BACE1 Processing of NRG1 Type III Produces a Myelin-Inducing Signal but Is Not Essential for the Stimulation of Myelination

Myelin sheath thickness is precisely adjusted to axon caliber, and in the peripheral nervous system, neuregulin 1 (NRG1) type III is a key regulator of this process. It has been proposed that the protease BACE1 activates NRG1 dependent myelination. Here, we characterize the predicted product of BACE1-mediated NRG1 type III processing in transgenic mice. Neuronal overexpression of a NRG1 type III-variant, designed to mimic prior cleavage in the juxtamembrane stalk region, induces hypermyelination in vivo and is sufficient to restore myelination of NRG1 type III-deficient neurons. This observation implies that the NRG1 cytoplasmic domain is dispensable and that processed NRG1 type III is sufficient for all steps of myelination. Surprisingly, transgenic neuronal overexpression of full-length NRG1 type III promotes hypermyelination also in BACE1 null mutant mice. Moreover, NRG1 processing is impaired but not abolished in BACE1 null mutants. Thus, BACE1 is not essential for the activation of NRG1 type III to promote myelination. Taken together, these findings suggest that multiple neuronal proteases collectively regulate NRG1 processing. © 2011 Wiley Periodicals, Inc

Assembly and maintenance of the node of Ranvier

Myelination of axons in the central and peripheral nervous system (CNS and PNS) is required for saltatory propagation of nerve impulses. Myelinated axons are organized in functionally distinct membrane domains and the correct formation and maintenance of these domains is fundamental for the correct propagation of the electrical impulse; however, the underlying mechanisms by which these domains are specified are just starting to be unravelled. The paranodal junctions (PNJs) have been shown to contribute to node formation in the CNS and to domain maintenance both in the CNS and PNS. In this thesis I have studied the function of the linkage of the PNJs to the axonal cytoskeleton in regulating these processes by using a combination of knock out and transgenic rescue strategies. Further, I have initiated studies on the live imaging of node assembly. I have shown that the link between the PNJ and the axonal cytoskeleton is required for both the correct timing of oligodendrocyte process migration and for clustering nodal proteins at heminodes, before nodes of Ranvier are formed. Failure to correctly regulate these events during development results in shorter internodes in adults. Further, I have shown the importance of the axonal paranodal cytoskeleton in the maintenance of the node of Ranvier, both in CNS and PNS. In the absence of a link between the PNJ and the axonal cytoskeleton, paranodes disassemble, which causes disruption of both nodal and juxtaparanodal domains. Electron microscopy shows that, despite paranodal disruption, transverse bands are preserved when the anchorage of the PNJ to the axonal cytoskeleton is removed. Surprisingly, the preservation of these structures is associated with the amelioration of the neurological defects seen in mice lacking PNJs. In order to study nodal assembly, I have initiated studies on the transport of the nodal proteins Neurofascin186 and β1Nav tagged with fluorescent tags in transgenic mice, in order to analyse axonal transport during development. I have exploited the triangularis muscle explant preparation and have analysed transport of nodal proteins in young and adult mice. I have shown that transport speeds decrease with age and that the two proteins are transported at different speeds in young animals, but these differences do not persist in adults. This suggests that during myelination these proteins are transported in different vesicles and that this may change during development

Assembly of CNS Nodes of Ranvier in Myelinated Nerves Is Promoted by the Axon Cytoskeleton

International audienc

Digital Marketing and Consumer Engagement: Concepts, Methodologies, Tools, and Applications

The interactive nature of social networking sites contributes to reinforce engagement between consumers and brands in terms of co-creation of shared values. According to Hollebeek (2011), consumer-brand engagement (CBE) implies cognitive, emotional, behavioral factors, which connect a brand with its followers. This chapter will show three successful Twitter strategies from three different brands, using a methodological approach focusing on the relational conditions that turn a brand into an engaging player on Twitter. Interviews with brand communication managers and followers were conducted. Moreover, initiatives were explored through the stream of tweets produced around the brands; pragmatic, semantic, syntactic and structural features of tweets were considered. Results show that, while the three initiatives considered here lean on a cognitive-based CBE, a full engagement in the/a brand\ue2\u80\u99s world is needed to build a long-lasting and successful relationship between brand and consumer, in order to co-construct a future shared reality

Quando i brand diventano influential su Twitter: Creare brand engagement con strategie di comunicazione virale

The interactive nature of social networking sites contributes to reinforce the engagement between consumers and brands in terms of cocreation of shared values. In this context, Twitter – the most popular microblogging service in the world – seems to act as a new frontier for viral marketing strategies and offers great opportunities to promote a brand as reference point and as a trusted partner among his followers. In a social network is possible to identify strategic and central nodes – the «influential» nodes – able to activate information and influence spread. These nodes could be influential persons as well as influential brands which intend to communicate and interact with their consumers promoting messages consistent with their brand personalities. The ultimate aim of influential brands is to increase brand awareness and brand engagement among their followers . However the conception of Twitter as a tool to promote brand engagement is far from being mature, both in management practices and academic research, and it is not clear how to best take advantage of this new marketing and communication channel. In light of what we have shown up to this point, in this paper we intend to develop a preliminary analysis of dialogic, interactive and relational conditions that turn a brand into an engaging and influential actor on Twitter. More specifically, we explore three main case histories of brands which have considered Twitter as main viral marketing tool

School Health Promotion at the Time of COVID-19: An Exploratory Investigation with School Leaders and Teachers

The Coronavirus pandemic has impacted the entire school population’s emotions and the disruption of the organization of the school world. In this context it is important to reflect on the role of health promotion at school. The present study aimed at exploring school leaders’ and teachers’ perspectives and experiences about COVID-19 pandemic and its effects in the school and education system. The first objective was to gather the experience of school leaders regarding the change in school organization, with particular attention to organizational and health promotion aspects. The second was to investigate the perception of health promotion and self-efficacy of teachers in primary, middle and high schools. The research was conducted using qualitative (focus groups for the school leaders) and quantitative methods (questionnaires for the teachers). The findings showed new ways of improving wellbeing at school and implementing health promotion through the sharing of good practice between school leaders. The need for time and space to reflect among school leaders on the educational and didactic aspects of school organization also emerged. Teachers showed a low to medium level of self-efficacy regarding the adoption of strategies in line with health promotion; specificities for each grade and level will be discussed

Evaluation in rabbits of different anti-SHIV vaccine strategies based on DNA/fowlpox priming and virus-like particles boosting

Two different prime-boost immunization protocols were tested in rabbits and their immune response was evaluated and compared with the final aim of defining a vaccine strategy that might be able to protect non-human primates from infection with the pathogenic simian/human immunodeficiency virus, SHIV(89.6P). The two regimens were based on three priming immunizations with either an expression plasmid plus a fowlpox (FP) recombinant vector or with two FP recombinant vectors, each one expressing either the SIV(mac239) gag/pol or the HIV-1env(89.6P) genes. In both protocols, priming immunizations were followed by two boosts with SHIV-mimicking virus-like particles (VLP). A complete SHIV-specific response was observed in all animals. Interestingly, the DNA vaccine was three to 10 times more efficient than the FP recombinant in inducing an anti-gag humoral response. Real-time PCR confirmed the memory effect on T-cell subsets secreting interleukin-4 and interferon-gamma, as a consequence of stimulation of both arms of the immune system. Although both protocols were almost equally effective in eliciting homologous neutralizing antibodies and highlighted the efficacy of VLP administration for boosting, protocol A seemed to be more effective in promoting a balanced T-cell memory immune response and appears more promising for vaccine purposes

Ruthenium(II)-Arene Curcuminoid Complexes as Photosensitizer Agents for Antineoplastic and Antimicrobial Photodynamic Therapy: In Vitro and In Vivo Insights

Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical–physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising