Developmental expression profile of the yy2 gene in mice

<p>Abstract</p> <p>Background</p> <p>The transcription factor Yin Yang 2 (YY2) shares a structural and functional highly homologue DNA-binding domain with the ubiquitously expressed YY1 protein, which has been implicated in regulating fundamental biological processes. However, the biological relevance of YY2 has not been identified yet.</p> <p>Results</p> <p>Towards the understanding of YY2 biology, we analyzed in detail the expression pattern of <it>yy</it>2 in various organs during embryonic and postnatal mouse development till adulthood. Thereby, a constant <it>yy2 </it>level was detected in heart and lung tissue, whereas in different brain regions <it>yy2 </it>expression was dynamically regulated. Interestingly, in any analyzed tissue neither the homologue <it>yy1 </it>nor the <it>mbtps2 </it>gene showed changes in mRNA expression levels like <it>yy2</it>, although the intronless <it>yy2 </it>gene is located within the <it>mbtps2 </it>locus.</p> <p>Furthermore, we detected <it>yy1</it>, <it>yy2</it>, and <it>mbtps2 </it>mRNA in primary mouse neurons, microglia cells, and astrocytes. In comparison to <it>yy2 </it>and <it>mbtps2</it>, <it>yy1 </it>revealed the highest expression level in all cell types. Again, only <it>yy2 </it>showed significantly altered gene expression levels among the cell types. Higher <it>yy2 </it>expression levels were detected in microglia cells and astrocytes than in primary neurons.</p> <p>Conclusion</p> <p><it>Yy</it>2 expression in the heart and lung is constitutively expressed during embryogenesis and in adult mice. For the first time, developmental changes of <it>yy2 </it>transcription became obvious in various areas of the brain. This suggests that yy2 is involved in developmental gene regulation.</p

Molecular mode of action and role of TP53 in the sensitivity to the novel epothilone sagopilone (ZK-EPO) in A549 non-small cell lung cancer cells

Sagopilone, an optimized fully synthetic epothilone, is a microtubule-stabilizing compound that has shown high in vitro and in vivo activity against a broad range of human tumor models. We analyzed the differential mechanism of action of sagopilone in non-small cell lung cancer cell lines in vitro. Sagopilone inhibited proliferation of non-small cell lung cancer cell lines at lower nanomolar concentration. The treatment with sagopilone caused strong disturbances of cellular cytoskeletal organization. Two concentration-dependent phenotypes were observed. At 2.5 nM sagopilone or 4 nM paclitaxel an aneuploid phenotype occur whereas a mitotic arrest phenotype was induced by 40 nM sagopilone or paclitaxel. Interestingly, treatment with 2.5 nM of sagopilone effectively inhibited cell proliferation, but - compared to high concentrations (40 nM) - only marginally induced apoptosis. Treatment with a high versus a low concentration of sagopilone or paclitaxel regulates a non-overlapping set of genes, indicating that both phenotypes substantially differ from each other. Genes involved in G2/M phase transition and the spindle assembly checkpoint, like Cyclin B1 and BUBR1 were upregulated by treatment with 40 nM sagopilone. Unexpectedly, also genes involved in DNA damage response were upregulated under that treatment. In contrast, treatment of A549 cells with a low concentration of sagopilone revealed an upregulation of direct transcriptional target genes of TP53, like CDKN1A, MDM2, GADD45A, FAS. Knockdown of TP53, which inhibited the transcriptional induction of TP53 target genes, led to a significant increase in apoptosis induction in A549 cells when treated with a low concentration of sagopilone. The results indicate that activation of TP53 and its downstream effectors like CDKN1A by low concentrations of sagopilone is responsible for the relative apoptosis resistance of A549 cells and might represent a mechanism of resistance to sagopilone

Identification of a novel type of spacer element required for imprinting in fission yeast

Asymmetrical segregation of differentiated sister chromatids is thought to be important for cellular differentiation in higher eukaryotes. Similarly, in fission yeast, cellular differentiation involves the asymmetrical segregation of a chromosomal imprint. This imprint has been shown to consist of two ribonucleotides that are incorporated into the DNA during laggingstrand synthesis in response to a replication pause, but the underlying mechanism remains unknown. Here we present key novel discoveries important for unravelling this process. Our data show that cis-acting sequences within the mat1 cassette mediate pausing of replication forks at the proximity of the imprinting site, and the results suggest that this pause dictates specific priming at the position of imprinting in a sequence-independent manner. Also, we identify a novel type of cis-acting spacer region important for the imprinting process that affects where subsequent primers are put down after the replication fork is released from the pause. Thus, our data suggest that the imprint is formed by ligation of a not-fullyprocessed Okazaki fragment to the subsequent fragment. The presented work addresses how differentiated sister chromatids are established during DNA replication through the involvement of replication barriers

Structure, dielectric relaxation and electrical conductivity of 2,3,7,8-Tetramethoxychalcogenanthrene-2,3-dichloro-5,6-dicyano-1,4-benzoquinone 1:1 charger-transfer complexes

[EN] 2,3,7,8-Tetramethoxychalcogenanthrenes (5,10-chalcogena-cyclo-diveratrylenes, 'Vn(2)E(2)', E = S, Se) form isotypical 1:1 charge-transfer (CT) complexes with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). X-ray analysis of Vn(2)S(2) . DDQ shows the compound to have a columnar structure with segregated stacks of donors and acceptors. The donors are virtually planar in accordance with a formulation of [Vn(2)E(2)](+)[DDQ](-). Donor cations and acceptor anions are equidistant in their respective stacks, but in each case they inclined to the stacking axis, nevertheless guaranteeing an optimum overlap of the half-filled frontier orbitals which are of pi-type character according to MNDO calculations. Dielectric ac measurements of permittivity epsilon' and loss factor E '' clearly reveal two processes, a dielectric one at low temperatures and a conductive one at high temperatures. The dielectric process can be described by the Havriliak-Negami (HN) and the Kohlrausch-Williams-Watts (KWW) model, and the conductive process by a Debye-type plot. Using these methods, the relevant parameters are evaluated. The de conductivities of polycrystalline samples moulded at 10(8) Pa show a temperature dependence in the plots of ln sigma vs. T-1, which is typical of semiconductors. Two slopes are found; that in the low-temperature region (<285 K) is explained by an easy-path model (intragrain conductivity with low activation energies), whereas in the high-temperature region conduction across the grain boundaries (with higher activation energies) is becoming predominant. The activation energies for the intrinsic conductivities obtained by the ac and de measurements are similar. Despite the columnar structure with segregated stacks, due to stoichiometric oxidation states of the components, the absolute values of conductivity are low ten. 10(-6) S cm(-1) at 293 K), though higher (by a factor of ca. 10(3)) than those of compounds like Vn(2)E(2) . TCNQ with stacks in which donor and acceptor molecules alternate.Behrens, U.; Díaz Calleja, R.; Dötze, M.; Franke, U.; Gunsser, W.; Klar, G.; Kudnig, J.... (1996). Structure, dielectric relaxation and electrical conductivity of 2,3,7,8-Tetramethoxychalcogenanthrene-2,3-dichloro-5,6-dicyano-1,4-benzoquinone 1:1 charger-transfer complexes. Journal of Materials Chemistry. 6(4):547-553. https://doi.org/10.1039/JM9960600547S54755364Behrens, J., Hinrichs, W., Link, T., Schiffling, C., & Klar, G. (1995). SELFSTACKING SYSTEMS, PART 6.1HOST LATTICE FUNCTION OF 2,3,8,9-TETRAMETHOXYDIBENZO[c,e][1,2]-DICHALCOGENINS IN THEIR ELECTRICALLY CONDUCTING IODINE COMPLEXES. Phosphorus, Sulfur, and Silicon and the Related Elements, 101(1-4), 235-244. doi:10.1080/10426509508042522Berges, P., Kudnig, J., Klar, G., Martínez, E. S., & Calleja, R. D. (1989). Elementorganische Verbindungen mit o-Phenylenresten, XVI . 2:1-Komplexe von 2,3,7,8-Tetramethoxychalcogenanthrenen mit Tetracyanethen / Organometallic Compounds with o-Phenylene Substituents, Part XVI 2:1-Complexes of 2,3,7,8-Tetramethoxychalcogenanthrenes with Tetracyanoethene. Zeitschrift für Naturforschung B, 44(2), 211-219. doi:10.1515/znb-1989-0219Hinrichs, W., Berges, P., Klar, G., Sánchez-Martínez, E., & Gunsser, W. (1987). Structure and electrical conductivity of TCNQ-2,3,7,8-tetramethoxychalcogenanthrene complexes. Synthetic Metals, 20(3), 357-364. doi:10.1016/0379-6779(87)90832-0Sánchez Martínez, E., Díaz Calleja, R., Gunsser, W., Berges, P., & Klar, G. (1989). Structure and dielectric relaxation of 2,3,7,8-tetramethoxychalcogenanthrene-TCNQ complexes. Synthetic Metals, 30(1), 67-78. doi:10.1016/0379-6779(89)90642-5Gunßer, W., Henning, J. H., Klar, G., & Martínez, E. S. (1989). Spin Density and Magnetic Susceptibility of Charge-Transfer Complexes with Chalkogenanthrene Donors. Berichte der Bunsengesellschaft für physikalische Chemie, 93(11), 1370-1373. doi:10.1002/bbpc.19890931148G. M. Sheldrick , SHELXTL-PLUS, Release 4.21/0, Siemens Analytical X-Ray Instruments, 1990.Bock, H., Rauschenbach, A., Näther, C., Havlas, Z., Gavezzotti, A., & Filippini, G. (1995). Orthorhombisches und monoklines 2,3,7,8-Tetramethoxythianthren: kleiner Strukturunterschied – große Gitteränderung. Angewandte Chemie, 107(1), 120-122. doi:10.1002/ange.19951070132Bock, H., Rauschenbach, A., Näther, C., Havlas, Z., Gavezzotti, A., & Filippini, G. (1995). Orthorhombic and Monoclinic 2,3,7,8-Tetramethoxythianthrene: Small Structural Difference–Large Lattice Change. 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Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry, 38(4), 1225-1229. doi:10.1107/s0567740882005330Zanotti, G., Bardi, R., & Del Pra, A. (1980). Structure of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry, 36(1), 168-171. doi:10.1107/s0567740880002750Handbook of Chemistry and Physics, ed. R. C. Weast, CRC Press, Cleveland, OH, 1977–1978, 58th edn., p. D–178.Sánchez Martínez, E., Díaz Calleja, R., Berges, P., Kudnig, J., & Klar, G. (1989). Structure, electrical conductivity and dielectric relaxation of a 1,2-dimethoxybenzene-tetracyanoethene 1:1 complex. Synthetic Metals, 32(1), 79-89. doi:10.1016/0379-6779(89)90831-xÅsbrink, L., Fridh, C., & Lindholm, E. (1977). HAM/3, a semi-empirical MO theory. I. The SCF method. Chemical Physics Letters, 52(1), 63-68. doi:10.1016/0009-2614(77)85121-xÅsbrink, L., Fridh, C., & Lindholm, E. (1977). HAM/3, a semi-empirical MO theory. III. Unoccupied orbitals. Chemical Physics Letters, 52(1), 72-75. doi:10.1016/0009-2614(77)85123-3Dewar, M. J. S., & Thiel, W. (1977). Ground states of molecules. 38. The MNDO method. Approximations and parameters. Journal of the American Chemical Society, 99(15), 4899-4907. doi:10.1021/ja00457a004Dewar, M. J. S., & Thiel, W. (1977). Ground states of molecules. 39. MNDO results for molecules containing hydrogen, carbon, nitrogen, and oxygen. Journal of the American Chemical Society, 99(15), 4907-4917. doi:10.1021/ja00457a005Åsbrink, L., Fridh, C., & Lindholm, E. (1978). Valence excitation of linear molecules.I. Excitation and UV spectra of N2, Co, acetylene and HCN. Chemical Physics, 27(2), 159-168. doi:10.1016/0301-0104(78)88001-xFridh, C., Åsbrink, L., & Lindholm, E. (1978). Valence excitation of linear molecules. II. Excitation and UV spectra of C2N2, CO2 and N2O. Chemical Physics, 27(2), 169-181. doi:10.1016/0301-0104(78)88002-1Lindholm, E., Bieri, G., Åsbrink, L., & Fridh, C. (1978). 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Size-dependent Correlation Effects in Ultrafast Optical Dynamics of Metal Nanoparticles

We study the role of collective surface excitations in the electron relaxation in small metal particles. We show that the dynamically screened electron-electron interaction in a nanoparticle contains a size-dependent correction induced by the surface. This leads to new channels of quasiparticle scattering accompanied by the emission of surface collective excitations. We calculate the energy and temperature dependence of the corresponding rates, which depend strongly on the nanoparticle size. We show that the surface-plasmon-mediated scattering rate of a conduction electron increases with energy, in contrast to that mediated by a bulk plasmon. In noble-metal particles, we find that the dipole collective excitations (surface plasmons) mediate a resonant scattering of d-holes to the conduction band. We study the role of the latter effect in the ultrafast optical dynamics of small nanoparticles and show that, with decreasing nanoparticle size, it leads to a drastic change in the differential absorption lineshape and a strong frequency dependence of the relaxation near the surface plasmon resonance. The experimental implications of our results in ultrafast pump-probe spectroscopy are also discussed.Comment: 29 pages including 6 figure

Rapid evolution of Anguillicola crassus in Europe: species diagnostic traits are plastic and evolutionarily labile

Background Since its introduction from Taiwan to Europe around 1980, Anguillicola crassus, a natural parasite of the Japanese eel (Anguilla japonica), has acquired the European eel (Anguilla anguilla) as a novel definitive host. In this host the nematode differs noticeably in its body mass and reproductive capacity from its Asian conspecifics. We conducted a common garden experiment under a reciprocal transplant design to investigate whether differences in species-diagnostic morphological traits exist between two European and one Asian population of A. crassus and if yes whether these have a genetically fixed component. Results We found that worms from Germany, Poland and Taiwan differ in the size and shape of their body, oesophagus and buccal capsule. These changes are induced by both phenotypic plasticity and genetic divergence: in the European eel, nematodes from Europe as well as from Taiwan responded plastically with larger body and oesophagus dimensions compared to infections in the Japanese eel. Interestingly, the oesophagus simultaneously shows a high degree of genetically based changes being largest in the Polish strain kept in A. anguilla. In addition, the size and shape of the buccal capsule has undergone a rapid evolutionary change. Polish nematodes evolved a genetically fixed larger buccal capsule than the German and Taiwanese populations. The German strain had the smallest buccal capsule. Conclusions This study provides evidence for the genetic divergence of morphological traits in A. crassus which evolved over a timescale of about 30 years. Within Europe and in the European eel host these alternations affect characters used as diagnostic markers for species differentiation. Thus we provide an explanation of the discrepancy between morphological and molecular features reported for the parasitic nematode featured here, demanding general caution in morphological diagnosis of parasites discovered in new hosts

Threshold Laws for the Break-up of Atomic Particles into Several Charged Fragments

The processes with three or more charged particles in the final state exhibit particular threshold behavior, as inferred by the famous Wannier law for (2e + ion) system. We formulate a general solution which determines the threshold behavior of the cross section for multiple fragmentation. Applications to several systems of particular importance with three, four and five leptons (electrons and positrons) in the field of charged core; and two pairs of identical particles with opposite charges are presented. New threshold exponents for these systems are predicted, while some previously suggested threshold laws are revised.Comment: 40 pages, Revtex, scheduled for the July issue of Phys.Rev.A (1998

Oscillatory Size-Dependence of the Surface Plasmon Linewidth in Metallic Nanoparticles

We study the linewidth of the surface plasmon resonance in the optical absorption spectrum of metallic nanoparticles, when the decay into electron-hole pairs is the dominant channel. Within a semiclassical approach, we find that the electron-hole density-density correlation oscillates as a function of the size of the particles, leading to oscillations of the linewidth. This result is confirmed numerically for alkali and noble metal particles. While the linewidth can increase strongly, the oscillations persist when the particles are embedded in a matrix.Comment: RevTeX4, 5 pages, 2 figures, final versio

Spin polarization of the Ar* 2p−11/2 4s and 2p−11/2 3d resonant Auger decay

The spin-resolved Auger decay of the Ar 2p−11/2 3d state was measured at moderate energy resolution and compared with the decay of the 2p−11/2 4s. The former shows a lower transferred spin polarization and a similar, if not higher, dynamical spin polarization, supporting the statement that a fully resolved spectrum is not a necessary condition for observing dynamical spin polarization. An interpretation of the spin polarization as configuration interaction induced effect in the final ionic state leads to partial agreement with our relativistic distorted wave calculation utilizing a 36 configuration state function basis set. Comparison of the experimental and numerical results leads to ambiguities for at least one Auger line. A hypothetical, qualitative interpretation is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58121/2/b7_17_012.pd

Optical Cloaking with Non-Magnetic Metamaterials

Artificially structured metamaterials have enabled unprecedented flexibility in manipulating electromagnetic waves and producing new functionalities, including the cloak of invisibility based on coordinate transformation. Here we present the design of a non-magnetic cloak operating at optical frequencies. The principle and structure of the proposed cylindrical cloak are analyzed, and the general recipe for the implementation of such a device is provided. The cloaking performance is verified using full-wave finite-element simulations.Comment: 10 pages, 4 figure