Le dispositif d'objets dans un nouveau type d'image au 16e siècle : les portraits de marchands

Le concept d’un « dispositif d’objets » présent dans le Portrait d’un marchand (v. 1530) de Jan Gossart et le Portrait du marchand Georg Gisze (1532) d’Hans Holbein le Jeune a pour objectif de porter un regard nouveau sur des œuvres trop souvent réduites à des notions d’esthétisme et de symbolisme. En utilisant une approche pluridisciplinaire à notre analyse, nous voulons promouvoir les objets comme acteur dominant dans la mise en scène de l’identité sociale du marchand au 16e siècle. L’association entre histoire de l’art et anthropologie des techniques permet la validation d’une scénographie de la culture matérielle marchande, ainsi que le dégagement d’un commentaire social inhérent à la proposition artistique de Gossart et Holbein. L’intérêt d’une étude orientée sur les objets promet également l’ouverture d’une réflexion sur la manière de concevoir le portrait d’occupation indépendamment de la valeur anagogique qui lui est généralement associée à la Renaissance. Le Portrait d’un marchand et le Portrait du marchand Georg Gisze attestent d’un moment ponctuel dans la production spatio-temporelle des portraits de marchands en Europe du Nord au 16e siècle. L’analogie confondante qui unit les deux œuvres prend son essence dans la thématique visuelle engendrée par le « dispositif d’objets ».The concept of an object system, as found in Jan Gossart’s Portrait of a Merchant (ca. 1530) and Hans Holbein the Younger’s Georg Gisze (1532) aims to reevaluate works which are too often reduced to aesthetics and symbolism. By means of a multidisciplinary approach, the study aims to promote the objects represented in the paintings as the dominant actors in the staging of the social identity of the sixteenth-century merchant. The association between art history and anthropology of techniques allows the validation of a scenography of the material merchant culture, as well as the emergence of a social commentary inherent to Gossart’s and Holbein’s artistic work. Attention to an object-oriented study also allows for new insights into how to understand the occupational portrait independently of an anagogical value, which is generally attributed to the Renaissance period. The Portrait of a Merchant and portrait of Georg Gisze attest to a specific moment in the production of merchant portraits in northern Europe during the sixteenth century. The apparently disparate works are united by the object system represented in the paintings

One-Pot Synthesis of an Amphiphilic ABC Triblock Copolymer PEO-b-PEHOx-b-PEtOz and Its Self-Assembly into Nanoscopic Asymmetric Polymersomes

We report an efficient one-pot synthesis of a new biocompatible amphiphilic ABC triblock terpolymer: poly(ethylene oxide)- block -poly(2-(3-ethylheptyl)-2-oxazoline)- block -poly(2-ethyl-2-oxazoline) (PEO- b -PEHOx- b -PEtOz) using sequential microwave-assisted polymerization. Depending on the hydrophilic weight fraction of the terpolymers, nanoscopic micelles, worms, and polymersomes, as well as multicompartment vesicles, were formed. The self-assemblies were thoroughly analyzed regarding their size and shape using dynamic and static light scattering, TEM, and cryogenic TEM. By varying the ratio of PEO to PEtOz, we were able to drive the asymmetry of the polymersome membranes, which was proved by two independent methods, bicinchoninic acid assay and 2D- 1 H-NOESY NMR spectroscopy, which confirmed the presence of a longer PEO block (45 units) and the absence of a shorter PEtOz (less than 32 units) on the outer surface of the polymersomes. Thus, from this new family of ABC triblock terpolymers, asymmetric polymersomes with a thin membrane (6-10 nm) can be obtained, justifying the potential use in biomedical applications with the direct insertion of transmembrane proteins

Bioluminescent Genetically Encoded Glutamate Indicators for Molecular Imaging of Neuronal Activity.

Genetically encoded optical sensors and advancements in microscopy instrumentation and techniques have revolutionized the scientific toolbox available for probing complex biological processes such as release of specific neurotransmitters. Most genetically encoded optical sensors currently used are based on fluorescence and have been highly successful tools for single-cell imaging in superficial brain regions. However, there remains a need to develop new tools for reporting neuronal activity in vivo within deeper structures without the need for hardware such as lenses or fibers to be implanted within the brain. Our approach to this problem is to replace the fluorescent elements of the existing biosensors with bioluminescent elements. This eliminates the need of external light sources to illuminate the sensor, thus allowing deeper brain regions to be imaged noninvasively. Here, we report the development of the first genetically encoded neurotransmitter indicators based on bioluminescent light emission. These probes were optimized by high-throughput screening of linker libraries. The selected probes exhibit robust changes in light output in response to the extracellular presence of the excitatory neurotransmitter glutamate. We expect this new approach to neurotransmitter indicator design to enable the engineering of specific bioluminescent probes for multiple additional neurotransmitters in the future, ultimately allowing neuroscientists to monitor activity associated with a specific neurotransmitter as it relates to behavior in a variety of neuronal and psychiatric disorders, among many other applications

Cocréation et validation d’un outil d’autorégulation en correction textuelle auprès d’élèves de 5e secondaire

L’objectif de cet article est d’exposer le processus de cocréation et de validation in situ d’un outil numérique d’autorégulation en correction textuelle, et ce, dans le cadre plus large d’une recherche-action d’envergure (Action concertée FRQSC-MÉQ 2020-2023 : projet MultiNumériC). Cet outil numérique permet aux élèves, par l’autoconsignation de leurs méprises rédactionnelles, d’établir leur propre portrait évolutif en temps réel – et mobile – de leurs forces et difficultés en français écrit : syntaxe, ponctuation, orthographes lexicale et grammaticale. L’équipe de cocréation (enseignant-chercheur et chercheur.e.s universitaires) a observé, pendant toute l’année scolaire 2021-2022, trois groupes d’élèves de cinquième secondaire qui ont expérimenté et critiqué l’outil numérique déployé, ce qui lui a permis d’en améliorer progressivement l’efficacité technologique et didactique.The main objective of this article is to expose the process underlying the co-creation and in situ validation of a digital tool for self-regulation correction, and this, within the broader framework of a large-scale action research (Action concertée FRQSC-MÉQ 2020-2023 : projet MultiNumériC). This digital tool allows students, through the self-recording of their writing mistakes, to establish their own evolving portrait in real time—and mobile—of their strengths and difficulties in syntax, punctuation as well as lexical and grammatical spelling. The co-creation team (teacher-researcher and university researchers) observed, throughout the 2021-2022 school year, three groups of secondary 5 students who experimented and criticized the digital tool deployed, which enabled them to gradually improve its technological and didactic efficiency

L’adénine, un acteur majeur en biologie et en chimie médicinale

International audienceAdenine is one of the most ubiquitous heterocycles in life. In addition of being one of the four nucleobases constituting DNA and RNA, adenine is also contained in many biological molecules (ATP, SAM, NAD, cAMP, coA…) that have fundamental roles in the functioning of living systems, e.g. energy source, cofactors of enzymes and proteins. As such, the adenine has naturally become a privileged scaffold explored in medicinal chemistry for biomedical applications. Many chemical modifications and Structure-Activity Relationships studies have been carried out on the adenine scaffold to result in potent analogues with various biological activities. Today, numerous adenine-based inhibitors are used to treat a wide range of diseases including cancer, viral and bacterial diseases. This review aims to introduce the adenine and discuss adenine-based inhibitors, their design and use for different therapeutic targets through examples of drugs and compounds that reached clinical and preclinical trials.L'adénine est l'un des hétérocycles les plus représentés dans la nature. En plus d'être l'une des quatre bases constituant l'ADN et l'ARN, elle est également présente dans de nombreuses molécules biologiques (ATP, SAM, NAD, cAMP, coA...) qui jouent un rôle fondamental dans le fonctionnement des systèmes vivants, comme source d'énergie, cofacteurs d'enzymes ou de protéines. L'adénine est ainsi devenue un hétérocycle largement exploré en chimie médicinale pour de nombreuses applications biomédicales. De multiples modifications chimiques associées à l’étude de Relations Structure-Activité ont été réalisées sur le squelette de l'adénine pour aboutir à des analogues puissants aux activités biologiques variées. Aujourd'hui, de nombreux inhibiteurs analogues d'adénine sont utilisés pour traiter un large éventail de maladies, comme le cancer et les maladies infectieuses. Cette revue a pour but de présenter l'adénine dans son contexte biologique et de discuter d’exemples d’inhibiteurs constitués d’une adénine (ou de l’un de ses analogues) en décrivant leur conception et utilisation pour différentes cibles thérapeutiques

Acridine–O6-benzylguanine hybrids: Synthesis, DNA binding, MGMT inhibition and antiproliferative activity

International audienceO6-Methylguanine-DNA-methyltransferase (MGMT) is a key DNA repair enzyme involved in chemoresistance to DNA-alkylating anti-cancer drugs such as Temozolomide (TMZ) through direct repair of drug-induced O6-methylguanine residues in DNA. MGMT substrate analogues, such as O6-benzylguanine (BG), efficiently inactivate MGMT in vitro and in cells; however, these drugs failed to reach the clinic due to adverse side effects. Here, we designed hybrid drugs combining a BG residue covalently linked to a DNA-interacting moiety (6-chloro-2-methoxy-9-aminoacridine). Specifically, two series of hybrids, encompassing three compounds each, were obtained by varying the position of the attachment point of BG (N9 of guanine vs. the benzyl group) and the length and nature of the linker. UV/vis absorption and fluorescence data indicate that all six hybrids adopt an intramolecularly stacked conformation in aqueous solutions in a wide range of temperatures. All hybrids interact with double-stranded DNA, as clearly evidenced by spectrophotometric titrations, without intercalation of the acridine ring and do not induce thermal stabilization of the duplex. All hybrids, as well as the reference DNA intercalator (6-chloro-2-methoxy-9-aminoacridine 8), irreversibly inhibit MGMT in vitro with variable efficiency, comparable to that of BG. In a multidrug-resistant glioblastoma cell line T98G, benzyl-linked hybrids 7a-c and the N9-linked hybrid 19b are moderately cytotoxic (GI50 ≥ 15 μM after 96 h), while N9-linked hybrids 19a and 19c are strongly cytotoxic (GI50 = 1-2 μM), similarly to acridine 8 (GI50 = 0.6 μM). Among all compounds, hybrids 19a and 19c, similarly to BG, display synergic cytotoxic effect upon co-treatment with subtoxic doses of TMZ, with combination index (CI) values as low as 0.2-0.3. In agreement with in vitro results, compound 19a inactivates cellular MGMT but, unlike BG, does not induce significant levels of DNA damage, either alone or in combination with TMZ, as indicated by the results of γH2AX immunostaining experiments. Instead, and unlike BG, compound 19a alone induces significant apoptosis of T98G cells, which is not further increased in a combination with TMZ. These results indicate that molecular mechanisms underlying the cytotoxicity of 19a and its combination with TMZ are distinct from that of BG. The strongly synergic properties of this combination represent an interesting therapeutic opportunity in treating TMZ-resistant cancers