On Birch and Swinnerton-Dyer's cubic surfaces

In a 1975 paper of Birch and Swinnerton-Dyer, a number of explicit norm form cubic surfaces are shown to fail the Hasse Principle. They make a correspondence between this failure and the Brauer--Manin obstruction, recently discovered by Manin. We generalize their work, making use of modern computer algebra software to show that a larger set of cubic surfaces have a Brauer--Manin obstruction to the Hasse principle, thus verifying the Colliot-Th\'el\`ene--Sansuc conjecture for infinitely many cubic surfaces

Adaptable P body physical states differentially regulate bicoid mRNA storage during early Drosophila development.

Ribonucleoprotein condensates can exhibit diverse physical states in vitro and in vivo. Despite considerable progress, the relevance of condensate physical states for in vivo biological function remains limited. Here, we investigated the physical properties of processing bodies (P bodies) and their impact on mRNA storage in mature Drosophila oocytes. We show that the conserved DEAD-box RNA helicase Me31B forms viscous P body condensates, which adopt an arrested physical state. We demonstrate that structurally distinct proteins and protein-protein interactions, together with RNA, regulate the physical properties of P bodies. Using live imaging and in situ hybridization, we show that the arrested state and integrity of P bodies support the storage of bicoid (bcd) mRNA and that egg activation modulates P body properties, leading to the release of bcd for translation in the early embryo. Together, this work provides an example of how physical states of condensates regulate cellular function in development

Mechano-chemical kinetics of DNA replication: identification of the translocation step of a replicative DNA polymerase

[EN] During DNA replication replicative polymerases move in discrete mechanical steps along the DNA template. To address how the chemical cycle is coupled to mechanical motion of the enzyme, here we use optical tweezers to study the translocation mechanism of individual bacteriophage Phi29 DNA polymerases during processive DNA replication. We determine the main kinetic parameters of the nucleotide incorporation cycle and their dependence on external load and nucleotide (dNTP) concentration. The data is inconsistent with power stroke models for translocation, instead supports a loose-coupling mechanism between chemical catalysis and mechanical translocation during DNA replication. According to this mechanism the DNA polymerase works by alternating between a dNTP/PPi-free state, which diffuses thermally between pre- and post-translocated states, and a dNTP/PPi-bound state where dNTP binding stabilizes the post-translocated state. We show how this thermal ratchet mechanism is used by the polymerase to generate work against large opposing loads (~50 pN).We thank Stephan Grill laboratory (MPI-CBG, Dresden) for help with data collection and E. Galburt, M. Manosas and M. De Vega for critical reading of the manuscript. Spanish Ministry of Economy and Competitiveness [BFU2011-29038 to J.L.C., BFU2013-44202 to J.M.V., BFU2011-23645 to M.S., FIS2010-17440, GR35/10-A920GR35/10-A-911 to F.J.C., MAT2013-49455-EXP to J.R.A.-G. and BFU2012-31825 to B.I.]; Regional Government of Madrid [S2009/MAT 1507 to J.L.C. and CDS2007-0015 to M.S.]; European Molecular Biology Organization [ASTF 276-2012 to J.M.L.]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness [BFU2012-31825 to B.I.].Morin, J.; Cao, F.; Lázaro, J.; Arias-Gonzalez, JR.; Valpuesta, J.; Carrascosa, J.; Salas, M.... (2015). 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The EMBO Journal, 25(15), 3458-3468. doi:10.1038/sj.emboj.7601211Zhang, H., Cao, W., Zakharova, E., Konigsberg, W., & De La Cruz, E. M. (2007). Fluorescence of 2-aminopurine reveals rapid conformational changes in the RB69 DNA polymerase-primer/template complexes upon binding and incorporation of matched deoxynucleoside triphosphates. Nucleic Acids Research, 35(18), 6052-6062. doi:10.1093/nar/gkm587Wang, W., Wu, E. Y., Hellinga, H. W., & Beese, L. S. (2012). Structural Factors That Determine Selectivity of a High Fidelity DNA Polymerase for Deoxy-, Dideoxy-, and Ribonucleotides. Journal of Biological Chemistry, 287(34), 28215-28226. doi:10.1074/jbc.m112.366609Berezhna, S. Y., Gill, J. P., Lamichhane, R., & Millar, D. P. (2012). Single-Molecule Förster Resonance Energy Transfer Reveals an Innate Fidelity Checkpoint in DNA Polymerase I. Journal of the American Chemical Society, 134(27), 11261-11268. doi:10.1021/ja3038273Hariharan, C., Bloom, L. B., Helquist, S. A., Kool, E. 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Measurement of the modulus and phase of the linear coupling coefficient by analysis of the transverse beam profile

We study the dynamics of transverse oscillations near the linear coupling resonance excited by a pair of skew quadrupoles at the Laboratório Nacional de Luz Síncrotron UVX electron storage ring through the analysis of the beam profile. Transverse coherent oscillations were excited with a fast kicker and the profile of the oscillating beam was observed by focusing visible synchrotron radiation from a bending magnet onto a fast charge-coupled device camera. Using a single resonance approximation, we calculated the border of the time-averaged transverse beam profile as a function of the complex coupling coefficient κ, which characterizes the distribution of coupling fields along the storage ring. A least-squares fit of the calculated beam profile border to the experimentally obtained isointensity contours provided a new method to determine both the modulus and the phase of κ. The values obtained for the modulus are in good agreement with those from the conventional normal mode tune separation technique, and the values obtained for the phase of κ agree with calculations based on the model lattice and the known skew quadrupole distribution