Single prazosin infusion in prelimbic cortex Fosters extinction of amphetamine-induced conditioned place preference

Exposure to drug-associated cues to induce extinction is a useful strategy to contrast cue-induced drug seeking. Norepinephrine (NE) transmission in medial prefrontal cortex has a role in the acquisition and extinction of conditioned place preference induced by amphetamine. We have reported recently that NE in prelimbic cortex delays extinction of amphetamine-induced conditioned place preference (CPP). A potential involvement of α1-adrenergic receptors in the extinction of appetitive conditioned response has been also suggested, although their role in prelimbic cortex has not been yet fully investigated. Here, we investigated the effects of the α1-adrenergic receptor antagonist prazosin infusion in the prelimbic cortex of C57BL/6J mice on expression and extinction of amphetamine-induced CPP. Acute prelimbic prazosin did not affect expression of amphetamine-induced CPP on the day of infusion, while in subsequent days it produced a clear-cut advance of extinction of preference for the compartment previously paired with amphetamine (Conditioned stimulus, CS). Moreover, prazosin-treated mice that had extinguished CS preference showed increased mRNA expression of brain-derived neurotrophic factor (BDNF) and post-synaptic density 95 (PSD-95) in the nucleus accumbens shell or core, respectively, thus suggesting that prelimbic α1-adrenergic receptor blockade triggers neural adaptations in subcortical areas that could contribute to the extinction of cue-induced drug-seeking behavior. These results show that the pharmacological blockade of α1-adrenergic receptors in prelimbic cortex by a single infusion is able to induce extinction of amphetamine-induced CPP long before control (vehicle) animals, an effect depending on contingent exposure to retrieval, since if infused far from or after reactivation it did not affect preference. Moreover, they suggest strongly that the behavioral effects depend on post-treatment neuroplasticity changes in corticolimbic network, triggered by a possible “priming” effect of prazosin, and point to a potential therapeutic power of the antagonist for maladaptive memories

SEDIMENTARY DYNAMICS OF THE MARETTIMO CONTINENTAL SHELF AND MARETTIMO CHANNEL (EGADI ISLANDS – WESTERN MEDITERRANEAN): ANALYSIS OF DEPOSITIONAL AND EROSIONAL FEATURES.

Sedimentary dynamics of the Marettimo continental shelf and Marettimo Channel (Egadi Island – Western Mediterranean), have been unveiled based on the erosive and depositional features observed at the seafloor. Different morphologic features were recognized through side scan sonar, multibeam and high-resolution seismics, acquired in the framework of national Research Projects (CARG, GebecSud, MaGIC) carried out by the Department of Earth and Marine Science (former Department of Geology and Geodesy) of the University of Palermo. Sediment samples have been also collected and analyzed. The Egadi Islands are part of the NW Sicilian offshore, and belong to the mountain chain that connects the Sicilian chain to the Maghrebides one. The Marettimo Island represents an isolated portion of the Egadi continental shelf and is separated from the rest of the archipelago by the Marettimo Channel. Previous studies allowed to recognize different kind of sedimentary structures along the seafloor. Lo Iacono and Guillén (2008) described extensive field of subaqueous dunes (Ashley, 1990) along the Marettimo inner shelf, forming on gravelly and pebbly sediments and related to strong storm events (H:5.5 m, T: 12 s). Larger dunes have been observed in the north-western sector of the inner shelf with wavelengths ranging from 1 to 2.5 m, heights between 15 cm and 30 cm and extending laterally for hundreds of meters. Moreover in the north-eastern sector of the inner shelf, sorted bedforms have been detected at a depth of 40 m: they are characterized by a width varying between 15 m and 50 m and a length that reaches hundreds of meters. In the south-eastern sector of the Marettimo outer shelf, Colantoni et al. (1993) map two groups of sedimentary structures. In the same area, Lo Iacono (2004) recognized two-dimensional and three-dimensional subaqueous dunes. 2D dunes are found at depths between 60 and 90 m and show a wavelength variable between 15 and 50 m. 3D dunes, which are found at a depth of 80 m, are characterized by a wavelength of 30 m and a lateral extent of 50 m. Morphological evidences of a strong hydrodynamic regime come also from the morphobathymetric analysis of the Marettimo Channel, that is a 24 km long submarine valley oriented NNW-SSE, with a depth ranging from a minimum of 180 m to a maximum of 370 m and a width from 2 km to 14 km. Inside the channel, south of its narrowest point, a 180 m deep bathymetric threshold separates two areas, which deepens towards opposite directions: north-west and south. The flanks of the sector that deepens towards the NW are affected by mass-wasting features (Lo Iacono et al., 2007). The western flank of the channel, which delimits the Marettimo continental shelf, is carved by gullies, making the shelf-edge very uneven. Gullies develop to a maximum depth of 280 m and have a length of 250 m and a width of 50 m. At the bottom of the channel a linear incision 20 m deep, 400 m wide and almost 3 km long, is probably generated by erosive bottom currents. On the whole, the morpho-sedimentary structures here described reveal a strong hydrodynamic regime. The morphological and textural features of the bedforms observed on the Marettimo inner continental shelf suggest the occurrence of sporadic medium to strong storm events coming from western sectors. The morphological characteristics of the Marettimo Channel reveal the occurrence of strong bottom currents probably related to the severe interchange of water masses between the Tyrrhenian Sea and the Sicily Channel. References: Ashley, G., 1990. Journal of Sedim. Petrology 60, 160–172. Colantoni, P., Ligi, M., Morsiani, M.P., Penitenti, D., 1993. UNESCO Reports in Mar. Science 58, 93–98. Lo Iacono, C., 2004. Università di Napoli ‘‘Federico II,’’ Naples, Italy. Ph.D. Thesis, 150pp... Lo Iacono, C., Catalano, R., Agate, M., 2007. VI Conv. FIST GeoItalia, Rimini (Italy), 12-14 Sept. Lo Iacono C., Guillén J., 2008. Continental Shelf Research 28, 245–256

Apelin-13 Increases Functional Connexin-43 through Autophagy Inhibition via AKT/mTOR Pathway in the Non-Myocytic Cell Population of the Heart

Studies have shown a link between the downregulation of connexin 43 (Cx43), the predominant isoform in cardiac gap junctions, and high susceptibility to cardiac arrhythmias and cardiomyocyte death. Non-myocytic cells (NMCs), the most abundant component of the heart, exert multiple cardiac functions and represent an important therapeutic target for diseased cardiac tissue. A few studies have investigated the effect of Apelin-13, an endogenous peptide with a key role in various cardiovascular functions, on Cx43 expression in cardiomyocytes. However, it remained unknown whether Apelin-13 influences Cx43 expression in NMCs. Here, we found that in NMCs, Cx43 protein expression increased after Apelin-13 treatment (100 nM for 48 h). Furthermore, dye transfer assays proved that Apelin-13-treated NMCs had a greater ability to communicate with surrounding cardiomyocytes, and this effect was abrogated by carbenoxolone, a gap junction inhibitor. Interestingly, we showed that Apelin-13 increased Cx43 through autophagy inhibition, as proved by the upregulation of p62 and LC3I, acting as 3-MA, a well-known autophagy inhibitor. In addition, Apelin-13-induced AKT and mTOR phosphorylation was abolished by LY294002 and rapamycin inhibitors resulting in Cx43 increased suppression. These results open the possibility of targeting gap junctions in NMCs with Apelin-13 as an exciting therapeutic approach with great potential

Geo-hazards of the San Vito peninsula offshore (southwestern Tyrrhenian Sea)

In this paper we present geomorphological hazard mapping of the San Vito Peninsula offshore (Sicilian margin of Tyrrhenian Sea), characterised by a very narrow continental shelf and a very dipping, tectonically active continental slope, no far from a seismogenic belt. The data set consists of morpho-bathymetric models achieved by means of multibeam survey and scattered high resolution seismic profiles. The morpho-bathymetric study highlighted some potential sites of geomorphological hazards, the most representative of which are: (i) two canyons developing from the upper slope off San Vito Cape down to the Erice basin; (ii) a dense network of small incisions across the upper slope; (iii) a very active landslide, developed onland and extending in the continental shelf close to the Scopello village. The geomorphological features that can generate submarine hazard are represented by: unstable sediment packages into canyon heads or along the upper slope; submarine canyons with regressive erosion; coastal landslides

Submarine Geomorphology and Sedimentary Features around the Egadi Islands (Western Mediterranean Sea)

The physiography, the geomorphological features and the sedimentary bedforms offshore Egadi Islands (Italy) have been illustrated and mapped through an integrated analysis of high-resolution bathymetric, seismo-acoustic and sedimentological data. The study area is characterized by a wide, up to 25 km, continental shelf which is separated by a NNW trending linear incision, the Marettimo Channel, along which several erosional and depositional features have been detected and mapped. Sedimentary prograding wedges were detected at water depths between 100-125 m along the shelf margin, which accumulated during sea level fall and lowstand stages of the last glacio-eustatic cycle (post- MIS 5.5). The study detected several slope breaks defining scarps across the continental shelf, which were interpreted as coastal cliffs that originated during the post-LGM eustatic sea level rise. Several fields of different types of sedimentary bedforms, including 2-D and 3-D hydraulic dunes and sorted bedforms, were found across the continental shelf, providing evidence of a high hydrodynamic regime affecting the seafloor. Further on, the study recognized erosive and depositional features related to bottom currents (contourites) in the Marettimo Channel. These findings provide a better understanding of the morpho-sedimentary evolution of the Egadi Islands offshore in the latest Quaternary. Moreover, they offer essential scientific support for effectively managing the most valuable priority habitats for conservation , such as Posidonia oceanica meadow and coralline algae bioconstructions (Coralligenous habitat)

Plio-Pleistocene geological evolution of the northern Sicily continental margin (southern Tyrrhenian Sea): new insights from high-resolution, multi-electrode sparker profiles

High-resolution seismic profiles were acquired in the north Sicily offshore region with an innovative, multi-tip sparker array which lacks ringing and has a base frequency around 600 Hz. The new data, combined with published data, suggest that intra-slope and extensional basins formed as a consequence of the late Miocene (?)–early Pliocene shortening and thrusting, and the middle (?)–late Pliocene continental rifting affecting the internal side of the Sicilian-Maghrebian chain. Early (?) Pleistocene to Holocene high-amplitude and high-frequency sea-level changes resulted in repeated sub-aerial exposure and flooding of the shelf, and the deposition of cyclically arranged hemipelagic and shelf sediments. An uplift of the shelf could explain the non-preservation of the transgressive and of the lowstand wedge systems tracts in the oldest sequences

Molecular mechanisms of mitotane action in adrenocortical cancer based on in vitro studies

SIMPLE SUMMARY: Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and for postoperative adjuvant therapy. It is known that mitotane destroys the adrenal cortex impairing steroidogenesis, although its exact molecular mechanism is still unclear. However, confounding factors affecting in vitro experiments could reduce the relevance of the studies. In this review, we explore in vitro studies on mitotane effects, highlighting how different experimental conditions might contribute to the controversial findings. On this basis, it may be necessary to re-evaluate the experiments taking into account their potential confounding factors such as cell strains, culture serum, lipoprotein concentration, and culture passages, which could hide important molecular results. As a consequence, the identification of novel pharmacological molecular pathways might be used in the future to implement personalized therapy, maximizing the benefit of mitotane treatment while minimizing its toxicity. ABSTRACT: Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and is increasingly used for postoperative adjuvant therapy. Mitotane action involves the deregulation of cytochromes P450 enzymes, depolarization of mitochondrial membranes, and accumulation of free cholesterol, leading to cell death. Although it is known that mitotane destroys the adrenal cortex and impairs steroidogenesis, its exact mechanism of action is still unclear. The most used cell models are H295-derived cell strains and SW13 cell lines. The diverging results obtained in presumably identical cell lines highlight the need for a stable in vitro model and/or a standard methodology to perform experiments on H295 strains. The presence of several enzymatic targets responsive to mitotane in mitochondria and mitochondria-associated membranes causes progressive alteration in mitochondrial structure when cells were exposed to mitotane. Confounding factors of culture affecting in vitro experiments could reduce the significance of any molecular mechanism identified in vitro. To ensure experimental reproducibility, particular care should be taken in the choice of culture conditions: aspects such as cell strains, culture serum, lipoproteins concentration, and culture passages should be carefully considered and explicated in the presentation of results. We aimed to review in vitro studies on mitotane effects, highlighting how different experimental conditions might contribute to the controversial findings. If the concerns pointed out in this review will be overcome, the new insights into mitotane mechanism of action observed in-vitro could allow the identification of novel pharmacological molecular pathways to be used to implement personalized therapy

Morphological description of the southeastern Cyprus outer shelf and slope regions (eastern Mediterranean)

We present here the first results of the analysis and interpretation of the swath bathymetry and side scan sonar data collected along the southeastern outer shelf and upper slope regions of the Cyprus insular margin (offshore Cape Greco). The resultant bathymetric model and the derivatives (e.g.: slope, aspect, benthic position index) are presented and analyzed in order to describe the morphology of the seabed and the main geomorphological features through quantitative indicators including morphometric indexes and statistical descriptors. The presence of deep sea coral communities (Dendrophylia ramea) in a particular location of the surveyed area is also discussed and tentatively related to the landscape morphology where the colonies are settle