The appearance and promotion of creativity by various levels of interdependent networks

Creativity and talent is promoted by specific network structures and positions. Creative nodes are positioned in the overlap of many network communities, and have a highly dynamic and independent status. Creative nodes appear at the molecular, cellular and social levels, and are supported by the rest of the network. As examples of talent support networks the Hungarian research student movement, its international network, the Network of Youth Excellence, the Hungarian talent support network (helping more than 25,000 talented people in the last two years) and the currently developing EU talent support network will be introduced. The establishment of a world-wide talent support network would uncover huge local talent reserves, would provide the best support to them, and by creating millions of novel creative node positions would magnify the talent-capacity of the whole Earth. © 2013 International Research Association for Talent Development and Excellence

Allo-network drugs: Extension of the allosteric drug concept to protein-protein interaction and signaling networks

Allosteric drugs are usually more specific and have fewer side effects than orthosteric drugs targeting the same protein. Here, we overview the current knowledge on allosteric signal transmission from the network point of view, and show that most intra-protein conformational changes may be dynamically transmitted across protein-protein interaction and signaling networks of the cell. Allo-network drugs influence the pharmacological target protein indirectly using specific inter-protein network pathways. We show that allo-network drugs may have a higher efficiency to change the networks of human cells than those of other organisms, and can be designed to have specific effects on cells in a diseased state. Finally, we summarize possible methods to identify allo-network drug targets and sites, which may develop to a promising new area of systems-based drug design

Hősokk és metabolikus stressz pályák kölcsönhatásai az öregedésben = Heat-shock and metabolic stress responses in aging

Az öregedés egyik oka a stresszválaszok, így az immunválasz gyengülése. A kalória csökkentés és a -mimetikus resveratrol élettartam-növelő hatását számos tanulmány kimutatta. A kalória csökkentés és a resveratrol aktiválja a szirtuin Sir2-t, a HSF1 hősokkválasz és az Nrf2 oxidatív stresszválasz regulátorokat, azonban háttérben meghúzódó molekuláris mechanizmusok és a különféle stresszpályák közötti kapcsolatok jórészt feltáratlanok. Pályázatunk a következő megfigyelésekhez vezetett: (1) a resveratrol-indukált élettartam-növekedés és hőstressztolerancia mind a SIR-2.1, mind a HSF1 ortológot, a kalória megvonás kizárólag a HSF1-et igényli C. elegans-ban (2) korábbi megfigyelésekkel ellentétben a SIR-2.1 túltermelés nem növeli meg a fonálférgek élettartamát (3) az emlős SIRT1 túltermelése deacetiláz aktivitásától függetlenül megvéd a denaturált fehérjék citotoxikus hatásától (4) a SIRT1 a Hsp90 chaperont igényli funkciójához (5) az oxidatív stressz gátolja a hőstressz-adaptációt és a hősokk választ (6) az antioxidatív regulátor SKN-1 szükséges a C. elegans természetes immunitásához. Munkánk hozzájárul a nemzeti öregedés- és C. elegans-kutatás fejlődéséhez. Eredményeink elősegítik a resveratrol és a Sir2 élettartamra és stresszadaptációra gyakorolt hatásának és az Nrf2/SKN-1 immunitásban betöltött szerepének megértését, valamint számos kapcsolatot azonosítanak a proteosztázis, oxidatív stressz, kalória csökkentés és immunitás élettartamot moduláló hatásaiban. | Aging is a progressive decline in self-maintenance due to the decrease in stress responses including the immune response. Dietary restriction and the dietary restriction-mimetic resveratrol have been shown to induce longevity and to activate the Sir2 sirtuin, HSF1 heat shock and Nrf2 oxidative stress response regulators. However, the underlying molecular mechanisms and crosstalks between stress-responsive pathways remained largely unclear. In the current project we report that (1) resveratrol-induced longevity and thermotolerance requires the SIR-2.1 and HSF1 orthologs, while dietary deprivation only depends on HSF1 in C. elegans (2) contrary to previous reports SIR-2.1 overexpression does not extend life-span in worms (3) SIRT1 overexpression protects from misfolding-induced cytotoxicity in a deacetylase-independent manner in mammalian cells (4) Hsp90 chaperones mammalian SIRT1 (5) oxidative stress inhibits thermotolerance and the heat-shock response (6) the antioxidant response regulator SKN-1 transcription factor is required for innate immunity in C. elegans. Our work contributes to both aging and C. elegans research in Hungary. Our findings help clarify the impact of resveratrol and Sir2 in longevity and stress adaptation, the role of Nrf2/SKN-1 in innate immunity and identify important crosstalks that connect proteostasis, oxidative stress, dietary restriction and immunity to longevity

Nodes having a major influence to break cooperation define a novel centrality measure

Cooperation played a significant role in the self-organization and evolution of living organisms. Both network topology and the initial position of cooperators heavily affect the cooperation of social dilemma games. We developed a novel simulation program package, called 'NetworGame', which is able to simulate any type of social dilemma games on any model, or real world networks with any assignment of initial cooperation or defection strategies to network nodes. The ability of initially defecting single nodes to break overall cooperation was called as 'game centrality'. The efficiency of this measure was verified on well-known social networks, and was extended to 'protein games', i.e. the simulation of cooperation between proteins, or their amino acids. Hubs and in particular, party hubs of yeast protein-protein interaction networks had a large influence to convert the cooperation of other nodes to defection. Simulations on methionyl-tRNA synthetase protein structure network indicated an increased influence of nodes belonging to intra-protein signaling pathways on breaking cooperation. The efficiency of single, initially defecting nodes to convert the cooperation of other nodes to defection in social dilemma games may be an important measure to predict the importance of nodes in the integration and regulation of complex systems. Game centrality may help to design more efficient interventions to cellular networks (in forms of drugs), to ecosystems and social networks. The NetworGame algorithm is downloadable from here: www.NetworGame.linkgroup.huComment: 18 pages, 2 figures, 3 Tables + a supplement containing 8 pages, 1 figure, 2 Tables and the pseudo-code of the algorithm, the NetworGame algorithm is downloadable from here: http://www.NetworGame.linkgroup.h

Learning of Signaling Networks: Molecular Mechanisms

Molecular processes of neuronal learning have been well described. However, learning mechanisms of non-neuronal cells are not yet fully understood at the molecular level. Here, we discuss molecular mechanisms of cellular learning, including conformational memory of intrinsically disordered proteins (IDPs) and prions, signaling cascades, protein translocation, RNAs [miRNA and long noncoding RNA (lncRNA)], and chromatin memory. We hypothesize that these processes constitute the learning of signaling networks and correspond to a generalized Hebbian learning process of single, non-neuronal cells, and we discuss how cellular learning may open novel directions in drug design and inspire new artificial intelligence methods. © 2020 The Author