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Bernard, Clé,mence,Vincent, Clé,mentine,Testa, Damien,Bertini, Eva,Ribot, Jé,rô,me,Di Nardo, Ariel A.,Volovitch, Michel,Prochiantz, Alain Public Library of Science 2016 PLoS genetics Vol.12 No.5
<▼1><P>During postnatal life the cerebral cortex passes through critical periods of plasticity allowing its physiological adaptation to the environment. In the visual cortex, critical period onset and closure are influenced by the non-cell autonomous activity of the Otx2 homeoprotein transcription factor, which regulates the maturation of parvalbumin-expressing inhibitory interneurons (PV cells). In adult mice, the maintenance of a non-plastic adult state requires continuous Otx2 import by PV cells. An important source of extra-cortical Otx2 is the choroid plexus, which secretes Otx2 into the cerebrospinal fluid. Otx2 secretion and internalization requires two small peptidic domains that are part of the DNA-binding domain. Thus, mutating these “transfer” sequences also modifies cell autonomous transcription, precluding this approach to obtain a cell autonomous-only mouse. Here, we develop a mouse model with inducible secretion of an anti-Otx2 single-chain antibody to trap Otx2 in the extracellular milieu. Postnatal secretion of this single-chain antibody by PV cells delays PV maturation and reduces plasticity gene expression. Induced adult expression of this single-chain antibody in cerebrospinal fluid decreases Otx2 internalization by PV cells, strongly induces plasticity gene expression and reopens physiological plasticity. We provide the first mammalian genetic evidence for a signaling mechanism involving intercellular transfer of a homeoprotein transcription factor. Our single-chain antibody mouse model is a valid strategy for extracellular neutralization that could be applied to other homeoproteins and signaling molecules within and beyond the nervous system.</P></▼1><▼2><P><B>Author Summary</B></P><P>Classically, cell signaling is based on the secretion of molecules that bind cell surface receptors. Lipophilic agents can do without cell-surface receptors due to their ability to diffuse through the plasma membrane, but this is normally not the case for proteins, which cannot pass the membrane barrier. However, homeoprotein transcription factors represent an exception as they are secreted and internalized by live cells owing to two peptidic domains. An important illustration of this novel signaling mechanism is provided by Otx2, a homeoprotein that travels from the choroid plexus to specific inhibitory neurons in the cerebral cortex, where it regulates physiological plasticity throughout life. Because the two transfer peptides are in the DNA-binding domain of Otx2, it is impossible to mutate them without altering both cell signaling and cell-autonomous functions. We have therefore developed a mouse in which a secreted anti-Otx2 single-chain antibody can be induced to trap extracellular Otx2 while leaving its cell autonomous function untouched. We show that neutralizing extracellular Otx2 modifies the expression of plasticity genes in the visual cortex, thus providing the first genetic demonstration for homeoprotein signaling in a mammal.</P></▼2>
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Electrofluorescence switching of tetrazine-modified TiO2 nanoparticles.
Seo, Seogjae,Allain, Cl?mence,Na, Jongbeom,Kim, Sehwan,Yang, Xu,Park, Chihyun,Malinge, J?r?my,Audebert, Pierre,Kim, Eunkyoung RSC Pub 2013 Nanoscale Vol.5 No.16
<P>Highly fluorescent tetrazine-modified TiO2 nanoparticles were prepared by the reaction of triethoxysilane-appended chloroalkoxy tetrazine (ESTZ) with TiO2 nanoparticles through a condensation reaction between the surface hydroxyl groups of an electrode and the silane anchor group of ESTZ. The prepared electrodes were used as robust fluorescent layers for electrochemical fluorescence switching (electrofluorochromism) applications in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) as a charge balancing mediator. The stable charge balancing mediator, TEMPO, in the electrolyte was found to be essential to reduce the intrinsic electron transport resistance of TiO2 in order to achieve reversible electrofluorescence switching. Furthermore it facilitated a fully reversible electrochemical reaction and provided a sufficient charge balance, which allowed us to realize semiconductor-based electrofluorescence switching with an on/off ratio of 4.0 and cyclability greater than 100 cycles.</P>
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Graded Otx2 activities demonstrate dose-sensitive eye and retina phenotypes
Bernard, Clé,mence,Kim, Hyoung-Tai,Torero Ibad, Raoul,Lee, Eun Jung,Simonutti, Manuel,Picaud, Serge,Acampora, Dario,Simeone, Antonio,Di Nardo, Ariel A.,Prochiantz, Alain,Moya, Kenneth L.,Kim, Ji Oxford University Press 2014 Human Molecular Genetics Vol.23 No.7
<P>In the human, mutations of <I>OTX2</I> (<I>Orthodenticle homeobox 2</I> transcription factor) translate into eye malformations of variable expressivity (even between the two eyes of the same individual) and incomplete penetrance, suggesting the existence of subtle thresholds in OTX2 activity. We have addressed this issue by analyzing retinal structure and function in six mutant mice with graded Otx2 activity: <I>Otx2<SUP>+/+</SUP></I>, <I>Otx2<SUP>+/AA</SUP></I>, <I>Otx2<SUP>+/GFP</SUP></I>, <I>Otx2<SUP>AA/AA</SUP></I>, <I>Otx2<SUP>AA/GFP</SUP></I> and <I>Otx2<SUP>GFP/GFP</SUP></I>. Null mice (<I>Otx2<SUP>GFP/GFP</SUP></I>) fail to develop the head and are embryonic lethal, and compound heterozygous <I>Otx2<SUP>AA/GFP</SUP></I> mice show a truncated head and die at birth. All other genotypes develop until adulthood. We analyzed eye structure and visual physiology in the genotypes that develop until adulthood and report that phenotype severity parallels Otx2 activity. <I>Otx2<SUP>+/AA</SUP></I> are only mildly affected whereas <I>Otx2<SUP>+/GFP</SUP></I> are more affected than <I>Otx2<SUP>+/AA</SUP></I> but less than <I>Otx2<SUP>AA/AA</SUP></I> mice. <I>Otx2<SUP>AA/AA</SUP></I> mice later manifest the most severe defects, with variable expressivity. Electrophysiological and histological analyses of the mouse retina revealed progressive death of bipolar cells and cone photoreceptors that is both Otx2 activity- and age-dependent with the same ranking of phenotypic severity. This study demonstrates the importance of gene dosage in the development of age-dependent pathologies and underscores the fact that small gene dosage differences can cause significant pathological states.</P>
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Anne-Flore Maman Larraufie,Clémence Freuslon 글로벌지식마케팅경영학회 2015 Global Fashion Management Conference Vol.2015 No.06
Luxury consumption is intrinsically related to unusual expectations from the consumers, among which some are equally shared around the globe. For instance, Europeans, Americans and Asians claim that luxury products should be flawless and their producers (i.e. the luxury brands) should have some history and heritage (Wiedmann et al., 2007). What they put behind these two last notions can fluctuate, but they are systematically stressed out in studies, be they academic or applied, qualitative or quantitative. Therefore, it sounds fundamental for the luxury Maisons to communicate on their heritage and history (Wiedmann et al., 2012). While until the end of the XXth century brands could rely upon different message content and copy to do so, due to localized options of communication, the Internet has implied to complete revision of their approach. The Maisons’ websites, even if available in different languages, are unique platforms to showcase the brand’s history, ambience and offering to a worldwide audience. They should be able to reach consumers, both cognitively and emotionally, recreate the store atmosphere, while simultaneously stimulating some desire to discover new collections. They stand for an open-window on a boundary-free world, be it from the geographical or from the time point of view. However, as pointed out by academics and professionals from the very beginning, the road is paved with risks, especially in terms of brand image management (Geerts & Veg-Sala, 2012). This comes from the apparent non-compatibility between luxury and the online environment. However, such discrepancies have led to a complete redefinition of the luxury concept, with its new semiotics economy (Maman & Kourdoughli, 2014). Part of it is ‘heritage and history’, with little surprise. We can therefore raise the issue of a lack of academic research regarding how such Maisons communicate about their history (even if short) and heritage on their website, be it an institutional or a transactional one. The only studies we have found deal with the automotive sector (Wiedmann et al., 2011) or watch one (Baum, 2011), the second one being a Master’s thesis. It is the objective of the present study to fill in this gap, and to uncover the various ‘signs’ used by luxury brands to communicate their heritage and heritage to their worldwide audience. Besides, we wanted to understand whether different semiotic systems were used by French vs. Italian luxury brands, and whether other variables such as the place of origin or the ‘age’ of the Maison would lead to different signs. To reach this goal, we used a two-pronged approach. First we gathered data from 56 websites of fashion luxury brands, using an inductive approach of content analysis (Kim & Kuljis, 2007). A coding grid was thus built while data was collected, with a back and forth coding process. We also built upon the Gestalt principles to ‘judge’ whether the websites were more focused on 1) current fashion trends, 2) the brand itself or its designer(s), 3) the products offered, or 4) the past of the brand. A first researcher built the grid and filled it in, while a second one directly used the grid for coding. The two coding outcomes were confronted and discrepancies discussed until agreement was reached. Then, major trends and clusters were identified from the data, leading us to understand the various sign-systems used by the Maisons, using Peircian semiotics. We end-up our study with theoretical conclusions regarding the online communication of luxury fashion brands, and with practical recommendations for luxury brand managers.
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