Cannabidiol as a potential preventative treatment in a Neuregulin 1 mouse model of schizophrenia

Cannabidiol (CBD) is a non-psychoactive cannabinoid that has antipsychotic-like and anti-inflammatory properties, however its potential as a preventative drug in schizophrenia has not yet been investigated. Brain maturation during adolescent development creates a window where CBD could potentially limit the development of schizophrenia. The Neuregulin 1 transmembrane domain heterozygous (Nrg1 TM HET) mouse shows face, predictive, and construct validity as a mouse model of schizophrenia. This project sought to determine if CBD given in adolescence could prevent the development of the schizophrenia-relevant phenotype in Nrg1 TM HET mice, as well as prevent susceptibility to the psychoactive cannabinoid Δ⁹-- tetrahydrocannabinol (THC), in these mice. In Experiment 1, the baseline behavioural and neuroinflammatory phenotype of Nrg1 TM HET mice was first re-established at the novel Western Sydney University behavioural laboratory. Nrg1 mutant mice exhibited hyperlocomotion, social interaction deficits, reduced startle response, and increased sensitivity to 3 mg/kg THC, with a trend for reduced sensorimotor gating. There were no changes in neuroinflammatory markers. In Experiment 2, Nrg1 mutant and wild type-like (WT) animals were treated daily with 30 mg/kg CBD for 3 weeks during adolescence, and then tested for hyperlocomotion, social behaviour, sensorimotor gating and fear-associated learning and memory (tests informed by Experiment 1) during the subsequent 3 weeks while treatment continued. A week after these, mice completed a behavioural test battery under acute THC treatment. Chronic CBD increased locomotion in both genotypes, and after an extended period increased social behaviours in all mice, as well as reducing levels of glutamate decarboxylase (GAD) in the hippocampus. Combined, prior CBD and acute THC impaired startle habituation in Nrg1 mutants, but not WT mice. THC alone increased social behaviours in Nrg1 mice. In Experiment 3, Nrg1 TM HET and WT mice were administered CBD during adolescence and then left in the home cage until adulthood (5-6 mo) before undergoing behavioural testing. CBD had converse effects, and reduced anxiety in mutants and overallsociability and hippocampal levels of cannabinoid 1 (CB1) receptors in both genotypes, though these were found to be increased in the hippocampus of mutant animals at this age. Combined, a prior chronic course of CBD then paired with later acute THC in adulthood decreased startle in Nrg1 mutants, but not WT mice. These data suggest chronic adolescent CBD has persistent effects on the brain and behaviour and may potentiate later effects of THC, particularly in Nrg1TM HET mice

LASSCI2009.2: layered earthquake rupture forecast model for central Italy, submitted to the CSEP project

The Collaboratory for the Study of Earthquake Predictability (CSEP) selected Italy as a testing region for probabilistic earthquake forecast models in October, 2008. The model we have submitted for the two medium-term forecast periods of 5 and 10 years (from 2009) is a time-dependent, geologically based, earthquake rupture forecast that is defined for central Italy only (11-15 ̊ E; 41-45 ̊ N). The model took into account three separate layers of seismogenic sources: background seismicity; seismotectonic provinces; and individual faults that can produce major earthquakes (seismogenic boxes). For CSEP testing purposes, the background seismicity layer covered a range of magnitudes from 5.0 to 5.3 and the seismicity rates were obtained by truncated Gutenberg-Richter relationships for cells centered on the CSEP grid. Then the seismotectonic provinces layer returned the expected rates of medium-to-large earthquakes following a traditional Cornell-type approach. Finally, for the seismogenic boxes layer, the rates were based on the geometry and kinematics of the faults that different earthquake recurrence models have been assigned to, ranging from pure Gutenberg- Richter behavior to characteristic events, with the intermediate behavior named as the hybrid model. The results for different magnitude ranges highlight the contribution of each of the three layers to the total computation. The expected rates for M > 6.0 on April 1, 2009 (thus computed before the L'Aquila, 2009, Mw = 6.3 earthquake) are of particular interest. They showed local maxima in the two seismogenic-box sources of Paganica and Sulmona, one of which was activated by the L'Aquila earthquake of April 6, 2009. Earthquake rates as of August 1, 2009, (now under test) also showed a maximum close to the Sulmona source for Mw ~ 6.5; significant seismicity rates (10-4 to 10-3 in 5 years) for destructive events (magnitude up to 7.0) were located in other individual sources identified as being capable of such earthquakes in the central part of this area of the Apennines

Holocene slip rate variability along the Pernicana fault system (Mt. Etna, Italy): Evidence from offset lava flows

The eastern flank of the Mount Etna stratovolcano is affected by extension and is slowly sliding eastward into the Ionian Sea. The Pernicana fault system forms the border of the northern part of this sliding area. It consists of three E-W−oriented fault sectors that are seismically active and characterized by earthquakes up to 4.7 in magnitude (M) capable of producing ground rupture and damage located mainly along the western and central sectors, and by continuous creep on the eastern sector. A new topographic study of the central sector of the Pernicana fault system shows an overall bell-shaped profile, with maximum scarp height of 35 m in the center of the sector, and two local minima that are probably due to the complex morphological relation between fault scarp and lava flows. We determined the ages of lava flows cut by the Pernicana fault system at 12 sites using cosmogenic 3He and 40Ar/39Ar techniques in order to determine the recent slip history of the fault. From the displacement-age relations, we estimate an average throw rate of ∼2.5 mm/yr over the last 15 k.y. The slip rate appears to have accelerated during the last 3.5 k.y., with displacement rates of up to ∼15 mm/yr, whereas between 3.5 and 15 ka, the throw rate averaged ∼1 mm/yr. This increase in slip rate resulted in significant changes in seismicity rates, for instance, decreasing the mean recurrence time of M ≥ 4.7 earthquakes from ∼200 to ∼20 yr. Based on empirical relationships, we attribute the variation in seismic activity on the Pernicana fault system to factors intrinsic to the system that are likely related to changes in the volcanic system. These internal factors could be fault interdependencies (such as those across the Taupo Rift, New Zealand) or they could represent interactions among magmatic, tectonic, and gravitational processes (e.g., Kīlauea volcano, Hawaii). Given their effect on earthquake recurrence intervals, these interactions need to be fully assessed in seismic hazard evaluations

Sequence-based hazard analysis for Italy considering a grid seismic source model

Earthquakes are usually clustered in both time and space and, within each cluster, the event of highest magnitude is conventionally identified as the mainshock, while the foreshocks and the aftershocks are the events that occur before and after it, respectively. Mainshocks are the earthquakes considered in the classical formulation of the probabilistic seismic hazard analysis (PSHA), where the contribution of foreshocks and aftershocks is usually neglected. In fact, it has been shown that it is possible to rigorously, within the hypotheses of the model, account for the effect of mainshock-aftershocks sequences by means of the sequence-based PSHA (i.e., SPSHA). SPSHA extends the usability of the homogeneous Poisson process, adopted for mainshocks within PSHA, to also describe the occurrence of clusters maintaining the same input data of PSHA; i.e., the seismic rates derived by a declustered catalog. The aftershocks’ occurrences are accounted for by means of conditional non-homogeneous Poisson processes based on the modified Omori law. The seismic source model for Italy has been recently investigated, and the objective of the study herein presented is to include and evaluate the effect of aftershocks, by means of SPSHA, based on a new grid model. In the paper, the results of PSHA and SPSHA are compared, considering the spectral and return periods that are of typical interest for earthquake engineering. Finally, a comparison with the SPSHA map based on a well- established source model for Italy is also provided

Fault2SHA Central Apennines database and structuring active fault data for seismic hazard assessment

We present a database of field data for active faults in the central Apennines, Italy, including trace, fault and main fault locations with activity and location certainties, and slip-rate, slip-vector and surface geometry data. As advances occur in our capability to create more detailed fault-based hazard models, depending on the availability of primary data and observations, it is desirable that such data can be organized in a way that is easily understood and incorporated into present and future models. The database structure presented herein aims to assist this process. We recommend stating what observations have led to different location and activity certainty and presenting slip-rate data with point location coordinates of where the data were collected with the time periods over which they were calculated. Such data reporting allows more complete uncertainty analyses in hazard and risk modelling. The data and maps are available as kmz, kml, and geopackage files with the data presented in spreadsheet files and the map coordinates as txt files. The files are available at: https://doi.org/10.1594/PANGAEA.922582

Virtual Exploration of the Ring Systems Chemical Universe

Here, we explore the chemical space of all virtually possible organic molecules focusing on ring systems, which represent the cyclic cores of organic molecules obtained by removing all acyclic bonds and converting all remaining atoms to carbon. This approach circumvents the combinatorial explosion encountered when enumerating the molecules themselves. We report the chemical universe database GDB4c containing 916 130 ring systems up to four saturated or aromatic rings and maximum ring size of 14 atoms and GDB4c3D containing the corresponding 6 555 929 stereoisomers. Almost all (98.6%) of these ring systems are unknown and represent chiral 3D-shaped macrocycles containing small rings and quaternary centers reminiscent of polycyclic natural products. We envision that GDB4c can serve to select new ring systems from which to design analogs of such natural products. The database is available for download at www.gdb.unibe.ch together with interactive visualization and search tools as a resource for molecular design

The 2016 Italian seismic hazard model

The Italian reference seismic hazard model was released in 2004, but it has been adopted for the definition of seismic zones in 2006 and for building code only in 2009. At the beginning of 2015 the Seismic Hazard Center (CPS) of INGV was commissioned to coordinate the national scientific community with the aim of elaborating a new reference seismic hazard model, mainly finalized to the update of seismic code. The CPS designed a roadmap to release within 2 years a significantly renewed model, with regard both to the updated input elements and to the strategies to follow, in order to obtain a shared and largely accepted PSHA. The main requirements of the model were discussed in meetings with the experts on earthquake engineering. A public call was opened according to a transparent procedure; we received 24 proposals from many national institutions. The activities were organized in 6 tasks: project coordination, input data, seismicity models, ground motion prediction equations, computation and rendering, validation. In the first phase, the working groups of each task worked separately; in the second phase of the project they collaborated to release a final model. During the project, many scientific aspects were carefully considered, as in many other seismic hazard projects: the use of a declustered catalogue versus a non declustered one, the adoption of the logic-tree approach instead of an ensemble modeling, the definition of objective strategies to assign the weight to each single model, and so on.PublishedSantiago Chile5T. Modelli di pericolosità sismica e da maremot