108,477 research outputs found
IDENTIFICATION AND FUNCTIONAL CHARACTERIZATION OF GPCR23/LPA4 AS A CANDIDATE G PROTEIN-COUPLED RECEPTOR FOR GUANOSINE
No full textLa guanosina esercita diverse funzioni a livello del Sistema Nervoso Centrale, coinvolgendo recettori di membrana accoppiati a proteine G (GPCR) non ancora identificati. Pertanto, l’obiettivo della ricerca è stato quello di individuare e caratterizzare uno specifico recettore funzionale per la Guanosina. I dati ottenuti su linee cellulari hanno dimostrato che il legame della guanosina con le membrane plasmatiche è incrementato dall’over-espressione del GPCR23 e ridotto dal suo silenziamento ed hanno evidenziato l’attivazione di un GPCR in risposta alla guanosina. A livello cerebrale il GPCR23 è risultato essere maggiormente espresso nella regione corticale, dove si è dimostrata anche una notevole interazione funzionale della guanosina con le membrane cellulari rispetto ad altre strutture cerebrali. Presi nel loro complesso questi dati suggeriscono che il GPCR23 possa agire come recettore funzionale di membrana responsivo alla guanosina.Several studies have shown that guanine-based purines exert biological effects on the central nervous system (CNS), possibly through membrane receptors, but at the present there are not reports related to the identification of such specific receptor(s).
According to the results shown in this thesis, we have identified the first guanosine G protein-coupled receptor GPCR23, also known as LPA4 receptor. [3H]-Guanosine radioligand binding assay reveals that [3H]-Guanosine binding to membrane fractions is greatly enhanced by GPCR23 overexpression and reduced by GPCR23 silencing. Furthermore, in [35S] GTPγS binding assay experiments, Guanosine causes a functional G-protein coupled receptor activation in U87-GPCR23 overexpressing cells with an EC50= 8,067 nM. The binding site for [3H]-guanosine is highly specific as well as both lysophosphatidic acid (LPA) and guanine agonists are 10 times less effective than guanosine in displacing 50 nM [3H]-guanosine binding.
In order to correlate the effects of guanosine in the CNS to a putative interaction with specific binding sites and in particular to GPCR activation, we performed, in different brain areas [3H]-Guanosine radioligand binding assay and [35S]-GTPγS binding assay. Among the examined brain tissues, the cerebral cortex showed the highest maximal number of binding sites for Guanosine as compared to other brain regions. In each tested brain area, the saturation curves indicates the presence of a single high affinity binding site since it is resolved by non-linear regression analysis with a one-site model. In cortical membranes KD value is 143,8 nM and Bmax 3713 fmol/mg protein. The other considered areas show lower Bmax values for [3H]-Guanosine, with the following rank order: cerebral cortex>hippocampus>striatum>spinal cord. The existence of a specific receptor coupled to a G protein for guanosine in cortical membranes, thus compatible with GPCR23, is also validated by [35S] GTPγS binding assay experiments that demonstrate the activation of a G protein-coupled receptor in response to guanosine both in autoradiography sagittal sections and in cerebral cortex membranes.
With the purpose of evaluate downstream signaling activated by guanosine interaction with its binding sites; we conducted in vivo and in vitro experiments. According to our
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results, Guanosine effects in cerebral cortex may be mediated by ERK1/2 and/or PLC pathways activation. In particular, i.p. administration of 7,5 mg/kg in rats induced ERK enhanced phosphorylation in cortical tissue, with a peak effect at 30 minutes after injection . On the other hand, treatment of cortical neurons with guanosine causes at 7,5 minutes both PLCγ and ERK1/2 pathways activation.
Taken together, our findings demonstrate that GPCR23 is the first Receptor for Guanosine and suggest an involvement of GPCR23 in the functional response of cerebral cortex to Guanosine. Even if these observations do not exclude a possible involvement of other unidentified receptors, our study lays the foundation for identification of receptors responsive to Guanine-based purines (GBPs), both in nervous system and in other peripheral tissues and may provide new targets for neuroprotection and neuromodulation
Fractional porous media equations: existence and uniqueness of weak solutions with measure data
No full textWe prove existence and uniqueness of solutions to a class of porous media equations driven by the fractional Laplacian when the initial data are positive finite Radon measures on the Euclidean space Rd. For given solutions without a prescribed initial condition, the problem of existence and uniqueness of the initial trace is also addressed. By the same methods we can also treat weighted fractional porous media equations, with a weight that can be singular at the origin, and must have a sufficiently slow decay at infinity (power-like). In particular, we show that the Barenblatt-type solutions exist and are unique. Such a result has a crucial role in Grillo et al. (Discret Contin Dyn Syst 35:5927–5962, 2015), where the asymptotic behavior of solutions is investigated. Our uniqueness result solves a problem left open, even in the non-weighted case, in Vázquez (J Eur Math Soc 16:769–803, 2014)
Nuove frontiere del ruolo genitoriale. Paternità e maternità nel mondo ispano-americano
No full textRadial fast diffusion on the hyperbolic space
No full textWe consider positive radial solutions to the fast diffusion equationon the hyperbolic
space. By radial, we mean solutions depending only on the geodesic distance r from a given point o ∈ H^N. We investigate their fine asymptotics near the extinction time T in terms of a separable solution defined in terms of the unique positive energy solution, radial with respect to
o, to a semilinear elliptic problem thoroughly studied in [G.
Mancini and K. Sandeep, ‘On a semilinear elliptic equation in Hn’, Ann. Sc. Norm. Super. Pisa
Cl. Sci. 7 (2008) 635–671; M. Bonforte, F. Gazzola, G. Grillo and J. L. Vazquez, ‘Classification
of radial solutions to the Emden–Fowler equation on the hyperbolic space’, Calc. Var. Partial
Differential Equations 46 (2013) 375–401]. We show that u converges to V in relative error. Solutions
are smooth, and bounds on derivatives are given as well. In particular, sharp convergence results
as t → T are shown for spatial derivatives, again in the form of convergence in relative error
Millerandage and flower abscission in ‘Grillo’, ‘Frappato’ and ‘Nero d’Avola’ grapevines: Some probable causes
No full textSome Sicilian cultivars, in particular vintage, showed a high percentage of flower abscissions and shot berries. In this paper, to understand these phenomena, some aspects of the flower morphology of three Sicilian cultivars (two black: ‘Nero d’Avola’ and ‘Frappato’; and one white: ‘Grillo’) was studied. The number of stamens, ovule adherence to the ovary wall and pollen germination were evaluated using standard light microscopy. At harvest, seed number was counted on 30 berries per cultivar. The percentage of six stamens was lowest in ‘Frappato’ and highest in ‘Grillo’. The ovule adherence to the ovary wall was highest in ‘Frappato’ and lowest in ‘Nero d’Avola’. The percentage of pollen germination and seed number was high in ‘Frappato’ while low in ‘Grillo’. Five or six stamens were found in all cultivars. These results could partially explain the different bunch density in ‘Nero d’Avola’, ‘Grillo’ and ‘Frappato’
New roses on parade, 1939[-40], originated and introduced by N. Grillo, floriculturist
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