Synergistic interactions of the anti‑casein kinase 2 CIGB‑300 peptide and chemotherapeutic agents in lung and cervical preclinical cancer models

CIGB‑300 is a novel clinical‑stage synthetic peptide that impairs the casein kinase 2 (CK2)‑mediated phosphorylation of B23/nucleophosmin in different experimental settings and cancer models. As a single agent, CIGB‑300 induces apoptosis in vitro and in vivo and modulates an array of proteins that are mainly involved in drug resistance, cell proliferation and apoptosis, as determined by proteomic analysis. However, the clinical oncology practice and cumulative knowledge on tumor biology suggest that drug combinations are more likely to cope with tumor complexity compared to single agents. in this study, we investigated the antiproliferative effect of CIGB‑300 when combined with different anticancer drugs, such as cisplatin (alkylating), paclitaxel (antimitotic), doxorubicin (antitopoisomerase II) or 5‑fluorouracil (DNA/RNA antimetabolite) in cell lines derived from lung and cervical cancer. Of note, using a Latin square design and subsequent analysis by Calcusyn software, we observed that paclitaxel and cisplatin exhibited the best synergistic/additive profile when combined with CIGB‑300, according to the combination and dose reduction indices. Such therapeutically favorable profiles may be explained by a direct cytotoxic effect and also by the observed cell cycle impairment following incubation of tumor cells with selected drug combinations. Importantly, on in vivo dose‑finding schedules in human cervical tumors xenografted in nude mice, we observed that concomitant administration of CIGB‑300 and cisplatin increased mice survival compared to single‑agent treatment. Collectively, these findings provide a rationale for combining the anti‑CK2 CIGB‑300 peptide with currently available anticancer agents in the clinical setting and indicate platins and taxanes as compounds with major perspectives.Fil: Perera, Yasser. Centro de Ingeniería Genética y Biotecnología; CubaFil: del Toro, Neylen. Centro de Ingeniería Genética y Biotecnología; CubaFil: Gorovaya, Larisa. Centro de Ingeniería Genética y Biotecnología; CubaFil: Fernandez de Cossio, Jorge. Centro de Ingeniería Genética y Biotecnología; CubaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perea, Silvio E.. Centro de Ingeniería Genética y Biotecnología; Cub

Chapter 3 PHYLOGEOGRAPHY OF SOUTHERN HEMISPHERE BLUE MUSSELS OF THE GENUS MYTILUS: EVOLUTION, BIOSECURITY, AQUACULTURE AND FOOD LABELLING

oceanography, climate change, reefs, marine science, marine conservation, marine researc

Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor

The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance

Naturaleza electrónica espín-metálica y propiedades termofísicas del molibdato de cobalto tipo perovskita Ba₂CoMoO₆

Perovskite-like materials which include magnetic elements have relevance due to the technological perspectives in the spintronics industry. In this work, the magnetic, structural and electronic properties of the Ba₂CoMoO₆ double perovskite are investigated. Calculations are carried out through the Full-Potential Linear Augmented Plane Wave method within the framework of the Density Functional Theory with exchange and correlation effects in the Generalized Gradient and Local Density approximations, including spin polarization. From the minimization of energy as a function of volume using Murnaghan’s state equation the equilibrium lattice parameter and cohesive properties of this compound were obtained. The study of the electronic structure was based in the analysis of the electronic density of states, and the band structure, showing that this compound evidences a conductive character for a spin channel and insulation for the other, and presents an integer value for the effective magnetic moment (3.0 μB), which allows it to be classified as a half-metallic material. The effects of pressure and temperature on thermophysical properties such as specific heat, Debye temperature, coefficient of thermal expansion and the Grüneisen parameter were calculated and analyzed from the state equation of the system. Obtained results reveal that, in the low-temperature regime, the specific heat at constant volume and pressure presents an analogous behavior to each other, with a tendency to the limit of Dulong-Petit typical of the structures of cubic perovskite-type, showing a value of 246.3 J/mol.K at constant volume and slightly higher values at constant pressure. The dependence of the thermal expansion coefficient, the temperature of Debye and the Grüneisen parameter with the increase in temperature are discussed in relation to other perovskite-like materials.Los materiales de tipo perovskita que incluyen elementos magnéticos tienen relevancia debido a las perspectivas tecnológicas en la industria de la espintrónica. En este trabajo se efectúa un estudio exhaustivo de las propiedades magnéticas, estructurales y electrónicas de la perovskita doble Ba₂CoMoO₆. Los cálculos se realizan a través del método de ondas planas aumentadas y linealizadas dentro del marco de la teoría del funcional de la densidad con efectos de intercambio y correlación en las aproximaciones del gradiente generalizado y de densidad local, incluyendo polarización de espín. A partir de la minimización de la energía en función del volumen, utilizando la ecuación de estado de Murnaghan, se obtuvieron el parámetro de red de equilibrio y las propiedades cohesivas de este compuesto. El estudio de la estructura electrónica se basó en el análisis de la densidad electrónica de estados y la estructura de bandas, mostrando que este compuesto evidencia un carácter conductor para un canal de espín y aislante para el otro, presentando un valor entero para el momento magnético efectivo (3.0 μB), que permite clasificarlo como un material espín-metálico. Los efectos de la presión y la temperatura sobre las propiedades termofísicas, como el calor específico, la temperatura de Debye, el coeficiente de expansión térmica y el parámetro Grüneisen, se calcularon y analizaron a partir de la ecuación de estado del sistema. Los resultados obtenidos revelan que, en el régimen de baja temperatura, el calor específico a volumen y presión constantes presenta un comportamiento análogo entre sí, con una tendencia al límite de Dulong-Petit típico de las estructuras de tipo perovskita cúbica, mostrando un valor de 246.3 J/mol.K a volumen constante y valores ligeramente más altos a presión constante. La dependencia del coeficiente de expansión térmica, la temperatura de Debye y el parámetro Grüneisen con el aumento de temperatura se discute en relación con otros materiales de tipo perovskita.Instituto de Física La PlataGrupo de Estudio de Materiales y Dispositivos Electrónico

Chromosome-Level Genome Assembly of the Blue Mussel Mytilus chilensis Reveals Molecular Signatures Facing the Marine Environment

The blue mussel Mytilus chilensis is an endemic and key socioeconomic species inhabiting the southern coast of Chile. This bivalve species supports a booming aquaculture industry, which entirely relies on artificially collected seeds from natural beds that are translocated to diverse physical–chemical ocean farming conditions. Furthermore, mussel production is threatened by a broad range of microorganisms, pollution, and environmental stressors that eventually impact its survival and growth. Herein, understanding the genomic basis of the local adaption is pivotal to developing sustainable shellfish aquaculture. We present a high-quality reference genome of M. chilensis, which is the first chromosome-level genome for a Mytilidae member in South America. The assembled genome size was 1.93 Gb, with a contig N50 of 134 Mb. Through Hi-C proximity ligation, 11,868 contigs were clustered, ordered, and assembled into 14 chromosomes in congruence with the karyological evidence. The M. chilensis genome comprises 34,530 genes and 4795 non-coding RNAs. A total of 57% of the genome contains repetitive sequences with predominancy of LTR-retrotransposons and unknown elements. Comparative genome analysis of M. chilensis and M. coruscus was conducted, revealing genic rearrangements distributed into the whole genome. Notably, transposable Steamer-like elements associated with horizontal transmissible cancer were explored in reference genomes, suggesting putative relationships at the chromosome level in Bivalvia. Genome expression analysis was also conducted, showing putative genomic differences between two ecologically different mussel populations. The evidence suggests that local genome adaptation and physiological plasticity can be analyzed to develop sustainable mussel production. The genome of M. chilensis provides pivotal molecular knowledge for the Mytilus complex

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured