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Abstract: Modelling hydrocarbon migration in complex depositional environments is a difficult task. This paper illustrates a workflow that has been developed in order to make use of information at seismic resolution for migration modelling purposes. After a regional identification of the main seismic sequence boundaries and systems tracts, the first step of the workflow consists in a semi-automatic classification of the sand and shale prone seismic facies that are interpretable in the seismic volume. A software based on supervised neural network techniques and textural seismic attributes supports volumetric classification. Each class represents a different facies with specific petrophysical properties (threshold pressure, porosity, irreducible water saturation, etc.), assigned according to concurrent sedimentological studies; the result is a 3D lithofacies model. Petroleum system modelling is performed on a 3D regional model up to the calculation of hydrocarbon quantities expelled from the source rock. Then migration modelling is performed on the smaller area covered by the 3D lithofacies model. Invasion percolation approach has been chosen because it allows to perform migration modelling at a scale that is small enough to maintain a sufficient detail of the channels'' shape and of their connections. A probabilistic approach allows to estimate charge risk in new prospects and to check modelling consistency. This workflow has been applied in a deep water setting in West Africa, characterized by an interconnected channel system, where a number of prospects had to be evaluated. A well was drilled in the area prior to this study, resulting dry in spite of being located in a position where the source rock is present and is deemed to have expelled interesting amounts of hydrocarbons. This study has shown that hydrocarbons expelled from the source appear to be deviated laterally by the presence of a local seal and therefore do not reach the channel system in the well location. [Copyright &y& Elsevier]

Abstract: Erbium containing glasses cover an important role in optical communications and laser technology. The local environment of the ions constituting the three dimensional network exerts a strong influence on the chemical and physical properties of the glasses. In particular the network modifier cations strongly influence the short and intermediate range order of the glass structure. The structural modifications induced by the alumina addition in the glass matrix, as a function of the erbium oxide concentration, have been studied using molecular dynamics (MD) simulations. While at low Er2O3 concentration the network former action of the Al3+ leads to a more polymerized glass network, at higher Er2O3 content the influence of the alumina on the erbium local structure is limited. Further investigation points out micro-heterogeneity in the Na+ and Ca2+ distribution as a function of the alumina concentration. [Copyright &y& Elsevier]

Abstract: Monodispersed silica colloidal spherical nanoparticles were synthesized from the hydrolysis and condensation of tetraethylorthosilicate (TEOS) by using a continuous microwave synthesis process. The flow rate was varied from 43 to 101mL/min in order to establish the optimum conditions required to obtain unagglomerated silica nanopowders. The results were compared with those obtained in batch systems. In particular the mean particle diameter became smaller than 50nm as the residence time was decreased by increasing the flow rate to 101mL/min. [Copyright &y& Elsevier]

Molecular dynamic simulations of glasses belonging to the anorthite-diopside system have been performed in order to obtain an atomistic description of the material's structure. The structural parameters obtained by the simulations allow to confirm that the glass materials are characterized by a very similar short-range environment. The main differences have been observed in the intermediate-range order of the structure that describe the distribution and the packing of the tetrahedra constituting the three-dimensional networks. It is shown that the glass materials with composition close to the two extremes, corresponding to the pure glass anorthite or pure glass diopside, display the typical structural features of the tectosilicates and inosilicates subclass of minerals, respectively, to which anorthite and diopside crystals belong. [ABSTRACT FROM AUTHOR]

Chemically inert and different coloured glasses were prepared by inserting up to 10 wt.% steel plant fly ash into different kinds of inorganic matrices. Three different matrices were tested: municipal incinerator grate ash, glass cullet and a low cost CMAS devetrifiable glass. The experimental techniques used to characterise both the starting and the heat treated (glass-ceramics) glasses were differential thermal analysis, durability and release tests, X-ray diffraction, scanning electron microscopy and colour analysis (CIELab method). The results reached suggest the possibility to recover the steel ash both as a starting material in glass and glass-ceramic formulations and as a colouring agent in place of a pure iron oxide into a colourless base system. [Copyright &y& Elsevier]

Examines the nucleation and crystal growth of diopside Ca(Mg,Al)(Si,Al)[sub 2])[sub 6] crystals. Completion of crystallization; Assessment of the activation energy; Reduction on the volume of residue.

Presents a structural and electrical study of polymeric haloplumbates(II) with heterocyclic diprotonated amines. Use of X-ray analysis in the investigation; Presence of different model type structures in polymeric haloplumbates(II); Examination of relationships between electrical properties and crystal structures.

R4092 --> Each year in the United States over 22,000 women are diagnosed with ovarian cancer leading to more than 14,000 deaths. Differential expression and activity of the Na+‐H+ Exchanger Isoform 1 (NHE1) has been demonstrated to regulate cell proliferation in ovarian cancer cells from patients. NHE1 is an 815 amino acid transmembrane transport protein that regulates intracellular pH. NHE1 is hyperactivated in various types of cancer cells leading to a pH inversion that supports both cell proliferation and invasion. A significant issue in ovarian cancer therapy is the development of drug resistance and disease recurrence. In an effort to combat these outcomes, it is hypothesized that combining common ovarian cancer therapeutic agents along with compounds that directly inhibit NHE1 activation will enhance the ability of the therapeutic agents to slow ovarian cancer progression. Two ovarian adenocarcinoma cell lines; CAOV‐3 and SKOV‐3 are used in this research. Utilizing a proliferation assay, the impact of the ovarian cancer therapeutics, Rucaparib, Olaparib, Carboplatin and Cisplatin, were assessed in the presence and absence of the NHE1 inhibitors Cariporide and Ethylisopropyl Amiloride (EIPA). Dose response curves have been generated for each therapeutic (mean ± SE n=36) to evaluate the impact of combination therapies and supplement IC50 and percent reduction values for each pair. One example includes a 46% reduction in IC50 value for carboplatin alone (47.09 mM) as compared to carboplatin plus Cariporide (25.28 mM) in CAOV‐3 cells. Reductions in IC50 values for each of the therapeutics in combination with NHE1 inhibitors ranging from 24% to 92% were seen in both cell lines. This work has been expanded to a three‐dimensional environment, investigating the impact of combination therapies in a spheroid assay. To begin to identify a mechanism for NHE1 involvement in ovarian cancer progression and treatment, a steady‐state intracellular pH was performed. It has been shown that when chemotherapeutics are paired with NHE1 inhibitors, a synergistic effect is exhibited in which the combination is more proficient at reducing cancer growth than either compound can alone. To confirm this relationship, NHE1 knockout cell lines are being created via CRISPR‐Cas9 gene editing. If this relationship is validated, it could allow a reduction in the required drug dosage while maintaining efficacy and hopefully reducing harmful side effects in patients. Our research indicates that the inhibition of NHE1 in combination with standard chemotherapeutics may serve as a potential therapeutic target in ovarian cancer treatment. [ABSTRACT FROM AUTHOR]

L5456 --> For the past decade, approximately 22,000 patients have been diagnosed annually with Ovarian Cancer which has resulted in over 13,000 deaths each year. Platinum‐based chemotherapeutics such as cisplatin and carboplatin are common first line treatments for ovarian cancer. One of the major challenges with these therapies is the development of platinum resistance and disease recurrence. The phosphatidylinositol 3‐kinase (PI3K)/AKT signaling pathway plays an important role in the regulation of cell survival, growth, and proliferation in ovarian cancer. Inhibition of PI3K and AKT signaling have been shown to negatively impact cell proliferation in ovarian cancer cells. Similarly, activation of the RhoA‐associated kinase (Rock) is known to enhance ovarian cancer cell migration and invasion. Here we evaluate the efficacy of specific kinase inhibitors to enhance the carboplatin induced reduction of cell proliferation in ovarian cancer cells. Cell proliferation is evaluated in SKOV‐3 cells in the presence of carboplatin alone and in combination with the PI3K inhibitor, LY294002, or the Rock inhibitor, Y27632. We hypothesize that combining carboplatin with a one of these kinase inhibitors will enhance carboplatin function thus decreasing the IC50 and enhancing the therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Presents the study on the structural, thermal and eletrical characterization of polymeric haloplumbate(II) systems of diprotonated amines. Role of diamine spacers in the inorganic systems; Availability of the halide atoms in bridging lead atoms; Electrical behavior of the polymeric haloplumbate systems.

Monodispersed zirconia colloidal spherical nanoparticles were synthesized from the hydrolysis and condensation of tetra- n-propylzirconate by using a continuous microwave synthesis process. The flow rate was varied from 50 to 100 mL/min in order to establish the optimum conditions required to obtain unagglomerated zirconia nanopowders. The results were compared with those obtained in batch systems. In particular as the flow rate is decreased from 100 to 50 mL/min the particle became spherical with a mean particle size of about 100 nm. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the conventional and microwave hydrothermal treatment of TiOCl2 solutions. Colloidal titania suspensions were prepared by forced hydrolysis at 195°C for different times ranging from 1 to 32 h for the conventional synthesis and from 5 min to 1 h for the microwave ones. The effect of the microwave technology on both the synthesis conditions and titania nanoparticles properties has been evaluated. Particles morphology and crystallinity were studied by using transmission electron microscopy and X-ray diffraction. The thermal and chemical stability of the obtained powders were determined by TG/DTA analysis. [ABSTRACT FROM AUTHOR]

The results of the interaction of microwave irradiation (multimode, 2.45 GHz, 100–600 W power) on tosylhydrazones, T.I., interesting intermediates in many organic reactions, were presented. T.I. were supported on silica, silica gel and alumina powders. Different inorganic salts (K2CO3Fe(NO3)39H2O) were added to the reaction mixture. The results obtained, starting from a range of different T.I., were investigated by means of mass spectrometry and1HNMR in order to understand the role of microwave irradiation and presence of inorganic additives on the reaction pathway and yields. [ABSTRACT FROM AUTHOR]

Proline-rich transmembrane protein 2 (PRRT2) is the single causative gene for pleiotropic paroxysmal syndromes, including epilepsy, kinesigenic dyskinesia, episodic ataxia, and migraine. PRRT2 is a neuron-specific type-2 membrane protein with a COOH-terminal intramembrane domain and a long proline-rich NH2-terminal cytoplasmic region. A large array of experimental data indicates that PRRT2 is a neuron stability gene that negatively controls intrinsic excitability by regulating surface membrane localization and biophysical properties of voltage-dependent Na+ channels Nav1.2 and Nav1.6, but not Nav1.1. To further investigate the regulatory role of PRRT2, we studied the structural features of this membrane protein with molecular dynamics simulations, and its structure-function relationships with Nav1.2 channels by biochemical and electrophysiological techniques. We found that the intramembrane COOH-terminal region maintains a stable conformation over time, with the first transmembrane domain forming a helix-loop-helix motif within the bilayer. The unstructured NH2- terminal cytoplasmic region bound to the Nav1.2 better than the isolated COOH-terminal intramembrane domain, mimicking full-length PRRT2, while the COOH-terminal intramembrane domain was able to modulate Na+ current and channel biophysical properties, still maintaining the striking specificity for Nav1.2 versus Nav1.1. channels. The results identify PRRT2 as a dual-domain protein in which the NH2-terminal cytoplasmic region acts as a binding antenna for Na+ channels, while the COOH-terminal membrane domain regulates channel exposure on the membrane and its biophysical properties. [ABSTRACT FROM AUTHOR]

Synapsin I (SynI) and synapsin II (SynII) are major synaptic vesicle (SV) proteins that function in the regulation of the availability of SVs for release in mature neurons. SynI and SynII show a high level of sequence similarity and share many functions in vivo, although distinct physiological roles for the two proteins have been proposed. Both SynI-/- and SynII-/- mice have a normal lifespan, but exhibit a decreased number of SVs and synaptic depression upon high-frequency stimulation. Because of the role of the synapsin proteins in synaptic organization and plasticity, we studied the long-lasting effects of synapsin deletion on the phenotype of SynI-/- and SynII-/- mice during aging. Both SynI-/- and SynII-/- mice displayed behavioural defects that emerged during aging and involved emotional memory in both mutants, and spatial memory in SynII-/- mice. These abnormalities, which were more pronounced in SynII-/- mice, were associated with neuronal loss and gliosis in the cerebral cortex and hippocampus. The data indicate that SynI and SynII have specific and non-redundant functions, and that synaptic dysfunctions associated with synapsin mutations negatively modulate cognitive performances and neuronal survival during senescence. [ABSTRACT FROM AUTHOR]

Human-induced pluripotent stem cells (hiPSCs) represent one of the main and powerful tools for the in vitro modeling of neurological diseases. Standard hiPSC-based protocols make use of animal-derived feeder systems to better support the neuronal differentiation process. Despite their efficiency, such protocols may not be appropriate to dissect neuronal specific properties or to avoid interspecies contaminations, hindering their future translation into clinical and drug discovery approaches. In this work, we focused on the optimization of a reproducible protocol in feeder-free conditions able to generate functional glutamatergic neurons. This protocol is based on a generation of neuroprecursor cells differentiated into human neurons with the administration in the culture medium of specific neurotrophins in a Geltrex-coated substrate. We confirmed the efficiency of this protocol through molecular analysis (upregulation of neuronal markers and neurotransmitter receptors assessed by gene expression profiling and expression of the neuronal markers at the protein level), morphological analysis, and immunfluorescence detection of pre-synaptic and post-synaptic markers at synaptic boutons. The hiPSC-derived neurons acquired Ca2+-dependent glutamate release properties as a hallmark of neuronal maturation. In conclusion, our study describes a new methodological approach to achieve feeder-free neuronal differentiation from hiPSC and adds a new tool for functional characterization of hiPSC-derived neurons. [ABSTRACT FROM AUTHOR]

Abstract: The management of electrical and electronic equipment waste (WEEE) is a significant problem of industrialized countries, in the last decades it has been noticed an appreciable increase of this residue, consisting of about 80% of television sets and computers containing end of life (EOL) cathode ray tubes (CRT). Specific technologies permit to dismantle the kinescope, obtaining different glasses with high quality level and specific chemical compositions. The presence of dangerous elements makes critical the re-use in many fields of application. The present work proposes the feasibility of CRT glass recycling in ceramic field using it into a base glaze formulation as substitute of “ceramic frits”. The study was conducted in two phases, laboratory scale in order to study the suitable glaze formulation and semi-industrial scale with the technological support of an Italian ceramic glaze producer. The glazes obtained have aesthetic and mechanical properties extremely similar to the standard ones. [Copyright &y& Elsevier]

Anthropogenic land subsidence can be evaluated and predicted by numerical models, which are often built over deterministic analyses. However, uncertainties and approximations are present, as in any other modeling activity of real-world phenomena. This study aims at combining data assimilation techniques with a physically-based numerical model of anthropogenic land subsidence in a novel and comprehensive workflow, to overcome the main limitations concerning the way traditional deterministic analyses use the available measurements. The proposed methodology allows to reduce uncertainties affecting the model, identify the most appropriate rock constitutive behavior and characterize the most significant governing geomechanical parameters. The proposed methodological approach has been applied in a synthetic test case representative of the Upper Adriatic basin, Italy. The integration of data assimilation techniques into geomechanical modeling appears to be a useful and effective tool for a more reliable study of anthropogenic land subsidence. [ABSTRACT FROM AUTHOR]

The opioidergic system and intrinsic brain activity, as organized in large-scale networks such as the salience network (SN), sensorimotor network (SMN), and default-mode network (DMN), play core roles in healthy behavior and psychiatric disorders. This work aimed to investigate how opioidergic signaling affects intrinsic brain activity in healthy individuals by reviewing relevant neuroanatomical, molecular, functional, and pharmacological magnetic resonance imaging studies in order to clarify their physiological links and changes in psychiatric disorders. The SN shows dense opioidergic innervations of subcortical structures and high expression levels of opioid receptors in subcortical-cortical areas, with enhanced or reduced activity with low or very high doses of opioids, respectively. The SMN shows high levels of opioid receptors in subcortical areas and functional disconnection caused by opioids. The DMN shows low levels of opioid receptors in cortical areas and inhibited or enhanced activity with low or high doses of opioids, respectively. Finally, we proposed a working model. Opioidergic signaling enhances SN and suppresses SMN (and DMN) activity, resulting in affective excitation with psychomotor inhibition; stronger increases in opioidergic signaling attenuate the SN and SMN while disinhibiting the DMN, dissociating affective and psychomotor functions from the internal states; the opposite occurs with a deficit of opioidergic signaling. [ABSTRACT FROM AUTHOR]

The study of the pathomechanisms by which gene mutations lead to neurological diseases has benefit from several cellular and animal models. Recently, induced Pluripotent Stem Cell (iPSC) technologies have made possible the access to human neurons to study nervous system disease-related mechanisms, and are at the forefront of the research into neurological diseases. In this review, we will focalize upon genetic epilepsy, and summarize the most recent studies in which iPSC-based technologies were used to gain insight on the molecular bases of epilepsies. Moreover, we discuss the latest advancements in epilepsy cell modeling. At the two dimensional (2D) level, single-cell models of iPSC-derived neurons lead to a mature neuronal phenotype, and now allow a reliable investigation of synaptic transmission and plasticity. In addition, functional characterization of cerebral organoids enlightens neuronal network dynamics in a three-dimensional (3D) structure. Finally, we discuss the use of iPSCs as the cutting-edge technology for cell therapy in epilepsy. [ABSTRACT FROM AUTHOR]

PRRT2 is a neuronal protein that controls neuronal excitability and network stability by modulating voltage-gated Na+ channel (Nav). PRRT2 pathogenic variants cause pleiotropic syndromes including epilepsy, paroxysmal kinesigenic dyskinesia and episodic ataxia attributable to loss-of-function pathogenetic mechanism. Based on the evidence that the transmembrane domain of PRRT2 interacts with Nav1.2/1.6, we focused on eight missense mutations located within the domain that show expression and membrane localization similar to the wild-type protein. Molecular dynamics simulations showed that the mutants do not alter the structural stability of the PRRT2 membrane domain and preserve its conformation. Using affinity assays, we found that the A320V and V286M mutants displayed respectively decreased and increased binding to Nav1.2. Accordingly, surface biotinylation showed an increased Nav1.2 surface exposure induced by the A320V mutant. Electrophysiological analysis confirmed the lack of modulation of Nav1.2 biophysical properties by the A320V mutant with a loss-of-function phenotype, while the V286M mutant displayed a gain-of-function with respect to wild-type PRRT2 with a more pronounced left-shift of the inactivation kinetics and delayed recovery from inactivation. The data confirm the key role played by the PRRT2-Nav interaction in the pathogenesis of the PRRT2-linked disorders and suggest an involvement of the A320 and V286 residues in the interaction site. Given the similar clinical phenotype caused by the two mutations, we speculate that circuit instability and paroxysmal manifestations may arise when PRRT2 function is outside the physiological range. [Display omitted] • Point mutations in the PRRT2 transmembrane region alter Nav1.2 channel function. • The PRRT2 elicits an increased surface exposure of Nav1.2 channels. • The PRRT2 A320V and V286M mutants have opposite effects on Nav1.2 biophysics. • The PRRT2 transmembrane region plays a key role in Nav interaction. [ABSTRACT FROM AUTHOR]

See Lerche (doi:10.1093/brain/awy073) for a scientific commentary on this article.Proline-rich transmembrane protein 2 (PRRT2) is the causative gene for a heterogeneous group of familial paroxysmal neurological disorders that include seizures with onset in the first year of life (benign familial infantile seizures), paroxysmal kinesigenic dyskinesia or a combination of both. Most of the PRRT2 mutations are loss-of-function leading to haploinsufficiency and 80% of the patients carry the same frameshift mutation (c.649dupC; p.Arg217Profs*8), which leads to a premature stop codon. To model the disease and dissect the physiological role of PRRT2, we studied the phenotype of neurons differentiated from induced pluripotent stem cells from previously described heterozygous and homozygous siblings carrying the c.649dupC mutation. Single-cell patch-clamp experiments on induced pluripotent stem cell-derived neurons from homozygous patients showed increased Na+ currents that were fully rescued by expression of wild-type PRRT2. Closely similar electrophysiological features were observed in primary neurons obtained from the recently characterized PRRT2 knockout mouse. This phenotype was associated with an increased length of the axon initial segment and with markedly augmented spontaneous and evoked firing and bursting activities evaluated, at the network level, by multi-electrode array electrophysiology. Using HEK-293 cells stably expressing Nav channel subtypes, we demonstrated that the expression of PRRT2 decreases the membrane exposure and Na+ current of Nav1.2/Nav1.6, but not Nav1.1, channels. Moreover, PRRT2 directly interacted with Nav1.2/Nav1.6 channels and induced a negative shift in the voltage-dependence of inactivation and a slow-down in the recovery from inactivation. In addition, by co-immunoprecipitation assays, we showed that the PRRT2-Nav interaction also occurs in brain tissue. The study demonstrates that the lack of PRRT2 leads to a hyperactivity of voltage-dependent Na+ channels in homozygous PRRT2 knockout human and mouse neurons and that, in addition to the reported synaptic functions, PRRT2 is an important negative modulator of Nav1.2 and Nav1.6 channels. Given the predominant paroxysmal character of PRRT2-linked diseases, the disturbance in cellular excitability by lack of negative modulation of Na+ channels appears as the key pathogenetic mechanism. [ABSTRACT FROM AUTHOR]

Heterozygous and rare homozygous mutations in PRoline-Rich Transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders including epilepsy, kinesigenic dyskinesia episodic ataxia and migraine. Most of the mutations lead to impaired PRRT2 expression and/or function. Recently, an important role for PRTT2 in the neurotransmitter release machinery, brain development and synapse formation has been uncovered. In this work, we have characterized the phenotype of a mouse in which the PRRT2 gene has been constitutively inactivated (PRRT2 KO). β-galactosidase staining allowed to map the regional expression of PRRT2 that was more intense in the cerebellum, hindbrain and spinal cord, while it was localized to restricted areas in the forebrain. PRRT2 KO mice are normal at birth, but display paroxysmal movements at the onset of locomotion that persist in the adulthood. In addition, adult PRRT2 KO mice present abnormal motor behaviors characterized by wild running and jumping in response to audiogenic stimuli that are ineffective in wild type mice and an increased sensitivity to the convulsive effects of pentylentetrazol. Patch-clamp electrophysiology in hippocampal and cerebellar slices revealed specific effects in the cerebellum, where PRRT2 is highly expressed, consisting in a higher excitatory strength at parallel fiber-Purkinje cell synapses during high frequency stimulation. The results show that the PRRT2 KO mouse reproduces the motor paroxysms present in the human PRRT2-linked pathology and can be proposed as an experimental model for the study of the pathogenesis of the disease as well as for testing personalized therapeutic approaches. [ABSTRACT FROM AUTHOR]

Proline-rich transmembrane protein 2 (PRRT2) has been identified as the single causative gene for a group of paroxysmal syndromes of infancy, including epilepsy, paroxysmal movement disorders, and migraine. On the basis of topology predictions, PRRT2 has been assigned to the recently characterized family of Dispanins, whose members share the two-transmembrane domain topology with a large N terminus and short C terminus oriented toward the outside of the cell. Because PRRT2 plays a role at the synapse, it is important to confirm the exact orientation of its N and C termini with respect to the plasma membrane to get clues regarding its possible function. Using a combination of different experimental approaches, including live immunolabeling, immunogold electron microscopy, surface biotinylation and computational modeling, we demonstrate a novel topology for this protein. PRRT2 is a type II transmembrane protein in which only the second hydrophobic segment spans the plasma membrane, whereas the first one is associated with the internal surface of the membrane and forms a helix-loop-helix structure without crossing it. Most importantly, the large proline-rich N-terminal domain is not exposed to the extracellular space but is localized intracellularly, and only the short C terminus is extracellular (Ncyt/Cexo topology). Accordingly, we show that PRRT2 interacts with the Src homology 3 domain-bearing protein Intersectin 1, an intracellular protein involved in synaptic vesicle cycling. These findings will contribute to the clarification of the role of PRRT2 at the synapse and the understanding of pathogenic mechanisms on the basis of PRRT2-related neurological disorders. [ABSTRACT FROM AUTHOR]

Cyclin-dependentkinase-5(Cdk5)wasreported todownscaleneurotransmissionbysequestering synaptic vesicles(SVs)in the release-reluctant resting pool, but the molecular targets mediating this activity remain unknown. Synapsin I (SynI), a major SV phosphoprotein involved in the regulation ofSVtrafficking and neurotransmitter release, is one of the presynaptic substrates of Cdk5, which phosphorylates it in its C-terminal region at Ser549 (site 6)andSer551 (site 7).Herewedemonstrate thatCdk5phosphorylation of SynI fine tunes the recruitment of SVsto the active recycling pool and contributes to the Cdk5-mediated homeostatic responses. Phosphorylation of SynI by Cdk5 is physiologically regulated and enhancesits binding to F-actin. The effects ofCdk5inhibitiononthe sizeanddepletion kinetics of the recycling pool, as well asonSVdistribution within the nerve terminal, are virtually abolished in mouse SynI knock-out (KO) neurons or in KO neurons expressing the dephosphomimetic SynI mutants at sites 6,7 or site 7 only. The observation that the single site-7 mutant phenocopies the effects of the deletion of SynI identifies this site as the central switch in mediating the synaptic effects ofCdk5anddemonstrates that SynI is necessaryandsufficient for achieving the effects of the kinase on SV trafficking. The phosphorylation state of SynI by Cdk5 at site 7 is regulated during chronic modification of neuronal activity and is an essential downstream effector for the Cdk5-mediated homeostatic scaling. [ABSTRACT FROM AUTHOR]

Abstract: Composites based on a commercial grade polystyrene (PS) resin containing non commercial perovskite particles were prepared by melt mixing and analyzed in terms of mechanical properties, dynamic-mechanical behavior and morphology. In particular, with the aim to study the influence of the filler size on the ultimate properties of PS based composites micro- and nano-sized perovskite La0.5Sr0.5MnO3 crystal particles, synthesized by using an efficient and rapid microwave-assisted hydrothermal route, were considered. Measurements of flexural parameters such as modulus and strength by static tests and storage modulus and damping factor by dynamic-mechanical evaluations showed better performance for nanofilled systems with respect to the ones containing micro particles, with the same filler content. Mechanical evidences were explained also by morphological observations from which a different level of filler dispersion seems to be obtained with the organization of perovskite nanosized crystals in superstructures able to support viscoelastic results. [Copyright &y& Elsevier]

Abstract: For the first time an archaeological and archaeometric work presents the discovery of glass-working evidences in the area of Dürres Roman Amphitheatre in Albania. Glasses, coming from a layer dating back to the 11th century A.D., have been object of an archaeometric characterization to determinate the chemical composition. Moreover the oxygen isotope ratio has been calculated to hypothesize the provenance of the sands used to melt the glass. Bricks and charcoals, elements linked to the kiln structure, were analyzed by thermoluminescence and radiocarbon respectively. [Copyright &y& Elsevier]

"Hypomyelination and Congenital Cataract", HCC (MIM #610532), is an autosomal recessive disorder characterized by congenital cataract and diffuse cerebral and peripheral hypomyelination. HCC is caused by deficiency of Hyccin, a protein whose biological role has not been clarified yet. Since the identification of the cell types expressing a protein of unknown function can contribute to define the physiological context in which the molecule is explicating its function, we analyzed the pattern of Hyccin expression in the central and peripheral nervous system (CNS and PNS). Using heterozygous mice expressing the b-galactosidase (LacZ) gene under control of the Hyccin gene regulatory elements, we show that the gene is primarily expressed in neuronal cells. Indeed, Hyccin-LacZ signal was identified in CA1 hippocampal pyramidal neurons, olfactory bulb, and cortical pyramidal neurons, while it did not colocalize with oligodendroglial or astrocytic markers. In the PNS, Hyccin was detectable only in axons isolated from newborn mice. In the brain, Hyccin transcript levels were higher in early postnatal development (postnatal days 2 and 10) and then declined in adult mice. In a model of active myelinogenesis, organotypic cultures of rat Schwann cells (SC)/Dorsal Root Ganglion (DRG) sensory neurons, Hyccin was detected along the neurites, while it was absent from SC. Intriguingly, the abundance of the molecule was upregulated at postnatal days 10 and 15, in the initial steps of myelinogenesis and then declined at 30 days when the process is complete. As Hyccin is primarily expressed in neurons and its mutation leads to hypomyelination in human patients, we suggest that the protein is involved in neuron-to-glia signalling to initiate or maintain myelination. [ABSTRACT FROM AUTHOR]

Post-tetanic potentiation (PTP) is a form of homosynaptic plasticity important for information processing and short-term memory in the nervous system. The synapsins, a family of synaptic vesicle (SV)-associated phosphoproteins, have been implicated in PTP. Although several synapsin functions are known to be regulated by phosphorylation by multiple protein kinases, the role of individual phosphorylation sites in synaptic plasticity is poorly understood. All the synapsins share a phosphorylation site in the N-terminal domain A (site 1) that regulates neurite elongation and SV mobilization. Here, we have examined the role of phosphorylation of synapsin domain A in PTP and other forms of short-term synaptic enhancement (STE) at synapses between cultured Helix pomatia neurons. To this aim, we cloned H. pomatia synapsin (helSyn) and overexpressed GFP-tagged wild-type helSyn or site-1-mutant helSyn mutated in the presynaptic compartment of C1-B2 synapses. We found that PTP at these synapses depends both on Ca2+/calmodulin-dependent and cAMP-dependent protein kinases, and that overexpression of the non-phosphorylatable helSyn mutant, but not wild-type helSyn, specifically impairs PTP, while not altering facilitation and augmentation. Our findings show that phosphorylation of site 1 has a prominent role in the expression of PTP, thus defining a novel role for phosphorylation of synapsin domain A in short-term homosynaptic plasticity. [ABSTRACT FROM AUTHOR]

Abstract: Charcot–Marie–Tooth neuropathies are frequent hereditary disorders of the nervous system and most cases remain without a molecular definition. Mutations in transcription factors have been previously associated to various types of this disease. Mice carrying a null mutation in Ebf2 transcription factor present peripheral nerve abnormalities. To get insight into Ebf2 function in peripheral nervous system, here we characterize the peripheral neuropathy affecting these mice. We first show that Ebf2 is largely expressed in peripheral nerve throughout postnatal development, its expression being not only restricted to non-myelin forming Schwann cells, but also involving myelin forming Schwann cells and the perineurium. As a consequence, the onset of myelination is delayed and Schwann cell differentiation markers are downregulated in Ebf2−/− mice. Later in development, myelin pathology appears less severe and characterized by isolated clusters of hypomyelinated fibers. However, we find defects in the nerve architecture, such as abnormalities of the nodal region and shorter internodal length. Furthermore, we demonstrate a significant decrease in axonal calibre, with a lack of large calibre axons, and a severe impairment of motor nerve conduction velocity and amplitude, whereas the sensory nerve parameters are less affected. Interestingly, a clinical case with peripheral motor neuropathy and clinical features similar to Ebf2−/− mice phenotype was associated with a deletion encompassing EBF2 human genomic locus. These findings demonstrate that Ebf2 is a new molecule implicated in peripheral nerve development and a potential candidate gene for peripheral nerve disorders. [Copyright &y& Elsevier]

Abstract: Municipal solid waste incinerators every year produce tons of fly ashes which, differently from coal fly ashes, contain large amounts of toxic substances (heavy metals, dioxins, furans). The stabilization/solidification (S/S) technology known as geopolymerization is proposed with the purpose to bond physically and chemically incinerator fly ashes (IFA) in a solid matrix, in order to reduce pollutant mobility. The chemical stability of geopolymers with Si/Al ratio of 1.8–1.9 and Na/Al ratio of 1.0, synthesized by alkali activation of metakaolin and the addition of 20wt% of two different kinds of IFA, is presented. The concentration of the alkaline solution, water to solid ratio and curing process have been optimized. The room temperature consolidation of IFA containing geopolymers has been tested for leachability in water for 1day, accordingly to EN 12457 regulation and extended to 7days to increase the water attack on solid granules. Leachable metals in the test solution, determined by ICP_AES, fall within limit values set by regulation for non-dangerous waste landfill disposal. Geopolymeric matrix evolution with leaching time has been also evaluated in terms of pH and electrical conductivity increase in solution. [Copyright &y& Elsevier]

Mutations in the PRRT2 gene are the main cause for a group of paroxysmal neurological diseases including paroxysmal kinesigenic dyskinesia, episodic ataxia, benign familial infantile seizures, and hemiplegic migraine. In the mature central nervous system, the protein has both a functional and a structural role at the synapse. Indeed, PRRT2 participates in the regulation of neurotransmitter release, as well as of actin cytoskeleton dynamics during synaptogenesis. Here, we show a role of the protein also during early stages of neuronal development. We found that PRRT2 accumulates at the growth cone in cultured hippocampal neurons. Overexpression of the protein causes an increase in the size and the morphological complexity of growth cones. In contrast, the growth cones of neurons derived from PRRT2 KO mice are smaller and less elaborated. Finally, we demonstrated that the aberrant shape of PRRT2 KO growth cones is associated with a selective alteration of the growth cone actin cytoskeleton. Our data support a key role of PRRT2 in the regulation of growth cone morphology during neuronal development. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s10596-021-10079-6 [ABSTRACT FROM AUTHOR]

Synapsins are synaptic vesicle-associated phosphoproteins implicated in the regulation of neurotransmitter release. Synapsin I is the major binding protein for the SH3 domain of the kinase c-Src in synaptic vesicles. Its binding leads to stimulation of synaptic vesicle-associated c-Src activity. We investigated the mechanism and role of Src activation by synapsins on synaptic vesicles. We found that synapsin is tyrosine phosphorylated by c-Src in vitro and on intact synaptic vesicles independently of its phosphorylation state on serine. Mass spectrometry revealed a single major phosphorylation site at Tyr301, which is highly conserved in all synapsin isoforms and orthologues. Synapsin tyro- sine phosphorylation triggered its binding to the SH2 domains of Src or Fyn. However, synapsin selectively activated and was phosphorylated by Src, consistent with the specific enrichment of c-Src in synaptic vesicles over Fyn or n-Src. The activity of Src on synaptic vesicles was controlled by the amount of vesicle-associated synapsin, which is in turn dependent on synapsin serine phosphorylation. Synaptic vesicles depleted of synapsin in vitro or derived from synapsin null mice exhibited greatly reduced Src activity and tyrosine phosphorylation of other synaptic vesicle proteins. Disruption of the Src-synapsin interaction by internalization of either the Src SH3 or SH2 domains into synaptosomes decreased synapsin tyrosine phosphorylation and concomitantly increased neurotransmitter release in response to Ca2+-ionophores. We conclude that synapsin is an endogenous substrate and activator of synaptic vesicle-associated c-Src and that regulation of Src activity on synaptic vesicles participates in the regulation of neurotransmitter release by synapsin. [ABSTRACT FROM AUTHOR]

Abstract: The evaluation of the exploration risk in the oil industry is a fundamental component of the decision process related to the exploratory phase. In this paper the two basic components of the exploratory risk: trap geometry and trapped hydrocarbon quantities (fluid), are compounded in a single coherent uncertainty and sensitivity approach. The results clarify that the model geometry influences each Petroleum System Modeling step and that the geometric uncertainty is correlated with the fluid uncertainty. The geometric uncertainty evaluation makes use of geostatistical techniques that produce a number of possible realizations of the trap geometry, all compatible with available data. The evaluation of the fluid uncertainty, through a Monte Carlo methodology, allows us to compute the possible quantities of oil and gas, generated in a basin and migrated from the hydrocarbon source location to each single trap. The final result is the probability distribution of oil and gas for each trap in the basin, together with other useful indicators like: the hydrocarbon filling probability map, the closure probability map, the drainage area probability map, the spilling paths probabilities, the trap-filling scenarios. [Copyright &y& Elsevier]

In developing neurons, synaptic vesicles (SVs) undergo cycles of exo-endocytosis along isolated axons. However, it is currently unknown whether SV exocytosis is regulated before synaptogenesis. Here, we show that cAMP-dependent pathways affect SV distribution and recycling in the axonal growth cone and that these effects are mediated by the SV-associated phosphoprotein synapsin I. The presence of synapsin I on SVs is necessary for the correct localization of the vesicles in the central portion of the growth cone. Phosphorylation of synapsin I by cAMP-dependent protein kinase (protein kinase A) causes the dissociation of the protein from the SV membrane, allowing diffusion of the vesicles to the periphery of the growth cone and enhancing their rate of recycling. These results provide new clues as to the bases of the well known activity of synapsin I in synapse maturation and indicate that molecular mechanisms similar to those operating at mature nerve terminals are active in developing neurons to regulate the SV life cycle before synaptogenesis. [ABSTRACT FROM AUTHOR]

• TRPV1 antagonists are effective in animal models of anxiety and depression. • TRPV1 antagonism reduces addictive-like behaviours in animal models. • TRPV1 modulation of endocannabinoid, opioid and reward systems might mediate these effects. • Few results include schizophrenic- and obsessive-compulsive-like behaviours and model of fibromyalgia. • Studies on clinical populations are lacking. Transient Receptor Potential Vanilloid 1 (TRPV1) channels are non-selective cationic polymodal receptors gated by several different chemical and physical stimuli. TRPV1 receptors are distributed in several brain areas and interact with important neurotransmitter systems linked to mental disorders, such as endocannabinoid and opioid systems. The increasing number of results obtained in this field has recently attracted growing attention to these receptors as potential targets for the treatment of different psychiatric conditions. To review the available results on this topic, we searched on PubMed, Embase and Science Direct databases up to May 2020 using the following search string: "TRPV1", thus including a total of 48 studies. The results, still limited to preclinical studies, suggest that TRPV1 antagonism could represent a potential mechanism for the treatment of depression and anxiety, as well as for opioids, methamphetamine and cocaine addiction. Few available results consider schizophrenia-like behaviours, suggesting an intriguing role of TRPV1 receptors in the neurobiology of major psychoses. Single studies report the effectiveness of TRPV1 antagonists in animal models of obsessive-compulsive disorder and fibromyalgia. Future preclinical and clinical studies are required to shed further light on the feasibility of the use of TRPV1 modulators in psychopharmacology. [ABSTRACT FROM AUTHOR]

MAPK/Erk is a protein kinase activated by neurotrophic factors involved in synapse formation and plasticity, which acts at both the nuclear and cytoplasmic level. Synapsin proteins are synaptic-vesicle-associated proteins that are well known to be MAPK/Erk substrates at phylogenetically conserved sites. However, the physiological role of MAPK/Erk-dependent synapsin phosphorylation in regulating synaptic formation and function is poorly understood. Here, we examined whether synapsin acts as a physiological effector of MAPK/Erk in synaptogenesis and plasticity. To this aim, we developed an in vitro model of soma-to-soma paired Helix B2 neurons, that establish bidirectional excitatory synapses. We found that the formation and activity-dependent short-term plasticity of these synapses is dependent on the MAPK/Erk pathway. To address the role of synapsin in this pathway, we generated non-phosphorylatable and pseudo-phosphorylated Helix synapsin mutants at the MAPK/Erk sites. Overexpression experiments revealed that both mutants interfere with presynaptic differentiation, synapsin clustering, and severely impair post-tetanic potentiation, a form of short-term homosynaptic plasticity. Our findings show that MAPK/Erk-dependent synapsin phosphorylation has a dual role both in the establishment of functional synaptic connections and their short-term plasticity, indicating that some of the multiple extranuclear functions of MAPK/Erk in neurons can be mediated by the same multifunctional presynaptic target. [ABSTRACT FROM AUTHOR]

Abstract: This work displays the lines of a project about vitreous materials used in Roman Republican Age opus vermiculatum mosaics from Italy. This mosaic technique, originated in Egypt and Greece during the Hellenistic Age, testifies the fist evidences of vitreous materials used in mosaics: faience and glasses. The use of these materials in vermiculata mosaics from Italy was almost unknown when this research was started, so it was necessary to map and characterize the whole mosaic production. After a survey operated by a portable digital microscope, a reduced number of samples were collected to perform a laboratory characterization (OM, SEM–EDS, XRD). Data have been completed by an isotope ratio characterization (SIMS) to investigate the glasses raw materials provenance. [Copyright &y& Elsevier]

Synapsins are synaptic-vesicle-associated phosphoproteins implicated in the regulation of neurotransmitter release and excitability of neuronal networks. Mutation of synapsin genes in mouse and human causes epilepsy. To understand the role of the highly conserved synapsin domain E in the dynamics of release from mammalian inhibitory neurons, we generated mice that selectively overexpress the most conserved part of this domain in cerebellar Purkinje cells. At Purkinje-cell--nuclear-neuron synapses, transgenic mice were more resistant to depression induced by short or prolonged high-frequency stimulations. The increased synaptic performance was accompanied by accelerated release kinetics and shorter synaptic delay. Despite a marked decrease in the total number of synaptic vesicles, vesicles at the active zone were preserved or slightly increased. The data indicate that synapsin domain E increases synaptic efficiency by accelerating both the kinetics of exocytosis and the rate of synaptic vesicle cycling and decreasing depression at the inhibitory Purkinje-cell--nuclear-neuron synapse. These effects may increase the sensitivity of postsynaptic neurons to inhibition and thereby contribute to the inhibitory control of network activity. [ABSTRACT FROM AUTHOR]

Early B-cell factor 2 (EBF2) is one of four mammalian members of an atypical helix-loop-helix transcription factor family (COE). COE proteins have been implicated in various aspects of nervous and immune system development. We and others have generated and described mice carrying a null mutation of Ebf2, a gene previously characterized in the context of Xenopus laevis primary neurogenesis and neuronal differentiation. In addition to deficits in neuroendocrine and olfactory development, and peripheral nerve maturation, Ebf2 null mice feature an ataxic gait and obvious motor deficits associated with clear-cut abnormalities of cerebellar development. The number of Purkinje cells (PCs) in the Ebf2 null is markedly decreased, resulting in a small cerebellum with notable foliation defects, particularly in the anterior vermis. We show that this stems from the defective migration of a molecularly defined PC subset that subsequently dies by apoptosis. Part of the striped cerebellar topography is disrupted due to cell death and, in addition, many of the surviving PCs, that would normally adopt a zebrin II-negative phenotype, transdifferentiate to Zebrin II-positive, an unprecedented finding suggesting that Ebf2 is required for the establishment of a proper cerebellar cortical map. [ABSTRACT FROM AUTHOR]