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Outlier based literature exploration for cross-domain linking of Alzheimer's disease and gut microbiota
Donatella Gubiani, Elsa Fabbretti, Bojan Cestnik, Nada Lavrač, Tanja Urbančič, 2017, original scientific article

Abstract: In knowledge discovery, experts frequently need to combine knowledge from different domains to get new insights and derive new conclusions. Intelligent systems should support the experts in the search for relationships between concepts from different domains, where huge amounts of possible combinations require the systems to be efficient but also sufficiently general, open and interactive to enable the experts to creatively guide the discovery process. The paper proposes a cross-domain literature mining methodology that achieves this functionality by combining the functionality of two complementary text mining tools: clustering and topic ontology creation tool OntoGen and cross-domain bridging terms exploration tool CrossBee. Focusing on outlier documents identified by OntoGen contributes to the efficiency, while CrossBee allows for flexible and user-friendly bridging concepts exploration and identification. The proposed approach, which is domain independent and can support cross-domain knowledge discovery in any field of science, is illustrated on a biomedical case study dealing with Alzheimer’s dis- ease, one of the most threatening age-related diseases, deteriorating lives of numerous individuals and challenging the ageing society as a whole. By applying the proposed methodology to Alzheimer’s disease and gut microbiota PubMed articles, we have identified Nitric oxide synthase (NOS) as a potentially valuable link between these two domains. The results support the hypothesis of neuroinflammatory nature of Alzheimer’s disease, and is indicative for the quest for identifying strategies to control nitric oxide- associated pathways in the periphery and in the brain. By addressing common mediators of inflammation using literature-based discovery, we have succeeded to uncover previously unidentified molecular links between Alzheimer’s disease and gut microbiota with a multi-target therapeutic potential.
Keywords: Literature-based discovery, Outlier detection, Alzheimer's disease, Gut microbiome
Published in RUNG: 26.05.2017; Views: 4847; Downloads: 0
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The scaffold protein calcium/calmodulin-dependent serine protein kinase controls ATP release in sensory ganglia upon P2X3 receptor activation and is part of an ATP keeper complex.
Tanja Bele, Elsa Fabbretti, 2016, original scientific article

Abstract: P2X3 receptors, gated by extracellular ATP, are expressed by sensory neurons and are involved in peripheral nociception and pain sensitization. The ability of P2X3 receptors to transduce extracellular stimuli into neuronal signals critically depends on the dynamic molecular partnership with the calcium/calmodulin-dependent serine protein kinase (CASK). The present work used trigeminal sensory neurons to study the impact that activation of P2X3 receptors (evoked by the agonist α,β-meATP) has on the release of endogenous ATP and how CASK modulates this phenomenon. P2X3 receptor function was followed by ATP efflux via Pannexin1 (Panx1) hemichannels, a mechanism that was blocked by the P2X3 receptor antagonist A-317491, and by P2X3 silencing. ATP efflux was enhanced by nerve growth factor, a treatment known to potentiate P2X3 receptor function. Basal ATP efflux was not controlled by CASK, and carbenoxolone or Pannexin silencing reduced ATP release upon P2X3 receptor function. CASK-controlled ATP efflux followed P2X3 receptor activity, but not depolarization-evoked ATP release. Molecular biology experiments showed that CASK was essential for the transactivation of Panx1 upon P2X3 receptor activation. These data suggest that P2X3 receptor function controls a new type of feed-forward purinergic signaling on surrounding cells, with consequences at peripheral and spinal cord level. Thus, P2X3 receptor-mediated ATP efflux may be considered for the future development of pharmacological strategies aimed at containing neuronal sensitization. P2X3 receptors are involved in sensory transduction and associate to CASK. We have studied in primary sensory neurons the molecular mechanisms downstream P2X3 receptor activation, namely ATP release and partnership with CASK or Panx1. Our data suggest that CASK and P2X3 receptors are part of an ATP keeper complex, with important feed-forward consequences at peripheral and central level.
Keywords: DRG, hemichannels, pain, purinergic signaling, sensory neurons
Published in RUNG: 19.01.2017; Views: 4120; Downloads: 0
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P2X receptors, sensory neurons and pain
Elsa Fabbretti, Tanja Bele, 2015, review article

Keywords: synapse, pain receptors, ATP, sensory neurons, MAGUK
Published in RUNG: 16.06.2016; Views: 4403; Downloads: 139
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ATP in peripheral sensory ganglia
Elsa Fabbretti, Tanja Bele, 2014, published scientific conference contribution abstract

Keywords: pain, ATP, scaffold, synaptic plasticity
Published in RUNG: 16.06.2016; Views: 3939; Downloads: 25
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Novel applications of oxygenic photosynthetic organisms : dissertation
Danijel Stojković, 2015, doctoral dissertation

Abstract: Inspired by natural microorganisms that possess a rigid cell wall to protect them in harsh conditions, individual cells of Chlamydomonas reinhardtii were artificially encapsulated with different materials and hydrogen production was enhanced. The first attempt was to cover the cells with hydrated silicon dioxide, which is naturally formed by diatoms. The cells covered with silica were not able to produce hydrogen, but the improved TiO2-encapsualtion of Chlamydomonas reinhardtii was found to positively affect their hydrogen production under sulfur-deprived conditions. It was shown that incubation of the cells in the dark before exposure to light was necessary in order to overcome the toxic effects of the (RKK)4D8 catalytic peptide that is essential for TiO2 formation. The TiO2-encapsulated cells were able to produce H2 with about double efficiency during 5-day period compared to non-encapsulated cells. The light-to-H2 conversion efficiency of TiO2-encapsulated Chlamydomonas reinhardtii system was estimated to be more than 4 % under optimized conditions. The encapsulation with platinum led us to discover the bioreductive properties of Chlamydomonas reinhardtii. Beside the homogeneous Pt reduction carried out by the algae, the most surprising discovery was the possibility to use algae culture for targeted heterogeneous nucleation. An important discovery was that is possible to control the nucleation mechanism and redirect predominantly homogeneous into fully heterogeneous nucleation.
Keywords: photosynthesis, H2 production, TiO2, encapsulation, Chlamydomonas reinhardtii, platinum reduction
Published in RUNG: 01.04.2015; Views: 8150; Downloads: 301
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