Dynamic localization of SMC5/6 complex proteins during mammalian meiosis and mitosis suggests functions in distinct chromosome processes

et al.Four members of the structural maintenance of chromosome (SMC) protein family have essential functions in chromosome condensation (SMC2/4) and sister-chromatid cohesion (SMC1/3). The SMC5/6 complex has been implicated in chromosome replication, DNA repair and chromosome segregation in somatic cells, but its possible functions during mammalian meiosis are unknown. Here, we show in mouse spermatocytes that SMC5 and SMC6 are located at the central region of the synaptonemal complex from zygotene until diplotene. During late diplotene both proteins load to the chromocenters, where they colocalize with DNA Topoisomerase IIα, and then accumulate at the inner domain of the centromeres during the first and second meiotic divisions. Interestingly, SMC6 and DNA Topoisomerase IIα colocalize at stretched strands that join kinetochores during the metaphase II to anaphase II transition, and both are observed on stretched lagging chromosomes at anaphase II following treatment with Etoposide. During mitosis, SMC6 and DNA Topoisomerase IIα colocalize at the centromeres and chromatid axes. Our results are consistent with the participation of SMC5 and SMC6 in homologous chromosome synapsis during prophase I, chromosome and centromere structure during meiosis I and mitosis and, with DNA Topoisomerase IIα, in regulating centromere cohesion during meiosis II.This work was supported by Ministerio de Economía y Competitividad (Spain) [grant number SAF2011-28842-C02-01 to J.A.S. and SAF2011-25252 to A.M.P.]; a UK-US Fulbright Distinguished Scholar Award; the US National Institutes of Health [grant number HD069458 to P.W.J.; HD33816 to M.A.H.; HD42137 to John Eppig, M.A.H. and J.C.S.]; the Priority Program SPP 1384 ‘Mechanisms of genome haploidization’ (to M.A. and R.J.) from the German Science Foundation.Peer Reviewe

A first step towards quantum energy potentials of electron pairs

A first step towards the construction of a quantum force field for electron pairs in direct space is taken. Making use of topological tools (Interacting Quantum Atoms and the Electron Localisation Function), we have analysed the dependency of electron pairs electrostatic, kinetic and exchange-correlation energies upon bond stretching. Simple correlations were found, and can be explained with elementary models such as the homogeneous electron gas. The resulting energy model is applicable to various bonding regimes: from homopolar to highly polarized and even to non-conventional bonds. Overall, this is a fresh approach for developing real space-based force fields including an exchange-correlation term. It provides the relative weight of each of the contributions, showing that, in common Lewis structures, the exchange correlation contribution between electron pairs is negligible. However, our results reveal that classical approximations progressively fail for delocalised electrons, including lone pairs. This theoretical framework justifies the success of the classic Bond Charge Model (BCM) approach in solid state systems and sets the basis of its limits. Finally, this approach opens the door towards the development of quantitative rigorous energy models based on the ELF topology

Enhancing sampling in atomistic simulations of solid state materials for batteries: a focus on olivine NaFePO4_4

The study of ion transport in electrochemically active materials for energy storage systems requires simulations on quantum-, atomistic- and meso-scales. The methods accessing these scales not only have to be effective but also well compatible to provide a full description of the underlying processes. We propose to adapt the Generalized Shadow Hybrid Monte Carlo (GSHMC) method to atomistic simulation of ion intercalation electrode materials for batteries. The method has never been applied to simulations in solid-state chemistry but it has been successfully used for simulation of biological macromolecules, demonstrating better performance and accuracy than can be achieved with the popular molecular dynamics (MD) method. It has been also extended to simulations on meso-scales, making it even more attractive for simulation of battery materials. We combine GSHMC with the dynamical core–shell model to incorporate polarizability into the simulation and apply the new Modified Adaptive Integration Approach, MAIA, which allows for a larger time step due to its excellent conservation properties. Also, we modify the GSHMC method, without losing its performance and accuracy, to reduce the negative effect of introducing a shell mass within a dynamical shell model. The proposed approach has been tested on olivine NaFePO$_4$, which is a promising cathode material for Na-ion batteries. The calculated Na-ion diffusion and structural properties have been compared with the available experimental data and with the results obtained using MD and the original GSHMC method. Based on these tests, we claim that the new technique is advantageous over MD and the conventional GSHMC and can be recommended for studies of other solid-state electrode and electrolyte materials whenever high accuracy and efficient sampling are critical for obtaining tractable simulation results.MTM2013-46553-C3-1-P Iberdrola Foundation “Grants for Research in Energy and Environment 2014” ELKARTEK Programme KK-2016/00026 BES-2014-068640 BERC 2014-2017 SEV-2013-032

Electron sharing and localization in real space for the Mott transition from 1RDMFT periodic calculations

One-particle reduced density matrix functional theory (1RDMFT) has been applied for the investigation of the real-space picture of the Mott transitions in archetypal hydrogen lattices. The evolution of the degree of electron localization during the transition has been evaluated using electron sharing indices for QTAIM atoms, and the connection between the strength of electronic correlation expressed by the 1RDMFT correlation energy and the degree of electron localization has been analyzed at various stages of transition. The spatial decay of the electron sharing indices in the course of transition has also been evaluated and compared with the results obtained for the Hubbard model and finite cluster calculations

Emergence of Bulk CsCl Structure in (CsCl)nCs+ Cluster Ions

The emergence of CsCl bulk structure in (CsCl)nCs+ cluster ions is investigated using a mixed quantum-mechanical/semiempirical theoretical approach. We find that rhombic dodecahedral fragments (with bulk CsCl symmetry) are more stable than rock-salt fragments after the completion of the fifth rhombic dodecahedral atomic shell. From this size (n=184) on, a new set of magic numbers should appear in the experimental mass spectra. We also propose another experimental test for this transition, which explicitely involves the electronic structure of the cluster. Finally, we perform more detailed calculations in the size range n=31--33, where recent experimental investigations have found indications of the presence of rhombic dodecahedral (CsCl)32Cs+ isomers in the cluster beams.Comment: LaTeX file. 6 pages and 4 pictures. Accepted for publication in Phys. Rev.

Ab Initio Calculation of the Lattice Distortions induced by Substitutional Ag- and Cu- Impurities in Alkali Halide Crystals

An ab initio study of the doping of alkali halide crystals (AX: A = Li, Na, K, Rb; X = F, Cl, Br, I) by ns2 anions (Ag- and Cu-) is presented. Large active clusters with 179 ions embedded in the surrounding crystalline lattice are considered in order to describe properly the lattice relaxation induced by the introduction of substitutional impurities. In all the cases considered, the lattice distortions imply the concerted movement of several shells of neighbors. The shell displacements are smaller for the smaller anion Cu-, as expected. The study of the family of rock-salt alkali halides (excepting CsF) allows us to extract trends that might be useful at a predictive level in the study of other impurity systems. Those trends are presented and discussed in terms of simple geometric arguments.Comment: LaTeX file. 8 pages, 3 EPS pictures. New version contains calculations of the energy of formation of the defects with model clusters of different size

STAG3 is a strong candidate gene for male infertility

Oligo- and azoospermia are severe forms of male infertility. However, known genetic factors account only for a small fraction of the cases. Recently, whole-exome sequencing in a large consanguineous family with inherited premature ovarian failure (POF) identified a homozygous frameshift mutation in the STAG3 gene leading to a premature stop codon. STAG3encodes a meiosis-specific subunit of the cohesin complex, alarge proteinaceous ring with DNA-entrapping ability that ensures sister chromatid cohesion and enables correct synapsis and segregation of homologous chromosomes during meiosis. The pathogenicity of the STAG3 mutations was functionally validated with a loss- of-function mouse model for STAG3 in oogenesis.However,and sincenone of the male members of this family was homozygous for the mutant allele, we only could hypothesized its putative involvement inmale infertility. In this report,we show that male mice devoid of Stag3 display a severe meiotic phenotype that includes a meiotic arrest at zygonema-like shortening of their chromosome axial elements/lateral elements, partial loss of centromeric cohesion at early prophase and maintenance of the ability to initiate but not complete RAD51- and DMC1-mediated double-strand break repair,demonstrating that STAG3 is a crucial cohesin subunit in mammalian gametogenesis and supporting our proposal that STAG3 is a strong candidate gene for human male infertility. © The Author 2014. Published by Oxford University Press. All rights reserved.This work was supported by grant SAF2011-25252 and Junta de Castilla y León (EL and AMP). SC and RAV are supported by the University Paris Diderot-Paris7, the Ligue Nationale contre le Cancer, the Centre National de la Recherche Scientifique (CNRS) and the GIS-Institut des Maladies Rares.Peer Reviewe

Electronic stress tensor analysis of hydrogenated palladium clusters

We study the chemical bonds of small palladium clusters Pd_n (n=2-9) saturated by hydrogen atoms using electronic stress tensor. Our calculation includes bond orders which are recently proposed based on the stress tensor. It is shown that our bond orders can classify the different types of chemical bonds in those clusters. In particular, we discuss Pd-H bonds associated with the H atoms with high coordination numbers and the difference of H-H bonds in the different Pd clusters from viewpoint of the electronic stress tensor. The notion of "pseudo-spindle structure" is proposed as the region between two atoms where the largest eigenvalue of the electronic stress tensor is negative and corresponding eigenvectors forming a pattern which connects them.Comment: 22 pages, 13 figures, published online, Theoretical Chemistry Account

Structural and Electronic Properties of Small Neutral (MgO)n Clusters

Ab initio Perturbed Ion (PI) calculations are reported for neutral stoichiometric (MgO)n clusters (n<14). An extensive number of isomer structures was identified and studied. For the isomers of (MgO)n (n<8) clusters, a full geometrical relaxation was considered. Correlation corrections were included for all cluster sizes using the Coulomb-Hartree-Fock (CHF) model proposed by Clementi. The results obtained compare favorably to the experimental data and other previous theoretical studies. Inclusion of correlaiotn is crucial in order to achieve a good description of these systems. We find an important number of new isomers which allows us to interpret the experimental magic numbers without the assumption of structures based on (MgO)3 subunits. Finally, as an electronic property, the variations in the cluster ionization potential with the cluster size were studied and related to the structural isomer properties.Comment: 24 pages, LaTeX, 7 figures in GIF format. Accepted for publication in Phys. Rev.