Chemical probes for the adenosine receptors

Research on the adenosine receptors has been supported by the continuous discovery of new chemical probes characterized by more and more anity and selectivity for the single adenosine receptor subtypes (A1, A2A, A2B and A3 adenosine receptors). Furthermore, the development of new techniques for the detection of G protein-coupled receptors (GPCR) requires new specific probes. In fact, if in the past radioligands were the most important GPCR probes for detection, compound screening and diagnostic purposes, nowadays, increasing importance is given to fluorescent and covalent ligands. In fact, advances in techniques such as fluorescence resonance energy transfer (FRET) and fluorescent polarization, as well as new applications in flow cytometry and dierent fluorescence-based microscopic techniques, are at the origin of the extensive research of new fluorescent ligands for these receptors. The resurgence of covalent ligands is due in part to a change in the common thinking in the medicinal chemistry community that a covalent drug is necessarily more toxic than a reversible one, and in part to the useful application of covalent ligands in GPCR structural biology. In this review, an updated collection of available chemical probes targeting adenosine receptors is reported

Hierarchies of stratigraphic discontinuity surfaces in siliciclastic, carbonate and mixed siliciclastic-bioclastic tidalites: Implications for fluid migration in reservoir quality assessment

The hierarchies of the stratigraphic discontinuity surfaces observed in ancient tidalites are qualitatively assessed, aiming to evaluate their role as possible preferential conduits for fluid migration. Three outcrop examples are presented from microtidal settings of southern Italy: (i) siliciclastic tidalites consisting of quartz-rich cross-stratified sandstones generated by strong two-directional tidal currents flowing along a tidal strait; (ii) carbonate tidalites, which accumulated in a Cretaceous lagoon and tidal flat where peritidal cycles formed vertically-stacked sequences of biopeloidal and fenestral packstones, wackestones and bindstones during repeated phases of Milankovitch-scale sea-level changes; (iii) mixed, siliciclastic-bioclastic tidalites, deposited in a bay and recording offshore-transition, to shoreface wave-dominated and tide-influenced environments. Observations made during this study suggest that fluid movement can be controlled by the presence of main bounding surfaces that occur at different dimensions, from large (hectometre)-scale, to medium (decametre)-scale, to smaller (metre)-scales. These surfaces produced either by depositional or erosional processes, are characterised by different features and geometries in siliciclastic, carbonate and mixed siliciclastic-bioclastic tidalites arguably revealing complex internal pathways for fluid flows. These results suggest that fluids propagating along the main discontinuities follow a dominant sub-horizontal direction of propagation, associated with minor sub-vertical movements, due to local internal surface geometries and interconnections and a general lack of fractures. This surface-based approach to the study of fluid-flow transmission within stratified rocks represents a conceptual attempt to predict fluid mobility and reservoir potential in tidalite-bearing siliciclastic, carbonate and mixed reservoir rocks

The current status of pharmacotherapy for the treatment of Parkinson's disease: transition from single-target to multitarget therapy

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons. Motor features such as tremor, rigidity, bradykinesia and postural instability are common traits of PD. Current treatment options provide symptomatic relief to the condition but are unable to reverse disease progression. The conventional single-target therapeutic approach might not always induce the desired effect owing to the multifactorial nature of PD. Hence, multitarget strategies have been proposed to simultaneously target multiple proteins involved in the development of PD. Herein, we provide an overview of the pathogenesis of PD and the current pharmacotherapies. Furthermore, rationales and examples of multitarget approaches that have been tested in preclinical trials for the treatment of PD are also discussed

Note Illustrative della Carta geologica d'Italia alla scala 1:50.000, F. 438 Bari

<p>Note illustrative redatte per il Foglio geologico n. 438 Bari della Carta Geologica d'Italia alla scala 1:50.000. 108 pp.</p&gt

Note Illustrative della Carta geologica d'Italia alla scala 1:50.000, F. 396 San Severo

<p>Note illustrative redatte per il Foglio geologico n. 396 San Severo della Carta Geologica d'Italia alla scala 1:50.000. 148 pp.</p&gt

Il nuovo Foglio Geologico 438 “Bari” in scala 1:50.000. Un importante contributo per la conoscenza geologica dell’area metropolitana di Bari

I risultati del rilevamento geologico del Foglio 438 “Bari” in scala 1:50.000 effettuato nell’ambito del progetto CARG (Cartografia Geologica) mostrano numerose differenze rispetto a quanto riportato nella Cartografia Ufficiale in scala 1:100.000, che rappresenta tuttora la cartografia di riferimento. Le differenze rilevate, o comunque le ulteriori informazioni ottenute dai nuovi studi, sono risultate molto significative soprattutto in corrispondenza dell’area metropolitana di Bari recentemente soggette ad intensa urbanizzazione ed espansione. Tenuto conto dei tempi necessari per poter divulgare tali dati, si è ritenuto importante, in occasione del Convegno sulla “Geologia urbana di Bari ed area metropolitana”, presentare una carta in scala 1:25.000 del territorio metropolitano barese, dove emergessero tutte le novità dei nuovi rilevamenti, al fine di poter fornire uno strumento utile a tutte le figure che operano sul territorio quotidianamente e che necessitano avere dati aggiornati

Murge and Pre-murge in southern Italy: the last piece of Adria, the (almost) lost continent, attempting to became an aUGGp candidate (MurGEOpark)

In 2019, the executive of the Alta Murgia National Park (southeastern Italy) decided to propose its territory as possible inclusion in the network of the UNESCO Global Geoparks. Since then, in cooperation with the Department of Earth and Environmental Sciences (Aldo Moro University of Bari) and SIGEA, it is working to candidate the area as an aUGGp (called “MurGEOpark”). The MurGEOpark comprises the Alta Murgia area, where a Cretaceous sector of the Apulia Carbonate Platform crops out, and the adjacent Pre-Murge area, where the southwestward lateral continuation of the same platform, being flexed toward the southern Apennines mountain chain, is thinly covered by Plio-Quaternary foredeep deposits. The worldwide geological uniqueness is that the area is the only in situ remnant of the AdriaPlate, the old continent almost entirely squeezed between Africa and Europe. In such a contest, AltaMurgia is a virtually undeformed sector of Adria (the Apulia Foreland), while other territories of theplate are, and/or were, involved in the subduction/collision processes. In the MurGEOpark, the crustof Adria is still rooted to its mantle, and the Cretaceous evolution of the continent is spectacularlyrecorded in Alta Murgia thanks to the limestone succession of one of the largest peri-Tethyancarbonate platform (the Apulia Carbonate Platform). The MurGEOpark comprises also the Pre-Murge area, which represents the outer south-Apennines foredeep, whose Plio-Quaternaryevolution is spectacularly exposed thanks to an “anomalous” regional middle-late Quaternary uplift.The international value of the proposal is enriched by the presence of several geological singularities such as two paleontological jewels of very different age: a Neanderthal skeletonpreserved in speleothems within a karst cave, and one of the largest surfaces in the world withupper Cretaceous dinosaur tracks (about 25.000 footprints). Moreover, the close relationships between man and geology are spectacularly documented in the MurGEOpark: among the others, the use and conservation of water in a karst area, the prehistoric and ancestral choices ofurbanization, karst caves traditionally used as religious sites, etc. All these examples demonstratehow the MurGEOpark could offer a good opportunity to spread the geological culture to a wide and diverse audienc