Sutural simplification in Physodoceratinae (Aspidoceratidae, Ammonitina)

The estructural analysis of the shell septum interrelationship in sorne Jurassic ammonites allows us to conclude that sutural simplifications occurred throughout the phylogeny, were originated by alterations in the external morphology of the shell. In the case of Physodoceratinae the simplification observed in the morphology of the septal suture may have a double origin. First, an increase in the size of periumbilical tubercles may determine a shallowing of sutural elements and a shortening of saddle and lobe frilling. In other cases, shallowing is determined by a decrease in the whorl expansion rate, an apparent shortening of secondary branching not being observed.El análisis estructural de la interrelación concha-septo en algunos ammonites del Jurásico superior lleva a concluir que las simplificaciones suturales aparecidas a lo largo de la filogenia fueron originadas por alteraciones ocurridas en la morfología externa de la concha. En el caso concreto de la subfamilia Physodoceratinae, la simplificación observada en la morfología de la sutura puede tener un doble origen. En primer lugar, un incremento en el tamaño de los tubérculos periumbilicales puede determinar una pérdida de profundidad de los elementos de la sutura. siempre acompañada de una disminución en las indentaciones (frilling) de sillas y lóbulos. En otros casos el acortamiento en profundidad está determinado por una disminución de la tasa de expansión de la espira, sin que se observe un acortamiento aparente de las ramificaciones secundarias

Oxfordian and Kimmeridgian "Aspidoceras" in the Mediterranean. A methodological approach

In this study we present a contrastive analysis of the Null Hypothesis, established as the methodological basis for the evolutive investigation of Mediterranean "Aspidoceras" (Checa & Olóriz, 1985). This contrast is carried out using new data, and is part of a research programme which has been carefully planned. Paleogeographic, sedimentological. stratigraphic and palcobiological considerations have provided new evolutive models which in turn lead to a structural reorganization of thc Null Hypothesis. In this new structure, the Basic Evolutionary Conformations are no longer considcred as mere morphological groupings, the result of a direct reading of thc fossil record. In this way we propose morphological blocks, representing evolutive units which can be related to one another.En el presente trabajo se lleva a cabo un análisis contrastador de la Hipótesis Nula establecida como base metodológica para la investigación evolutiva de los"Aspidoceras" mediterráneos (Checa & Olóriz, 1985). Esta contrastación se lleva a cabo integrando nuevos datos y forma parte de un programa de investigación cuidadosamente planificado. Las diversas consideraciones paleogeográficas, sedimentológicas, estratigráficas y paleobiológicas han proporcionado nuevos modelos evolutivos que suponen una sustancial reorganización estructural de la Hipótesis Nula. En esta estructuración, las Configuraciones Evolutivas Básicas no son consideradas como meros grupos morfológicos, resultado de una lectura del registro fósil, sino que constituyen unidades evolutivas que pueden, por tanto, relacionarse entre sí

Crystallographic orientation inhomogeneity and crystal splitting in biogenic calcite

The calcitic prismatic units forming the outer shell of the bivalve Pinctada margaritifera have been analysed using scanning electron microscopy–electron back-scatter diffraction, transmission electron microscopy and atomic force microscopy. In the initial stages of growth, the individual prismatic units are single crystals. Their crystalline orientation is not consistent but rather changes gradually during growth. The gradients in crystallographic orientation occur mainly in a direction parallel to the long axis of the prism, i.e. perpendicular to the shell surface and do not show preferential tilting along any of the calcite lattice axes. At a certain growth stage, gradients begin to spread and diverge, implying that the prismatic units split into several crystalline domains. In this way, a branched crystal, in which the ends of the branches are independent crystalline domains, is formed. At the nanometre scale, the material is composed of slightly misoriented domains, which are separated by planes approximately perpendicular to the c-axis. Orientational gradients and splitting processes are described in biocrystals for the first time and are undoubtedly related to the high content of intracrystalline organic molecules, although the way in which these act to induce the observed crystalline patterns is a matter of future research

UBQLN4 Represses Homologous Recombination and Is Overexpressed in Aggressive Tumors

Genomic instability can be a hallmark of both human genetic disease and cancer. We identify a deleterious UBQLN4 mutation in families with an autosomal recessive syndrome reminiscent of genome instability disorders. UBQLN4 deficiency leads to increased sensitivity to genotoxic stress and delayed DNA double-strand break (DSB) repair. The proteasomal shuttle factor UBQLN4 is phosphorylated by ATM and interacts with ubiquitylated MRE11 to mediate early steps of homologous recombination-mediated DSB repair (HRR). Loss of UBQLN4 leads to chromatin retention of MRE11, promoting non-physiological HRR activity in vitro and in vivo. Conversely, UBQLN4 overexpression represses HRR and favors non-homologous end joining. Moreover, we find UBQLN4 overexpressed in aggressive tumors. In line with an HRR defect in these tumors, UBQLN4 overexpression is associated with PARP1 inhibitor sensitivity. UBQLN4 therefore curtails HRR activity through removal of MRE11 from damaged chromatin and thus offers a therapeutic window for PARP1 inhibitor treatment in UBQLN4-overexpressing tumors

Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis.

Palmitic acid (PA) induces hepatocyte apoptosis and fuels de novo ceramide synthesis in the endoplasmic reticulum (ER). Myristic acid (MA), a free fatty acid highly abundant in copra/palmist oils, is a predictor of nonalcoholic steatohepatitis (NASH) and stimulates ceramide synthesis. Here we investigated the synergism between MA and PA in ceramide synthesis, ER stress, lipotoxicity and NASH. Unlike PA, MA is not lipotoxic but potentiated PA-mediated lipoapoptosis, ER stress, caspase-3 activation and cytochrome c release in primary mouse hepatocytes (PMH). Moreover, MA kinetically sustained PA-induced total ceramide content by stimulating dehydroceramide desaturase and switched the ceramide profile from decreased to increased ceramide 14:0/ceramide16:0, without changing medium and long-chain ceramide species. PMH were more sensitive to equimolar ceramide14:0/ceramide16:0 exposure, which mimics the outcome of PA plus MA treatment on ceramide homeostasis, than to either ceramide alone. Treatment with myriocin to inhibit ceramide synthesis and tauroursodeoxycholic acid to prevent ER stress ameliorated PA plus MA induced apoptosis, similar to the protection afforded by the antioxidant BHA, the pan-caspase inhibitor z-VAD-Fmk and JNK inhibition. Moreover, ruthenium red protected PMH against PA and MA-induced cell death. Recapitulating in vitro findings, mice fed a diet enriched in PA plus MA exhibited lipodystrophy, hepatosplenomegaly, increased liver ceramide content and cholesterol levels, ER stress, liver damage, inflammation and fibrosis compared to mice fed diets enriched in PA or MA alone. The deleterious effects of PA plus MA-enriched diet were largely prevented by in vivo myriocin treatment. These findings indicate a causal link between ceramide synthesis and ER stress in lipotoxicity, and imply that the consumption of diets enriched in MA and PA can cause NASH associated with lipodystrophy

Stability of liquid bridges between twisted elliptical disks

The influence in the stability of long liquid bridges supported between two elliptical-shaped disks of their main axis relative orientation is investigated. A numerical continuation method capable of finding equilibrium shapes, both stable and unstable, is used to calculate a series of equilibrium shapes supported by disks of increasing eccentricity for different relative orientation of the disks axis. The stable or unstable character of each of the shapes is calculated to determine the position of the stability limit and its characte

Vibrational Characterization of Active Drug to the Treatment of Chagas Disease, Benznidazole by Using Force Fields and Internal Coordinates

Two experimental structures of benznidazole active drug used to the treatment of Chagas disease have been structurally characterized and its vibrational spectra completely assigned combining B3LYP/6-311++G** calculations with the experimental FT-IR and FT-Raman spectra and the SQMFF methodology. The most stable conformer of benznidazole found in the study of the potential energy surface is in agreement with that experimentally observed by X-ray diffraction at room temperature while the other one was observed with the heating up to 195 ºC. Both differs in the positions of CH2 groups of acetamide fragment. Their structural properties in gas phase and ethanol solution were computed by using natural bond orbital (NBO), atoms in molecules (AIM), Merz-Kollman (MK) charges, molecular electrostatic potentials (MEP) and frontier orbitals calculations by using the hybrid B3LYP method and the 6-31G* and 6-311++G** basis sets. Additional WB97XD/6-311++G** calculations show that the energy values optimized for the most stable species in both media present lower values than the obtained with the B3LYP/6-31G* method. The vibrational assignments for those two conformers in both media were obtained from their corresponding harmonic force fields together with the scaled force constants

Historical tropospheric and stratospheric ozone radiative forcing using the CMIP6 database

We calculate ozone radiative forcing (RF) and stratospheric temperature adjustments for the period 1850-2014 using the newly availableCMIP6 ozone dataset. The CMIP6 total ozone RF (1850s-2000s) is 0.28+/-0.17 W m-2 (which is 80% higher than our CMIP5 estimation), and 0.30+/-0.17 W m-2 out to the present day (2014). The total ozone RF grows rapidly until the 1970s, slows towards the 2000s, and shows a renewed growth thereafter. Since the 1990s the shortwave RF exceeds the longwave RF. Global stratospheric ozone RF is positive between 1930 and 1970 and then turns negative, but remains positive in the Northern Hemisphere throughout. Derived stratospheric temperature changes show a localized cooling in the subtropical lower stratosphere due to tropospheric ozone increases, and cooling in the upper stratosphere due to ozone depletion by more than 1K already prior to the satellite era (1980), and by more than 2K out to the present day(2014)