALHE cases lacked FOS gene abnormalities, suggesting different pathogenesis. In conclusion, FOS rearrangement was present in a third of EHs across different locations and histologic variants; however, it was more prevalent in cellular EH and intraosseous lesions, compared with those in skin, soft tissue, and head and neck. This genetic abnormality can be useful in challenging

  18. Diagnosis of a constitutional five-chromosome rearrangement by fluorescent in situ hybridization (FISH)

    SciTech Connect

    Tsien, F.; Shapira, E.; Carvalho, T.

    1994-09-01

    Complex chromosomal rearrangements are structural rearrangements involving at least three chromosomes and three or more chromosome breakpoints. Such karyotypes are often acquired during cancer multi-step development and in chromosome instability syndromes. However, extremely rare constitutional forms have been reported, most of which are incompatible with life. We present a 2-year-old female with de novo complex rearrangement consisting of five chromosomes and nine breakpoints. Clinical evaluation at two years of age revealed a weight of 5 kg, length of 66 cm, and had circumference of 38 cm, all below the 5th percentile, microcephaly, trigonocephaly, epicanthal folds, inguinal hernia, left clubfoot, hypertonicity, and developmental delay. The neurological examination revealed chorea-acanthocytosis and psychomotor delay. Cultured lymphocytes and fibroblasts revealed a karyotype consisting of five derivative chromosomes. The metaphases were further analyzed by FISH using chromosome-specific libraries and telomeric probes in order to delineate the composition of the rearranged chromosomes; FISH results demonstrated a karyotype of: 46,XX,1pter{r_arrow}1q25::1q42.1{r_arrow}1qter, 2pter{r_arrow}q32.3::1q32.3{r_arrow}2q41::2q37.3{r_arrow}2qter, 7qter{r_arrow}7q21.2::6q22.3{r_arrow}6qter::1q31{r_arrow}1q32.3::6p23{r_arrow}6q22.3, 7pter{r_arrow}7q21.1::6p23{r_arrow}6pter, 2q33{r_arrow}2q37, 1::9p21{r_arrow}9qter. This analysis demonstrates the usefulness of FISH in characterizing complex chromosome rearrangements otherwise difficult to correctly interpret using classical cytogenetics alone.

  19. Contact rearrangements form coupled networks from local motions in allosteric proteins.

    PubMed

    Daily, Michael D; Upadhyaya, Tarak J; Gray, Jeffrey J

    2008-04-01

    Allosteric proteins bind an effector molecule at one site resulting in a functional change at a second site. We hypothesize that networks of contacts altered, formed, or broken are a significant contributor to allosteric communication in proteins. In this work, we identify which interactions change significantly between the residue-residue contact networks of two allosteric structures, and then organize these changes into graphs. We perform the analysis on 15 pairs of allosteric structures with effector and substrate each present in at least one of the two structures. Most proteins exhibit large, dense regions of contact rearrangement, and the graphs form connected paths between allosteric effector and substrate sites in five of these proteins. In the remaining 10 proteins, large-scale conformational changes such as rigid-body motions are likely required in addition to contact rearrangement networks to account for substrate-effector communication. On average, clusters which contain at least one substrate or effector molecule comprise 20% of the protein. These allosteric graphs are small worlds; that is, they typically have mean shortest path lengths comparable to those of corresponding random graphs and average clustering coefficients enhanced relative to those of random graphs. The networks capture 60-80% of known allostery-perturbing mutants in three proteins, and the metrics degree and closeness are statistically good discriminators of mutant residues from nonmutant residues within the networks in two of these three proteins. For two proteins, coevolving clusters of residues which have been hypothesized to be allosterically important differ from the regions with the most contact rearrangement. Residues and contacts which modulate normal mode fluctuations also often participate in the contact rearrangement networks. In summary, residue-residue contact rearrangement networks provide useful representations of the portions of allosteric pathways resulting from

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

    PubMed Central

    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. PMID:24904495

  1. Generation of genetically stable recombinant rotaviruses containing novel genome rearrangements and heterologous sequences by reverse genetics.

    PubMed

    Navarro, Aitor; Trask, Shane D; Patton, John T

    2013-06-01

    The rotavirus (RV) genome consists of 11 segments of double-stranded RNA (dsRNA). Typically, each segment contains 5' and 3' untranslated regions (UTRs) that flank an open reading frame (ORF) encoding a single protein. RV variants with segments of atypical size owing to sequence rearrangements have been described. In many cases, the rearrangement originates from a partial head-to-tail sequence duplication that initiates after the stop codon of the ORF, leaving the protein product of the segment unaffected. To probe the limits of the RV genome to accommodate additional genetic sequence, we used reverse genetics to insert duplications (analogous to synthetic rearrangements) and heterologous sequences into the 3' UTR of the segment encoding NSP2 (gene 8). The approach allowed the recovery of recombinant RVs that contained sequence duplications (up to 200 bp) and heterologous sequences, including those for FLAG, the hepatitis C virus E2 epitope, and the internal ribosome entry site of cricket paralysis virus. The recombinant RVs grew to high titer (>10(7) PFU/ml) and remained genetically stable during serial passage. Despite their longer 3' UTRs, rearranged RNAs of recombinant RVs expressed wild-type levels of protein in vivo. Competitive growth experiments indicated that, unlike RV segments with naturally occurring sequence duplications, genetically engineered segments were less efficiently packaged into progeny viruses. Thus, features of naturally occurring rearranged segments, other than their increased length, contribute to their enhanced packaging phenotype. Our results define strategies for developing recombinant RVs as expression vectors, potentially leading to next-generation RV vaccines that induce protection against other infectious agents. PMID:23536662

  2. Separate elements control DJ and VDJ rearrangement in a transgenic recombination substrate.

    PubMed Central

    Ferrier, P; Krippl, B; Blackwell, T K; Furley, A J; Suh, H; Winoto, A; Cook, W D; Hood, L; Costantini, F; Alt, F W

    1990-01-01

    We describe transgenic mice that carry an antigen receptor gene minilocus comprised of germline T cell receptor (TCR) beta variable gene elements (V, D and J) linked to an immunoglobulin (Ig) C mu constant region gene with or without a DNA segment containing the Ig heavy chain transcriptional enhancer (E mu). Transgenic constructs lacking the E mu-containing segment did not undergo detectable rearrangement in any tissue of six independent transgenic lines. In contrast, transgenic constructs containing this DNA segment underwent rearrangement at high frequency in lymphoid tissues, but not other tissues, of four independent lines. Analyses of purified B and T cells, as well as B and T cell lines, from transgenic animals demonstrated that the E mu-containing segment within the construct allowed partial TCR gene assembly (D to J) in both B and T cells. However, complete TCR gene rearrangement within the construct (V to DJ) occurred only in T cells. Therefore, we have demonstrated elements that can control two separate aspects of TCR beta VDJ rearrangement within this construct. One lies within the E mu-containing DNA segment and represents a dominant, cis-acting element that initiates lymphoid cell-specific D beta to J beta rearrangement; various considerations suggest this activity may be related to that of the E mu element. The second element provides T cell-specific control of complete (V beta to DJ beta) variable region gene assembly; it correlates in activity with expression of the unrearranged V beta segment. Images Fig. 1. Fig. 2. Fig. 4. Fig. 5. PMID:2153073

  3. Reconstruction of the ancestral plastid genome in Geraniaceae reveals a correlation between genome rearrangements, repeats, and nucleotide substitution rates.

    PubMed

    Weng, Mao-Lun; Blazier, John C; Govindu, Madhumita; Jansen, Robert K

    2014-03-01

    Geraniaceae plastid genomes are highly rearranged, and each of the four genera already sequenced in the family has a distinct genome organization. This study reports plastid genome sequences of six additional species, Francoa sonchifolia, Melianthus villosus, and Viviania marifolia from Geraniales, and Pelargonium alternans, California macrophylla, and Hypseocharis bilobata from Geraniaceae. These genome sequences, combined with previously published species, provide sufficient taxon sampling to reconstruct the ancestral plastid genome organization of Geraniaceae and the rearrangements unique to each genus. The ancestral plastid genome of Geraniaceae has a 4 kb inversion and a reduced, Pelargonium-like small single copy region. Our ancestral genome reconstruction suggests that a few minor rearrangements occurred in the stem branch of Geraniaceae followed by independent rearrangements in each genus. The genomic comparison demonstrates that a series of inverted repeat boundary shifts and inversions played a major role in shaping genome organization in the family. The distribution of repeats is strongly associated with breakpoints in the rearranged genomes, and the proportion and the number of large repeats (>20 bp and >60 bp) are significantly correlated with the degree of genome rearrangements. Increases in the degree of plastid genome rearrangements are correlated with the acceleration in nonsynonymous substitution rates (dN) but not with synonymous substitution rates (dS). Possible mechanisms that might contribute to this correlation, including DNA repair system and selection, are discussed. PMID:24336877

  4. Further delineation of nonhomologous-based recombination and evidence for subtelomeric segmental duplications in 1p36 rearrangements.

    PubMed

    D'Angelo, Carla S; Gajecka, Marzena; Kim, Chong A; Gentles, Andrew J; Glotzbach, Caron D; Shaffer, Lisa G; Koiffmann, Célia P

    2009-06-01

    The mechanisms involved in the formation of subtelomeric rearrangements are now beginning to be elucidated. Breakpoint sequencing analysis of 1p36 rearrangements has made important contributions to this line of inquiry. Despite the unique architecture of segmental duplications inherent to human subtelomeres, no common mechanism has been identified thus far and different nonexclusive recombination-repair mechanisms seem to predominate. In order to gain further insights into the mechanisms of chromosome breakage, repair, and stabilization mediating subtelomeric rearrangements in humans, we investigated the constitutional rearrangements of 1p36. Cloning of the breakpoint junctions in a complex rearrangement and three non-reciprocal translocations revealed similarities at the junctions, such as microhomology of up to three nucleotides, along with no significant sequence identity in close proximity to the breakpoint regions. All the breakpoints appeared to be unique and their occurrence was limited to non-repetitive, unique DNA sequences. Several recombination- or cleavage-associated motifs that may promote non-homologous recombination were observed in close proximity to the junctions. We conclude that NHEJ is likely the mechanism of DNA repair that generates these rearrangements. Additionally, two apparently pure terminal deletions were also investigated, and the refinement of the breakpoint regions identified two distinct genomic intervals ~25-kb apart, each containing a series of 1p36 specific segmental duplications with 90-98% identity. Segmental duplications can serve as substrates for ectopic homologous recombination or stimulate genomic rearrangements. PMID:19271239

  5. High concordance of ALK rearrangement between primary tumor and paired metastatic lymph node in patients with lung adenocarcinoma

    PubMed Central

    Hou, Likun; Ren, Shengxiang; Su, Bo; Zhang, Liping; Wu, Wei; Zhang, Wei; Dong, Zhengwei; Huang, Yan

    2016-01-01

    Background Lung cancer has heterogeneous features. It remains unclear whether ALK rearrangement was distributed heterogeneously in tumor from different anatomic sites. To address this issue, we investigate the concordance of ALK rearrangement between primary tumors and paired metastatic lymph nodes in pulmonary adenocarcinoma patients. Methods From Sep 2013 to May 2014, resectable lung adenocarcinoma patients with EGFR wildtype and paired metastatic lymph nodes from Tongji University affiliated Shanghai pulmonary hospital were selected into this study. An auto-mated Ventana ALK with clone D5F3 antibody immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to detected ALK rearrangement. Discordant cases between IHC and RT-PCR were further validated by fluorescence in situ hybridization (FISH). Results A total of 101 patients were enrolled into this study with a median age of 60 years old (range, 35–78 years). ALK rearrangement was found in 20 primary lesions, while in 18 paired metastatic lymph nodes. ALK rearrangement was more frequently happened in younger (P<0.001), Nonsmokers (P=0.012), high-stage disease (P=0.021) and predominantly solid growth pattern (P=0.024). The concordance rate between primary tumor and paired metastatic lymph nodes was 98%. Two patients with ALK rearrangement on primary tumor didn’t show ALK gene fusion on paired metastatic lymph nodes. Sixty-eight cases had more than two stations of metastatic lymph nodes. ALK rearrangement in the different station of metastatic lymph nodes of the same patient was consistent. Conclusions High concordant rate of ALK rearrangement between primary tumors and paired metastatic lymph nodes were found in this study. The authors concluded that specimens from metastatic lesions and primary tumors are equally suitable for detection ALK rearrangement. PMID:27293826

  6. Gene rearrangements in the mitochondrial genome of Cynoglossus bilineatus (Pleuronectiformes: Cynoglossidae).

    PubMed

    Shi, Wei; Li, Dong-He; Kong, Xiao-Yu

    2016-05-01

    Cynoglossus bilineatus (Cynoglossidae, Soleoidei) is characterized by both eyes on the left side of the body and with a rounded snout and a short rostral hook. Here we first report the mitogenome of this tongue sole, which is 16,454 bp in length, and gene rearrangements have been observed. Particularly, the tRNA-Gln gene encoded by the light strand (L-strand) has translocated to the heavy strand (H-strand), along with the tRNA-Ile gene shuffling. In addition, the putative control region has translocated downstream to a position between the ND1 and tRNA-Gln genes, leaving a 26-bp intergenic spacer in its original position. However, the arrangement of the rest genes is identical to that of the typical teleost. This result could contribute to a better understanding the molecular mechanisms of gene rearrangement in fish mitogenome as well as phylogenetic study of Cynoglossidae and Pleuronectiformes. PMID:25423523

  7. Alternative Ac/Ds transposition induces major chromosomal rearrangements in maize.

    PubMed

    Zhang, Jianbo; Yu, Chuanhe; Pulletikurti, Vinay; Lamb, Jonathan; Danilova, Tatiana; Weber, David F; Birchler, James; Peterson, Thomas

    2009-03-15

    Barbara McClintock reported that the Ac/Ds transposable element system can generate major chromosomal rearrangements (MCRs), but the underlying mechanism has not been determined. Here, we identified a series of chromosome rearrangements derived from maize lines containing pairs of closely linked Ac transposable element termini. Molecular and cytogenetic analyses showed that the MCRs in these lines comprised 17 reciprocal translocations and two large inversions. The breakpoints of all 19 MCRs are delineated by Ac termini and characteristic 8-base-pair target site duplications, indicating that the MCRs were generated by precise transposition reactions involving the Ac termini of two closely linked elements. This alternative transposition mechanism may have contributed to chromosome evolution and may also occur during V(D)J recombination resulting in oncogenic translocations. PMID:19299561

  8. Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement.

    PubMed

    David, Nadège; Pasceri, Raffaele; Kitson, Russell R A; Pradal, Alexandre; Moody, Christopher J

    2016-07-25

    A short formal total synthesis of the marine natural product diazonamide A is described. The route is based on indole oxidative rearrangement, and a number of options were investigated involving migration of tyrosine or oxazole fragments upon oxidation of open chain or macrocyclic precursors. The final route proceeds from 7-bromoindole by sequential palladium-catalysed couplings of an oxazole fragment at C-2, followed by a tyrosine fragment at C-3. With the key 2,3-disubstituted indole readily in hand, formation of a macrocyclic lactam set the stage for the crucial oxidative rearrangement to a 3,3-disubstituted oxindole. Notwithstanding the concomitant formation of the unwanted indoxyl isomer, the synthesis successfully delivered, after deprotection, the key oxindole intermediate, thereby completing a formal total synthesis of diazonamide A. PMID:27346186

  9. Dynamic force measurement of rearrangements in a 2D network of droplets

    NASA Astrophysics Data System (ADS)

    Barkley, Solomon; Backholm, Matilda; Dalnoki-Veress, Kari

    2015-03-01

    The interaction between two liquid droplets in an immiscible liquid is well understood. However, the emulsions relevant to biological and industrial processes involve high concentrations of these droplets, and multi-body effects cannot be ignored. As droplets rearrange in response to a disturbance, the importance of individual pair-wise interactions between droplets changes with the geometry of neighbours. Here we report on an experimental setup consisting of a two- dimensional network of monodisperse droplets stabilized with a surfactant. The system is studied with micropipette deflection, which permits direct measurement of forces along with simultaneous imaging of the droplet network. One micropipette is used to apply a tensile or compressive force to the droplet cluster, while a second pipette acts as a force-transducing cantilever, deflecting in response to rearrangements of the droplets.

  10. Coupled-rearrangement-channels calculation of the three-body system under the absorbing boundary condition

    NASA Astrophysics Data System (ADS)

    Iwasaki, M.; Otani, R.; Ito, M.; Kamimura, M.

    2016-06-01

    We formulate the absorbing boundary condition (ABC) in the coupled rearrangement-channels variational method (CRCVM) for the three-body problem. The absorbing potential is introduced in the system of the identical three-bosons, on which the boson symmetry is explicitly imposed by considering the rearrangement channels. The resonance parameters and the strength of the monopole breakup are calculated by the CRCVM + ABC method, and the results are compared with the complex scaling method (CSM). We have found that the results of the ABC method are consistent with the CSM results. The effect of the boson symmetry, which is often neglected in the calculation of the triple α reactions, is also discussed.

  11. Replication stress in early S phase generates apparent micronuclei and chromosome rearrangement in fission yeast

    PubMed Central

    Sabatinos, Sarah A.; Ranatunga, Nimna S.; Yuan, Ji-Ping; Green, Marc D.; Forsburg, Susan L.

    2015-01-01

    DNA replication stress causes genome mutations, rearrangements, and chromosome missegregation, which are implicated in cancer. We analyze a fission yeast mutant that is unable to complete S phase due to a defective subunit of the MCM helicase. Despite underreplicated and damaged DNA, these cells evade the G2 damage checkpoint to form ultrafine bridges, fragmented centromeres, and uneven chromosome segregations that resembles micronuclei. These micronuclei retain DNA damage markers and frequently rejoin with the parent nucleus. Surviving cells show an increased rate of mutation and chromosome rearrangement. This first report of micronucleus-like segregation in a yeast replication mutant establishes underreplication as an important factor contributing to checkpoint escape, abnormal chromosome segregation, and chromosome instability. PMID:26246602

  12. Timing of a mtDNA gene rearrangement and intercontinental dispersal of varanid lizards.

    PubMed

    Amer, Sayed A M; Kumazawa, Yoshinori

    2008-06-01

    The mitochondrial genomes of the Komodo monitor (Varanus komodoensis) and the Nile monitor (V. niloticus) were previously shown to have an extensive gene rearrangement. Here, we show that this gene arrangement widely occurs in varanid taxa originated from Africa, Asia and Australasia. Based on phylogenetic relationships of the varanids constructed using mitochondrial DNA sequences encoding the NADH dehydrogenase subunit 2 gene and seven flanking tRNA genes, we estimated their divergence times by the Bayesian method without assuming the molecular clock. The results suggested that the mitochondrial DNA gene rearrangement took place once in an ancestral varanid lineage in the Paleocene or earlier. Our results are more consistent with Cenozoic over-water dispersal of Southeast Asian varanids across the Indonesian Archipelago rather than the Cretaceous Gondwanan vicariance for the origin of Australasian varanids. PMID:18670139

  13. Activation of lipid peroxidation as a mechanism of plant cell rearrangements under microgravity

    NASA Astrophysics Data System (ADS)

    Baranenko, V. V.

    Activation of the lipid peroxidation (LP) is a universal process perturbating cell membranes under different unfavourable conditions. It is suggested that the LP can be one of the important mechanisms of plant cell rearrangements under altered gravity as well. The purpose of this investigation is to study the LP intensity in pea leaves and chloroplasts under 7- and 14-day clinorotation. The intensification of the LP under both terms of clinorotation particularly under more prolonged, is detected. The adaptive increase in the unsaturated fatty acid content under 7-day clinorotation and their minor decrease under 14-day clinorotation are revealed. The lowering of electron transport rate in both photosystems, particularly in PSI, is established. The results confirm that the LPmay be one of the mechanisms of plant cell rearrangements under microgravity.

  14. To bridge or not to bridge: The role of sulfuric acid in the Beckmann rearrangement

    NASA Astrophysics Data System (ADS)

    Lin, Chester R.; Yu, Li-Juan; Li, Shuhua; Karton, Amir

    2016-08-01

    Based on ab initio calculations using the Gaussian-4 method, we propose a new catalytic mechanism for the Beckmann rearrangement in concentrated H2SO4. Our calculations suggest that H2SO4 catalyzes the 1,2-proton-shift step via a cyclic transition structure, in which H2SO4 acts as a proton-transfer bridge. The reaction barrier for this mechanism is lower by 48.1 kJ mol-1 than the barrier for the previously suggested catalytic mechanism, which involves a strained 3-memberd-ring transition structure. According to the previous mechanism the 1,2-proton shift has the highest activation energy, while in the revised mechanism the highest activation energy is obtained for the ensuing rearrangement/dehydration step.

  15. Mutations affecting both the rearranged and the unrearranged PML alleles in refractory acute promyelocytic leukaemia.

    PubMed

    Iaccarino, Licia; Ottone, Tiziana; Divona, Mariadomenica; Cicconi, Laura; Cairoli, Roberto; Voso, Maria Teresa; Lo-Coco, Francesco

    2016-03-01

    Acute promyelocytic leukaemia (APL) is characterized by the PML/RARA fusion transcript. PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). We analysed the prevalence of PML mutations in 32 patients with de novo or therapy-related APL (t-APL; n = 5), treated with ATO. We identified one ATO-resistant t-APL patient, who presented a PML A216T mutation in both the rearranged and unrearranged PML alleles, and two mutations in the rearranged RARA gene. In this patient, subclones with different PML and RARA mutations acquired clonal dominance during the disease course, probably leading to treatment resistance. PMID:26728337

  16. Synthesis of 1,4-enamino ketones by [3,3]-rearrangements of dialkenylhydroxylamines.

    PubMed

    Pecak, Wiktoria H; Son, Jongwoo; Burnstine, Amy J; Anderson, Laura L

    2014-07-01

    The synthesis of 1,4-enamino ketones has been achieved through the [3,3]-rearrangement of dialkenylhydroxylamines generated from the addition of N-alkenylnitrones to electron-deficient allenes. The mild conditions required for this reaction, and the simultaneous installation of a fluorenyl imine N-protecting group as a consequence of the rearrangement, avoid spontaneous cyclization of the 1,4-enamino ketones to form the corresponding pyrroles and allow for the isolation and controlled divergent functionalization of these reactive intermediates. The optimization, scope, and tolerance of the new method are discussed with demonstrations of the utility of the products for the synthesis of pyrroles, 1,4-diones, and furans. PMID:24961680

  17. EBV-based plasmid DNA rearrangements after transfection of eukaryotic cells.

    PubMed

    Morozova, O V; Maksimova, T G; Kostenko, E V

    2000-05-01

    The cDNA encoding influenza virus (A/Udorn/307/72 strain) M2 protein was subcloned into the EBV-based vector pREP9. Three continuous kidney cellular lines of different origin were transfected with recombinant plasmid pREP9-M2. One and 5 months after transfection plasmid DNA rearrangements were detected by means of restriction analysis of recovered plasmids and their hybridization with an influenza-virus-specific radioactive probe. Deletions were the most frequent type of pREP9-M2 mutations. PCR with primers corresponding to cellular genome and plasmid DNA followed by Southern blot analysis with the [(32)P]-labeled M2-fragment allowed host DNA rearrangements to be revealed in transfected cells. PMID:10783296

  18. Limited heterogeneity of rearranged T-cell receptor Vα transcripts in brains of multiple sclerosis patients

    NASA Astrophysics Data System (ADS)

    Oksenberg, Jorge R.; Stuart, Simon; Begovich, Ann B.; Bell, Robert B.; Erlich, Henry A.; Steinman, Lawrence; Bernard, Claude C. A.

    1990-05-01

    THE identification of activated ? cells in the brain of individuals with multiple sclerosis (MS) indicates that these cells are critical in the pathogenesis of this disease. In an attempt to elucidate the nature of the lymphocytic infiltration, we used the polymerase chain reaction to amplify T-cell antigen receptor (TCR) Vα sequences from transcripts derived from MS brain lesions. In each of three MS brains, only two to four rearranged TCR Vα transcripts were detected. No Vα transcripts could be found in control brains. Sequence analysis of transcripts encoded by the Vα 12.1 region showed rearrangements to a limited number of Jα region segments. These results imply that TCR Vα gene expression in MS brain lesions is restricted.

  19. Transposition of reversed Ac element ends generates chromosome rearrangements in maize.

    PubMed Central

    Zhang, Jianbo; Peterson, Thomas

    2004-01-01

    In classical "cut-and-paste" transposition, transposons are excised from donor sites and inserted at new locations. We have identified an alternative pathway in which transposition involves the 5' end of an intact Ac element and the 3' end of a nearby terminally deleted fAc (fractured Ac). The Ac and fAc elements are inserted at the maize p1 locus on chromosome 1s in the same orientation; the adjacent ends of the separate elements are thus in reversed orientation with respect to each other and are separated by a distance of approximately 13 kb. Transposition involving the two ends in reversed orientation generates inversions, deletions, and a novel type of local rearrangement. The rearrangement breakpoints are bounded by the characteristic footprint or target site duplications typical of Ac transposition reactions. These results demonstrate a new intramolecular transposition mechanism by which transposons can greatly impact genome evolution. PMID:15342530

  20. Alignment-free microbial phylogenomics under scenarios of sequence divergence, genome rearrangement and lateral genetic transfer

    PubMed Central

    Bernard, Guillaume; Chan, Cheong Xin; Ragan, Mark A.

    2016-01-01

    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. PMID:27363362

  1. T cell receptor rearrangements in a patient with γ-heavy chain disease: A case report

    PubMed Central

    ZHOU, HEBING; CHEN, WENMING; ZHANG, JUAN; ZENG, HUI; JIAN, YUAN; FU, CHENXIAO

    2016-01-01

    Heavy chain diseases (HCDs) are rare B cell lymphoplasma cell proliferative disorders that are characterized by the production of incomplete monoclonal immunoglobulin (Ig) heavy chains without the associated light chains. γ-HCD (IgG subtype) is a rare subtype, with ~150 cases reported in the literature to date; however, to the best of our knowledge, no reports of T cell receptor (TCR) gene rearrangement in γ-HCD exist in the literature. The present study reports the case of an 81-year-old man with γ-heavy chain disease associated with TCR gene rearrangement, identified in lymph node biopsy and bone marrow aspirate specimens. The present case revealed an alternative manifestation of γ-HCD, which may provide additional biological insights into this rare B cell disorder. PMID:27313757

  2. Cyclo-biphenalenyl biradicaloid molecular materials: conformation, rearrangement, magnetism, and thermochromism

    SciTech Connect

    Huang, Jingsong; Sumpter, Bobby G; Meunier, Vincent; Tian, Yong-Hui; Kertesz, Prof. Miklos

    2010-01-01

    Cyclo-biphenalenyl biradicaloid molecular materials with chair- and boat-conformations are studied by restricted and broken-symmetry DFT using the M06 family of meta-GGA functionals. The global minima of these molecular materials are magnetically silent due to the sigma-bond connecting the two phenalenyls, while the sigma-bond may undergo low-barrier sigmatropic rearrangements via pi-pi bonded paramagnetic intermediates. The validation of theory is performed for the chair-conformation by comparing the sigma-bonded structures and the rearrangement barriers with experimental data. The boat-conformation is then studied using the validated functional. The electronic spectra of both chair- and boat-conformations are calculated and their applications in thermochromism are discussed.

  3. Aza Cope Rearrangement of Propargyl Enammonium Cations Catalyzed By a Self-Assembled `Nanozyme

    SciTech Connect

    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.

  4. Enantioselective Catalysis of the Aza-Cope Rearrangement by a Chiral Supramolecular Assembly

    SciTech Connect

    Brown, Casey J.; Bergman, Robert G.; Raymond, Kenneth N.

    2009-07-29

    The chiral supramolecular catalyst Ga{sub 4}L{sub 6} [L = 1,5-bis(2,3-dihydroxybenzoylamino)naphthalene] is a molecular tetrahedron that catalyzes the 3-aza-Cope rearrangement of allyl enammonium cations. This catalysis is accomplished by preorganizing the substrate in a reactive conformation within the host. This work demonstrates that through the use of enantiopure assembly, its chiral cavity is capable of catalyzing the 3-aza-Cope rearrangement enantioselectively, with yields of 21-74% and enantiomeric excesses from 6 to 64% at 50 C. At lower temperatures, the enantioselectivity improved, reaching 78% ee at 5 C. This is the highest enantioselectivity to date induced by the chiral cavity of a supramolecular assembly.

  5. The role of SPINK1 in ETS rearrangement-negative prostate cancers.

    PubMed

    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

    2008-06-01

    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 ( approximately 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively 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

  6. Dual Palladium(II)/Tertiary Amine Catalysis for Asymmetric Regioselective Rearrangements of Allylic Carbamates.

    PubMed

    Bauer, Johannes Moritz; Frey, Wolfgang; Peters, René

    2016-04-11

    The streamlined catalytic access to enantiopure allylic amines as valuable precursors towards chiral β- and γ-aminoalcohols as well as α- and β-aminoacids is desirable for industrial purposes. In this article an enantioselective method is described that transforms achiral allylic alcohols and N-tosylisocyanate in a single step into highly enantioenriched N-tosyl protected allylic amines via an allylic carbamate intermediate. The latter is likely to undergo a cyclisation-induced [3,3]-rearrangement catalysed by a planar chiral pentaphenylferrocene palladacycle in cooperation with a tertiary amine base. The otherwise often indispensable activation of palladacycle catalysts by a silver salt is not required in the present case and there is also no need for an inert gas atmosphere. To further improve the synthetic value, the rearrangement was used to form dimethylaminosulfonyl-protected allylic amines, which can be deprotected under non-reductive conditions. PMID:26990446

  7. On the significance of germline cytogenetic rearrangements at MYCN locus in neuroblastoma

    PubMed Central

    2013-01-01

    Background MYCN oncogene amplification is the most important prognostic factor in neuroblastoma. 25% neuroblastoma tumors have somatic amplifications at this locus but little is known about its constitutional aberrations and their potential role in carcinogenesis. Here, we have performed an array-CGH and qPCR characterization of two patients with constitutional partial 2p trisomy including MYCN genomic region. Results One of the patients had congenital neuroblastoma and showed presence of minute areas of gains and losses within the common fragile site FRA2C at 2p24 encompassing MYCN. The link between 2p24 germline rearrangements and neuroblastoma development was reassessed by reviewing similar cases in the literature. Conclusions It appears that constitutional rearrangements involving chromosome 2p24 may play role in NB development. PMID:24131700

  8. Skeletal rearrangement of carane structure under conditions of solvolysis of trans-4-tosyloxymethyl-2-carene

    SciTech Connect

    Manukov, E.N.; Vyglazov, O.G.; Chuiko, V.A.; Mardilovich, E.S.

    1988-12-10

    A skeletal rearrangement with cleavage of the gem-dimethylcyclopropane ring and the closure of a new three-membered carbocycle is observed under the conditions of the solvolysis of trans-4-tosyloxymethyl-2-carene. The initial ester was obtained from trans-4-hydroxymethyl-2-carene. The solvolysis was conducted in acetic acid in the presence of potassium acetate and in methanol in the presence of potassium hydroxide.

  9. Hapmnioides A-C, Rearranged Labdane-Type Diterpenoids from the Chinese Liverwort Haplomitrium mnioides.

    PubMed

    Zhou, Jinchuan; Zhang, Jiaozhen; Li, Ruijuan; Liu, Jun; Fan, Peihong; Li, Yi; Ji, Mei; Dong, Yiwen; Yuan, Huiqing; Lou, Hongxiang

    2016-09-01

    Many exceptional labdane-type diterpenoids have been exclusively found in liverworts, which serve as taxonomic molecules or play important ecological roles in interactions among organisms. Three unprecedented labdane-type diterpenoids hapmnioides A (1), B (2), and C (3) formed through cascade rearrangement from the Chinese liverwort Haplomitrium mnioides are reported. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction, and their anti-inflammatory activities were also preliminarily tested. PMID:27513610

  10. Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen-Cope rearrangement.

    PubMed

    Mei, Qinggang; Wang, Chun; Zhao, Zhigang; Yuan, Weicheng; Zhang, Guolin

    2015-01-01

    The hemisynthesis of the naturally occurring bioactive flavonoid glycoside icariin (1) has been accomplished in eleven steps with 7% overall yield from kaempferol. The 4'-OH methylation of kaempferol, the 8-prenylation of 3-O-methoxymethyl-4'-O-methyl-5-O-prenyl-7-O-benzylkaempferol (8) via para-Claisen-Cope rearrangement catalyzed by Eu(fod)3 in the presence of NaHCO3, and the glycosylation of icaritin (3) are the key steps. PMID:26425179

  11. Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms

    PubMed Central

    Sinha, Amit U; Meller, Jaroslaw

    2007-01-01

    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 . 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. Cinteny can also be used to interactively browse

  12. Rearrangements of the transcriptional regulatory networks of metabolic pathways in fungi

    PubMed Central

    Lavoie, Hugo; Hogues, Hervé; Whiteway, Malcolm

    2013-01-01

    Growing evidence suggests that transcriptional regulatory networks in many organisms are highly flexible. Here, we discuss the evolution of transcriptional regulatory networks governing the metabolic machinery of sequenced ascomycetes. In particular, recent work has shown that transcriptional rewiring is common in regulons controlling processes such as production of ribosome components and metabolism of carbohydrates and lipids. We note that dramatic rearrangements of the transcriptional regulatory components of metabolic functions have occurred among ascomycetes species. PMID:19875326

  13. Preparation and Reactivity of Acyclic Chiral Allylzinc Species by a Zinc-Brook Rearrangement.

    PubMed

    Leibeling, Markus; Shurrush, Khriesto A; Werner, Veronika; Perrin, Lionel; Marek, Ilan

    2016-05-10

    The zinc-Brook rearrangement of enantiomerically enriched α-hydroxy allylsilane produces a chiral allylzinc intermediate, which reacts with retention of configuration in the presence of an electrophile. Two remarkable features of this transformation are the stereochemical outcome during the formation of the allylzinc species and the complete stereocontrol in the organized six-membered transition state, which leads to an overall and complete transfer of chirality within the reaction sequence. PMID:27061357

  14. Brook Rearrangement as a Trigger for the Ring Opening of Strained Carbocycles.

    PubMed

    Zhang, Fa-Guang; Eppe, Guillaume; Marek, Ilan

    2016-01-11

    The combined regio- and stereoselective carbometalation of cyclopropenyl amides, followed by the addition of an acyl silane, led to the formation of polysubstituted cyclopropyl derivatives as unique diastereoisomers. Upon warming of the reaction mixture to room temperature, a Brook rearrangement proceeded with inversion of configuration to provide ready access to δ-ketoamides possessing a quaternary carbon center with high enantiomeric ratios through selective C-C bond cleavage of the ring. PMID:26663399

  15. Computational strategies and improvements in the linear algebraic variational approach to rearrangement scattering

    NASA Technical Reports Server (NTRS)

    Schwenke, David W.; Mladenovic, Mirjana; Zhao, Meishan; Truhlar, Donald G.; Sun, Yan

    1988-01-01

    The computational steps in calculating quantum mechanical reactive scattering amplitudes by the L2 generalized Newton variational principle are discussed with emphasis on computational strategies and recent improvements that make the calculations more efficient. Special emphasis is placed on quadrature techniques, storage management strategies, use of symmetry, and boundary conditions. It is concluded that an efficient implementation of these procedures provides a powerful algorithm for the accurate solution of the Schroedinger equation for rearrangements.

  16. Product Rearrangement from Altering a Single Residue in the Rice syn-Copalyl Diphosphate Synthase.

    PubMed

    Potter, Kevin C; Jia, Meirong; Hong, Young J; Tantillo, Dean; Peters, Reuben J

    2016-03-01

    Through site-directed mutagenesis targeted at identification of the catalytic base in the rice (Oryza sativa) syn-copalyl diphosphate synthase OsCPS4, changes to a single residue (H501) were found to induce rearrangement rather than immediate deprotonation of the initially formed bicycle, leading to production of the novel compound syn-halimadienyl diphosphate. These mutational results are combined with quantum chemical calculations to provide insight into the underlying reaction mechanism. PMID:26878189

  17. Prenatally diagnosed de novo complex chromosome rearrangements: Two new cases and review of the literature

    SciTech Connect

    Ruiz, C.; Grubs, R.E.; Jewett, T.

    1994-09-01

    Complex chromosome rearrangements (CCR) are rare structural rearrangements involving at least three chromosomes with three or more breakpoints. Although there have been numerous reports of individuals with CCR, most have been ascertained through the presence of multiple congenital anomalies, recurrent pregnancy loss, or infertility. Few cases have been ascertained prenatally. We present two new cases of prenatally ascertained CCR. In the first case, an amniocentesis revealed an apparently balanced de novo rearrangement in which chromosomes 5, 6 and 11 were involved in a three-way translocation: 46,XY,t(6;5)(5;11)(q23;p14.3;q15;p13). The pregnancy was unevenful. Recently, at the age of 9 months, a physical and developmental evaluation were normal but, height, weight, and head circumference were below the 5th percentile. In the second case an amniocentesis revealed an unbalanced de novo rearrangement involving separate translocations and an interstitial deletion: 46,XY,del(6)(q25.3q27),t(3;8)(p13;q21.3),t(6;18)(p11.2;q11.2). A meconium plug was present at birth and at 6 months of age surgery for Hirschsprung`s disease was required. Currently, at 10 months of age, the patient has hypotonia and developmental delay. The paucity of information regarding prenatally diagnosed CCR poses a problem in counseling families. Of the four prenatally diagnosed balanced de novo CCR cases, three had abnormal outcomes. In a review of the literature, approximately 70% of the postnatally ascertained balanced de novo CCR cases were associated with congenital anomalies, growth retardation and/or mental retardation. More information regarding the outcome of prenatally ascertained balanced de novo CCR is required for accurate risk assessment.

  18. Meiotic Recombination Analyses in Pigs Carrying Different Balanced Structural Chromosomal Rearrangements

    PubMed Central

    Mary, Nicolas; Barasc, Harmonie; Ferchaud, Stéphane; Priet, Aurélia; Calgaro, Anne; Loustau-Dudez, Anne-Marie; Bonnet, Nathalie; Yerle, Martine; Ducos, Alain; Pinton, Alain

    2016-01-01

    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. PMID:27124413

  19. 1p/19q codeletion and RET rearrangements in small-cell lung cancer

    PubMed Central

    Lu, Hongyang; Xu, Haimiao; Xie, Fajun; Qin, Jing; Han, Na; Fan, Yun; Mao, Weimin

    2016-01-01

    The prognosis of small-cell lung cancer (SCLC) is poor despite reports suggesting modest improvement in survival. To date, chemotherapy remains the cornerstone treatment for SCLC patients, and many studies have focused on identifying the molecular characteristics of SCLC, which serve as the basis for precision treatments that improve the prognosis of SCLC. For instance, the therapeutic effect of temozolomide, recommended for patients with relapsed SCLC, is linked to 1p/19q codeletion in anaplastic oligodendroglial tumors. A subpopulation of SCLC patients may derive benefit from tyrosine kinase inhibitors targeting RET. In order to identify 1p/19q codeletion and RET rearrangement in SCLC patients, 32 SCLC resected specimens were retrospectively collected between 2008 and 2014 from the Zhejiang Cancer Hospital in People’s Republic of China. Fluorescence in situ hybridization was used to detect 1p/19q codeletion and RET rearrangement in the specimens. A 1p single deletion was detected in eight specimens, 19q single deletion was detected in three specimens, and only three specimens had a 1p/19q codeletion. None of the specimens had a RET rearrangement. The three patients whose specimens had a 1p/19q codeletion were alive after 58, 50, and 30 months of follow-up care. There was a trend toward prolonged overall survival for the patients with codeletion compared to no codeletion, 1p single deletion, 19q single deletion, and without 1p and 19q deletion (P=0.113, 0.168, 0.116, and 0.122, respectively). Our data showed that RET rearrangement may be not an ideal molecular target for SCLC therapies in People’s Republic of China. Instead, 1p/19q codeletion is a promising marker for a good prognosis and treatment with temozolomide in SCLC. PMID:27366094

  20. Unusual rearrangement in the photochemical addition of bis(alkylidene)disilacyclobutanes to C[sub 60

    SciTech Connect

    Kusukawa, Takahiro; Kabe, Yoshio; Erata, Tomoki; Nestler, B.; Ando, Wataru )

    1994-11-01

    The photochemical reaction of bis(alkylidene)-disilacyclobutanes 1a, b with C[sub 60] afforded the stable 1:1 adducts 3a,b, resulting from an unexpected rearrangement of the disilacyclobutane unit. The structures of 3a,b were determined by spectroscopic methods, including [sup 29]Si-[sup 1]H HMBC hetero nuclear shift correlation experiments. 18 refs., 2 figs.

  1. Prospective screening for subtelomeric rearrangements in children with mental retardation of unknown aetiology: the Amsterdam experience

    PubMed Central

    van Karnebeek, C D M; Koevoets, C; Sluijter, S; Bijlsma, E; Smeets, D; Redeker, E; Hennekam, R; Hoovers, J

    2002-01-01

    Objective: The frequency of subtelomeric rearrangements in patients with unexplained mental retardation (MR) is uncertain, as most studies have been retrospective and case retrieval may have been biased towards cases more likely to have a chromosome anomaly. To ascertain the frequency of cytogenetic anomalies, including subtelomeric rearrangements, we prospectively screened a consecutive cohort of cases with unexplained MR in an academic tertiary centre. Methods: Inclusion criteria were: age <18 years at referral, IQ<85, no aetiological diagnosis after complete examination, which included karyotyping with high resolution banding (HRB). Results: In 266 karyotyped children, anomalies were detected in 20 (7.5%, seven numerical, 13 structural); 39 cases were analysed by FISH for specific interstitial microdeletions, and anomalies were found in nine (23%). FISH analyses for subtelomeric microdeletions were performed in 184 children (44% moderate-profound MR, 51% familial MR), and one rearrangement (0.5%) was identified in a non-familial MR female with mild MR (de novo deletion 12q24.33-qter). The number of probable polymorphisms was considerable: 2qter (n=7), Xpter (n=3), and Ypter (n=1). A significantly higher total number of malformations and minor anomalies was present in the cytogenetic anomaly group compared to the group without cytogenetic anomalies. Conclusions: The total frequency of cytogenetic anomalies in this prospective study was high (1:10), but the frequency of subtelomeric rearrangements was low. The most likely explanations are the high quality of HRB cytogenetic studies and the lack of clinical selection bias. Conventional cytogenetic analyses, combined with targeted microdeletion testing, remain the single most effective way of additional investigation in mentally retarded children, also in a tertiary centre. PMID:12161591

  2. Synthesis of the anti-HIV agent (-)-hyperolactone C by using oxonium ylide formation-rearrangement.

    PubMed

    Hodgson, David M; Man, Stanislav

    2011-08-22

    Starting from readily available (S)-styrene oxide an asymmetric synthesis is described of the naturally occurring anti-HIV spirolactone (-)-hyperolactone C, which possesses adjacent fully substituted stereocenters. The key step involves a stereocontrolled Rh(II) -catalysed oxonium ylide formation-[2,3] sigmatropic rearrangement of an α-diazo-β-ketoester bearing allylic ether functionality. From the resulting furanone, an acid-catalysed lactonisation and dehydrogenation gives the natural product. PMID:21766363

  3. Regioselective hypervalent iodine-induced Favorskii rearrangement of 3-oxo-5β-steroids.

    PubMed

    Viviano-Posadas, Alejandro O; Flores-Álamo, Marcos; Iglesias-Arteaga, Martín A

    2016-09-01

    Treatment of 3-oxo-5β-steroids with diacetoxyiodobenzene/KOH triggered a fast and regioselective Favorskii rearrangement that exclusively led to 3β-methoxycarbonyl-5β-4-norsteroids in good yields. The outcome of the reaction indicates that although both Cyclopropanone and Semi-benzylic pathways are possible, in the case of 3-oxo-5β-steroids, only the last participates. Unambiguous characterization of the products was achieved by NMR and X-ray Diffraction studies. PMID:27288301

  4. Array-CGH and multipoint FISH to decode complex chromosomal rearrangements

    PubMed Central

    Darai-Ramqvist, Eva; de Ståhl, Teresita Diaz; Sandlund, Agneta; Mantripragada, Kiran; Klein, George; Dumanski, Jan; Imreh, Stefan; Kost-Alimova, Maria

    2006-01-01

    Background Recently, several high-resolution methods of chromosome analysis have been developed. It is important to compare these methods and to select reliable combinations of techniques to analyze complex chromosomal rearrangements in tumours. In this study we have compared array-CGH (comparative genomic hybridization) and multipoint FISH (mpFISH) for their ability to characterize complex rearrangements on human chromosome 3 (chr3) in tumour cell lines. We have used 179 BAC/PAC clones covering chr3 with an approximately 1 Mb resolution to analyze nine carcinoma lines. Chr3 was chosen for analysis, because of its frequent rearrangements in human solid tumours. Results The ploidy of the tumour cell lines ranged from near-diploid to near-pentaploid. Chr3 locus copy number was assessed by interphase and metaphase mpFISH. Totally 53 chr3 fragments were identified having copy numbers from 0 to 14. MpFISH results from the BAC/PAC clones and array-CGH gave mainly corresponding results. Each copy number change on the array profile could be related to a specific chromosome aberration detected by metaphase mpFISH. The analysis of the correlation between real copy number from mpFISH and the average normalized inter-locus fluorescence ratio (ANILFR) value detected by array-CGH demonstrated that copy number is a linear function of parameters that include the variable, ANILFR, and two constants, ploidy and background normalized fluorescence ratio. Conclusion In most cases, the changes in copy number seen on array-CGH profiles reflected cumulative chromosome rearrangements. Most of them stemmed from unbalanced translocations. Although our chr3 BAC/PAC array could identify single copy number changes even in pentaploid cells, mpFISH provided a more accurate analysis in the dissection of complex karyotypes at high ploidy levels. PMID:17196103

  5. The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements

    PubMed Central

    2012-01-01

    Background Somatostatin and its related neuroendocrine peptides have a wide variety of physiological functions that are mediated by five somatostatin receptors with gene names SSTR1-5 in mammals. To resolve their evolution in vertebrates we have investigated the SSTR genes and a large number of adjacent gene families by phylogeny and conserved synteny analyses in a broad range of vertebrate species. Results We find that the SSTRs form two families that belong to distinct paralogons. We observe not only chromosomal similarities reflecting the paralogy relationships between the SSTR-bearing chromosome regions, but also extensive rearrangements between these regions in teleost fish genomes, including fusions and translocations followed by reshuffling through intrachromosomal rearrangements. These events obscure the paralogy relationships but are still tractable thanks to the many genomes now available. We have identified a previously unrecognized SSTR subtype, SSTR6, previously misidentified as either SSTR1 or SSTR4. Conclusions Two ancestral SSTR-bearing chromosome regions were duplicated in the two basal vertebrate tetraploidizations (2R). One of these ancestral SSTR genes generated SSTR2, -3 and -5, the other gave rise to SSTR1, -4 and -6. Subsequently SSTR6 was lost in tetrapods and SSTR4 in teleosts. Our study shows that extensive chromosomal rearrangements have taken place between related chromosome regions in teleosts, but that these events can be resolved by investigating several distantly related species. PMID:23194088

  6. Describing Sequencing Results of Structural Chromosome Rearrangements with a Suggested Next-Generation Cytogenetic Nomenclature

    PubMed Central

    Ordulu, Zehra; Wong, Kristen E.; Currall, Benjamin B.; Ivanov, Andrew R.; Pereira, Shahrin; Althari, Sara; Gusella, James F.; Talkowski, Michael E.; Morton, Cynthia C.

    2014-01-01

    With recent rapid advances in genomic technologies, precise delineation of structural chromosome rearrangements at the nucleotide level is becoming increasingly feasible. In this era of “next-generation cytogenetics” (i.e., an integration of traditional cytogenetic techniques and next-generation sequencing), a consensus nomenclature is essential for accurate communication and data sharing. Currently, nomenclature for describing the sequencing data of these aberrations is lacking. Herein, we present a system called Next-Gen Cytogenetic Nomenclature, which is concordant with the International System for Human Cytogenetic Nomenclature (2013). This system starts with the alignment of rearrangement sequences by BLAT or BLAST (alignment tools) and arrives at a concise and detailed description of chromosomal changes. To facilitate usage and implementation of this nomenclature, we are developing a program designated BLA(S)T Output Sequence Tool of Nomenclature (BOSToN), a demonstrative version of which is accessible online. A standardized characterization of structural chromosomal rearrangements is essential both for research analyses and for application in the clinical setting. PMID:24746958

  7. Palindrome-Mediated Translocations in Humans: A New Mechanistic Model for Gross Chromosomal Rearrangements

    PubMed Central

    Inagaki, Hidehito; Kato, Takema; Tsutsumi, Makiko; Ouchi, Yuya; Ohye, Tamae; Kurahashi, Hiroki

    2016-01-01

    Palindromic DNA sequences, which can form secondary structures, are widely distributed in the human genome. Although the nature of the secondary structure—single-stranded “hairpin” or double-stranded “cruciform”—has been extensively investigated in vitro, the existence of such unusual non-B DNA in vivo remains controversial. Here, we review palindrome-mediated gross chromosomal rearrangements possibly induced by non-B DNA in humans. Recent advances in next-generation sequencing have not yet overcome the difficulty of palindromic sequence analysis. However, a dozen palindromic AT-rich repeat (PATRR) sequences have been identified at the breakpoints of recurrent or non-recurrent chromosomal translocations in humans. The breakages always occur at the center of the palindrome. Analyses of polymorphisms within the palindromes indicate that the symmetry and length of the palindrome affect the frequency of the de novo occurrence of these palindrome-mediated translocations, suggesting the involvement of non-B DNA. Indeed, experiments using a plasmid-based model system showed that the formation of non-B DNA is likely the key to palindrome-mediated genomic rearrangements. Some evidence implies a new mechanism that cruciform DNAs may come close together first in nucleus and illegitimately joined. Analysis of PATRR-mediated translocations in humans will provide further understanding of gross chromosomal rearrangements in many organisms. PMID:27462347

  8. Complex Genomic Rearrangements at the PLP1 Locus Include Triplication and Quadruplication

    PubMed Central

    Beck, Christine R.; Carvalho, Claudia M. B.; Banser, Linda; Gambin, Tomasz; Stubbolo, Danielle; Yuan, Bo; Sperle, Karen; McCahan, Suzanne M.; Henneke, Marco; Seeman, Pavel; Hobson, Grace M.; Lupski, James R.

    2015-01-01

    Inverted repeats (IRs) can facilitate structural variation as crucibles of genomic rearrangement. Complex duplication—inverted triplication—duplication (DUP-TRP/INV-DUP) rearrangements that contain breakpoint junctions within IRs have been recently associated with both MECP2 duplication syndrome (MIM#300260) and Pelizaeus-Merzbacher disease (PMD, MIM#312080). We investigated 17 unrelated PMD subjects with copy number gains at the PLP1 locus including triplication and quadruplication of specific genomic intervals—16/17 were found to have a DUP-TRP/INV-DUP rearrangement product. An IR distal to PLP1 facilitates DUP-TRP/INV-DUP formation as well as an inversion structural variation found frequently amongst normal individuals. We show that a homology—or homeology—driven replicative mechanism of DNA repair can apparently mediate template switches within stretches of microhomology. Moreover, we provide evidence that quadruplication and potentially higher order amplification of a genomic interval can occur in a manner consistent with rolling circle amplification as predicted by the microhomology-mediated break induced replication (MMBIR) model. PMID:25749076

  9. Nucleotide composition of CO1 sequences in Chelicerata (Arthropoda): detecting new mitogenomic rearrangements.

    PubMed

    Arabi, Juliette; Judson, Mark L I; Deharveng, Louis; Lourenço, Wilson R; Cruaud, Corinne; Hassanin, Alexandre

    2012-02-01

    Here we study the evolution of nucleotide composition in third codon-positions of CO1 sequences of Chelicerata, using a phylogenetic framework, based on 180 taxa and three markers (CO1, 18S, and 28S rRNA; 5,218 nt). The analyses of nucleotide composition were also extended to all CO1 sequences of Chelicerata found in GenBank (1,701 taxa). The results show that most species of Chelicerata have a positive strand bias in CO1, i.e., in favor of C nucleotides, including all Amblypygi, Palpigradi, Ricinulei, Solifugae, Uropygi, and Xiphosura. However, several taxa show a negative strand bias, i.e., in favor of G nucleotides: all Scorpiones, Opisthothelae spiders and several taxa within Acari, Opiliones, Pseudoscorpiones, and Pycnogonida. Several reversals of strand-specific bias can be attributed to either a rearrangement of the control region or an inversion of a fragment containing the CO1 gene. Key taxa for which sequencing of complete mitochondrial genomes will be necessary to determine the origin and nature of mtDNA rearrangements involved in the reversals are identified. Acari, Opiliones, Pseudoscorpiones, and Pycnogonida were found to show a strong variability in nucleotide composition. In addition, both mitochondrial and nuclear genomes have been affected by higher substitution rates in Acari and Pseudoscorpiones. The results therefore indicate that these two orders are more liable to fix mutations of all types, including base substitutions, indels, and genomic rearrangements. PMID:22362465

  10. History of chromosome rearrangements reflects the spatial organization of yeast chromosomes.

    PubMed

    Khrameeva, Ekaterina E; Fudenberg, Geoffrey; Gelfand, Mikhail S; Mirny, Leonid A

    2016-04-01

    Three-dimensional (3D) organization of genomes affects critical cellular processes such as transcription, replication, and deoxyribo nucleic acid (DNA) repair. While previous studies have investigated the natural role, the 3D organization plays in limiting a possible set of genomic rearrangements following DNA repair, the influence of specific organizational principles on this process, particularly over longer evolutionary time scales, remains relatively unexplored. In budding yeast S.cerevisiae, chromosomes are organized into a Rabl-like configuration, with clustered centromeres and telomeres tethered to the nuclear periphery. Hi-C data for S.cerevisiae show that a consequence of this Rabl-like organization is that regions equally distant from centromeres are more frequently in contact with each other, between arms of both the same and different chromosomes. Here, we detect rearrangement events in Saccharomyces species using an automatic approach, and observe increased rearrangement frequency between regions with higher contact frequencies. Together, our results underscore how specific principles of 3D chromosomal organization can influence evolutionary events. PMID:27021249

  11. Low rate of interchromosomal rearrangements during old radiation of gekkotan lizards (Squamata: Gekkota).

    PubMed

    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. PMID:25665924

  12. QTAIM study on the degenerate cope rearrangements of 1,5-hexadiene and semibullvalene.

    PubMed

    Brown, Eric C; Bader, Richard F W; Werstiuk, Nick H

    2009-04-01

    Using the homotropylium cation (1) as an archetypal example of a homoaromatic molecule, we carried out a quantum theory of atoms-in-molecules (QTAIM) computational study--at DFT (density functional theory), CCSD (coupled cluster with singles and doubles), and CASSCF (complete active space self-consistent field) levels--on 1 and the degenerate Cope rearrangements of 1,5-hexadiene (2) and semibullvalene (3) including the evaluation of delocalization indexes and a visualization of atomic basins. This study yielded new insights into the factors determining the reaction barriers and the bonding of the ground and transitions states of 2 and 3. Contrary to conclusions reached in earlier studies, we found that the transition state for the degenerate rearrangement of 2 is not aromatic and that the driving force for the very facile Cope rearrangement of semibullvalene is caused by the stabilization of individual atoms as well as electronic delocalization, not by the release of strain in the three-membered ring. PMID:19275139

  13. Complex genomic rearrangements at the PLP1 locus include triplication and quadruplication.

    PubMed

    Beck, Christine R; Carvalho, Claudia M B; Banser, Linda; Gambin, Tomasz; Stubbolo, Danielle; Yuan, Bo; Sperle, Karen; McCahan, Suzanne M; Henneke, Marco; Seeman, Pavel; Garbern, James Y; Hobson, Grace M; Lupski, James R

    2015-03-01

    Inverted repeats (IRs) can facilitate structural variation as crucibles of genomic rearrangement. Complex duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) rearrangements that contain breakpoint junctions within IRs have been recently associated with both MECP2 duplication syndrome (MIM#300260) and Pelizaeus-Merzbacher disease (PMD, MIM#312080). We investigated 17 unrelated PMD subjects with copy number gains at the PLP1 locus including triplication and quadruplication of specific genomic intervals-16/17 were found to have a DUP-TRP/INV-DUP rearrangement product. An IR distal to PLP1 facilitates DUP-TRP/INV-DUP formation as well as an inversion structural variation found frequently amongst normal individuals. We show that a homology-or homeology-driven replicative mechanism of DNA repair can apparently mediate template switches within stretches of microhomology. Moreover, we provide evidence that quadruplication and potentially higher order amplification of a genomic interval can occur in a manner consistent with rolling circle amplification as predicted by the microhomology-mediated break induced replication (MMBIR) model. PMID:25749076

  14. Detection of Chromosomal Rearrangements Derived From Homeologous Recombination in Four Mapping Populations of Brassica napus L.

    PubMed Central

    Udall, Joshua A.; Quijada, Pablo A.; Osborn, Thomas C.

    2005-01-01

    Genetic maps of Brassica napus were constructed from four segregating populations of doubled haploid lines. Each mapping population had the same male parent and used the same set of RFLP probes, facilitating the construction of a consensus map. Chromosomal rearrangements were identified in each population by molecular marker analysis and were classified as de novo homeologous nonreciprocal transpositions (HNRTs), preexisting HNRTs, and homeologous reciprocal transpositions (HRTs). Ninety-nine de novo HNRTs were identified by the presence of a few lines having duplication of a chromosomal region and loss of the corresponding homeologous region. These de novo HNRTs were more prevalent in one population that had a resynthesized B. napus as a parent. Preexisting HNRTs were identified by fragment duplication or fragment loss in many DH lines due to the segregation of HNRTs preexisting in one of the parents. Nine preexisting HNRTs were identified in the three populations involving natural B. napus parents, which likely originated from previous homeologous exchanges. The male parent had a previously described HRT between N7 and N16, which segregated in each population. These data suggest that chromosomal rearrangements caused by homeologous recombination are widespread in B. napus. The effects of these rearrangements on allelic and phenotypic diversity are discussed. PMID:15520255

  15. Chromosomal rearrangements and karyotype evolution in carnivores revealed by chromosome painting.

    PubMed

    Nie, W; Wang, J; Su, W; Wang, D; Tanomtong, A; Perelman, P L; Graphodatsky, A S; Yang, F

    2012-01-01

    Chromosomal evolution in carnivores has been revisited extensively using cross-species chromosome painting. Painting probes derived from flow-sorted chromosomes of the domestic dog, which has one of the most rearranged karyotypes in mammals and the highest dipoid number (2n=78) in carnivores, are a powerful tool in detecting both evolutionary intra- and inter-chromosomal rearrangements. However, only a few comparative maps have been established between dog and other non-Canidae species. Here, we extended cross-species painting with dog probes to seven more species representing six carnivore families: Eurasian lynx (Lynx lynx), the stone marten (Martes foina), the small Indian civet (Viverricula indica), the Asian palm civet (Paradoxurus hermaphrodites), Javan mongoose (Hepestes javanicas), the raccoon (Procyon lotor) and the giant panda (Ailuropoda melanoleuca). The numbers and positions of intra-chromosomal rearrangements were found to differ among these carnivore species. A comparative map between human and stone marten, and a map among the Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), stone marten and human were also established to facilitate outgroup comparison and to integrate comparative maps between stone marten and other carnivores with such maps between human and other species. These comparative maps give further insight into genome evolution and karyotype phylogenetic relationships among carnivores, and will facilitate the transfer of gene mapping data from human, domestic dog and cat to other species. PMID:22086079

  16. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

    PubMed

    Zody, Michael C; Garber, Manuel; Adams, David J; Sharpe, Ted; Harrow, Jennifer; Lupski, James R; Nicholson, Christine; Searle, Steven M; Wilming, Laurens; Young, Sarah K; Abouelleil, Amr; Allen, Nicole R; Bi, Weimin; Bloom, Toby; Borowsky, Mark L; Bugalter, Boris E; Butler, Jonathan; Chang, Jean L; Chen, Chao-Kung; Cook, April; Corum, Benjamin; Cuomo, Christina A; de Jong, Pieter J; DeCaprio, David; Dewar, Ken; FitzGerald, Michael; Gilbert, James; Gibson, Richard; Gnerre, Sante; Goldstein, Steven; Grafham, Darren V; Grocock, Russell; Hafez, Nabil; Hagopian, Daniel S; Hart, Elizabeth; Norman, Catherine Hosage; Humphray, Sean; Jaffe, David B; Jones, Matt; Kamal, Michael; Khodiyar, Varsha K; LaButti, Kurt; Laird, Gavin; Lehoczky, Jessica; Liu, Xiaohong; Lokyitsang, Tashi; Loveland, Jane; Lui, Annie; Macdonald, Pendexter; Major, John E; Matthews, Lucy; Mauceli, Evan; McCarroll, Steven A; Mihalev, Atanas H; Mudge, Jonathan; Nguyen, Cindy; Nicol, Robert; O'Leary, Sinéad B; Osoegawa, Kazutoyo; Schwartz, David C; Shaw-Smith, Charles; Stankiewicz, Pawel; Steward, Charles; Swarbreck, David; Venkataraman, Vijay; Whittaker, Charles A; Yang, Xiaoping; Zimmer, Andrew R; Bradley, Allan; Hubbard, Tim; Birren, Bruce W; Rogers, Jane; Lander, Eric S; Nusbaum, Chad

    2006-04-20

    Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome. PMID:16625196

  17. Low-copy repeats at the human VIPR2 gene predispose to recurrent and nonrecurrent rearrangements

    PubMed Central

    Beri, Silvana; Bonaglia, Maria Clara; Giorda, Roberto

    2013-01-01

    Submicroscopic structural variations, including deletions, duplications, inversions and more complex rearrangements, are widespread in normal human genomes. Inverted segmental duplications or highly identical low-copy repeat (LCR) sequences can mediate the formation of inversions and more complex structural rearrangements through non-allelic homologous recombination. In a patient with 7q36 inverted duplication/terminal deletion, we demonstrated the central role of a pair of short inverted LCRs in the vasoactive intestinal peptide receptor gene (VIPR2)-LCRs in generating the rearrangement. We also revealed a relatively common VIPR2-LCR-associated inversion polymorphism disrupting the gene in almost 1% of healthy subjects, and a small number of complex duplications/triplications. In genome-wide studies of several thousand patients, a significant association of rare microduplications with variable size, all involving VIPR2, with schizophrenia was recently described, suggesting that altered vasoactive intestinal peptide signaling is likely implicated in the pathogenesis of schizophrenia. Genetic testing for VIPR2-LCR-associated inversions should be performed on available cohorts of psychiatric patients to evaluate their potential pathogenic role. PMID:23073313

  18. Wide Distribution of Mitochondrial Genome Rearrangements in Wild Strains of the Cultivated Basidiomycete Agrocybe aegerita

    PubMed Central

    Barroso, G.; Blesa, S.; Labarere, J.

    1995-01-01

    We used restriction fragment length polymorphisms to examine mitochondrial genome rearrangements in 36 wild strains of the cultivated basidiomycete Agrocybe aegerita, collected from widely distributed locations in Europe. We identified two polymorphic regions within the mitochondrial DNA which varied independently: one carrying the Cox II coding sequence and the other carrying the Cox I, ATP6, and ATP8 coding sequences. Two types of mutations were responsible for the restriction fragment length polymorphisms that we observed and, accordingly, were involved in the A. aegerita mitochondrial genome evolution: (i) point mutations, which resulted in strain-specific mitochondrial markers, and (ii) length mutations due to genome rearrangements, such as deletions, insertions, or duplications. Within each polymorphic region, the length differences defined only two mitochondrial types, suggesting that these length mutations were not randomly generated but resulted from a precise rearrangement mechanism. For each of the two polymorphic regions, the two molecular types were distributed among the 36 strains without obvious correlation with their geographic origin. On the basis of these two polymorphisms, it is possible to define four mitochondrial haplotypes. The four mitochondrial haplotypes could be the result of intermolecular recombination between allelic forms present in the population long enough to reach linkage equilibrium. All of the 36 dikaryotic strains contained only a single mitochondrial type, confirming the previously described mitochondrial sorting out after cytoplasmic mixing in basidiomycetes. PMID:16534984

  19. Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca2+

    PubMed Central

    Waldeck-Weiermair, Markus; Malli, Roland; Parichatikanond, Warisara; Gottschalk, Benjamin; Madreiter-Sokolowski, Corina T.; Klec, Christiane; Rost, Rene; Graier, Wolfgang F.

    2015-01-01

    Mitochondrial Ca2+ uptake is a vital process that controls distinct cell and organelle functions. Mitochondrial calcium uptake 1 (MICU1) was identified as key regulator of the mitochondrial Ca2+ uniporter (MCU) that together with the essential MCU regulator (EMRE) forms the mitochondrial Ca2+ channel. However, mechanisms by which MICU1 controls MCU/EMRE activity to tune mitochondrial Ca2+ signals remain ambiguous. Here we established a live-cell FRET approach and demonstrate that elevations of cytosolic Ca2+ rearranges MICU1 multimers with an EC50 of 4.4 μM, resulting in activation of mitochondrial Ca2+ uptake. MICU1 rearrangement essentially requires the EF-hand motifs and strictly correlates with the shape of cytosolic Ca2+ rises. We further show that rearrangements of MICU1 multimers were independent of matrix Ca2+ concentration, mitochondrial membrane potential, and expression levels of MCU and EMRE. Our experiments provide novel details about how MCU/EMRE is regulated by MICU1 and an original approach to investigate MCU/EMRE activation in intact cells. PMID:26489515

  20. Molecular Rearrangements Involved in the Capsid Shell Maturation of Bacteriophage T7*♦

    PubMed Central

    Ionel, Alina; Velázquez-Muriel, Javier A.; Luque, Daniel; Cuervo, Ana; Castón, José R.; Valpuesta, José M.; Martín-Benito, Jaime; Carrascosa, José L.

    2011-01-01

    Maturation of dsDNA bacteriophages involves assembling the virus prohead from a limited set of structural components followed by rearrangements required for the stability that is necessary for infecting a host under challenging environmental conditions. Here, we determine the mature capsid structure of T7 at 1 nm resolution by cryo-electron microscopy and compare it with the prohead to reveal the molecular basis of T7 shell maturation. The mature capsid presents an expanded and thinner shell, with a drastic rearrangement of the major protein monomers that increases in their interacting surfaces, in turn resulting in a new bonding lattice. The rearrangements include tilting, in-plane rotation, and radial expansion of the subunits, as well as a relative bending of the A- and P-domains of each subunit. The unique features of this shell transformation, which does not employ the accessory proteins, inserted domains, or molecular interactions observed in other phages, suggest a simple capsid assembling strategy that may have appeared early in the evolution of these viruses. PMID:20962334

  1. Mapping genomic rearrangements in titi monkeys by chromosome flow sorting and multidirectional in-situ hybridization.

    PubMed

    Dumas, F; Bigoni, F; Stone, G; Sineo, L; Stanyon, R

    2005-01-01

    We developed chromosome painting probes for Callicebus pallescens from flow-sorted chromosomes and used multidirectional chromosome painting to investigate the genomic rearrangements in C. cupreus and C. pallescens. Multidirectional painting provides information about chromosomal homologies at the subchromosomal level and rearrangement break points, allowing chromosomes to be used as cladistic markers. Chromosome paints of C. pallescens were hybridized to human metaphases and 43 signals were detected. Then, both human and C. pallescens probes were hybridized to the chromosomes of another titi monkey, C. cupreus. The human chromosome paints detected 45 segments in the haploid karyotype of C. cupreus. We found that all the syntenic associations proposed for the ancestral platyrrhine karyotype are present in C. cupreus and in C. pallescens. The rearrangements differentiating C. pallescens from C. cupreus re one inversion, one fission and three fusions (two tandem and one Robertsonian)that occurred on the C. cupreus lineage. Our results support the hypothesis that karyological evolution in titi monkeys has resulted in reduction in diploid number and that species with higher diploid numbers (with less derived, more ancestral karyotypes)are localized in the centre of the geographic range of the genera, while more derived species appear to occupy the periphery. PMID:15791414

  2. Quantification of Somatic Chromosomal Rearrangements in Circulating Cell-Free DNA from Ovarian Cancers

    PubMed Central

    Harris, Faye R.; Kovtun, Irina V.; Smadbeck, James; Multinu, Francesco; Jatoi, Aminah; Kosari, Farhad; Kalli, Kimberly R.; Murphy, Stephen J.; Halling, Geoffrey C.; Johnson, Sarah H.; Liu, Minetta C.; Mariani, Andrea; Vasmatzis, George

    2016-01-01

    Recently, the use of a liquid biopsy has shown promise in monitoring tumor burden. While point mutations have been extensively studied, chromosomal rearrangements have demonstrated greater tumor specificity. Such rearrangements can be identified in the tumor and subsequently detected in the plasma of patients using quantitative PCR (qPCR). In this study we used a whole-genome mate-pair protocol to characterize a landscape of genomic rearrangements in the primary tumors of ten ovarian cancer patients. Individualized tumor-specific primer panels of aberrant chromosomal junctions were identified for each case and detected by qPCR within the cell-free DNA. Selected chromosomal junctions were detected in pre-surgically drawn blood in eight of the ten patients. Of these eight, three demonstrated the continued presence of circulating tumor DNA (ctDNA) post-surgery, consistent with their documented presence of disease, and in five ctDNA was undetectable in the post-surgical blood collection, consistent with their lack of detectable disease. The ctDNA fraction was calculated using a novel algorithm designed for the unique challenges of quantifying ctDNA using qPCR to allow observations of real-time tumor dynamics. In summary, a panel of individualized junctions derived from tumor DNA could be an effective way to monitor cancer patients for relapse and therapeutic efficacy using cfDNA. PMID:27436510

  3. Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity.

    PubMed

    Maier, Helena J; Neuman, Benjamin W; Bickerton, Erica; Keep, Sarah M; Alrashedi, Hasan; Hall, Ross; Britton, Paul

    2016-01-01

    Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts. PMID:27255716

  4. Automation of ALK gene rearrangement testing with fluorescence in situ hybridization (FISH): a feasibility study.

    PubMed

    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. PMID:25576649

  5. Conformational Preadjustment in Aqueous Claisen Rearrangement Revealed by SITS-QM/MM MD Simulations.

    PubMed

    Zhang, Jun; Yang, Yi Isaac; Yang, Lijiang; Gao, Yi Qin

    2015-04-30

    An efficient sampling method was implemented in QM/MM hybrid molecular simulations to study aliphatic Claisen rearrangement in aqueous solutions. On the basis of the computational results, the necessary conformational adjustment to trap the reactant into a favorable compact conformation specifically in water was observed. The conformational equilibrium was shown to be important to the elucidation of the "water-acceleration" effect of Claisen rearrangement. Thus, a two-step process of aqueous Claisen rearrangement was proposed. It was similar to the pseudodiaxial-pseudodiequatorial conformational equilibrium observed in the enzymatic reaction of chorismate acid but with explicit inclusion of the solvent coordinates to explain the solvation effects. Polarization was found to occur during the reactant conformational transition. A solvent with high cohesive energy density (CED) like water was suggested to accommodate compact conformers better, thus facilitating the following reaction by concentrating the real "active" reactant. The substituent effects also manifested, leading to varied conformational distributions of different substituted allyl vinyl ethers (AVEs). The application of the enhanced sampling method allowed a systematic analysis of thermodynamic information without loss of solvent coordinates. These data showed the conformational transition of AVEs was an entropy-driving process which was sensitive to the substituent, and enthalpy played an important role in the solvation effect on the conformational equilibrium. PMID:25849201

  6. Pyrolysis of silica-immobilized benzyl phenyl ether: Competing radical rearrangement pathways under restricted diffusion

    SciTech Connect

    Buchanan, A.C. III; Britt, P.F.; Skeen, J.T.; Struss, J.A.; Elam, C.L.

    1998-12-25

    Pyrolysis studies of silica-immobilized benzyl phenyl ether ({approx}PhOCH{sub 2}Ph or {approx}BPE), a model for related ether structures in fuel resources, have been conducted at 275--325 C to examine the impact of restricted mass transport on the pyrolysis mechanism compared with previous studies in fluid phases. Significant rearrangement chemistry is observed for {approx}BPE occurring through two competitive free-radical pathways that are both promoted by the diffusional constraints. One path involves recombination of incipient benzyl and surface-bound phenoxy radicals to form benzylphenol isomers, 10. The second, previously unreported rearrangement path for {approx}BPE involves a 1,2-phenyl shift in an intermediate radical, {approx}PhOCH{center_dot}Ph, leading to formation of benzhydrol (8) and benzophenone (9) as principal products. The rearrangement products 8--10 typically account for ca. 50% of the pyrolysis products. However, the path selectivity is a sensitive function of {approx}BPE surface coverage and the presence of spacer molecules that either facilitate or hinder hydrogen atom transfer steps on the surface.

  7. Aminocarbonyloxymethyl ester prodrugs of flufenamic acid and diclofenac: suppressing the rearrangement pathway in aqueous media.

    PubMed

    Ribeiro, Lina; Silva, Nuno; Iley, Jim; Rautio, Jarkko; Järvinen, Tomi; Mota-Filipe, Hélder; Moreira, Rui; Mendes, Eduarda

    2007-01-01

    Aminocarbonyloxymethyl ester prodrugs are known to undergo rearrangement in aqueous solutions to form the corresponding N-acylamine side product via an O-->N intramolecular acyl transfer from the carbamate conjugate base. Novel aminocarbonyloxymethyl esters of diclofenac and flufenamic acid containing amino acid amide carriers were synthesized and evaluated as potential prodrugs displaying less ability to undergo rearrangement. These compounds were prepared in reasonable yield by a four-step synthetic method that uses the appropriate N-Boc-protected amino acid N-hydroxysuccinimide ester and secondary amine and chloromethyl chloroformate as key reactants. Their reactivity in pH 7.4 buffer and 80% human plasma at 37 degrees C was assessed by RP-HPLC. The aminocarbonyloxymethyl esters containing a secondary carbamate group derived from amino acids such as glycine or phenylalanine were hydrolyzed quantitatively to the parent drug both in non-enzymatic and enzymatic conditions, with no rearrangement product being detected. The oral bioavailability in rats was determined for selected diclofenac derivatives. These derivatives displayed a bioavailability of 25 to 68% relative to that of diclofenac, probably due to their poor aqueous solubility and lipophilicity. These results suggest that further optimization of aminocarbonyloxymethyl esters as potential prodrugs for non-steroidal anti-inflammatory drugs require the use of amino acid carriers with ionizable groups to improve aqueous solubility. PMID:17206608

  8. Chromosomal rearrangements and karyotype evolution in carnivores revealed by chromosome painting

    PubMed Central

    Nie, W; Wang, J; Su, W; Wang, D; Tanomtong, A; Perelman, P L; Graphodatsky, A S; Yang, F

    2012-01-01

    Chromosomal evolution in carnivores has been revisited extensively using cross-species chromosome painting. Painting probes derived from flow-sorted chromosomes of the domestic dog, which has one of the most rearranged karyotypes in mammals and the highest dipoid number (2n=78) in carnivores, are a powerful tool in detecting both evolutionary intra- and inter-chromosomal rearrangements. However, only a few comparative maps have been established between dog and other non-Canidae species. Here, we extended cross-species painting with dog probes to seven more species representing six carnivore families: Eurasian lynx (Lynx lynx), the stone marten (Martes foina), the small Indian civet (Viverricula indica), the Asian palm civet (Paradoxurus hermaphrodites), Javan mongoose (Hepestes javanicas), the raccoon (Procyon lotor) and the giant panda (Ailuropoda melanoleuca). The numbers and positions of intra-chromosomal rearrangements were found to differ among these carnivore species. A comparative map between human and stone marten, and a map among the Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), stone marten and human were also established to facilitate outgroup comparison and to integrate comparative maps between stone marten and other carnivores with such maps between human and other species. These comparative maps give further insight into genome evolution and karyotype phylogenetic relationships among carnivores, and will facilitate the transfer of gene mapping data from human, domestic dog and cat to other species. PMID:22086079

  9. Treatment of ALK-Rearranged Non-Small Cell Lung Cancer: Recent Progress and Future Directions.

    PubMed

    Cameron, Laird; Solomon, Benjamin

    2015-07-01

    Rearrangements of the anaplastic lymphoma kinase (ALK) gene originally discovered nearly 20 years ago in the context of anaplastic large cell lymphoma were identified as oncogenic drivers in a subset of non-small cell lung cancers (NSCLCs) in 2007. These ALK gene rearrangements are present in 3-5 % of NSCLC patients, typically younger, never or light smokers with adenocarcinomas. Crizotinib is a first-in-class ALK tyrosine kinase inhibitor with significant activity in ALK-positive NSCLC that received accelerated US Food and Drug Administration approval for treatment of ALK-positive NSCLC in 2011, just 4 years after identification of ALK rearrangements in this setting. Subsequently, two phase III trials have shown crizotinib to have a tolerable toxicity profile and to be superior to standard chemotherapy for the first- or second-line treatment of advanced ALK-positive lung cancer and numerous countries have approved its use. Despite initial responses, acquired resistance to crizotinib invariably leads to disease progression. Mechanisms of resistance have been described to include ALK tyrosine kinase mutations, activation of bypass signalling pathways and pharmacokinetic failure of crizotinib. Several next-generation ALK inhibitors, including ceritinib and alectinib, are in clinical development and show efficacy in both the crizotinib naïve and crizotinib refractory settings. Ongoing clinical trials will identify the optimal strategy to incorporate these novel agents in the treatment of patients with ALK-positive NSCLC. PMID:26076736

  10. Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca(2.).

    PubMed

    Waldeck-Weiermair, Markus; Malli, Roland; Parichatikanond, Warisara; Gottschalk, Benjamin; Madreiter-Sokolowski, Corina T; Klec, Christiane; Rost, Rene; Graier, Wolfgang F

    2015-01-01

    Mitochondrial Ca(2+) uptake is a vital process that controls distinct cell and organelle functions. Mitochondrial calcium uptake 1 (MICU1) was identified as key regulator of the mitochondrial Ca(2+) uniporter (MCU) that together with the essential MCU regulator (EMRE) forms the mitochondrial Ca(2+) channel. However, mechanisms by which MICU1 controls MCU/EMRE activity to tune mitochondrial Ca(2+) signals remain ambiguous. Here we established a live-cell FRET approach and demonstrate that elevations of cytosolic Ca(2+) rearranges MICU1 multimers with an EC50 of 4.4 μM, resulting in activation of mitochondrial Ca(2+) uptake. MICU1 rearrangement essentially requires the EF-hand motifs and strictly correlates with the shape of cytosolic Ca(2+) rises. We further show that rearrangements of MICU1 multimers were independent of matrix Ca(2+) concentration, mitochondrial membrane potential, and expression levels of MCU and EMRE. Our experiments provide novel details about how MCU/EMRE is regulated by MICU1 and an original approach to investigate MCU/EMRE activation in intact cells. PMID:26489515

  11. Palindrome-Mediated Translocations in Humans: A New Mechanistic Model for Gross Chromosomal Rearrangements.

    PubMed

    Inagaki, Hidehito; Kato, Takema; Tsutsumi, Makiko; Ouchi, Yuya; Ohye, Tamae; Kurahashi, Hiroki

    2016-01-01

    Palindromic DNA sequences, which can form secondary structures, are widely distributed in the human genome. Although the nature of the secondary structure-single-stranded "hairpin" or double-stranded "cruciform"-has been extensively investigated in vitro, the existence of such unusual non-B DNA in vivo remains controversial. Here, we review palindrome-mediated gross chromosomal rearrangements possibly induced by non-B DNA in humans. Recent advances in next-generation sequencing have not yet overcome the difficulty of palindromic sequence analysis. However, a dozen palindromic AT-rich repeat (PATRR) sequences have been identified at the breakpoints of recurrent or non-recurrent chromosomal translocations in humans. The breakages always occur at the center of the palindrome. Analyses of polymorphisms within the palindromes indicate that the symmetry and length of the palindrome affect the frequency of the de novo occurrence of these palindrome-mediated translocations, suggesting the involvement of non-B DNA. Indeed, experiments using a plasmid-based model system showed that the formation of non-B DNA is likely the key to palindrome-mediated genomic rearrangements. Some evidence implies a new mechanism that cruciform DNAs may come close together first in nucleus and illegitimately joined. Analysis of PATRR-mediated translocations in humans will provide further understanding of gross chromosomal rearrangements in many organisms. PMID:27462347

  12. Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity

    PubMed Central

    Maier, Helena J.; Neuman, Benjamin W.; Bickerton, Erica; Keep, Sarah M.; Alrashedi, Hasan; Hall, Ross; Britton, Paul

    2016-01-01

    Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts. PMID:27255716

  13. Carbamoyl Radical-Mediated Synthesis and Semipinacol Rearrangement of β-Lactam Diols

    PubMed Central

    Betou, Marie; Male, Louise; Steed, Jonathan W; Grainger, Richard S

    2014-01-01

    In an approach to the biologically important 6-azabicyclo[3.2.1]octane ring system, the scope of the tandem 4-exo-trig carbamoyl radical cyclization—dithiocarbamate group transfer reaction to ring-fused β-lactams is evaluated. β-Lactams fused to five-, six-, and seven-membered rings are prepared in good to excellent yield, and with moderate to complete control at the newly formed dithiocarbamate stereocentre. No cyclization is observed with an additional methyl substituent on the terminus of the double bond. Elimination of the dithiocarbamate group gives α,β- or β,γ-unsaturated lactams depending on both the methodology employed (base-mediated or thermal) and the nature of the carbocycle fused to the β-lactam. Fused β-lactam diols, obtained from catalytic OsO4-mediated dihydroxylation of α,β-unsaturated β-lactams, undergo semipinacol rearrangement via the corresponding cyclic sulfite or phosphorane to give keto-bridged bicyclic amides by exclusive N-acyl group migration. A monocyclic β-lactam diol undergoes Appel reaction at a primary alcohol in preference to semipinacol rearrangement. Preliminary investigations into the chemo- and stereoselective manipulation of the two carbonyl groups present in a representative 7,8-dioxo-6-azabicyclo[3.2.1]octane rearrangement product are also reported. PMID:24711140

  14. Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation.

    PubMed

    Lorenc, Chris; Saurí, Josep; Moser, Arvin; Buevich, Alexei V; Williams, Antony J; Williamson, R Thomas; Martin, Gary E; Peczuh, Mark W

    2015-10-01

    Invited for this month's cover picture is the group of Professor Mark Peczuh at the University of Connecticut. The cover picture compares the rearrangement of a small molecule to the process of turning a stuffed animal inside out. The recycled, inside-out stuffed animals are both artistic and philosophically provocative. They capture the essence of the rearrangement reaction because the compounds themselves turn inside out over the course of the reaction, extending the diversity of products that can arise from simple starting materials. Small molecules often have functional groups with latent reactivity; under the appropriate conditions, those groups can react with other compounds (e.g., reagents) and also with other groups in the same molecule in an intramolecular reaction. The research team found that the epoxidation of some highly functionalized spiroketal compounds promoted rearrangements of their structures that turned them inside out. Some of the features of the products led them to use X-ray crystallography or a combination of computer-assisted structure elucidation, computation, and a new version of the 1,1-ADEQUATE NMR experiment to determine their structures. For more details, see the Communication on p. 577 ff. PMID:26491628

  15. Rearrangements of a Water Molecule in Both Directions between Two Hydrogen-Bonding Sites of 5-Hydroxyindole Cation: Experimental Determination of the Energy Threshold for the Rearrangement.

    PubMed

    Ikeda, Takamasa; Sakota, Kenji; Sekiya, Hiroshi

    2016-03-24

    Rearrangements of a water molecule in both directions between two hydrogen-bonding (H-bonding) sites of the 5-hydroxyindole (5HI) cation was investigated in the gas phase. IR-dip spectra of jet-cooled 5HI-(H2O)1 revealed that two structural isomers, 5HI(OH)-(H2O)1 and 5HI(NH)-(H2O)1, in which a water molecule is bound to either the OH group or the NH group of 5HI, were formed in the S0 state. The IR photodissociation spectrum of [5HI-(H2O)1](+) generated by two-color resonant two-photon ionization (2C-R2PI) via the S1-S0 origin of 5HI(NH)-(H2O)1 clearly showed that [5HI(OH)-(H2O)1](+) and [5HI(NH)-(H2O)1](+) coexist in the D0 state. The appearance of [5HI(OH)-(H2O)1](+) after R2PI via the S1-S0 origin of 5HI(NH)-(H2O)1 is explained by isomerization of [5HI(NH)-(H2O)1](+) to [5HI(OH)-(H2O)1](+), which corresponds to the rearrangement of the water. In addition, isomerization in the opposite direction was also observed when [5HI-(H2O)1](+) was generated via the S1-S0 origin of 5HI(OH)-(H2O)1. The upper limit of the energy threshold for the rearrangement of the water in [5HI(NH)-(H2O)1](+) was experimentally determined to be 2127 ± 30 cm(-1) from the adiabatic ionization energy of 5HI(NH)-(H2O)1. Above the energy threshold, the water molecule in [5HI-(H2O)1](+) may fluctuate between the two preferential H-bonding sites of 5HI(+). PMID:26950041

  16. Appearance and evolution of the specific chromosomal rearrangements associated with malignant transformation of mouse m5S cells

    SciTech Connect

    Kodama, S.; Okumura, Y.; Komatsu, K.; Sasaki, M.S. )

    1991-06-01

    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.

  17. The effects of chromosome rearrangements on the expression of heterochromatic genes in chromosome 2L of Drosophila melanogaster

    SciTech Connect

    Wakimoto, B.T.; Hearn, M.G. )

    1990-05-01

    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{sup +} 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.

  18. Clonal rearrangement for immunoglobulin and T-cell receptor genes in systemic Castleman's disease. Association with Epstein-Barr virus.

    PubMed Central

    Hanson, C. A.; Frizzera, G.; Patton, D. F.; Peterson, B. A.; McClain, K. L.; Gajl-Peczalska, K. J.; Kersey, J. H.

    1988-01-01

    Castleman's disease is a morphologically and clinically heterogeneous lymphoproliferative disorder. Both a localized benign variant and an aggressive form with systemic manifestations have been described. To investigate the differences between these variants of Castleman's disease, the authors analyzed lymph node DNA from 4 patients with the localized type and 4 with the systemic type of Castleman's disease for immunoglobulin and T-cell receptor gene rearrangements. The role of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was also studied by viral genomic DNA probes. They detected clonal rearrangements in 3 of the 4 patients with the systemic variant of Castleman's; no patients with localized disease had rearrangements. Copies of EBV genome were also detected in 2 of the 3 patients with clonal rearrangements. These results suggest that systemic Castleman's disease is a disorder distinct from the classical localized variant in that it may evolve into a clonal lymphoproliferation. Images Figure 1 PMID:2833104

  19. Partial versus Productive Immunoglobulin Heavy Locus Rearrangements in Chronic Lymphocytic Leukemia: Implications for B-Cell Receptor Stereotypy

    PubMed Central

    Tsakou, Eugenia; Agathagelidis, Andreas; Boudjoghra, Myriam; Raff, Thorsten; Dagklis, Antonis; Chatzouli, Maria; Smilevska, Tatjana; Bourikas, George; Merle-Beral, Helene; Manioudaki-Kavallieratou, Eleni; Anagnostopoulos, Achilles; Brüggemann, Monika; Davi, Frederic; Stamatopoulos, Kostas; Belessi, Chrysoula

    2012-01-01

    The frequent occurrence of stereotyped heavy complementarity-determining region 3 (VH CDR3) sequences among unrelated cases with chronic lymphocytic leukemia (CLL) is widely taken as evidence for antigen selection. Stereotyped VH CDR3 sequences are often defined by the selective association of certain immunoglobulin heavy diversity (IGHD) genes in specific reading frames with certain immunoglobulin heavy joining (IGHJ ) genes. To gain insight into the mechanisms underlying VH CDR3 restrictions and also determine the developmental stage when restrictions in VH CDR3 are imposed, we analyzed partial IGHD-IGHJ rearrangements (D-J) in 829 CLL cases and compared the productively rearranged D-J joints (that is, in-frame junctions without junctional stop codons) to (a) the productive immunoglobulin heavy variable (IGHV )-IGHD-IGHJ rearrangements (V-D-J) from the same cases and (b) 174 D-J rearrangements from 160 precursor B-cell acute lymphoblastic leukemia cases (pre-B acute lymphoblastic leukemia [ALL]). Partial D-J rearrangements were detected in 272/829 CLL cases (32.8%). Sequence analysis was feasible in 238 of 272 D-J rearrangements; 198 of 238 (83.2%) were productively rearranged. The D-J joints in CLL did not differ significantly from those in pre-B ALL, except for higher frequency of the IGHD7-27 and IGHJ6 genes in the latter. Among CLL carrying productively rearranged D-J, comparison of the IGHD gene repertoire in productive V-D-J versus D-J revealed the following: (a) overuse of IGHD reading frames encoding hydrophilic peptides among V-D-J and (b) selection of the IGHD3-3 and IGHD6-19 genes in V-D-J junctions. These results document that the IGHD and IGHJ gene biases in the CLL expressed VH CDR3 repertoire are not stochastic but are directed by selection operating at the immunoglobulin protein level. PMID:21968789

  20. The Inference of Phased Haplotypes for the Immunoglobulin H Chain V Region Gene Loci by Analysis of VDJ Gene Rearrangements

    PubMed Central

    Kidd, Marie J.; Chen, Zhiliang; Wang, Yan; Jackson, Katherine J.; Zhang, Lyndon; Boyd, Scott D.; Fire, Andrew Z.; Tanaka, Mark M.; Gaëta, Bruno A.; Collins, Andrew M.

    2014-01-01

    The existence of many highly similar genes in the lymphocyte receptor gene loci makes them difficult to investigate, and the determination of phased “haplotypes” has been particularly problematic. However, V(D)J gene rearrangements provide an opportunity to infer the association of Ig genes along the chromosomes. The chromosomal distribution of H chain genes in an Ig genotype can be inferred through analysis of VDJ rearrangements in individuals who are heterozygous at points within the IGH locus. We analyzed VDJ rearrangements from 44 individuals for whom sufficient unique rearrangements were available to allow comprehensive genotyping. Nine individuals were identified who were heterozygous at the IGHJ6 locus and for whom sufficient suitable VDJ rearrangements were available to allow comprehensive haplotyping. Each of the 18 resulting IGHV|IGHD|IGHJ haplotypes was unique. Apparent deletion polymorphisms were seen that involved as many as four contiguous, functional IGHV genes. Two deletion polymorphisms involving multiple contiguous IGHD genes were also inferred. Three previously unidentified gene duplications were detected, where two sequences recognized as allelic variants of a single gene were both inferred to be on a single chromosome. Phased genomic data brings clarity to the study of the contribution of each gene to the available repertoire of rearranged VDJ genes. Analysis of rearrangement frequencies suggests that particular genes may have substantially different yet predictable propensities for rearrangement within different haplotypes. Together with data highlighting the extent of haplotypic variation within the population, this suggests that there may be substantial variability in the available Ab repertoires of different individuals. PMID:22205028

  1. Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations.

    PubMed

    Lorenz, Susanne; Barøy, Tale; Sun, Jinchang; Nome, Torfinn; Vodák, Daniel; Bryne, Jan-Christian; Håkelien, Anne-Mari; Fernandez-Cuesta, Lynnette; Möhlendick, Birte; Rieder, Harald; Szuhai, Karoly; Zaikova, Olga; Ahlquist, Terje C; Thomassen, Gard O S; Skotheim, Rolf I; Lothe, Ragnhild A; Tarpey, Patrick S; Campbell, Peter; Flanagan, Adrienne; Myklebost, Ola; Meza-Zepeda, Leonardo A

    2016-02-01

    In contrast to many other sarcoma subtypes, the chaotic karyotypes of osteosarcoma have precluded the identification of pathognomonic translocations. We here report hundreds of genomic rearrangements in osteosarcoma cell lines, showing clear characteristics of microhomology-mediated break-induced replication (MMBIR) and end-joining repair (MMEJ) mechanisms. However, at RNA level, the majority of the fused transcripts did not correspond to genomic rearrangements, suggesting the involvement of trans-splicing, which was further supported by typical trans-splicing characteristics. By combining genomic and transcriptomic analysis, certain recurrent rearrangements were identified and further validated in patient biopsies, including a PMP22-ELOVL5 gene fusion, genomic structural variations affecting RB1, MTAP/CDKN2A and MDM2, and, most frequently, rearrangements involving TP53. Most cell lines (7/11) and a large fraction of tumor samples (10/25) showed TP53 rearrangements, in addition to somatic point mutations (6 patient samples, 1 cell line) and MDM2 amplifications (2 patient samples, 2 cell lines). The resulting inactivation of p53 was demonstrated by a deficiency of the radiation-induced DNA damage response. Thus, TP53 rearrangements are the major mechanism of p53 inactivation in osteosarcoma. Together with active MMBIR and MMEJ, this inactivation probably contributes to the exceptional chromosomal instability in these tumors. Although rampant rearrangements appear to be a phenotype of osteosarcomas, we demonstrate that among the huge number of probable passenger rearrangements, specific recurrent, possibly oncogenic, events are present. For the first time the genomic chaos of osteosarcoma is characterized so thoroughly and delivered new insights in mechanisms involved in osteosarcoma development and may contribute to new diagnostic and therapeutic strategies. PMID:26672768

  2. Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations

    PubMed Central

    Lorenz, Susanne; Barøy, Tale; Sun, Jinchang; Nome, Torfinn; Vodák, Daniel; Bryne, Jan-Christian; Håkelien, Anne-Mari; Fernandez-Cuesta, Lynnette; Möhlendick, Birte; Rieder, Harald; Szuhai, Karoly; Zaikova, Olga; Ahlquist, Terje C.; Thomassen, Gard O. S.; Skotheim, Rolf I.; Lothe, Ragnhild A.; Tarpey, Patrick S.; Campbell, Peter; Flanagan, Adrienne

    2016-01-01

    In contrast to many other sarcoma subtypes, the chaotic karyotypes of osteosarcoma have precluded the identification of pathognomonic translocations. We here report hundreds of genomic rearrangements in osteosarcoma cell lines, showing clear characteristics of microhomology-mediated break-induced replication (MMBIR) and end-joining repair (MMEJ) mechanisms. However, at RNA level, the majority of the fused transcripts did not correspond to genomic rearrangements, suggesting the involvement of trans-splicing, which was further supported by typical trans-splicing characteristics. By combining genomic and transcriptomic analysis, certain recurrent rearrangements were identified and further validated in patient biopsies, including a PMP22-ELOVL5 gene fusion, genomic structural variations affecting RB1, MTAP/CDKN2A and MDM2, and, most frequently, rearrangements involving TP53. Most cell lines (7/11) and a large fraction of tumor samples (10/25) showed TP53 rearrangements, in addition to somatic point mutations (6 patient samples, 1 cell line) and MDM2 amplifications (2 patient samples, 2 cell lines). The resulting inactivation of p53 was demonstrated by a deficiency of the radiation-induced DNA damage response. Thus, TP53 rearrangements are the major mechanism of p53 inactivation in osteosarcoma. Together with active MMBIR and MMEJ, this inactivation probably contributes to the exceptional chromosomal instability in these tumors. Although rampant rearrangements appear to be a phenotype of osteosarcomas, we demonstrate that among the huge number of probable passenger rearrangements, specific recurrent, possibly oncogenic, events are present. For the first time the genomic chaos of osteosarcoma is characterized so thoroughly and delivered new insights in mechanisms involved in osteosarcoma development and may contribute to new diagnostic and therapeutic strategies. PMID:26672768

  3. Direct Conversion of Aldehydes and Ketones to Allylic Halides by a NbX5-[3,3] Rearrangement

    PubMed Central

    Fleming, Fraser F.; Ravikumar, P. C.; Yao, Lihua

    2009-01-01

    Sequential addition of vinylmagnesium bromide and NbCl5, or NbBr5, to a series of aldehydes and ketones directly provides homologated, allylic halides. Transposition of the intermediate vinyl alkoxide is envisaged through a metalla-halo-[3,3] rearrangement with concomitant delivery of the halogen to the terminal carbon. The [3,3] rearrangement is equally effective for the conversion of a propargyllic alcohol to the corresponding allenyl bromide. PMID:20046989

  4. Heat capacity, glass transition temperature, size of cooperatively rearranging regions, and network connectivity of sodium silicate and alkali borate glasses

    SciTech Connect

    Borisova, N.V.; Ushakov, V.M.; Shultz, M.M.

    1994-07-01

    The radius of cooperatively rearranging domains at the glass transition in sodium silicate glasses and the number of bridging oxygen atoms in these domains are assessed within the framework of the kinetic theory of thermal fluctuations. The tendencies of the heat capacity, T{sub g}, and the cooperative rearrangement scale with the alkali oxide concentration in sodium silicate and alkali borate glasses are compared. The points of similarity and distinctions between them are revealed.

  5. Curtius-like Rearrangement of an Iron-Nitrenoid Complex and Application in Biomimetic Synthesis of Bisindolylmethanes.

    PubMed

    Li, Dashan; Wu, Ting; Liang, Kangjiang; Xia, Chengfeng

    2016-05-01

    A Curtius-like rearrangement of hydroxamates to isocyanates was discovered. This reaction was initiated from an iron(II)-nitrenoid complex, which was generated by the iron(II)-catalyzed cleavage of N-O bonds of functionalized hydroxamates. To demonstrate the efficiency of this new Curtius-like rearrangement in synthetic chemistry, a biomimetic strategy for the one-pot preparation of bisindolylmethanes was developed. PMID:27116426

  6. One-Pot Synthesis of Benzothiazole-Tethered Chromanones/Coumarins via Claisen Rearrangement Using the Solid State Melt Reaction.

    PubMed

    Bakthadoss, Manickam; Selvakumar, Raman

    2016-04-15

    A novel protocol has been successfully established for the efficient synthesis of benzothiazole-tethered chromanone/coumarin scaffolds via Claisen rearrangement using a solid state melt reaction in a one-pot manner. Benzothiazole formation and Claisen rearrangement involve the cleavage of S-S and C-O bonds and formation of C-S, C═N, and C-C bonds in a single operation without using a catalyst or solvent. PMID:26991666

  7. TP53 intron 1 hotspot rearrangements are specific to sporadic osteosarcoma and can cause Li-Fraumeni syndrome

    PubMed Central

    Edison; Teo, Audrey S.M.; Madan, Babita; Zhang, Kang; Kohlmann, Wendy K.; Yao, Fei; Lee, Wah Heng; Hoi, Qiangze; Cai, Shaojiang; Woo, Xing Yi; Tan, Patrick; Jundt, Gernot; Smida, Jan; Nathrath, Michaela; Sung, Wing-Kin; Schiffman, Joshua D.; Virshup, David M.; Hillmer, Axel M.

    2015-01-01

    Somatic mutations of TP53 are among the most common in cancer and germline mutations of TP53 (usually missense) can cause Li-Fraumeni syndrome (LFS). Recently, recurrent genomic rearrangements in intron 1 of TP53 have been described in osteosarcoma (OS), a highly malignant neoplasm of bone belonging to the spectrum of LFS tumors. Using whole-genome sequencing of OS, we found features of TP53 intron 1 rearrangements suggesting a unique mechanism correlated with transcription. Screening of 288 OS and 1,090 tumors of other types revealed evidence for TP53 rearrangements in 46 (16%) OS, while none were detected in other tumor types, indicating this rearrangement to be highly specific to OS. We revisited a four-generation LFS family where no TP53 mutation had been identified and found a 445 kb inversion spanning from the TP53 intron 1 towards the centromere. The inversion segregated with tumors in the LFS family. Cancers in this family had loss of heterozygosity, retaining the rearranged allele and resulting in TP53 expression loss. In conclusion, intron 1 rearrangements cause p53-driven malignancies by both germline and somatic mechanisms and provide an important mechanism of TP53 inactivation in LFS, which might in part explain the diagnostic gap of formerly classified “TP53 wild-type” LFS. PMID:25762628

  8. Characterization of gene rearrangements resulted from genomic structural aberrations in human esophageal squamous cell carcinoma KYSE150 cells.

    PubMed

    Hao, Jia-Jie; Gong, Ting; Zhang, Yu; Shi, Zhi-Zhou; Xu, Xin; Dong, Jin-Tang; Zhan, Qi-Min; Fu, Song-Bin; Wang, Ming-Rong

    2013-01-15

    Chromosomal rearrangements and involved genes have been reported to play important roles in the development and progression of human malignancies. But the gene rearrangements in esophageal squamous cell carcinoma (ESCC) remain to be identified. In the present study, array-based comparative genomic hybridization (array-CGH) was performed on the ESCC cell line KYSE150. Eight disrupted genes were detected according to the obviously distinct unbalanced breakpoints. The splitting of these genes was validated by dual-color fluorescence in-situ hybridization (FISH). By using rapid amplification of cDNA ends (RACE), genome walking and sequencing analysis, we further identified gene disruptions and rearrangements. A fusion transcript DTL-1q42.2 was derived from an intrachromosomal rearrangement of chromosome 1. Highly amplified segments of DTL and PTPRD were self-rearranged. The sequences on either side of the junctions possess micro-homology with each other. FISH results indicated that the split DTL and PTPRD were also involved in comprising parts of the derivative chromosomes resulted from t(1q;9p;12p) and t(9;1;9). Further, we found that regions harboring DTL (1q32.3) and PTPRD (9p23) were also splitting in ESCC tumors. The data supplement significant information on the existing genetic background of KYSE150, which may be used as a model for studying these gene rearrangements. PMID:23026210

  9. Mechanistic studies of highly enantio- and diastereoselective aza-Petasis-Ferrier rearrangement catalyzed by chiral phosphoric acid.

    PubMed

    Terada, Masahiro; Komuro, Takazumi; Toda, Yasunori; Korenaga, Toshinobu

    2014-05-14

    The precise mechanism of the highly anti- and enantioselective aza-Petasis-Ferrier (APF) rearrangement of hemiaminal vinyl ethers catalyzed by a chiral phosphoric acid was investigated by undertaking experimental and theoretical studies. The APF rearrangement is characterized by the following unique mechanistic features: (i) efficient optical kinetic resolution of the starting racemic hemiaminal vinyl ether, (ii) enantioconvergent process from racemic hemiaminal vinyl ethers to optically active β-amino aldehyde products, and (iii) anomalous temperature effects on the enantioselectivity (enantioselectivity increases as reaction temperature increases). The following experiments were conducted to elucidate the unique mechanistic features as well as to uncover the overall scheme of the present rearrangement: (A) X-ray crystallographic analysis of the recovered hemiaminal vinyl ether to determine its absolute configuration, (B) rearrangements of enantiomerically pure hemiaminal vinyl ethers to validate the stereochemical relationship between the hemiaminal vinyl ethers and β-amino aldehydes, (C) theoretical studies on the transition states of the C-O bond cleavage and C-C bond formation steps to gain an insight into the optical kinetic resolution of the hemiaminal vinyl ether and the origin of the stereoselectivity, as well as to elucidate the overall scheme of the present rearrangement, and (D) crossover experiments of two hemiaminal vinyl ethers having different vinyl ether and aliphatic substituents to comprehend the mechanism of the anomalous temperature effect and the enantioconvergent process. The results of experiments and theoretical studies fully support the proposed mechanism of the present anti- and enantioselective APF rearrangement. PMID:24746095

  10. TP53 intron 1 hotspot rearrangements are specific to sporadic osteosarcoma and can cause Li-Fraumeni syndrome.

    PubMed

    Ribi, Sebastian; Baumhoer, Daniel; Lee, Kristy; Edison; Teo, Audrey S M; Madan, Babita; Zhang, Kang; Kohlmann, Wendy K; Yao, Fei; Lee, Wah Heng; Hoi, Qiangze; Cai, Shaojiang; Woo, Xing Yi; Tan, Patrick; Jundt, Gernot; Smida, Jan; Nathrath, Michaela; Sung, Wing-Kin; Schiffman, Joshua D; Virshup, David M; Hillmer, Axel M

    2015-04-10

    Somatic mutations of TP53 are among the most common in cancer and germline mutations of TP53 (usually missense) can cause Li-Fraumeni syndrome (LFS). Recently, recurrent genomic rearrangements in intron 1 of TP53 have been described in osteosarcoma (OS), a highly malignant neoplasm of bone belonging to the spectrum of LFS tumors. Using whole-genome sequencing of OS, we found features of TP53 intron 1 rearrangements suggesting a unique mechanism correlated with transcription. Screening of 288 OS and 1,090 tumors of other types revealed evidence for TP53 rearrangements in 46 (16%) OS, while none were detected in other tumor types, indicating this rearrangement to be highly specific to OS. We revisited a four-generation LFS family where no TP53 mutation had been identified and found a 445 kb inversion spanning from the TP53 intron 1 towards the centromere. The inversion segregated with tumors in the LFS family. Cancers in this family had loss of heterozygosity, retaining the rearranged allele and resulting in TP53 expression loss. In conclusion, intron 1 rearrangements cause p53-driven malignancies by both germline and somatic mechanisms and provide an important mechanism of TP53 inactivation in LFS, which might in part explain the diagnostic gap of formerly classified "TP53 wild-type" LFS. PMID:25762628

  11. [Clinical applications of the study of immunoglobulin and T-cell receptor gene rearrangements in acute leukemia and non-Hodgkin's lymphoma in children].

    PubMed

    Schütt, S; Seeger, K; Henze, G

    1990-01-01

    In addition to conventional morphological, histological and immunological marker studies, cells from 150 children with leukemia or non Hodgkin's lymphoma were analysed using the Southern blot hybridization technique to examine immunoglobulin- (Ig) and T-cell receptor (TCR) gene rearrangements. Patients with B-lineage leukemia or NHL demonstrated in 90% an Ig heavy chain gene rearrangement, 6% with an additional light chain kappa gene rearrangement. Combined Ig- with TCR-beta-gene rearrangements were mainly found in patients with common ALL: 19% at first presentation, and 33% in relapse. Moreover, 6 c-ALL patients showed rearrangements in all 3 gene loci (JH-, Ck- and TCR). Based on the developmental hierarchy of Ig- and TCR gene rearrangements it was possible to further subclassify c-ALL into different stages of B cell development. No correlation could be established between the different constellations of gene rearrangements, the number of rearranged fragments and the course of illness. All patients with T-lineage leukemia or NHL demonstrated TCR rearrangements of the beta-, g- and delta-gene loci, two with an additional Ig gene rearrangement. These data confirm recent reports indicating that immunoglobulin heavy chain gene rearrangements are not restricted to B-lineage neoplasms. Furthermore, non-germline configuration was found in tumor cells of every patient with AUL, O-ALL and AHL, permitting a classification to B- or T-cell lineage. Noteworthy is that every AML patient with Ig- and/or TCR gene rearrangements showed a poor or non-response towards therapy. Specimens of individual patients with differently involved tissues at diagnosis always showed an identical rearrangement. The intensity depended on the number of infiltrating blast cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2395311

  12. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements

    PubMed Central

    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

  13. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements.

    PubMed

    Dickson, Laura B; Sharakhova, Maria V; Timoshevskiy, Vladimir A; Fleming, Karen L; Caspary, Alex; Sylla, Massamba; Black, William C

    2016-04-01

    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

  14. Salt Bridge Rearrangement (SaBRe) Explains the Dissociation Behavior of Noncovalent Complexes.

    PubMed

    Loo, Rachel R Ogorzalek; Loo, Joseph A

    2016-06-01

    Native electrospray ionization-mass spectrometry, with gas-phase activation and solution compositions that partially release subcomplexes, can elucidate topologies of macromolecular assemblies. That so much complexity can be preserved in gas-phase assemblies is remarkable, although a long-standing conundrum has been the differences between their gas- and solution-phase decompositions. Collision-induced dissociation of multimeric noncovalent complexes typically distributes products asymmetrically (i.e., by ejecting a single subunit bearing a large percentage of the excess charge). That unexpected behavior has been rationalized as one subunit "unfolding" to depart with more charge. We present an alternative explanation based on heterolytic ion-pair scission and rearrangement, a mechanism that inherently partitions charge asymmetrically. Excessive barriers to dissociation are circumvented in this manner, when local charge rearrangements access a lower-barrier surface. An implication of this ion pair consideration is that stability differences between high- and low-charge state ions usually attributed to Coulomb repulsion may, alternatively, be conveyed by attractive forces from ion pairs (salt bridges) stabilizing low-charge state ions. Should the number of ion pairs be roughly inversely related to charge, symmetric dissociations would be favored from highly charged complexes, as observed. Correlations between a gas-phase protein's size and charge reflect the quantity of restraining ion pairs. Collisionally-facilitated salt bridge rearrangement (SaBRe) may explain unusual size "contractions" seen for some activated, low charge state complexes. That some low-charged multimers preferentially cleave covalent bonds or shed small ions to disrupting noncovalent associations is also explained by greater ion pairing in low charge state complexes. Graphical Abstract ᅟ. PMID:27052739

  15. Effects of sulfur-deficient defect and water on rearrangements of formamide on pyrite (100) surface.

    PubMed

    Nguyen, Huyen Thi; Nguyen, Minh Tho

    2014-06-12

    The efficient formation of HCN/HNC from formamide (FM) combining the advantages of water-assistance, self-catalyzed reactions, and the mineral surfaces was investigated. Periodic density functional theory calculations with plane-wave pseudopotential basis sets were performed to study the interaction of FM with pyrite (100) ideal and defect surfaces. Effects of sulfur vacancy defect and water on tautomerization and rearrangement barriers of FM on the (100) surface were evaluated. Calculated results show that FM adsorbs more strongly on the defect surface than on the ideal surface, with the lowest adsorption energy on the defect surface being -22 kcal/mol. The energy barriers for rearrangements of FM on these two surfaces being close to each other suggests that the adsorptions on the surfaces have small effects on the energy barriers. The energy barriers for formimic acid isomer formations are 44.5 and 46.0 kcal/mol, and those of aminohydroxymethylene formations are 72.6 and 71.9 kcal/mol on the ideal and defect surfaces, respectively. A reduction of ∼30 kcal/mol in tautomerization energy barriers is observed in water-assisted process on the defect surface. Because this reduction is close to that of the gas-phase reactions, the catalytic effect is clearly due to the presence of water molecule instead of the interaction with the surface. In this case, the pyrite surfaces with the ability to accumulate reactive species only play the role of connecting bridges between the two steps of the proposed reaction mechanism: the water-assisted rearrangement and the self-catalyzed dehydration. PMID:24832217

  16. Genome Rearrangements Detected by SNP Microarrays in Individuals with Intellectual Disability Referred with Possible Williams Syndrome

    PubMed Central

    Pani, Ariel M.; Hobart, Holly H.; Morris, Colleen A.; Mervis, Carolyn B.; Bray-Ward, Patricia; Kimberley, Kendra W.; Rios, Cecilia M.; Clark, Robin C.; Gulbronson, Maricela D.; Gowans, Gordon C.; Gregg, Ronald G.

    2010-01-01

    Background 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 ∼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. Methodology/Principal Findings 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. Conclusions/Significance 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

  17. Involvement of interstitial telomeric sequences in two new cases of mosaicism for autosomal structural rearrangements.

    PubMed

    Lévy, Jonathan; Receveur, Aline; Jedraszak, Guillaume; Chantot-Bastaraud, Sandra; Renaldo, Florence; Gondry, Jean; Andrieux, Joris; Copin, Henri; Siffroi, Jean-Pierre; Portnoï, Marie-France

    2015-02-01

    Mosaicism for an autosomal structural rearrangement that does not involve ring or marker chromosomes is rare. The mechanisms responsible for genome instability have not always been explained. Several studies have shown that interstitial telomeric sequences (ITSs), involved in some mosaic constitutional anomalies, are potent sources of genomic instability. Here we describe two cases of mosaicism for uncommon constitutional autosomal rearrangements, involving ITSs, identified by karyotyping and characterized by FISH and SNP-array analysis. The first patient, a boy with global developmental delay, had a rare type of pure distal 1q inverted duplication (1q32-qter), attached to the end of the short arm of the same chromosome 1, in approximately 35% of his cells. The second patient, a phenotypically normal man, was diagnosed as having mosaic for a balanced non-reciprocal translocation of the distal segment of 7q (7q33qter), onto the terminal region of the short arm of a whole chromosome 12, in approximately 80% of his cells. The remaining 20% of the cells showed an unbalanced state of the translocation, with only the der(7) chromosome. He was ascertained through his malformed fetus carrying a non-mosaic partial monosomy 7q, identified at prenatal diagnosis. We show that pan-telomeric and subtelomeric sequences were observed at the interstitial junction point of the inv dup(1q) and of the der(12)t(7;12), respectively. The present cases and review of the literature suggest that the presence of ITSs at internal sites of the chromosomes may explain mechanisms of the patients's mosaic structural rearrangements. PMID:25428228

  18. Chitosan: a novel platform in proton-driven DNA strand rearrangement actuation.

    PubMed

    Lee, Dami; Singha, Kaushik; Jang, Mi-Kyeong; Nah, Jae-Woon; Park, In-Kyu; Kim, Won Jong

    2009-04-01

    Nanometre-scaled DNA machine based on molecular recognition properties of DNA has now become a powerful tool in nanodevices, miniaturized structure, and nanofabrication. The common principle behind designing a DNA nanomachine is DNA strand exchange or rearrangement, which is solely controlled by the stabilization through associative and dissociative forces arising from base pair interaction of DNA molecules. Thus, highly effective DNA reaction actuator will make DNA nanomachine more flexible, controllable, and powerful device. Here, we report the novel polymer-mediated platform in proton-driven DNA strand rearrangement actuation. This cationic low molecular weight water-soluble chitosan (LMWSC) exhibited pH-dependent complexation with oligodeoxynucleotides (ODN). It formed complex with ODN only at low pH and accelerated the DNA strand exchange (or rearrangement) reaction between dsDNA and its complementary ssDNA at pH 5.0. However, no complexation was observed between LMWSC and ODN at neutral pH. We assume that at physiological pH, LMWSC is not protonated enough for formation of complex with ODN. Therefore, it can not diminish the electrostatic repulsion among the negatively charged DNA strands of the three-stranded intermediate formed during the strand exchange reaction. In contrast, LMWSC becomes positively charged at acidic pH, and it stabilizes the three-stranded intermediate by spreading out the accumulated counter-ions and increasing the entropy of the system. This fascinating observation prompted us to believe that this intelligent proton-driven DNA reaction actuator has a potential for the precise control of DNA nanomachine and would be applied for operating and controlling nanoscaled machine. PMID:19396376

  19. Unusual Large-Scale Chromosomal Rearrangements in Mycobacterium tuberculosis Beijing B0/W148 Cluster Isolates

    PubMed Central

    Shitikov, Egor A.; Bespyatykh, Julia A.; Ischenko, Dmitry S.; Alexeev, Dmitry G.; Karpova, Irina Y.; Kostryukova, Elena S.; Isaeva, Yulia D.; Nosova, Elena Y.; Mokrousov, Igor V.; Vyazovaya, Anna A.; Narvskaya, Olga V.; Vishnevsky, Boris I.; Otten, Tatiana F.; Zhuravlev, Valery Y.; Yablonsky, Peter K.; Ilina, Elena N.; Govorun, Vadim M.

    2014-01-01

    The Mycobacterium tuberculosis (MTB) Beijing family isolates are geographically widespread, and there are examples of Beijing isolates that are hypervirulent and associated with drug resistance. One-fourth of Beijing genotype isolates found in Russia belong to the B0/W148 group. The aim of the present study was to investigate features of these endemic strains on a genomic level. Four Russian clinical isolates of this group were sequenced, and the data obtained was compared with published sequences of various MTB strain genomes, including genome of strain W-148 of the same B0/W148 group. The comparison of the W-148 and H37Rv genomes revealed two independent inversions of large segments of the chromosome. The same inversions were found in one of the studied strains after deep sequencing using both the fragment and mate-paired libraries. Additionally, inversions were confirmed by RFLP hybridization analysis. The discovered rearrangements were verified by PCR in all four newly sequenced strains in the study and in four additional strains of the same Beijing B0/W148 group. The other 32 MTB strains from different phylogenetic lineages were tested and revealed no inversions. We suggest that the initial largest inversion changed the orientation of the three megabase (Mb) segment of the chromosome, and the second one occurred in the previously inverted region and partly restored the orientation of the 2.1 Mb inner segment of the region. This is another remarkable example of genomic rearrangements in the MTB in addition to the recently published of large-scale duplications. The described cases suggest that large-scale genomic rearrangements in the currently circulating MTB isolates may occur more frequently than previously considered, and we hope that further studies will help to determine the exact mechanism of such events. PMID:24416324

  20. Salt Bridge Rearrangement (SaBRe) Explains the Dissociation Behavior of Noncovalent Complexes

    NASA Astrophysics Data System (ADS)

    Loo, Rachel R. Ogorzalek; Loo, Joseph A.

    2016-04-01

    Native electrospray ionization-mass spectrometry, with gas-phase activation and solution compositions that partially release subcomplexes, can elucidate topologies of macromolecular assemblies. That so much complexity can be preserved in gas-phase assemblies is remarkable, although a long-standing conundrum has been the differences between their gas- and solution-phase decompositions. Collision-induced dissociation of multimeric noncovalent complexes typically distributes products asymmetrically (i.e., by ejecting a single subunit bearing a large percentage of the excess charge). That unexpected behavior has been rationalized as one subunit "unfolding" to depart with more charge. We present an alternative explanation based on heterolytic ion-pair scission and rearrangement, a mechanism that inherently partitions charge asymmetrically. Excessive barriers to dissociation are circumvented in this manner, when local charge rearrangements access a lower-barrier surface. An implication of this ion pair consideration is that stability differences between high- and low-charge state ions usually attributed to Coulomb repulsion may, alternatively, be conveyed by attractive forces from ion pairs (salt bridges) stabilizing low-charge state ions. Should the number of ion pairs be roughly inversely related to charge, symmetric dissociations would be favored from highly charged complexes, as observed. Correlations between a gas-phase protein's size and charge reflect the quantity of restraining ion pairs. Collisionally-facilitated salt bridge rearrangement (SaBRe) may explain unusual size "contractions" seen for some activated, low charge state complexes. That some low-charged multimers preferentially cleave covalent bonds or shed small ions to disrupting noncovalent associations is also explained by greater ion pairing in low charge state complexes.

  1. Salt Bridge Rearrangement (SaBRe) Explains the Dissociation Behavior of Noncovalent Complexes

    NASA Astrophysics Data System (ADS)

    Loo, Rachel R. Ogorzalek; Loo, Joseph A.

    2016-06-01

    Native electrospray ionization-mass spectrometry, with gas-phase activation and solution compositions that partially release subcomplexes, can elucidate topologies of macromolecular assemblies. That so much complexity can be preserved in gas-phase assemblies is remarkable, although a long-standing conundrum has been the differences between their gas- and solution-phase decompositions. Collision-induced dissociation of multimeric noncovalent complexes typically distributes products asymmetrically (i.e., by ejecting a single subunit bearing a large percentage of the excess charge). That unexpected behavior has been rationalized as one subunit "unfolding" to depart with more charge. We present an alternative explanation based on heterolytic ion-pair scission and rearrangement, a mechanism that inherently partitions charge asymmetrically. Excessive barriers to dissociation are circumvented in this manner, when local charge rearrangements access a lower-barrier surface. An implication of this ion pair consideration is that stability differences between high- and low-charge state ions usually attributed to Coulomb repulsion may, alternatively, be conveyed by attractive forces from ion pairs (salt bridges) stabilizing low-charge state ions. Should the number of ion pairs be roughly inversely related to charge, symmetric dissociations would be favored from highly charged complexes, as observed. Correlations between a gas-phase protein's size and charge reflect the quantity of restraining ion pairs. Collisionally-facilitated salt bridge rearrangement (SaBRe) may explain unusual size "contractions" seen for some activated, low charge state complexes. That some low-charged multimers preferentially cleave covalent bonds or shed small ions to disrupting noncovalent associations is also explained by greater ion pairing in low charge state complexes.

  2. Rearrangement as a probe for radical formation: bromomethylcyclopropane on oxygen-covered Mo(1 1 0)

    NASA Astrophysics Data System (ADS)

    Levinson, J. A.; Kretzschmar, I.; Sheehy, M. A.; Deiner, L. J.; Friend, C. M.

    2001-05-01

    The reactions of bromomethylcyclopropane on oxygen-covered Mo(1 1 0) were studied in order to investigate the lifetimes of radical intermediates, which are important in heterogeneous oxidation catalysis. The methylcyclopropyl radical is known to rearrange on the nanosecond time scale, providing us with a means of probing for radical formation. Surprisingly, no rearrangement occurs subsequent to C-Br bond dissociation, which commences at ˜220 K. Instead, displacement of bromine by oxygen occurs to yield adsorbed methylcyclopropoxide, which is identified using infrared spectroscopy. The C-O bond of methylcyclopropoxide is cleaved at ˜400 K to yield a transient methylcyclopropyl radical. As shown previously, the methylcyclopropyl radical rearranges and the ring-opened butenyl species is trapped on the surface. Addition to oxygen yields 3-buten-1-oxy and addition to the metal affords the butenyl-Mo moiety. Infrared spectroscopy is used to identify these intermediates. The same linear species are formed from the reaction of 4-bromo-1-butene. The 3-buten-1-oxy species is also formed from reactions of 3-buten-1-ol on O-covered Mo(1 1 0). Upon further heating, the 3-buten-1-oxy reacts to form 1,3-butadiene, 1-butene, water, and dihydrogen between 450 and 600 K. Ethene is also evolved at ˜560 K. The primary mechanism for ethene evolution is elimination from metal-bound butenyl. Carbon monoxide is also formed above 900 K, due to reaction of surface carbon and oxygen. The implications of our results for studies where alkyl halides are used as models for radical reactions on surfaces are discussed.

  3. Quantum coupled-channels model of nuclear fusion with a semiclassical consideration of neutron rearrangement

    NASA Astrophysics Data System (ADS)

    Karpov, A. V.; Rachkov, V. A.; Samarin, V. V.

    2015-12-01

    Background: Significant enhancement of sub-barrier fusion cross sections owing to neutron transfer with positive Q values was observed in many combinations of colliding nuclei. This degree of freedom has not yet been included into the rigorous quantum coupled-channels (QCC) approach. However, the empirical coupled-channels model with neutron rearrangement [Zagrebaev, Phys. Rev. C 67, 061601 (2003), 10.1103/PhysRevC.67.061601] has already been successfully used in several papers to reproduce and predict cross sections for sub-barrier fusion reactions of stable nuclei. Purpose: The objective of this study is to combine the QCC approach and the empirical model to account for additional channels of neutron rearrangement. Method: Coupling of relative motion to collective degrees of freedom (rotation of nuclei and/or their surface vibrations) are taken into account within the QCC approach. The probability of transfer of x neutrons with a given Q value is estimated semiclassically. Results: The proposed new model was successfully tested on a few combinations of fusing nuclei 40Ca+90,96Zr, 32S+96,90, and 60,64Ni+100Mo. The calculated fusion cross sections and barrier distribution functions agree well with experimental data. Conclusions: The model developed in this work confirms all the conclusions previously made within the empirical coupled-channels model with neutron rearrangement [see Rachkov et al., Phys. Rev. C 90, 014614 (2014), 10.1103/PhysRevC.90.014614]. Moreover, it has an advantage of a more reliable microscopic account for the coupling between relative motion and the collective degrees of freedom. The proposed model can also be used to reproduce the structure of the barrier distribution function. This is a step forward to a complete solution of the long-term problem of accounting for neutron transfer channels in the QCC model.

  4. CREBBP re-arrangements affect protein function and lead to aberrant neuronal differentiation.

    PubMed

    Sharma, Neeti; Jadhav, Shweta P; Bapat, Sharmila A

    2010-01-01

    Biallelic inactivation of the CREB-binding protein (CREBBP) a transcriptional co-activator produces an embryonic lethal phenotype in mice. In humans, re-arrangements in CREBBP are associated with the Rubinstein-Taybi Syndrome (RSTS) that is characterised by craniofacial, skeletal and neuronal symptoms. Neuronal defects in RSTS can be attributed to genetic re-arrangements in CREBBP, which has been implicated in synaptic plasticity and long-term memory. The present study was designed to investigate the role of CREBBP re-arrangements during neuronal differentiation. Towards this, deletion constructs of pCREBBP, viz. pDeltaCB-HAT and pDeltaHAT-CT were generated and transfected into NT2 cells. Expression profiling of the components of Notch, Wnt, SHH and Retinoid signaling along with screening of the neuronal markers was carried out in the NT2 cells and their mutant derivatives. ChIP-PCRs along with co-immunoprecipitations were also performed in these cells to investigate defects due to inappropriate interaction of mutated CREEBP with the corresponding transcription factor and other transcription regulatory proteins both at steady state as well as during differentiation. Mutant NT2 cells lacking the CREB, BROMO and HAT domains (CB-HAT) were highly proliferative and showed limited differentiation; while mutant NT2 cells expressing CREBBP lacking the HAT and CTAD domains (HAT-CT) are proliferation deficient and differentiate rapidly albeit generating an insufficient number of neurons. Altered CREBBP structure resulted in changes in HAT activity, cell cycle profiles and expression of basal levels of components of Notch, SHH, Wnt and retinoid pathways known to be critical in the proliferation and differentiation of neuronal progenitors. At the chromatin level, aberrant signaling correlated with altered binding affinities of the (CREBBP-transcription factor) complexes to promoter regions of components of these pathways. Thus, differentiation defects are manifested early at

  5. The role of APCDD1 in epithelial rearrangement in tooth morphogenesis.

    PubMed

    Neupane, Sanjiv; Sohn, Wern-Joo; Gwon, Gi-Jeong; Kim, Ki-Rim; Lee, Sanggyu; An, Chang-Hyeon; Suh, Jo-Young; Shin, Hong-In; Yamamoto, Hitoshi; Cho, Sung-Won; Lee, Youngkyun; Kim, Jae-Young

    2015-10-01

    Adenomatosis polyposis coli downregulated 1 (APCDD1), a negative regulator of Wnt signaling, was examined to understand detailed mechanisms underlying Wnt signaling tooth development. In situ hybridization showed that Apcdd1 was expressed in the condensed mesenchyme at the bud stage, and in the inner enamel epithelium (IEE), including enamel knot (EK) at the cap stage. In vitro organ cultivation by using Apcdd1 antisense oligodeoxynucleotides was performed at E13.5 for 2 days to define the developmental functions of APCDD1 during tooth development. Analysis of histogenesis and cellular events such as cell adhesion, proliferation, apoptosis and epithelial rearrangement after Apcdd1 knockdown showed altered morphogenesis of the tooth germ with decreased cell proliferation and altered localization of cell adhesion molecules. Actin filament staining and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) labeling of IEE cells showed that Apcdd1 knockdown enhanced epithelial rearrangement in the IEE and EK. To understand the precise signaling regulations of Apcdd1, we evaluated the altered expression patterns of signaling molecules, related with Wnt and enamel knot signalings using RT-qPCR. Tooth germs at cap stage were transplanted into the kidney capsules and were allowed to develop into calcified teeth for 3 weeks. Apcdd1 knockdown increased the number of ectopic cusps on the mesial side of the tooth. Our results suggested that APCDD1 modulates the gene expression of Wnt- and EK-related signaling molecules at the cap stage of tooth development, and is involved in tooth cusp patterning by modulating the epithelial rearrangement in the IEE. PMID:26170146

  6. Mechanisms for nonrecurrent genomic rearrangements associated with CMT1A or HNPP: rare CNVs as a cause for missing heritability.

    PubMed

    Zhang, Feng; Seeman, Pavel; Liu, Pengfei; Weterman, Marian A J; Gonzaga-Jauregui, Claudia; Towne, Charles F; Batish, Sat Dev; De Vriendt, Els; De Jonghe, Peter; Rautenstrauss, Bernd; Krause, Klaus-Henning; Khajavi, Mehrdad; Posadka, Jan; Vandenberghe, Antoon; Palau, Francesc; Van Maldergem, Lionel; Baas, Frank; Timmerman, Vincent; Lupski, James R

    2010-06-11

    Genomic rearrangements involving the peripheral myelin protein gene (PMP22) in human chromosome 17p12 are associated with neuropathy: duplications cause Charcot-Marie-Tooth disease type 1A (CMT1A), whereas deletions lead to hereditary neuropathy with liability to pressure palsies (HNPP). Our previous studies showed that >99% of these rearrangements are recurrent and mediated by nonallelic homologous recombination (NAHR). Rare copy number variations (CNVs) generated by nonrecurrent rearrangements also exist in 17p12, but their underlying mechanisms are not well understood. We investigated 21 subjects with rare CNVs associated with CMT1A or HNPP by oligonucleotide-based comparative genomic hybridization microarrays and breakpoint sequence analyses, and we identified 17 unique CNVs, including two genomic deletions, ten genomic duplications, two complex rearrangements, and three small exonic deletions. Each of these CNVs includes either the entire PMP22 gene, or exon(s) only, or ultraconserved potential regulatory sequences upstream of PMP22, further supporting the contention that PMP22 is the critical gene mediating the neuropathy phenotypes associated with 17p12 rearrangements. Breakpoint sequence analysis reveals that, different from the predominant NAHR mechanism in recurrent rearrangement, various molecular mechanisms, including nonhomologous end joining, Alu-Alu-mediated recombination, and replication-based mechanisms (e.g., FoSTeS and/or MMBIR), can generate nonrecurrent 17p12 rearrangements associated with neuropathy. We document a multitude of ways in which gene function can be altered by CNVs. Given the characteristics, including small size, structural complexity, and location outside of coding regions, of selected rare CNVs, their identification remains a challenge for genome analysis. Rare CNVs may potentially represent an important portion of "missing heritability" for human diseases. PMID:20493460

  7. Genetic and clinical characterization of 45 acute leukemia patients with MLL gene rearrangements from a single institution.

    PubMed

    Cerveira, Nuno; Lisboa, Susana; Correia, Cecília; Bizarro, Susana; Santos, Joana; Torres, Lurdes; Vieira, Joana; Barros-Silva, João D; Pereira, Dulcineia; Moreira, Cláudia; Meyer, Claus; Oliva, Tereza; Moreira, Ilídia; Martins, Ângelo; Viterbo, Luísa; Costa, Vítor; Marschalek, Rolf; Pinto, Armando; Mariz, José M; Teixeira, Manuel R

    2012-10-01

    Chromosomal rearrangements affecting the MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemia. In this study, conventional cytogenetic, fluorescence in situ hybridization, and molecular genetic studies were used to characterize the type and frequency of MLL rearrangements in a consecutive series of 45 Portuguese patients with MLL-related leukemia treated in a single institution between 1998 and 2011. In the group of patients with acute lymphoblastic leukemia and an identified MLL fusion partner, 47% showed the presence of an MLL-AFF1 fusion, as a result of a t(4;11). In the remaining cases, a MLL-MLLT3 (27%), a MLL-MLLT1 (20%), or MLL-MLLT4 (7%) rearrangement was found. The most frequent rearrangement found in patients with acute myeloid leukemia was the MLL-MLLT3 fusion (42%), followed by MLL-MLLT10 (23%), MLL-MLLT1 (8%), MLL-ELL (8%), MLL-MLLT4 (4%), and MLL-MLLT11 (4%). In three patients, fusions involving MLL and a septin family gene (SEPT2, SEPT6, and SEPT9), were identified. The most frequently identified chromosomal rearrangements were reciprocal translocations, but insertions and deletions, some cryptic, were also observed. In our series, patients with MLL rearrangements were shown to have a poor prognosis, regardless of leukemia subtype. Interestingly, children with 1 year or less showed a statistically significant better overall survival when compared with both older children and adults. The use of a combined strategy in the initial genetic evaluation of acute leukemia patients allowed us to characterize the pattern of MLL rearrangements in our institution, including our previous discovery of two novel MLL fusion partners, the SEPT2 and CT45A2 genes, and a very rare MLL-MLLT4 fusion variant. PMID:22846743

  8. RET/PTC rearrangements preferentially occurred in papillary thyroid cancer among atomic bomb survivors exposed to high radiation dose.

    PubMed

    Hamatani, Kiyohiro; Eguchi, Hidetaka; Ito, Reiko; Mukai, Mayumi; Takahashi, Keiko; Taga, Masataka; Imai, Kazue; Cologne, John; Soda, Midori; Arihiro, Koji; Fujihara, Megumu; Abe, Kuniko; Hayashi, Tomayoshi; Nakashima, Masahiro; Sekine, Ichiro; Yasui, Wataru; Hayashi, Yuzo; Nakachi, Kei

    2008-09-01

    A major early event in papillary thyroid carcinogenesis is constitutive activation of the mitogen-activated protein kinase signaling pathway caused by alterations of a single gene, typically rearrangements of the RET and NTRK1 genes or point mutations in the BRAF and RAS genes. In childhood papillary thyroid cancer, regardless of history of radiation exposure, RET/PTC rearrangements are a major event. Conversely, in adult-onset papillary thyroid cancer among the general population, the most common molecular event is BRAF(V600E) point mutation, not RET/PTC rearrangements. To clarify which gene alteration, chromosome aberration, or point mutation preferentially occurs in radiation-associated adult-onset papillary thyroid cancer, we have performed molecular analyses on RET/PTC rearrangements and BRAF(V600E) mutation in 71 papillary thyroid cancer cases among atomic bomb survivors (including 21 cases not exposed to atomic bomb radiation), in relation to radiation dose as well as time elapsed since atomic bomb radiation exposure. RET/PTC rearrangements showed significantly increased frequency with increased radiation dose (P(trend) = 0.002). In contrast, BRAF(V600E) mutation was less frequent in cases exposed to higher radiation dose (P(trend) < 0.001). Papillary thyroid cancer subjects harboring RET/PTC rearrangements developed this cancer earlier than did cases with BRAF(V600E) mutation (P = 0.03). These findings were confirmed by multivariate logistic regression analysis. These results suggest that RET/PTC rearrangements play an important role in radiation-associated thyroid carcinogenesis. PMID:18757433

  9. Actin cytoskeleton rearrangements in Arabidopsis roots under stress and during gravitropic response

    NASA Astrophysics Data System (ADS)

    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

  10. Synthesis and reactivity of nitrogen nucleophiles-induced cage-rearrangement silsesquioxanes.

    PubMed

    Jaroentomeechai, Thapakorn; Yingsukkamol, Pa-Kwan; Phurat, Chuttree; Somsook, Ekasith; Osotchan, Tanakorn; Ervithayasuporn, Vuthichai

    2012-11-19

    Novel phthalimide and o-sulfobenzimide-functionalized silsesquioxanes were successfully synthesized via nucleophilic substitution reactions from octakis(3-chloropropyl)octasilsesquioxane. Surprisingly, the formation of deca- and dodecasilsesquioxanes cages was discovered during substitution with phthalimide, but only octasilsesquioxane maintained a cage in the o-sulfobenzimide substitution reaction. Moreover, we report the electronic effect of nitrogen nucleophiles to promote cage-rearrangement of inorganic silsesquioxane core for the first time. Structures of products were confirmed by (1)H, (13)C, and (29)Si NMR spectroscopy, ESI-MS analysis, and single-crystal X-ray diffraction. PMID:23134535

  11. The first example of the Fischer–Hepp type rearrangement in pyrimidines

    PubMed Central

    Jonusis, Mantas; Jakubkiene, Virginija

    2013-01-01

    Summary A N-nitroso moiety can be used for the activation of chloropyrimidines toward a nucleophilic substitution reaction with amines. The subsequent treatment of the obtained products with aq H2SO4 can lead to either N-denitrosation to obtain 4,6-pyrimidinediamines or to a Fischer–Hepp type rearrangement to obtain 5-nitroso-4,6-pyrimidinediamines. It was found that the outcome of the reaction strongly depends on the structure of the pyrimidines. Activation of the pyrimidine ring by three groups with a positive mesomeric effect is crucial for the intramolecular nitroso group migration. PMID:24062848

  12. Gross chromosome rearrangements are occurring in an accession of the grass Lolium rigidum.

    PubMed

    Thomas, H M; Harper, J A; Morgan, W G

    2001-01-01

    Chromosome structure was analysed at mitosis in root tip meristems of eight genotypes of Lolium rigidum. FISH revealed changed positions in the rDNA sites indicating extensive chromosome rearrangements; indeed no two genotypes were the same. In one genotype, there were differences between cells within individual root tips. The changed positions of the rDNA sites appear to be reflections of chromosome translocations and this was confirmed by the presence of quadrivalents at metaphase I of meiosis. Possible mechanisms are discussed for this exceptional level of chromosome instability. PMID:11721955

  13. Toward Singlet-Triplet Bistable Nonalternant Kekulé Hydrocarbons: Azulene-to-Naphthalene Rearrangement.

    PubMed

    Das, Soumyajit; Wu, Jishan

    2015-12-01

    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. PMID:26569547

  14. Stereochemistry of valine biosynthesis. Configuration of the product of rearrangement of alpha-acetolactate.

    PubMed

    Crout, D H; Hedgecock, C J; Lipscomb, E L; Armstrong, F B

    1980-09-01

    When alpha-aceto[1,3,5-13C3]lactate (2-hydroxy-2-methyl-3-oxo[1,3,5-13C3]butanoate) was incubated with a cell-free system prepared from Salmonella typhimurium, the valine produced was labelled in the C-4 pro-S position. This result proves that during the tertiary ketol rearrangement catalysed by the reductoisomerase of the isoleucine-valine pathway, the methyl group transfer is to the re face of the trigonal centre at C-3 of alpha-acetolactate. PMID:7002550

  15. Molecular Rearrangement of an Aza-Scorpiand Macrocycle Induced by pH: A Computational Study.

    PubMed

    De Julián-Ortiz, Jesus Vicente; Verdejo, Begoña; Polo, Víctor; Besalú, Emili; García-España, Enrique

    2016-01-01

    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. PMID:27428955

  16. Quantum description of coupling to neutron-rearrangement channels in fusion reactions near the Coulomb barrier

    SciTech Connect

    Samarin, V. V.

    2015-10-15

    The fusion cross sections for the {sup 17,18}O+{sup 27}Al, {sup 18}O+{sup 58}Ni, and {sup 6}He+{sup 197}Au reactions were calculated by the coupled-channel method. The radial dependence of matrices that describe coupling to valence-neutron-rearrangement channels was determined with the aid of two-center wave functions. The coupling-strength parameters were evaluated on the basis of numerically solving the time-dependent Schrödinger equation. Satisfactory agreement with experimental data was obtained.

  17. Cooperative rearranging region size and free volume in As-Se glasses.

    PubMed

    Saiter, A; Saiter, J-M; Golovchak, R; Shpotyuk, M; Shpotyuk, O

    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 Å(3) leads to a significant decrease in the CRR size. PMID:21817320

  18. Energy barrier by cyclopropylchlorocarbene rearrangement measured by direct observation of the carbene in laser flash spectroscopy

    SciTech Connect

    Liu, M.T.H.; Bonneau, R. )

    1989-10-19

    A transient absorption in the 250-265-nm range is assigned to cyclopropylchlorocarbene generated from the laser flash photolysis of 3-chloro-3-cyclopropyldiazirine. Confidence in this assignment was obtained from the following: (a) the decay of this absorption matches the growth of the pyridinium ylide: (b) the values for the rate constant for reaction of the carbene with 1-hexane obtained by monitoring the carbene at 250 nm and the ylide at 370 nm are similar. The kinetic parameters for the rearrangement of cyclopropylchlorocarbene to 1-chlorocyclobutene are log A = 11.1 and E{sub a} = 7.4 kcal/mol.

  19. Free electron laser-driven ultrafast rearrangement of the electronic structure in Ti

    PubMed Central

    Principi, E.; Giangrisostomi, E.; Cucini, R.; Bencivenga, F.; Battistoni, A.; Gessini, A.; Mincigrucci, R.; Saito, M.; Di Fonzo, S.; D'Amico, F.; Di Cicco, A.; Gunnella, R.; Filipponi, A.; Giglia, A.; Nannarone, S.; Masciovecchio, C.

    2015-01-01

    High-energy density extreme ultraviolet radiation delivered by the FERMI seeded free-electron laser has been used to create an exotic nonequilibrium state of matter in a titanium sample characterized by a highly excited electron subsystem at temperatures in excess of 10 eV and a cold solid-density ion lattice. The obtained transient state has been investigated through ultrafast absorption spectroscopy across the Ti M2,3-edge revealing a drastic rearrangement of the sample electronic structure around the Fermi level occurring on a time scale of about 100 fs. PMID:26798835

  20. The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

    PubMed Central

    Adanitsch, Florian; Stütz, Arnold E

    2012-01-01

    Summary The Amadori rearrangement was investigated as a potential method for the conjugation of carbohydrate moieties to suitable amino components. Starting from selected aldoheptoses, which are readily available by means of the Kiliani–Fischer C-elongation reaction of the corresponding aldohexoses, glycoconjugates presenting D-gluco, D-manno and D-galacto as well as GlcNAc motifs have been synthesised. Following this strategy, non-natural C-glycosyl type glycoconjugates, which can be utilised as building blocks for the composition of larger molecular constructions, are available by a very short synthetic approach. PMID:23209494

  1. Sigmatropic Rearrangement of Vinyl Aziridines: Expedient Synthesis of Cyclic Sulfoximines from Chiral Sulfinimines.

    PubMed

    Moragas, Toni; Liffey, Ryan M; Regentová, Dominika; Ward, Jon-Paul S; Dutton, Justine; Lewis, William; Churcher, Ian; Walton, Lesley; Souto, José A; Stockman, Robert A

    2016-08-16

    A novel rearrangement of 2-vinyl aziridine 2-carboxylates to unusual chiral cyclic sulfoximines is described herein. The method allows the synthesis of substituted cyclic sulfoximines in high yields with complete stereocontrol, and tolerates a wide substrate scope. A one-pot process starting directly from sulfinimines provides access to complex chiral sulfoximines in only two steps from commercially available aldehydes. A mechanistic hypothesis and synthetic application in the formal synthesis of trachelanthamidine, by transformation of a cyclic sulfoximine into a pyrroline, is also disclosed. PMID:27409574

  2. Mitogenomic sequences and evidence from unique gene rearrangements corroborate evolutionary relationships of myctophiformes (Neoteleostei)

    PubMed Central

    2013-01-01

    Background A skewed assemblage of two epi-, meso- and bathypelagic fish families makes up the order Myctophiformes – the blackchins Neoscopelidae and the lanternfishes Myctophidae. The six rare neoscopelids show few morphological specializations whereas the divergent myctophids have evolved into about 250 species, of which many show massive abundances and wide distributions. In fact, Myctophidae is by far the most abundant fish family in the world, with plausible estimates of more than half of the oceans combined fish biomass. Myctophids possess a unique communication system of species-specific photophore patterns and traditional intrafamilial classification has been established to reflect arrangements of photophores. Myctophids present the most diverse array of larval body forms found in fishes although this attribute has both corroborated and confounded phylogenetic hypotheses based on adult morphology. No molecular phylogeny is available for Myctophiformes, despite their importance within all ocean trophic cycles, open-ocean speciation and as an important part of neoteleost divergence. This study attempts to resolve major myctophiform phylogenies from both mitogenomic sequences and corroborating evidence in the form of unique mitochondrial gene order rearrangements. Results Mitogenomic evidence from DNA sequences and unique gene orders are highly congruent concerning phylogenetic resolution on several myctophiform classification levels, corroborating evidence from osteology, larval ontogeny and photophore patterns, although the lack of larval morphological characters within the subfamily Lampanyctinae stands out. Neoscopelidae is resolved as the sister family to myctophids with Solivomer arenidens positioned as a sister taxon to the remaining neoscopelids. The enigmatic Notolychnus valdiviae is placed as a sister taxon to all other myctophids and exhibits an unusual second copy of the tRNA-Met gene – a gene order rearrangement reminiscent of that found in

  3. Biogenetically Inspired Synthesis of Lingzhiol.

    PubMed

    Sharmah Gautam, Krishna; Birman, Vladimir B

    2016-04-01

    A concise stereo- and enantioselective synthesis of lingzhiol has been achieved featuring a biogenetically inspired Brønsted acid catalyzed semipinacol rearrangement of a glycidyl alcohol intermediate. PMID:26974229

  4. Rearranged Anaplastic Lymphoma Kinase (ALK) Gene in Adult-Onset Papillary Thyroid Cancer Amongst Atomic Bomb Survivors

    PubMed Central

    Mukai, Mayumi; Takahashi, Keiko; Hayashi, Yuzo; Nakachi, Kei; Kusunoki, Yoichiro

    2012-01-01

    Background We previously noted that among atomic bomb survivors (ABS), the relative frequency of cases of adult papillary thyroid cancer (PTC) with chromosomal rearrangements (mainly RET/PTC) was significantly greater in those with relatively higher radiation exposure than those with lower radiation exposure. In contrast, the frequency of PTC cases with point mutations (mainly BRAFV600E) was significantly lower in patients with relatively higher radiation exposure than those with lower radiation exposure. We also found that among ABS, the frequency of PTC cases with no detectable gene alterations in RET, neurotrophic tyrosine kinase receptor 1 (NTRK1), BRAF, or RAS was significantly higher in patients with relatively higher radiation exposure than those with lower radiation exposure. However, in ABS with PTC, the relationship between the presence of the anaplastic lymphoma kinase (ALK) gene fused with other gene partners and radiation exposure has received little study. In this study, we tested the hypothesis that the relative frequency of rearranged ALK in ABS with PTC, and with no detectable gene alterations in RET, NTRK1, BRAF, or RAS, would be greater in those having relatively higher radiation exposures. Methods The 105 subjects in the study were drawn from the Life Span Study cohort of ABS of Hiroshima and Nagasaki who were diagnosed with PTC between 1956 and 1993. Seventy-nine were exposed (>0 mGy), and 26 were not exposed to A-bomb radiation. In the 25 ABS with PTC, and with no detectable gene alterations in RET, NTRK1, BRAF, or RAS, we examined archival, formalin-fixed, paraffin-embedded PTC specimens for rearrangement of ALK using reverse transcription–polymerase chain reaction and 5′ rapid amplification of cDNA ends (5′ RACE). Results We found rearranged ALK in 10 of 19 radiation-exposed PTC cases, but none among 6 patients with PTC with no radiation exposure. In addition, solid/trabecular-like architecture in PTC was closely associated with ALK

  5. Association between BRAF and RAS mutations, and RET rearrangements and the clinical features of papillary thyroid cancer

    PubMed Central

    Ming, Jie; Liu, Zeming; Zeng, Wen; Maimaiti, Yusufu; Guo, Yawen; Nie, Xiu; Chen, Chen; Zhao, Xiangwang; Shi, Lan; Liu, Chunping; Huang, Tao

    2015-01-01

    Objective: To evaluate the significance of BRAF V600E and Ras mutations, and RET rearrangements in papillary thyroid cancer (PTC) in the South central region of China. Methods: We included patients from Union hospital’s pathology archive diagnosed with PTC and meeting the criteria for BRAF mutation, RAS mutation, and RET rearrangement testing. Medical records were analyzed for BRAF and RAS mutation status, RET rearrangements (positive or negative), and a list of standardized clinicopathologic features. Results: Positive BRAF mutation was found to be significantly associated with age and extrathyroidal extension (P=0.011 and P=0.013, respectively). However, there was no significant association between BRAF mutation and sex, tumor size, histological subtype, multifocality, or accompanying nodular goiter and Hashimoto’s. On the other hand, none of these characteristics of PTC were been found to be associated with RAS mutation. Additionally, the frequency of RET rearrangements was higher in patients ≤45 years old than that in patients >45 years old. Conclusions: We demonstrated that the BRAF V600E mutation slightly correlated with the clinicopathological characteristics of PTC in the Han population. Furthermore, neither RAS mutation nor RET rearrangements were found to be associated with the clinicopathological characteristics of PTCs. Our work provides useful information on somatic mutations to predict the risk of PTC in different ethnic groups. PMID:26823860

  6. Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

    SciTech Connect

    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. Droplet Digital PCR for Absolute Quantification of EML4-ALK Gene Rearrangement in Lung Adenocarcinoma.

    PubMed

    Wang, Qiushi; Yang, Xin; He, Yong; Ma, Qiang; Lin, Li; Fu, Ping; Xiao, Hualiang

    2015-09-01

    Crizotinib treatment significantly prolongs progression-free survival, increases response rates, and improves the quality of life in patients with ALK-positive non-small-cell lung cancer. Droplet Digital PCR (ddPCR), a recently developed technique with high sensitivity and specificity, was used in this study to evaluate the association between the abundance of ALK rearrangements and crizotinib effectiveness. FFPE tissues were obtained from 103 consecutive patients with lung adenocarcinoma. Fluorescent in situ hybridization (FISH) and ddPCR were performed. The results revealed that 14 (13.6%) of the 103 patients were positive by dual-color, break-apart FISH. Three variants (1, 2, and 3) of the EML4-ALK gene rearrangements were detected. Thirteen of 14 ALK-positive cases identified by FISH were confirmed by ddPCR (four with variant 1, two with variant 2, and seven with variant 3). The case missed by ddPCR was identified as KIF5B-ALK gene rearrangement by PCR-based direct sequencing. Sixteen patients were detected with low copy numbers of EML4-ALK gene rearrangement, which failed to meet the positive cutoff point of FISH. Two of them responded well to crizotinib after unsuccessful chemotherapy. Our study indicates that ddPCR can be used as a molecular analytical tool to accurately measure the EML4-ALK rearrangement copy numbers in FFPE samples of lung adenocarcinoma patients. PMID:26142544

  8. Comparative Mitogenomics of the Genus Odontobutis (Perciformes: Gobioidei: Odontobutidae) Revealed Conserved Gene Rearrangement and High Sequence Variations

    PubMed Central

    Ma, Zhihong; Yang, Xuefen; Bercsenyi, Miklos; Wu, Junjie; Yu, Yongyao; Wei, Kaijian; Fan, Qixue; Yang, Ruibin

    2015-01-01

    To understand the molecular evolution of mitochondrial genomes (mitogenomes) in the genus Odontobutis, the mitogenome of Odontobutis yaluensis was sequenced and compared with those of another four Odontobutis species. Our results displayed similar mitogenome features among species in genome organization, base composition, codon usage, and gene rearrangement. The identical gene rearrangement of trnS-trnL-trnH tRNA cluster observed in mitogenomes of these five closely related freshwater sleepers suggests that this unique gene order is conserved within Odontobutis. Additionally, the present gene order and the positions of associated intergenic spacers of these Odontobutis mitogenomes indicate that this unusual gene rearrangement results from tandem duplication and random loss of large-scale gene regions. Moreover, these mitogenomes exhibit a high level of sequence variation, mainly due to the differences of corresponding intergenic sequences in gene rearrangement regions and the heterogeneity of tandem repeats in the control regions. Phylogenetic analyses support Odontobutis species with shared gene rearrangement forming a monophyletic group, and the interspecific phylogenetic relationships are associated with structural differences among their mitogenomes. The present study contributes to understanding the evolutionary patterns of Odontobutidae species. PMID:26492246

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

    PubMed Central

    Ohlsson, Ewa; Hasemann, Marie Sigurd; Willer, Anton; Lauridsen, Felicia Kathrine Bratt; Rapin, Nicolas; Jendholm, Johan

    2014-01-01

    MLL-fusion proteins are potent inducers of oncogenic transformation, and their expression is considered to be the main oncogenic driving force in ∼10% of human acute myeloid leukemia (AML) patients. These oncogenic fusion proteins are responsible for the initiation of a downstream transcriptional program leading to the expression of factors such as MEIS1 and HOXA9, which in turn can replace MLL-fusion proteins in overexpression experiments. To what extent MLL fusion proteins act on their own during tumor initiation, or if they collaborate with other transcriptional regulators, is unclear. Here, we 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 to MLL-ENL–induced leukemic transformation, whereas C/EBPα was dispensable in already established AMLs. Furthermore, we show that Cebpa-deficient granulocytic-monocytic progenitors were equally resistant to transformation and that C/EBPα collaborates with MLL-ENL in the induction of a transcriptional program, which is also apparent in human AML. Thus, our studies demonstrate a key role of C/EBPα in MLL fusion–driven transformation and find that it sharply demarcates tumor initiation and maintenance. PMID:24367003

  10. Selective Sirt2 inhibition by ligand-induced rearrangement of the active site

    PubMed Central

    Rumpf, Tobias; Schiedel, Matthias; Karaman, Berin; Roessler, Claudia; North, Brian J.; Lehotzky, Attila; Oláh, Judit; Ladwein, Kathrin I.; Schmidtkunz, Karin; Gajer, Markus; Pannek, Martin; Steegborn, Clemens; Sinclair, David A.; Gerhardt, Stefan; Ovádi, Judit; Schutkowski, Mike; Sippl, Wolfgang; Einsle, Oliver; Jung, Manfred

    2015-01-01

    Sirtuins are a highly conserved class of NAD+-dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis of cancer, inflammation and neurodegeneration, which makes the modulation of Sirt2 activity a promising strategy for pharmaceutical intervention. A rational basis for the development of optimized Sirt2 inhibitors is lacking so far. Here we present high-resolution structures of human Sirt2 in complex with highly selective drug-like inhibitors that show a unique inhibitory mechanism. Potency and the unprecedented Sirt2 selectivity are based on a ligand-induced structural rearrangement of the active site unveiling a yet-unexploited binding pocket. Application of the most potent Sirtuin-rearranging ligand, termed SirReal2, leads to tubulin hyperacetylation in HeLa cells and induces destabilization of the checkpoint protein BubR1, consistent with Sirt2 inhibition in vivo. Our structural insights into this unique mechanism of selective sirtuin inhibition provide the basis for further inhibitor development and selective tools for sirtuin biology. PMID:25672491

  11. Theoretical study of the mechanism of the rearrangement-cleavage reactions of allylenammonium salts

    SciTech Connect

    Kletskii, M.E.; Minkin, V.I.; Babayan, A.T.

    1988-03-10

    In a theoretical study of the mechanism of the rearrangement-cleavage of tetra-substituted ammonium salts containing 1,2- and 3,4-unsaturated groups using the CNDO/2 and MINDO/3 semiempirical methods, calculations were carried out to determine the electron density in trimethylvinylammonium, trimethylethynylammonium, and phosphonium cations and the minimal energy pathways for the 3,3-sigmatropic shift reactions in the vinylallylammonium cation and of the product of the /alpha/-addition of a hydride ion to it (nucleophilic catalysis model). According to the calculation data, the nucleophilic attack of enammonium compounds in basic media is directed toward the /alpha/-position of the 1,2-unsaturated group. The driving force for the rearrangement-cleavage is the attack of the /alpha/-position by the nucleophile which results in intramolecular C-alkylation by a concerted 3,3-sigmatropic shift mechanism. The calculated activation barrier of the catalyzed reaction (15.8 kcal/mole) is 7.4 kcal/mole lower than in the absence of nucleophilic action.

  12. Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation

    PubMed Central

    Lorenc, Chris; Saurí, Josep; Moser, Arvin; Buevich, Alexei V; Williams, Antony J; Williamson, R Thomas; Martin, Gary E; Peczuh, Mark W

    2015-01-01

    Spiroketals organize small molecule structures into well-defined, three-dimensional configurations that make them good ligands of proteins. We recently discovered a tandem cycloisomerization–dimerization reaction of alkynyl hemiketals that delivered polycyclic, enol-ether-containing spiroketals. Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them “inside out”. Due to the high level of substitution on the carbon skeletons of the substrates and products, characterization resorted to X-ray crystallography and advanced computation and NMR techniques to solve the structures of representative compounds. In particular, a new proton-detected ADEQUATE NMR experiment (1,1-HD-ADEQUATE) enabled the unequivocal assignment of the carbon skeleton of one of the new compounds. Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series. Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds. PMID:26491634

  13. Genomic rearrangements and the evolution of clusters of locally adaptive loci

    PubMed Central

    Yeaman, Sam

    2013-01-01

    Numerous studies of ecological genetics have found that alleles contributing to local adaptation sometimes cluster together, forming “genomic islands of divergence.” Divergence hitchhiking theory posits that these clusters evolve by the preferential establishment of tightly linked locally adapted mutations, because such linkage reduces the rate that recombination breaks up locally favorable combinations of alleles. Here, I use calculations based on previously developed analytical models of divergence hitchhiking to show that very few clustered mutations should be expected in a single bout of adaptation, relative to the number of unlinked mutations, suggesting that divergence hitchhiking theory alone may often be insufficient to explain empirical observations. Using individual-based simulations that allow for the transposition of a single genetic locus from one position on a chromosome to another, I then show that tight clustering of the loci involved in local adaptation tends to evolve on biologically realistic time scales. These results suggest that genomic rearrangements may often be an important component of local adaptation and the evolution of genomic islands of divergence. More generally, these results suggest that genomic architecture and functional neighborhoods of genes may be actively shaped by natural selection in heterogeneous environments. Because small-scale changes in gene order are relatively common in some taxa, comparative genomic studies could be coupled with studies of adaptation to explore how commonly such rearrangements are involved in local adaptation. PMID:23610436

  14. Characterizing local forces and rearrangements inside a gravity-driven granular flow

    NASA Astrophysics Data System (ADS)

    Thackray, Emma; Nordstrom, Kerstin

    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 well-understood. 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 and by adding external forcing to the top of the flowing pile. 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. We are therefore able to correlate local forces with rearrangements within the system, and characterize the evolution of this interplay on the approach to the clogging transition.

  15. Structural Rearrangements in CHO Cells After Disruption of Individual Cytoskeletal Elements and Plasma Membrane.

    PubMed

    Jokhadar, Špela Zemljič; Derganc, Jure

    2015-04-01

    Cellular structural integrity is provided primarily by the cytoskeleton, which comprises microtubules, actin filaments, and intermediate filaments. The plasma membrane has been also recognized as a mediator of physical forces, yet its contribution to the structural integrity of the cell as a whole is less clear. In order to investigate the relationship between the plasma membrane and the cytoskeleton, we selectively disrupted the plasma membrane and each of the cytoskeletal elements in Chinese hamster ovary cells and assessed subsequent changes in cellular structural integrity. Confocal microscopy was used to visualize cytoskeletal rearrangements, and optical tweezers were utilized to quantify membrane tether extraction. We found that cholesterol depletion from the plasma membrane resulted in rearrangements of all cytoskeletal elements. Conversely, the state of the plasma membrane, as assessed by tether extraction, was affected by disruption of any of the cytoskeletal elements, including microtubules and intermediate filaments, which are located mainly in the cell interior. The results demonstrate that, besides the cytoskeleton, the plasma membrane is an important contributor to cellular integrity, possibly by acting as an essential framework for cytoskeletal anchoring. In agreement with the tensegrity model of cell mechanics, our results support the notion of the cell as a prestressed structure. PMID:25395197

  16. Enantioselective Total Syntheses of Various Amphilectane and Serrulatane Diterpenoids via Cope Rearrangements.

    PubMed

    Yu, Xuerong; Su, Fan; Liu, Chang; Yuan, Haosen; Zhao, Shan; Zhou, Zhiyao; Quan, Tianfei; Luo, Tuoping

    2016-05-18

    Ampilectane and serrulatane natural products are structurally and stereochemically complex compounds that display various potent pharmacological activities ranging from anti-inflammatory to antituberculosis. A general synthetic route toward this family of natural products has been developed, which accomplished a number of amphilectane and serrulatane natural products. The key step employed a stereoselective Cope rearrangement either promoted by gold catalysis or thermal conditions, while a regioselective gold-catalyzed 6-endo-dig cyclization was optimized to afford a precursor. The preparation of the chiral β-ketoester as a starting material was established via an optimized asymmetric 1,4-addition followed by trapping with Mander's reagent, and this initially installed stereogenic center provided good control in the subsequent introduction of all the other stereocenters. A rarely investigated one-pot conversion of α-pyrone into phenol was also examined to enable the syntheses. DFT calculations explain the high stereoselectivity of the Cope rearrangement of the intermediate that eventually led to amphilectolide and caribenol A. PMID:27115064

  17. Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase.

    PubMed

    Klein, Tobias; Vajpai, Navratna; Phillips, Jonathan J; Davies, Gareth; Holdgate, Geoffrey A; Phillips, Chris; Tucker, Julie A; Norman, Richard A; Scott, Andrew D; Higazi, Daniel R; Lowe, David; Thompson, Gary S; Breeze, Alexander L

    2015-01-01

    Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp-Phe-Gly (DFG) motif of the activation loop, with some, including FGFR1 kinase, appearing refractory to this so-called 'DFG flip'. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the first time in a 'DFG-out' state. Here we use conformationally selective inhibitors as chemical probes for interrogation of the structural and dynamic features that appear to govern the DFG flip in FGFR1. Our detailed structural and biophysical insights identify contributions from altered dynamics in distal elements, including the αH helix, towards the outstanding stability of the DFG-out complex with the inhibitor ponatinib. We conclude that the αC-β4 loop and 'molecular brake' regions together impose a high energy barrier for this conformational rearrangement, and that this may have significance for maintaining autoinhibition in the non-phosphorylated basal state of FGFR1. PMID:26203596

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

    PubMed

    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

    2016-01-01

    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. PMID:26384565

  19. Testing for anaplastic lymphoma kinase rearrangement to target crizotinib therapy: oncology, pathology and health economic perspectives.

    PubMed

    Lee, James A; Bubendorf, Lukas; Stahel, Rolf; Peters, Solange

    2013-05-01

    Crizotinib is a first-in-class oral anaplastic lymphoma kinase (ALK) inhibitor targeting ALK-rearranged non-small-cell lung cancer. The therapy was approved by the US FDA in August 2011 and received conditional marketing approval by the European Commission in October 2012 for advanced non-small-cell lung cancer. A break-apart FISH-based assay was jointly approved with crizotinib by the FDA. This assay and an immunohistochemistry assay that uses a D5F3 rabbit monoclonal primary antibody were also approved for marketing in Europe in October 2012. While ALK rearrangement has relatively low prevalence, a clinical benefit is exhibited in more than 85% of patients with median progression-free survival of 8-10 months. In this article, the authors summarize the therapy and alternative test strategies for identifying patients who are likely to respond to therapy, including key issues for effective and efficient testing. The key economic considerations regarding the joint companion diagnostic and therapy are also presented. Given the observed clinical benefit and relatively high cost of crizotinib therapy, companion diagnostics should be evaluated relative to response to therapy versus correlation alone whenever possible, and both high inter-rater reliability and external quality assessment programs are warranted. PMID:23617353

  20. A new dopachrome-rearranging enzyme from the ejected ink of the cuttlefish Sepia officinalis.

    PubMed Central

    Palumbo, A; d'Ischia, M; Misuraca, G; De Martino, L; Prota, G

    1994-01-01

    A melanogenic enzyme catalysing the rearrangement of dopachrome has been identified in the ejected ink of the cuttlefish Sepia officinalis. This enzyme occurs as a heat-labile protein which co-migrates with tyrosinase under a variety of chromatographic and electrophoretic conditions. On SDS/PAGE it shows like a single band with an approx. molecular mass of 85 kDa. The enzyme possesses high substrate specificity, acting on L-dopachrome (Km = 1 mM at pH 6.8) and on L-alpha-methyl-dopachrome, but not on D-dopachrome, L-dopachrome methyl ester, dopaminochrome and adrenochrome. Significant inhibition of the catalytic activity was observed with tropolone and L-mimosine. H.p.1.c. analysis of the enzyme-catalysed rearrangement of L-dopachrome revealed the quantitative formation of the decarboxylated product, 5,6-dihydroxyindole. These results point to marked differences between melanogenesis in cephalopod pigment cells and in melanocytes, which may have important implications in relation to the use of sepiomelanin as a model for studies of mammalian melanins. Images Figure 2 PMID:8192674