Palmitoylethanolamide counteracts autistic-like behaviours in BTBR T+tf/J mice: Contribution of central and peripheral mechanisms

Abstract Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental conditions characterized by impaired social interaction, and repetitive stereotyped behaviours. Interestingly, functional and inflammatory gastrointestinal diseases are often reported as a comorbidity in ASDs, indicating gut-brain axis as a novel emerging approach. Recently, a central role for peroxisome-proliferator activated receptor (PPAR)-α has been addressed in neurological functions, associated with the behaviour. Among endogenous lipids, palmitoylethanolamide (PEA), a PPAR-α agonist, has been extensively studied for its anti-inflammatory effects both at central and peripheral level. Based on this background, the aim of this study was to investigate the pharmacological effects of PEA on autistic-like behaviour of BTBR T+tf/J mice and to shed light on the contributing mechanisms. Our results showed that PEA reverted the altered behavioural phenotype of BTBR mice, and this effect was contingent to PPAR-α activation. Moreover, PEA was able to restore hippocampal BDNF signalling pathway, and improve mitochondrial dysfunction, both pathological aspects, known to be consistently associated with ASDs. Furthermore, PEA reduced the overall inflammatory state of BTBR mice, reducing the expression of pro-inflammatory cytokines at hippocampal, serum, and colonic level. The analysis of gut permeability and the expression of colonic tight junctions showed a reduction of leaky gut in PEA-treated BTBR mice. This finding together with PEA effect on gut microbiota composition suggests an involvement of microbiota-gut-brain axis. In conclusion, our results demonstrated a therapeutic potential of PEA in limiting ASD symptoms, through its pleiotropic mechanism of action, supporting neuroprotection, anti-inflammatory effects, and the modulation of gut-brain axis

The Hepatic Mitochondrial Alterations Exacerbate Meta-Inflammation in Autism Spectrum Disorders

The role of the liver in autism spectrum disorders (ASD), developmental disabilities characterized by impairments in social interactions and repetitive behavioral patterns, has been poorly investigated. In ASD, it has been shown a dysregulation of gut-brain crosstalk, a communication system able to influence metabolic homeostasis, as well as brain development, mood and cognitive functions. The liver, with its key role in inflammatory and metabolic states, represents the crucial metabolic organ in this crosstalk. Indeed, through the portal vein, the liver receives not only nutrients but also numerous factors derived from the gut and visceral adipose tissue, which modulate metabolism and hepatic mitochondrial functions. Here, we investigated, in an animal model of ASD (BTBR mice), the involvement of hepatic mitochondria in the regulation of inflammatory state and liver damage. We observed increased inflammation and oxidative stress linked to hepatic mitochondrial dysfunction, steatotic hepatocytes, and marked mitochondrial fission in BTBR mice. Our preliminary study provides a better understanding of the pathophysiology of ASD and could open the way to identifying hepatic mitochondria as targets for innovative therapeutic strategies for the disease

B23 Cartridge Prototype Manufacturing and Integration Report

This document reports on the manufacturing and assembly of the B23 Prototype cartridge to perform cryogenic noise tests @ INAF/IASF-Bologna

AlpArray-Italy: Site description and noise characterization

Within the framework of the European collaborative research initiative AlpArray (http://www.alparray.ethz. ch), the Istituto Nazionale di Geofisica e Vulcanolgia (INGV) deployed overall 20 broad-band seismic stations in Northern Italy and on two islands in the Tyrrhenian Sea (Capraia and Montecristo) during Fall-Winter 2015. The temporary deployment (16 stations) will run for two to three years and 4 INGV National Seismic Network accelerometric sites are now equipped with additional per- manent broad-band sensors. The 16 temporary stations are equipped with REF TEK 130 digitizers and Nanometrics Trillium Compact 120 s sensors, a couple have Nanometrics Trillium 120P sensors and one a Streckeisen STS2. For each site we describe the settings and discuss the noise levels, the site effects and the preliminary sensitivity analysis.Published39-528T. Sismologia in tempo realeJCR Journa

Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice

Fatty liver, oxidative stress, and mitochondrial dysfunction are key pathophysiological features of insulin resistance and obesity. Butyrate, produced by fermentation in the large intestine by gut microbiota, and its synthetic derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide, FBA, have been demonstrated to be protective against insulin resistance and fatty liver. Here, hepatic mitochondria were identified as the main target of the beneficial effect of both butyrate-based compounds in reverting insulin resistance and fat accumulation in diet-induced obese mice. In particular, butyrate and FBA improved respiratory capacity and fatty acid oxidation, activated the AMPK-acetyl-CoA carboxylase pathway, and promoted inefficient metabolism, as shown by the increase in proton leak. Both treatments consistently increased utilization of substrates, especially fatty acids, leading to the reduction of intracellular lipid accumulation and oxidative stress. Finally, the shift of the mitochondrial dynamic toward fusion by butyrate and FBA resulted in the improvement not only of mitochondrial cell energy metabolism but also of glucose homeostasis. In conclusion, butyrate and its more palatable synthetic derivative, FBA, modulating mitochondrial function, efficiency, and dynamics, can be considered a new therapeutic strategy to counteract obesity and insulin resistance

Ambient-noise tomography of the wider Vienna Basin region

We present a new 3-D shear-velocity model for the top 30 km of the crust in the wider Vienna Basin region based on surface waves extracted from ambient-noise cross-correlations. We use continuous seismic records of 63 broad-band stations of the AlpArray project to retrieve interstation Green’s functions from ambient-noise cross-correlations in the period range from 5 to 25 s. From these Green’s functions, we measure Rayleigh group traveltimes, utilizing all four components of the cross-correlation tensor, which are associated with Rayleigh waves (ZZ, RR, RZ and ZR), to exploit multiple measurements per station pair. A set of selection criteria is applied to ensure that we use high-quality recordings of fundamental Rayleigh modes. We regionalize the interstation group velocities in a 5 km × 5 km grid with an average path density of ∼20 paths per cell. From the resulting group-velocity maps, we extract local 1-D dispersion curves for each cell and invert all cells independently to retrieve the crustal shear-velocity structure of the study area. The resulting model provides a previously unachieved lateral resolution of seismic velocities in the region of ∼15 km. As major features, we image the Vienna Basin and Little Hungarian Plain as low-velocity anomalies, and the Bohemian Massif with high velocities. The edges of these features are marked with prominent velocity contrasts correlated with faults, such as the Alpine Front and Vienna Basin transfer fault system. The observed structures correlate well with surface geology, gravitational anomalies and the few known crystalline basement depths from boreholes. For depths larger than those reached by boreholes, the new model allows new insight into the complex structure of the Vienna Basin and surrounding areas, including deep low-velocity zones, which we image with previously unachieved detail. This model may be used in the future to interpret the deeper structures and tectonic evolution of the wider Vienna Basin region, evaluate natural resources, model wave propagation and improve earthquake locations, among others

Arrival angles of teleseismic fundamental mode Rayleigh waves across the AlpArray

The dense AlpArray network allows studying seismic wave propagation with high spatial resolution. Here we introduce an array approach to measure arrival angles of teleseismic Rayleigh waves. The approach combines the advantages of phase correlation as in the two-station method with array beamforming to obtain the phase-velocity vector. 20 earthquakes from the first two years of the AlpArray project are selected, and spatial patterns of arrival-angle deviations across the AlpArray are shown in maps, depending on period and earthquake location. The cause of these intriguing spatial patterns is discussed. A simple wave-propagation modelling example using an isolated anomaly and a Gaussian beam solution suggests that much of the complexity can be explained as a result of wave interference after passing a structural anomaly along the wave paths. This indicates that arrival-angle information constitutes useful additional information on the Earth structure, beyond what is currently used in inversions

Shear-wave velocity structure beneath the Dinarides from the inversion of Rayleigh-wave dispersion

Highlights • Rayleigh-wave phase velocity in the wider Dinarides region using the two-station method. • Uppermost mantle shear-wave velocity model of the Dinarides-Adriatic Sea region. • Velocity model reveals a robust high-velocity anomaly present under the whole Dinarides. • High-velocity anomaly reaches depth of 160 km in the northern Dinarides to more than 200 km under southern Dinarides. • New structural model incorporating delamination as one of the processes controlling the continental collision in the Dinarides. The interaction between the Adriatic microplate (Adria) and Eurasia is the main driving factor in the central Mediterranean tectonics. Their interplay has shaped the geodynamics of the whole region and formed several mountain belts including Alps, Dinarides and Apennines. Among these, Dinarides are the least investigated and little is known about the underlying geodynamic processes. There are numerous open questions about the current state of interaction between Adria and Eurasia under the Dinaric domain. One of the most interesting is the nature of lithospheric underthrusting of Adriatic plate, e.g. length of the slab or varying slab disposition along the orogen. Previous investigations have found a low-velocity zone in the uppermost mantle under the northern-central Dinarides which was interpreted as a slab gap. Conversely, several newer studies have indicated the presence of the continuous slab under the Dinarides with no trace of the low velocity zone. Thus, to investigate the Dinaric mantle structure further, we use regional-to-teleseismic surface-wave records from 98 seismic stations in the wider Dinarides region to create a 3D shear-wave velocity model. More precisely, a two-station method is used to extract Rayleigh-wave phase velocity while tomography and 1D inversion of the phase velocity are employed to map the depth dependent shear-wave velocity. Resulting velocity model reveals a robust high-velocity anomaly present under the whole Dinarides, reaching the depths of 160 km in the north to more than 200 km under southern Dinarides. These results do not agree with most of the previous investigations and show continuous underthrusting of the Adriatic lithosphere under Europe along the whole Dinaric region. The geometry of the down-going slab varies from the deeper slab in the north and south to the shallower underthrusting in the center. On-top of both north and south slabs there is a low-velocity wedge indicating lithospheric delamination which could explain the 200 km deep high-velocity body existing under the southern Dinarides

Crustal Thinning From Orogen to Back-Arc Basin: The Structure of the Pannonian Basin Region Revealed by P-to-S Converted Seismic Waves

We present the results of P-to-S receiver function analysis to improve the 3D image of the sedimentary layer, the upper crust, and lower crust in the Pannonian Basin area. The Pannonian Basin hosts deep sedimentary depocentres superimposed on a complex basement structure and it is surrounded by mountain belts. We processed waveforms from 221 three-component broadband seismological stations. As a result of the dense station coverage, we were able to achieve so far unprecedented spatial resolution in determining the velocity structure of the crust. We applied a three-fold quality control process; the first two being applied to the observed waveforms and the third to the calculated radial receiver functions. This work is the first comprehensive receiver function study of the entire region. To prepare the inversions, we performed station-wise H-Vp/Vs grid search, as well as Common Conversion Point migration. Our main focus was then the S-wave velocity structure of the area, which we determined by the Neighborhood Algorithm inversion method at each station, where data were sub-divided into back-azimuthal bundles based on similar Ps delay times. The 1D, nonlinear inversions provided the depth of the discontinuities, shear-wave velocities and Vp/Vs ratios of each layer per bundle, and we calculated uncertainty values for each of these parameters. We then developed a 3D interpolation method based on natural neighbor interpolation to obtain the 3D crustal structure from the local inversion results. We present the sedimentary thickness map, the first Conrad depth map and an improved, detailed Moho map, as well as the first upper and lower crustal thickness maps obtained from receiver function analysis. The velocity jump across the Conrad discontinuity is estimated at less than 0.2 km/s over most of the investigated area. We also compare the new Moho map from our approach to simple grid search results and prior knowledge from other techniques. Our Moho depth map presents local variations in the investigated area: the crust-mantle boundary is at 20–26 km beneath the sedimentary basins, while it is situated deeper below the Apuseni Mountains, Transdanubian and North Hungarian Ranges (28–33 km), and it is the deepest beneath the Eastern Alps and the Southern Carpathians (40–45 km). These values reflect well the Neogene evolution of the region, such as crustal thinning of the Pannonian Basin and orogenic thickening in the neighboring mountain belts

Rainfall Induced Horizontal Deformation in the European Eastern Alps Measured by GPS

We analyzed the time-series of continuous GPS stations operating in the Italian, Austrian, Slovenian and Croatian Alps and Dinarides with a blind-source-separation algorithm based on a variational Bayesian Independent Component Analysis method, characterizing the spatiotemporal evolution of ground displacements and crustal deformation associated to hydrological processes over a vast area of ~70.000 km2. The study area is part of the broad zone of deformation where the N-S Adria-Eurasia convergence and the E-ward escape of the Eastern Alps toward the Pannonian basin are accommodated. We characterized the spatial response and the temporal evolution of several signals, among which the most significant ones are two annual signals with spatially uniform response in the vertical and horizontal components, respectively, and a time-variable, non-cyclic, signal characterized by a spatially variable response in the horizontal components. Because of its non-uniform spatial response, this latter signal induces a succession of extensional/compressional deformation, which is larger in areas characterized by karst geology, varying in amplitudes during the study time-span (2007-2016). The orientation of the principal time-variable strain-axes is normal to the orientation of lineaments and fractures detected from the analysis of a digital elevation model and parallel to the direction of tectonic stress. We have compared the time evolution of this signal with hydrological observations by exploiting the availability of gridded datasets for the European area. The detected deformation signal is highly correlated with cumulated rainfall over a period of 180 days, suggesting that the opening of fractures in karst rocks caused by cumulated rainfall is likely the primary mechanism of this deformation signal, whose kinematics is guided by the orientation of rock's fractures. We discuss the implication that this time-variable non-tectonic deformation may have for the estimate of the long-term interseismic strain accumulation and the seismic potential of active faults in the study area