01988nas a2200133 4500008004100000245010500041210006900146260003000215520151100245100002101756700002201777700001901799856003601818 2013 en d00aEarly phase of plasticity-related gene regulation and SRF dependent transcription in the hippocampus0 aEarly phase of plasticityrelated gene regulation and SRF depende bPublic Library of Science3 aHippocampal organotypic cultures are a highly reliable in vitro model for studying neuroplasticity: in this paper, we analyze the early phase of the transcriptional response induced by a 20 µM gabazine treatment (GabT), a GABA-Ar antagonist, by using Affymetrix oligonucleotide microarray, RT-PCR based time-course and chromatin-immuno-precipitation. The transcriptome profiling revealed that the pool of genes up-regulated by GabT, besides being strongly related to the regulation of growth and synaptic transmission, is also endowed with neuro-protective and pro-survival properties. By using RT-PCR, we quantified a time-course of the transient expression for 33 of the highest up-regulated genes, with an average sampling rate of 10 minutes and covering the time interval [10:90] minutes. The cluster analysis of the time-course disclosed the existence of three different dynamical patterns, one of which proved, in a statistical analysis based on results from previous works, to be significantly related with SRF-dependent regulation (p-value<0.05). The chromatin immunoprecipitation (chip) assay confirmed the rich presence of working CArG boxes in the genes belonging to the latter dynamical pattern and therefore validated the statistical analysis. Furthermore, an in silico analysis of the promoters revealed the presence of additional conserved CArG boxes upstream of the genes Nr4a1 and Rgs2. The chip assay confirmed a significant SRF signal in the Nr4a1 CArG box but not in the Rgs2 CArG box.1 aIacono, Giovanni1 aAltafini, Claudio1 aTorre, Vincent uhttp://hdl.handle.net/1963/728701414nas a2200145 4500008004100000245008300041210006900124260002800193520092600221100002001147700002201167700002101189700002201210856003601232 2012 en d00aDecompositions of large-scale biological systems based on dynamical properties0 aDecompositions of largescale biological systems based on dynamic bOxford University Press3 aMOTIVATION: Given a large-scale biological network represented as an influence graph, in this article we investigate possible decompositions of the network aimed at highlighting specific dynamical properties.\\r\\nRESULTS: The first decomposition we study consists in finding a maximal directed acyclic subgraph of the network, which dynamically corresponds to searching for a maximal open-loop subsystem of the given system. Another dynamical property investigated is strong monotonicity. We propose two methods to deal with this property, both aimed at decomposing the system into strongly monotone subsystems, but with different structural characteristics: one method tends to produce a single large strongly monotone component, while the other typically generates a set of smaller disjoint strongly monotone subsystems.\\r\\nAVAILABILITY: Original heuristics for the methods investigated are described in the article.1 aSoranzo, Nicola1 aRamezani, Fahimeh1 aIacono, Giovanni1 aAltafini, Claudio uhttp://hdl.handle.net/1963/522601741nas a2200133 4500008004100000245007700041210006900118260001000187520130700197100002401504700002101528700002201549856003601571 2012 en d00aExploring the low-energy landscape of large-scale signed social networks0 aExploring the lowenergy landscape of largescale signed social ne bSISSA3 aAnalogously to a spin glass, a large-scale signed social network is characterized by the presence of disorder, expressed in this context (and in the social network literature) by the concept of structural balance. If, as we have recently shown, the signed social networks currently available have a limited amount of true disorder (or frustration), it is also interesting to investigate how this frustration is organized, by exploring the landscape of near-optimal structural balance. What we obtain in this paper is that while one of the networks analyzed shows a unique valley of minima, and a funneled landscape that gradually and smoothly worsens as we move away from the optimum, another network shows instead several distinct valleys of optimal or near-optimal structural balance, separated by energy barriers determined by internally balanced subcommunities of users, a phenomenon similar to the replica-symmetry breaking of spin glasses. Multiple, essentially isoenergetic, arrangements of these communities are possible. Passing from one valley to another requires one to destroy the internal arrangement of these balanced subcommunities and then to reform it again. It is essentially this process of breaking the internal balance of the subcommunities which gives rise to the energy barriers.1 aFacchetti, Giuseppe1 aIacono, Giovanni1 aAltafini, Claudio uhttp://hdl.handle.net/1963/650401286nas a2200145 4500008004100000245007900041210006900120260003300189520078400222653003101006100002401037700002101061700002201082856003601104 2011 en d00aComputing global structural balance in large-scale signed social networks.0 aComputing global structural balance in largescale signed social bNational Academy of Sciences3 aStructural balance theory affirms that signed social networks (i.e., graphs whose signed edges represent friendly/hostile interactions among individuals) tend to be organized so as to avoid conflictual situations, corresponding to cycles of negative parity. Using an algorithm for ground-state calculation in large-scale Ising spin glasses, in this paper we compute the global level of balance of very large online social networks and verify that currently available networks are indeed extremely balanced. This property is explainable in terms of the high degree of skewness of the sign distributions on the nodes of the graph. In particular, individuals linked by a large majority of negative edges create mostly \\\"apparent disorder,\\\" rather than true \\\"frustration.\\\"10aCombinatorial optimization1 aFacchetti, Giuseppe1 aIacono, Giovanni1 aAltafini, Claudio uhttp://hdl.handle.net/1963/642602106nas a2200121 4500008004300000245013400043210006900177260001900246520164000265100002101905700002201926856003601948 2010 en_Ud 00aMonotonicity, frustration, and ordered response: an analysis of the energy landscape of perturbed large-scale biological networks0 aMonotonicity frustration and ordered response an analysis of the bBioMed Central3 aBackground. \\nFor large-scale biological networks represented as signed graphs, the index of frustration measures how far a network is from a monotone system, i.e., how incoherently the system responds to perturbations.\\nResults. \\nIn this paper we find that the frustration is systematically lower in transcriptional networks (modeled at functional level) than in signaling and metabolic networks (modeled at stoichiometric level). A possible interpretation of this result is in terms of energetic cost of an interaction: an erroneous or contradictory transcriptional action costs much more than a signaling/metabolic error, and therefore must be avoided as much as possible. Averaging over all possible perturbations, however, we also find that unlike for transcriptional networks, in the signaling/metabolic networks the probability of finding the system in its least frustrated configuration tends to be high also in correspondence of a moderate energetic regime, meaning that, in spite of the higher frustration, these networks can achieve a globally ordered response to perturbations even for moderate values of the strength of the interactions. Furthermore, an analysis of the energy landscape shows that signaling and metabolic networks lack energetic barriers around their global optima, a property also favouring global order.\\nConclusion. \\nIn conclusion, transcriptional and signaling/metabolic networks appear to have systematic differences in both the index of frustration and the transition to global order. These differences are interpretable in terms of the different functions of the various classes of networks.1 aIacono, Giovanni1 aAltafini, Claudio uhttp://hdl.handle.net/1963/4055