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Achieving selectivity in space and time with DNA double-strand-break response and repair: molecular stages and scaffolds come with strings attached

When double-strand breaks (DSBs) in DNA remain unrepaired, catastrophic loss of genes occurs, leading to translocations, mutations and carcinogenesis. If a sister chromatid is not available at the DNA DSB, nonhomologous end joining (NHEJ) is used to join broken ends. The NHEJ pathway comprises synapsis, end processing and ligation. Here, we ask how DSBs in DNA are repaired efficiently. We suggest that colocation of proteins is achieved over time by the following components: stages, where the main actors are assembled, scaffolds that are erected quickly around broken parts to give access, and strings that tether proteins together. In NHEJ, a $\textit{stage}$ is provided by the Ku heterodimer interacting with DSBs and several other proteins including DNA-PKcs, APLF, BRCA1 and PAXX. A further $\textit{stage}$, DNA-PKcs, links the kinase with DNA, Ku, PARP1, BRCA1 and Artemis. A temporary $\textit{scaffold}$ facilitates repair and is constructed from XRCC4/XLF filaments that bridge Ku bound at DSB ends. LigIV bound to XRCC4 C-termini likely terminates the scaffold, bringing LigIV close to the DNA broken ends. A $\textit{string}$, provided by the Artemis C-terminal region, is intrinsically disordered but includes short linear ‘‘epitopes’’ that recognise DNA-PKcs, LigIV and PTIP, so keeping these components nearby. We show that these stages, scaffolds and strings facilitate colocation and efficient DSB repair. Understanding these processes provides insight into the biology of DNA repair and possible therapeutic intervention in cancer and other diseases.Wellcome Trust (Programme Grant ID: 093167/Z/ 10/Z), National Health and Medical Research Council of Australia (C. J. Martin Research Fellowship, Grant ID: APP1072476), Gates Cambridge ScholarshipThis is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s11224-016-0841-

π\piNN coupling and two-pion photoproduction on the nucleon

Effects of non-resonant photoproductions arising from two different $\pi NN$ couplings are investigated in the $\gamma N\to\pi\pi N$ reaction. We find that the pseudoscalar (PS) $\pi NN$ coupling is generally preferable to the pseudovector (PV) $\pi NN$ coupling and particularly the total cross sections are successfully described by the model with the PS $\pi NN$ coupling. In order to see the difference between the two couplings, we also show the results of invariant mass spectra and helicity-dependent cross sections in various isospin channels calculated with the PS and PV couplings.Comment: 35 pages, 11 figures, minor changes and version to be published in Phys.Rev.

First astronomical unit scale image of the GW Ori triple. Direct detection of a new stellar companion

Young and close multiple systems are unique laboratories to probe the initial dynamical interactions between forming stellar systems and their dust and gas environment. Their study is a key building block to understanding the high frequency of main-sequence multiple systems. However, the number of detected spectroscopic young multiple systems that allow dynamical studies is limited. GW Orionis is one such system. It is one of the brightest young T Tauri stars and is surrounded by a massive disk. Our goal is to probe the GW Orionis multiplicity at angular scales at which we can spatially resolve the orbit. We used the IOTA/IONIC3 interferometer to probe the environment of GW Orionis with an astronomical unit resolution in 2003, 2004, and 2005. By measuring squared visibilities and closure phases with a good UV coverage we carry out the first image reconstruction of GW Ori from infrared long-baseline interferometry. We obtain the first infrared image of a T Tauri multiple system with astronomical unit resolution. We show that GW Orionis is a triple system, resolve for the first time the previously known inner pair (separation $\rho\sim$1.4 AU) and reveal a new more distant component (GW Ori C) with a projected separation of $\sim$8 AU with direct evidence of motion. Furthermore, the nearly equal (2:1) H-band flux ratio of the inner components suggests that either GW Ori B is undergoing a preferential accretion event that increases its disk luminosity or that the estimate of the masses has to be revisited in favour of a more equal mass-ratio system that is seen at lower inclination. Accretion disk models of GW Ori will need to be completely reconsidered because of this outer companion C and the unexpected brightness of companion B.Comment: 5 pages, 9 figures, accepted Astronomy and Astrophysics Letters. 201

Finite-Size and surface effects in maghemite nanoparticles: Monte Carlo simulations

Finite-size and surface effects in fine particle systems are investigated by Monte Carlo simulation of a model of a $\gamma$-Fe$_2$O$_3$ (maghemite) single particle. Periodic boundary conditions have been used to simulate the bulk properties and the results compared with those for a spherical shaped particle with free boundaries to evidence the role played by the surface on the anomalous magnetic properties displayed by these systems at low temperatures. Several outcomes of the model are in qualitative agreement with the experimental findings. A reduction of the magnetic ordering temperature, spontaneous magnetization, and coercive field is observed as the particle size is decreased. Moreover, the hysteresis loops become elongated with high values of the differential susceptibility, resembling those from frustrated or disordered systems. These facts are consequence of the formation of a surface layer with higher degree of magnetic disorder than the core, which, for small sizes, dominates the magnetization processes of the particle. However, in contradiction with the assumptions of some authors, our model does not predict the freezing of the surface layer into a spin-glass-like state. The results indicate that magnetic disorder at the surface simply facilitates the thermal demagnetization of the particle at zero field, while the magnetization is increased at moderate fields, since surface disorder diminishes ferrimagnetic correlations within the particle. The change in shape of the hysteresis loops with the particle size demonstrates that the reversal mode is strongly influenced by the reduced atomic coordination and disorder at the surface.Comment: Twocolumn RevTex format. 19 pages, 15 Figures included. Submitted to Phys. Rev.

Photoproduction of scalar mesons on protons and nuclei

We study the photoproduction of scalar mesons close to the threshold of f_0(980) and a_0(980) using a unitary chiral model. Peaks for both resonances show up in the invariant mass distributions of pairs of pseudoscalar mesons. A discussion is made on the photoproduction of these resonances in nuclei, which can shed light on their nature, a subject of continuous debate.Comment: 25 pages, 9 figures, accepted for publication in Phys Rev

Study of the Gauge Mediation Signal with Non-pointing Photons at the CERN LHC

In this paper we study the gauge mediation signal with the ATLAS detector at the CERN LHC. We focus on the case where the NLSP is the long-lived lightest neutralino ($\tilde{\chi}^0_1$) which decays dominantly into a photon ($\gamma$) and a gravitino ($\tilde{G}$). A non-pointing photon from the neutralino decay can be detected with good position and time resolutions by the electormagnetic calorimeter (ECAL), while the photon momentum would be precisely measured if the photon is converted inside the inner tracking detector before reaching the ECAL. A new technique is developed to determine the masses of the slepton ($\tilde{\ell}$) and the neutralino from events with a lepton and a converted non-pointing photon arising from the cascade decay $\tilde{\ell}\to \ell\tilde{\chi}^0_1\to \ell\gamma \tilde{G}$. A Monte Carlo simulation at a sample point shows that the masses would be measured with an error of 3% for $\cal{O}$(100) selected $\ell\gamma$ pairs. Once the sparticle masses are determined by this method, the decay time and momentum of the neutralino are solved using the ECAL data and the lepton momentum only, for all $\ell\gamma$ pairs without the photon conversion. We estimate the sensitivity to the neutralino lifetime for $c\tau=10$ cm to $\cal{O}$(10) m.Comment: 19 page, 7 figures, revte

Subthreshold rho^0 photoproduction on 3He

A large reduction of the rho^0 mass in the nuclear medium is reported, inferred from dipion photoproduction spectra in the 1 GeV region, for the reaction 3He(gamma,pi+ pi-)X with a 10% duty factor tagged-photon beam and the TAGX multi-particle spectrometer. The energy range covered (800 < E(gamma) < 1120 MeV) lies mostly below the free rho^0 production threshold, a region which is believed sensitive to modifications of light vector-meson properties at nuclear-matter densities. The rho^0 masses extracted from the MC fitting of the data, m*(rho^0) = 642 +/- 40, 669 +/- 32, and 682 +/- 56 MeV/c^2 for E(gamma) in the 800-880, 880-960, and 960-1040 MeV regions respectively, are independently corroborated by a measured, assumption-free, kinematical observable. This mass shift, far exceeding current mean-field driven theoretical predictions, may be suggestive of rho^0 decay within the range of the nucleonic field.Comment: 40 pages, 13 figures, submitted to Phys. Rev.