Obtaining the lattice energy of the anthracene crystal by modern yet affordable first-principles methods

The non-covalent interactions in organic molecules are known to drive their self-assembly to form molecular crystals. We compare, in the case of anthracene and against experimental (electronic-only) sublimation energy, how modern quantum-chemical methods are able to calculate this cohesive energy taking into account all the interactions between occurring dimers in both first-and second-shells. These include both O(N 6)- and O(N 5)-scaling methods, Local Pair Natural Orbital-parameterized Coupled-Cluster Single and Double, and Spin-Component-Scaled-Møller-Plesset perturbation theory at second-order, respectively, as well as the most modern family of conceived density functionals: double-hybrid expressions in several variants (B2-PLYP, mPW2-PLYP, PWPB95) with customized dispersion corrections (–D3 and –NL). All-in-all, it is shown that these methods behave very accurately producing errors in the 1–2 kJ/mol range with respect to the experimental value taken into account the experimental uncertainty. These methods are thus confirmed as excellent tools for studying all kinds of interactions in chemical systems.Financial support by the “Ministerio de Economía y Competitividad” of Spain and the “European Regional Development Fund” through projects CTQ2011-27253, CTQ2012-31914, and Consolider-Ingenio CSD2007-00010 in Molecular Nanoscience, and by the Generalitat Valenciana (ISIC 2012/008 and PROMETEO/2012/053) is acknowledged. The work in Mons is supported by the Belgian National Fund for Scientific Research (FNRS). Y.O. is a FNRS Post-doctoral Research Fellow. J.C.S.G. is a FNRS Visiting Professor

Poling effect on distribution of quenched random fields in a uniaxial relaxor ferroelectric

The frequency dependence of the dielectric permitivity's maximum has been studied for poled and unpoled doped relaxor strontium barium niobate $Sr_{0.61}Ba_{0.39}Nb_{2}O_{6}:Cr^{3+}$ (SBN-61:Cr). In both cases the maximum found is broad and the frequency dispersion is strong. The present view of random fields compensation in the unpoled sample is not suitable for explaining this experimental result. We propose a new mechanism where the dispersion of quenched random electric fields, affecting the nanodomains, is minimized after poling. We test our proposal by numerical simulations on a random field Ising model. Results obtained are in agreement with the polarization's measurements presented by Granzow et al. [Phys. Rev. Lett {\bf 92}, 065701 (2004)].Comment: 7 pages, 4 figure

A Columnar Liquid Crystal with Permanent Polar Order

The self-assembly of axial dipolar subphthalocyanine molecules in the presence of electric fields leads to uniaxially oriented columnar liquid crystalline materials that exhibit permanent polarizationFunding from MINECO (MAT2012-38538-CO3-01, 02 and CTQ2012- 31914), MICINN and MEC (F.P.U. fellowship (JG), CTQ-2011- 24187/BQU, CTQ2011-23659 and Consolider-Ingenio Nanociencia Molecular, CDS2007-00010), Comunidad de Madrid (MADRISOLAR-2, S2009/PPQ/1533), European Research Council (StG-279548), Aragon government, E04, Basque Country Government GI/IT-449-10, Generalitat Valenciana (PROMETEO/ 2012/053), and FEDER is acknowledge

Phosphoenolpyruvate from Glycolysis and PEPCK Regulate Cancer Cell Fate by Altering Cytosolic Ca2+

Changes in phosphoenolpyruvate (PEP) concentrations secondary to variations in glucose availability can regulate calcium signaling in T cells as this metabolite potently inhibits the sarcoplasmic reticulum Ca2+/ATPase pump (SERCA). This regulation is critical to assert immune activation in the tumor as T cells and cancer cells compete for available nutrients. We examined here whether cytosolic calcium and the activation of downstream effector pathways important for tumor biology are influenced by the presence of glucose and/or cataplerosis through the phosphoenolpyruvate carboxykinase (PEPCK) pathway, as both are hypothesized to feed the PEP pool. Our data demonstrate that cellular PEP parallels extracellular glucose in two human colon carcinoma cell lines, HCT-116 and SW480. PEP correlated with cytosolic calcium and NFAT activity, together with transcriptional up-regulation of canonical targets PTGS2 and IL6 that was fully prevented by CsA pre-treatment. Similarly, loading the metabolite directly into the cell increased cytosolic calcium and NFAT activity. PEP-stirred cytosolic calcium was also responsible for the calmodulin (CaM) dependent phosphorylation of c-Myc at Ser62, resulting in increased activity, probably through enhanced stabilization of the protein. Protein expression of several c-Myc targets also correlated with PEP levels. Finally, the participation of PEPCK in this axis was interrogated as it should directly contribute to PEP through cataplerosis from TCA cycle intermediates, especially in glucose starvation conditions. Inhibition of PEPCK activity showed the expected regulation of PEP and calcium levels and consequential downstream modulation of NFAT and c-Myc activities. Collectively, these results suggest that glucose and PEPCK can regulate NFAT and c-Myc activities through their influence on the PEP/Ca2+ axis, advancing a role for PEP as a second messenger communicating metabolism, calcium cell signaling, and tumor biology

Glycosylation defects, offset by PEPCK-M, drive entosis in breast carcinoma cells

On glucose restriction, epithelial cells can undergo entosis, a cell-in-cell cannibalistic process, to allow considerable withstanding to this metabolic stress. Thus, we hypothesized that reduced protein glycosylation might participate in the activation of this cell survival pathway. Glucose deprivation promoted entosis in an MCF7 breast carcinoma model, as evaluated by direct inspection under the microscope, or revealed by a shift to apoptosis + necrosis in cells undergoing entosis treated with a Rho-GTPase kinase inhibitor (ROCKi). In this context, curbing protein glycosylation defects with N-acetyl-glucosamine partially rescued entosis, whereas limiting glycosylation in the presence of glucose with tunicamycin or NGI-1, but not with other unrelated ER-stress inducers such as thapsigargin or amino-acid limitation, stimulated entosis. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M; PCK2) is upregulated by glucose deprivation, thereby enhancing cell survival. Therefore, we presumed that PEPCK-M could play a role in this process by offsetting key metabolites into glycosyl moieties using alternative substrates. PEPCK-M inhibition using iPEPCK-2 promoted entosis in the absence of glucose, whereas its overexpression inhibited entosis. PEPCK-M inhibition had a direct role on total protein glycosylation as determined by Concanavalin A binding, and the specific ratio of fully glycosylated LAMP1 or E-cadherin. The content of metabolites, and the fluxes from C-13-glutamine label into glycolytic intermediates up to glucose-6-phosphate, and ribose- and ribulose-5-phosphate, was dependent on PEPCK-M content as measured by GC/MS. All in all, we demonstrate for the first time that protein glycosylation defects precede and initiate the entosis process and implicates PEPCK-M in this survival program to dampen the consequences of glucose deprivation. These results have broad implications to our understanding of tumor metabolism and treatment strategies