99 research outputs found

    Perception of the object attributes for sound synthesis purposes

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    International audienceThis paper presents a work in progress on the perception of the attributes of the shape of a resonant object. As part of the ecological approach to perception-assuming that a sound contains specific morphologies that convey perceptually relevant information responsible for its recognition, called invariants-the PRISM laboratory has developed an environmental sound synthesizer aiming to provide perceptual and intuitive controls for a non-expert user. Following a brief presentation of the di↵erent strategies for controlling the perceptual attributes of the object, we present an experiment conducted with calibrated sounds generated by a physically-informed synthesis model. This test focuses on the perception of the shape of the object, more particularly its width and thickness since these attributes, especially the thickness, have not been much studied in the literature from a perceptual point of view. The first results show that the perception of width is di cult for listeners, while the perception of thickness is much easier. This study allows us to validate the proposed control strategy. Further works are planned to better characterize the perceptual invariants relevant for shape perception

    Cis-regulation of microRNA expression by scaffold/matrix-attachment regions

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    microRNAs (miRNAs) spatio-temporally modulate gene expression; however, very little is known about the regulation of their expression. Here, we hypothesized that the well-known cis-regulatory elements of gene expression, scaffold/matrix-attachment regions (MARs) could modulate miRNA expression. Accordingly, we found MARs to be enriched in the upstream regions of miRNA genes. To determine their role in cell type-specific expression of miRNAs, we examined four individual miRNAs (let-7b, miR-17, miR-93 and miR-221) and the miR-17–92 cluster, known to be overexpressed in neuroblastoma. Our results show that MARs indeed define the cell-specific expression of these miRNAs by tethering the chromatin to nuclear matrix. This is brought about by cell type-specific binding of HMG I/Y protein to MARs that then promotes the local acetylation of histones, serving as boundary elements for gene activation. The binding, chromatin tethering and gene activation by HMG I/Y was not observed in fibroblast control cells but were restricted to neuroblastoma cells. This study implies that the association of MAR binding proteins to MARs could dictate the tissue/context specific regulation of miRNA genes by serving as a boundary element signaling the transcriptional activation

    A Direct Link between Abscisic Acid Sensing and the Chromatin-Remodeling ATPase BRAHMA via Core ABA Signaling Pathway Components

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    [EN] Optimal response to drought is critical for plant survival and will affect biodiversity and crop performance during climate change. Mitotically heritable epigenetic or dynamic chromatin state changes have been implicated in the plant response to the drought stress hormone abscisic acid (ABA). The Arabidopsis SWI/SNF chromatin-remodeling ATPase BRAHMA (BRM) modulates response to ABA by preventing premature activation of stress response pathways during germination. We show that core ABA signaling pathway components physically interact with BRM and post-translationally modify BRM by phosphorylation/dephosphorylation. Genetic evidence suggests that BRM acts downstream of SnRK2.2/2.3 kinases, and biochemical studies identified phosphorylation sites in the C-terminal region of BRM at SnRK2 target sites that are evolutionarily conserved. Finally, the phosphomimetic BRMS1760D (S1762D) mutant displays ABA hypersensitivity. Prior studies showed that BRM resides at target loci in the ABA pathway in the presence and absence of the stimulus, but is only active in the absence of ABA. Our data suggest that SnRK2-dependent phosphorylation of BRM leads to its inhibition, and PP2CA-mediated dephosphorylation of BRM restores the ability of BRM to repress ABA response. These findings point to the presence of a rapid phosphorylation-based switch to control BRM activity; this property could be potentially harnessed to improve drought tolerance in plants.Work in Dr. Rodriguez's laboratory was supported by the Ministerio de Ciencia e Innovacion, Fondo Europeo de Desarrollo Regional and Consejo Superior de Investigaciones Cientificas (grant BIO2014-52537-R). M.P.-L. and L.R. were supported by FPI fellowships, and M.G.-G. by a JAE-DOC research contract. Funding of chromatin research in the Wagner laboratory is supported by National Science Foundation grant MCB-0925071.Peirats-Llobet, M.; Han, S.; González Guzmán, M.; Jeong, CW.; Rodríguez Solovey, LN.; Belda Palazón, B.; Wagner, D.... (2016). A Direct Link between Abscisic Acid Sensing and the Chromatin-Remodeling ATPase BRAHMA via Core ABA Signaling Pathway Components. Molecular Plant. 9(1):136-147. https://doi.org/10.1016/j.molp.2015.10.0031361479

    Dynamic assembly of chromatin complexes during cellular senescence: implications for the growth arrest of human melanocytic nevi

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    The retinoblastoma (RB)/p16INK4a pathway regulates senescence of human melanocytes in culture and oncogene-induced senescence of melanocytic nevi in vivo. This senescence response is likely due to chromatin modifications because RB complexes from senescent melanocytes contain increased levels of histone deacetylase (HDAC) activity and tethered HDAC1. Here we show that HDAC1 is prominently detected in p16INK4a-positive, senescent intradermal melanocytic nevi but not in proliferating, recurrent nevus cells that localize to the epidermal/dermal junction. To assess the role of HDAC1 in the senescence of melanocytes and nevi, we used tetracycline-based inducible expression systems in cultured melanocytic cells. We found that HDAC1 drives a sequential and cooperative activity of chromatin remodeling effectors, including transient recruitment of Brahma (Brm1) into RB/HDAC1 mega-complexes, formation of heterochromatin protein 1β (HP1β)/SUV39H1 foci, methylation of H3-K9, stable association of RB with chromatin and significant global heterochromatinization. These chromatin changes coincide with expression of typical markers of senescence, including the senescent-associated β-galactosidase marker. Notably, formation of RB/HP1β foci and early tethering of RB to chromatin depends on intact Brm1 ATPase activity. As cells reached senescence, ejection of Brm1 from chromatin coincided with its dissociation from HP1β/RB and relocalization to protein complexes of lower molecular weight. These results provide new insights into the role of the RB pathway in regulating cellular senescence and implicate HDAC1 as a likely mediator of early chromatin remodeling events

    Interaction of HP1 and Brg1/Brm with the Globular Domain of Histone H3 Is Required for HP1-Mediated Repression

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    The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. These proteins contain two related domains known as the chromo- and the chromoshadow-domain. The chromo-domain binds histone H3 tails methylated on lysine 9. However, in vivo and in vitro experiments have shown that the affinity of HP1 proteins to native methylated chromatin is relatively poor and that the opening of chromatin occurring during DNA replication facilitates their binding to nucleosomes. These observations prompted us to investigate whether HP1 proteins have additional histone binding activities, envisioning also affinity for regions potentially occluded by the nucleosome structure. We find that the chromoshadow-domain interacts with histone H3 in a region located partially inside the nucleosomal barrel at the entry/exit point of the nucleosome. Interestingly, this region is also contacted by the catalytic subunits of the human SWI/SNF complex. In vitro, efficient SWI/SNF remodeling requires this contact and is inhibited in the presence of HP1 proteins. The antagonism between SWI/SNF and HP1 proteins is also observed in vivo on a series of interferon-regulated genes. Finally, we show that SWI/SNF activity favors loading of HP1 proteins to chromatin both in vivo and in vitro. Altogether, our data suggest that HP1 chromoshadow-domains can benefit from the opening of nucleosomal structures to bind chromatin and that HP1 proteins use this property to detect and arrest unwanted chromatin remodeling

    Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry

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    Sound perception of objects for intuitive control of synthesis : towards a language of sounds

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    Aujourd’hui les processus de synthèse sont aptes à engendrer des sons au réalisme impressionnant ou à créer des sons inouïs. Cependant le contrôle perceptif de ces outils reste une problématique d'actualité. Sur la base de l'approche écologique de la perception, un synthétiseur proposant un paradigme de contrôle intuitif, appelé {action-objet}, a été développé au laboratoire. Il permet de créer des sons à partir des évocations liées à l’action et à l’objet via une description sémantique. Ce dernier présente encore des limitations, en particulier les contrôles relatifs à la forme perçue des objets. Ce travail de thèse vise à définir une nouvelle stratégie de contrôle perceptif d’un objet virtuel à partir de l’étude de la perception sonore des objets du quotidien. En particulier, quels sont les attributs perceptifs et les structures sonores invariantes liés à la forme d'un objet? Au cours de ce travail, nous avons mis en évidence les invariants associés à la perception de la forme via une approche d’analyse par synthèse. Des méthodes de simulation physique ont été utilisées afin de modéliser des transitions continues entre catégories de formes. Ces résultats ont permis de définir des modèles de signaux reproduisant les morphologies sonores observées par la simulation. Ces modèles ont ensuite été évalués et calibrés perceptivement. L’ensemble de ces données a permis de proposer une nouvelle stratégie de contrôle basée sur les principaux attributs perceptifs de l’objet. Ce travail de thèse a ainsi contribué à la construction d’un véritable langage des sons. Il ouvre par ailleurs de nombreuses perspectives dans les domaines de la réalité virtuelle ou de la création sonoreToday's synthesis processes are capable of generating impressively realistic sounds or creating unheard-of sounds. However, the perceptual control of these tools remains a current problem. Based on the ecological approach to perception, a synthesizer with an intuitive control paradigm, called {action-object}, has been developed in the laboratory. It allows the creation of sounds from evocations related to the action and the object via a semantic description. This synthesizer presents limitations, in particular, at the level of the controls relating to the perceived shape of the objects. This thesis aims to define a new strategy for the perceptual control of a virtual object based on the study of the sound perception of everyday objects. In particular, what are the perceptual attributes and invariant sound structures related to the shape of an object? In the course of this work, we have highlighted the invariants associated with the perception of shape via a synthesis analysis approach. Physical simulation methods were used to model continuous transitions between shape categories. These results were used to define signal models that reproduce the sound morphologies observed by the simulation. These models were then evaluated and perceptually calibrated. All of these data allowed us to propose a new control strategy based on the main perceptual attributes of the object. This thesis work has thus contributed to the construction of a true language of sounds. It also opens up numerous perspectives in the fields of virtual reality and sound creatio
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