Geochemistry and thermodynamic modelling of low-grade metasedimentary rocks from the Sakar-Strandja region, SE Bulgaria

Carbonate-silicate metasedimentary rocks of Triassic protolith age from the Sakar-Strandja region were affected by low-grade metamorphism in the frame of the Maritsa shear zone, which separates two first-order units of the Balkan orogenic system - Rhodopes and Srednogorie zones. The metamorphism was contemporaneous with strike-slip deformation and ductile shearing. We focus attention on whole-rock and mineral chemistry for better understanding of protoliths origin and metamorphic evolution. The major minerals assemblage comprises calcite, dolomite quartz and white mica in variable proportions, minor chlorite, feldspars and rarely biotite. The accessory phases are ilmenite, rutile, monazite and zircon. Most of the samples show well-defined foliation. The siliciclastic component corresponds to shale, wacke or arkose origin and suggests a quartzose sedimentary provenance. The majority of trace elements tend to incorporate in silicate minerals, while Sr shows pronounced preference for calcite. Chondrite normalized REE patterns correspond to continental crust. Immobile elements (La, Th, Sc, Zr, Ti) used for discrimination of tectonic regimes suggest continental island arc setting for the siliciclastic component origin. The P-T pseudosections (Perple_X 6.7.4, Connolly, 1990) combined with observed mineral assemblages and mineral chemistry isopleths of white mica, chlorite and plagioclase correspond to metamorphism in the range 200-400°C and 0.2-0.4 GPa. The results are supported by chlorite solid solution geothermometer. The thermodynamic modelling corroborates petrographic observations and confirms metamorphism at greenschist facies. Geochemical data suggest protoliths origin due to shallow marine terrigenous-carbonate sedimentation with a provenance of typical upper continental crustal composition at continental island arc tectonic setting

Computational solutions in redox lipidomics – Current strategies and future perspectives

Abstract The high chemical diversity of lipids allows them to perform multiple biological functions ranging from serving as structural building blocks of biological membranes to regulation of metabolism and signal transduction. In addition to the native lipidome, lipid species derived from enzymatic and non-enzymatic modifications (the epilipidome) make the overall picture even more complex, as their functions are still largely unknown. Oxidized lipids represent the fraction of epilipidome which has attracted high scientific attention due to their apparent involvement in the onset and development of numerous human disorders. Development of high-throughput analytical methods such as liquid chromatography coupled on-line to mass spectrometry provides the possibility to address epilipidome diversity in complex biological samples. However, the main bottleneck of redox lipidomics, the branch of lipidomics dealing with the characterization of oxidized lipids, remains the lack of optimal computational tools for robust, accurate and specific identification of already discovered and yet unknown modified lipids. Here we discuss the main principles of high-throughput identification of lipids and their modified forms and review the main software tools currently available in redox lipidomics. Different levels of confidence for software assisted identification of redox lipidome are defined and necessary steps toward optimal computational solutions are proposed

Continuous vs. discontinuous garnet growth in mylonitic micaschists from northeastern Sardinia, Italy: Evidence from LA-ICPMS trace element mapping

Garnet with complex, discontinuous zoning is a common occurrence in metamorphic terrains, and the rela tionship between major and trace element zoning can provide insight into the metamorphic evolution of the host rock. Mylonitic micaschists along the Posada-Asinara Shear Zone in the Axial Zone of the Sardinia Variscan chain contain garnet porphyroblasts, enveloped by the S2 schistosity, with distinct core and rim domains. A large garnet porphyroblasts was investigated by laser ablation-inductively coupled plasma-mass spectrometry (LA ICPMS) mapping. The major element compositional variation follows a bell-shaped zoning, with Ca and Mn contents progressively decreasing, and Fe and Mg increasing, from the core to the outer rim. LA-ICPMS mapping revealed a thin and sharp annular enrichment zone in Y, Sc, Dy, Ho, Er, Tm at the mantle-rim boundary. The trace element (TE) compositional profiles show a central enrichment area for HREE (Tm, Yb, Lu). This enrich ment decreases progressively, as a function of atomic number, for Er, Ho and Dy. Elements with even lower atomic number (Tb, Gd, Eu and Sm), are depleted in this central domain, but their content increases in broad shoulders towards the garnet rim. The position of these lateral shoulders migrates progressively rimwards with decreasing atomic number. The REE distribution, trend and behavior in the growth zones of the garnet is an example of TE control during a continuous growth ruled by diffusion-limited REE uptake. The Y + HREE annular enrichment zone, interpreted as resulting from a decrease in the garnet growth rate, reflects a short-lived episode in the garnet growth history

Multilayer corona textures in the high-pressure ultrabasic amphibolite of Mt. Nieddu, NE Sardinia (Italy): equilibrium versus disequilibrium

Rocks with coronitic textures around igneous relics of olivine and plagioclase were sampled from the ultrabasic amphibolite of Mt. Nieddu being part of the so-called Migmatite Complex of northeast Sardinia. These textures are characterized by layers of orthopyroxene and clinopyroxene around olivine, and a symplectite of clinopyroxene+spinel and garnet around plagioclase; all these minerals were overgrown by amphibole. We applied conventional geothermobarometry and pressure-temperature (P-T) pseudosection modelling of microdomains in order to constrain the main steps of the evolution of the sampled rocks. The igneous crystallization occurred at 0.2-0.5 GPa and minimum T of 780-850 °C. Garnet is the last coronitic phase formed at estimated pressures of 1.3-1.7 GPa at 680-730 °C. As similar conditions were previously determined for the pressure peak on an adjacent rock, we conclude that during corona formation chemical equilibrium was reached probably over a much wider range than of mm-sized microdomains. Slow reaction kinetics is responsible for the partial preservation of the igneous phases

Geology of the Zicavo Metamorphic Complex, southern Corsica (France)

In this study, we investigated the Zicavo Metamorphic Complex (southern Corsica), which ispart of the innermost Axial Zone of the Corsica-Sardinia Variscan belt. To better evaluate itsgeological and structural outline, a 1:5000 geological map, coupled with new structural/microstructural and petrographic data, is presented. The complex is formed by threetectonic units, from bottom to top: (i) an Orthogneiss Unit, (ii) a Leptyno-Amphibolite Unit,and (iii) a Micaschist Unit. They are separated by ductile shear zones with a top-to-the-SEsense of shear. They underwent a polyphase deformation and polymetamorphic history,with a shortening stage in the amphibolite facies, responsible for the main structures andshearing, followed by an exhumation phase

Garnet‐rich veins in an ultrabasic amphibolite from NE Sardinia, Italy: An example of vein mineralogical re‐equilibration during the exhumation of a granulite terrane

A complex system of mono‐ and polymineralic centimeter‐thick veins occurs within the ultrabasic amphibolites of Montigiu Nieddu hill in northeastern Sardinia, and they are filled with garnet, amphibole, chlorite, and epidote. Some garnet‐rich veins are margined by an amphibole layer at the interface with the host rock and/or show replacement of epidote concentrated in the vein core. Together with homogeneous matrix garnet (Grt1), millimetric, euhedral, and strongly zoned garnet porphyroblasts occur within these veins. The estimated pressure–temperature conditions (P = 1.0–1.7 GPa, T = 650–750 °C) for the formation of Grt1 match the metamorphic peak and early exhumation derived previously for the host rocks and confirm that the garnet veins also formed under high‐pressure (HP) conditions. The igneous protolith of the host rocks experienced HP metamorphism in a subduction zone and underwent exhumation in an exhumation channel. The vein system in the ultrabasic amphibolites formed by cyclic hydrofracturing as rapid and transient events such as crack‐seal veining. The growth of multiple vein‐filling mineral assemblages indicates the formation of separate vein‐producing cycles

Human Cytomegalovirus Inhibitor AL18 Also Possesses Activity against Influenza A and B Viruses

AL18, an inhibitor of human cytomegalovirus DNA polymerase, was serendipitously found to also block the interaction between the PB1 and PA polymerase subunits of influenza A virus. Furthermore, AL18 effectively inhibited influenza A virus polymerase activity and the overall replication of influenza A and B viruses. A molecular model to explain the binding of AL18 to both cytomegalovirus and influenza targets is proposed. Thus, AL18 represents an interesting lead for the development of new antivirals

Detecting similar binding pockets to enable systems polypharmacology

In the era of systems biology, multi-target pharmacological strategies hold promise for tackling disease-related networks. In this regard, drug promiscuity may be leveraged to interfere with multiple receptors: the so-called polypharmacology of drugs can be anticipated by analyzing the similarity of binding sites across the proteome. Here, we perform a pairwise comparison of 90,000 putative binding pockets detected in 3,700 proteins, and find that 23,000 pairs of proteins have at least one similar cavity that could, in principle, accommodate similar ligands. By inspecting these pairs, we demonstrate how the detection of similar binding sites expands the space of opportunities for the rational design of drug polypharmacology. Finally, we illustrate how to leverage these opportunities in protein-protein interaction networks related to several therapeutic classes and tumor types, and in a genome-scale metabolic model of leukemia

Discovery of a new class of triazole based inhibitors of acetyl transferase KAT2A

We have recently developed a new synthetic methodology that provided both N-aryl-5-hydroxytriazoles and N-pyridine-4-alkyl triazoles. A selection of these products was carried through virtual screening towards targets that are contemporary and validated for drug discovery and development. This study determined a number of potential structure target dyads of which N-pyridinium-4-carboxylic-5-alkyl triazole displayed the highest score specificity towards KAT2A. Binding affinity tests of abovementioned triazole and related analogs towards KAT2A confirmed the predictions of the in-silico assay. Finally, we have run in vitro inhibition assays of selected triazoles towards KAT2A; the ensemble of binding and inhibition assays delivered pyridyl-triazoles carboxylates as the prototype of a new class of inhibitors of KAT2A