Ketamine induction of p53-dependent apoptosis and oxidative stress in zebrafish (Danio rerio) embryos

Ketamine is a widely used pharmaceutical that has been detected in water sources worldwide. Zebrafish embryos were used in this study to investigate the oxidative stress and apoptotic signals following a 24h exposure to different ketamine concentrations (0, 50, 70 and 90 mg L-1). Early blastula embryos (∼2 h post fertilisation-hpf) were exposed for 24 h and analysed at 8 and 26 hpf. Reactive oxygen species and apoptotic cells were identified in vivo, at 26 hpf. Enzymatic activities (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE)), glutathione levels (oxidised (GSSG) and reduced (GSH)), oxidative damage (lipid peroxidation (LPO) and protein carbonyls (CO)) as well as oxidative stress (gclc, gstp1, sod1 and cat), apoptosis (casp3a, casp6, casp8, casp9, aifm1 and tp53) and cell proliferation (pcna) related-genes were evaluated at 8 and 26 hpf. Caspase (3 and 9) activity was also determined at both time-points by colorimetric methods. Superoxide dismutase (SOD), catalase (CAT), glutathione levels (GSSG), caspase-9 and reactive oxygen species (ROS) were shown to be affected by ketamine exposure while in vivo analysis showed no difference in ROS. A significant up-regulation of superoxide dismutase (sod1) and catalase (cat) genes expression was also perceived. Ketamine-induced apoptosis was observed in vivo and confirmed by the apoptotic-related genes up-regulation. The overall results suggest that ketamine induced oxidative stress and apoptosis through the involvement of p53-dependent pathways in zebrafish embryos which could be important for the evaluation of the overall risk of ketamine in aquatic environments.This work was supported by European Investment Funds by FEDER/COMPETE/POCI– Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and FCOMP-01-0124-FEDER-028683 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the projects PTDC/CVT-WEL/4672/2012 and UID/AGR/04033/2013 and by individual funding provided by postdoctoral fellowship SFRH/BPD/103006/2014 issued by FCT

A new Early Cretaceous lizard in Myanmar amber with exceptionally preserved integument

We here report on a well-preserved juvenile lizard specimen in Albian amber (ca. 110 mya) from the Hkamti site (Myanmar). This new taxon is represented by an articulated skull and the anterior portion of the trunk, including the pectoral girdle and forelimbs. The scleral ossicles and eyelid are also visible, and the specimen exhibits pristine detail of the integument (of both head and body). In a combined molecular and morphological analysis, it was consistently recovered as a scincoid lizard (Scinciformata), as sister to Tepexisaurus + Xantusiidae. However, the phylogenetic position of the new taxon should be interpreted with caution as the holotype is an immature individual. We explored the possibility of miscoding ontogenetically variable characters by running alternative analyses in which these characters were scored as missing data for our taxon. With the exception of one tree, in which it was sister to Amphisbaenia, the specimen was recovered as a Pan-xantusiid. Moreover, we cannot rule out the possibility that it represents a separate lineage of uncertain phylogenetic position, as it is the case for many Jurassic and Cretaceous taxa. Nonetheless, this fossil offers a rare opportunity to glimpse the external appearance of one group of lizards during the Early Cretaceous

Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults

It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-ꞵ (Aꞵ42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in two samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein [FABP3], total-tau, neurogranin, and neurofilament light [NFL] (n=189, scans=721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy. Brain atrophy was not moderated by Aꞵ42 and the associations between NFL and FABP3 with brain atrophy were independent of p-tau. The spatial pattern of cortical atrophy associated with the biomarkers overlapped with neurogenetic profiles associated with expression in the axonal (total-tau, NFL) and dendritic (neurogranin) components. CSF biomarkers of neurodegeneration are useful for predicting specific features of brain atrophy in older adults, independently of amyloid and tau pathology biomarkers

Cohabitation in Brazil : historical legacy and recent evolution

The availability of the micro data in the IPUMS samples for several censuses spanning a period of 40 years permits a detailed study of differentials and trends in cohabitation in Brazil than has hitherto been the case. The gist of the story is that the historical race/class and religious differentials and the historical spatial contrasts have largely been maintained, but are now operating at much higher levels than in the 1970s. During the last 40 years cohabitation has dramatically increased in all strata of the Brazilian population, and it has spread geographically to all areas in tandem with further expansions in the regions that had historically higher levels to start with. Moreover, the probability of cohabiting depends not only on individual-level characteristics but also on additional contextual effects operating at the level of meso-regions. The rise of cohabitation in Brazil fits the model of the "Second demographic transition", but it is grafted onto a historical pattern which is still manifesting itself in a number of ways

Quantum States and Phases in Driven Open Quantum Systems with Cold Atoms

An open quantum system, whose time evolution is governed by a master equation, can be driven into a given pure quantum state by an appropriate design of the system-reservoir coupling. This points out a route towards preparing many body states and non-equilibrium quantum phases by quantum reservoir engineering. Here we discuss in detail the example of a \emph{driven dissipative Bose Einstein Condensate} of bosons and of paired fermions, where atoms in an optical lattice are coupled to a bath of Bogoliubov excitations via the atomic current representing \emph{local dissipation}. In the absence of interactions the lattice gas is driven into a pure state with long range order. Weak interactions lead to a weakly mixed state, which in 3D can be understood as a depletion of the condensate, and in 1D and 2D exhibits properties reminiscent of a Luttinger liquid or a Kosterlitz-Thouless critical phase at finite temperature, with the role of the ``finite temperature'' played by the interactions.Comment: 9 pages, 2 figure

The Structural Architecture of an Infectious Mammalian Prion Using Electron Cryomicroscopy

The structure of the infectious prion protein (PrPSc), which is responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has escaped all attempts at elucidation due to its insolubility and propensity to aggregate. PrPSc replicates by converting the non-infectious, cellular prion protein (PrPC) into the misfolded, infectious conformer through an unknown mechanism. PrPSc and its N-terminally truncated variant, PrP 27-30, aggregate into amorphous aggregates, 2D crystals, and amyloid fibrils. The structure of these infectious conformers is essential to understanding prion replication and the development of structure-based therapeutic interventions. Here we used the repetitive organization inherent to GPI-anchorless PrP 27-30 amyloid fibrils to analyze their structure via electron cryomicroscopy. Fourier-transform analyses of averaged fibril segments indicate a repeating unit of 19.1 Å. 3D reconstructions of these fibrils revealed two distinct protofilaments, and, together with a molecular volume of 18,990 Å3, predicted the height of each PrP 27-30 molecule as ~17.7 Å. Together, the data indicate a four-rung β-solenoid structure as a key feature for the architecture of infectious mammalian prions. Furthermore, they allow to formulate a molecular mechanism for the replication of prions. Knowledge of the prion structure will provide important insights into the self-propagation mechanisms of protein misfolding

Libration-driven flows in ellipsoidal shells

Planets and satellites can undergo physical librations, which consist of forced periodic variations in their rotation rate induced by gravitational interactions with nearby bodies. This mechanical forcing may drive turbulence in interior fluid layers such as subsurface oceans and metallic liquid cores through a libration‐driven elliptical instability (LDEI) that refers to the resonance of two inertial modes with the libration‐induced base flow. LDEI has been studied in the case of a full ellipsoid. Here we address for the first time the question of the persistence of LDEI in the more geophysically relevant ellipsoidal shell geometries. In the experimental setup, an ellipsoidal container with spherical inner cores of different sizes is filled with water. Direct side view flow visualizations are made in the librating frame using Kalliroscope particles. A Fourier analysis of the light intensity fluctuations extracted from recorded movies shows that the presence of an inner core leads to spatial heterogeneities but does not prevent LDEI. Particle image velocimetry and direct numerical simulations are performed on selected cases to confirm our results. Additionally, our survey at a fixed forcing frequency and variable rotation period (i.e., variable Ekman number, E) shows that the libration amplitude at the instability threshold varies as ∼E⁰·⁶⁵. This scaling is explained by a competition between surface and bulk dissipation. When extrapolating to planetary interior conditions, this leads to the E1/2 scaling commonly considered. We argue that Enceladus' subsurface ocean and the core of the exoplanet 55 CnC e should both be unstable to LDEI

The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel

Erosion Surface and Granitic Morphology in the Sierra de Lihuel Calel, Province of La Pampa, Argentina

Fil: Aguilera, Emilia Yolanda. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Sato, Ana María. Centro de Investigaciones Geológicas (CIG). Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Llambías, Eduardo Jorge. Centro de Investigaciones Geológicas (CIG). Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Tickyj, Hugo. Departamento de Ciencias Naturales. Facultad de Ciencias Exactas y Naturales. Universidad Nacional de La Pampa; Argentin