Jean-Baptiste Perronneau (ca. 1715-1783). Un portraitiste dans l'Europe des Lumières

Les monographies consacrées à Jean-Baptiste Perronneau (ca 1715-1783) à la fin du XIXe siècle et au début du XXe siècle traduisaient l'engouement pour l'art du XVIIIesiècle qui se déployait dans le Tout Paris de la Belle Époque. Elles rendaient justice au peintre de l'Académie royale de peinture et de sculpture de Paris, et à l'un des peintres favoris des contemporains des Impressionnistes qu'elles présentaient comme un artiste éclipsé de son vivant par son prestigieux aîné, Maurice Quentin Delatour (1704-1788). La première partie de la thèse étudie la carrière parisienne du peintre, ses appuis artistiques et sociaux, ses pratiques au pastel et à l'huile, de l'agrément en 1746 à la réception en 1753 et avant le début de la période des voyages en 1756. La rivalité avec Delatour, mise en scène dans un esprit d'émulation au Salon du Louvre pendant plus de vingt ans, y est largement évoquée. Un même nombre de portraits exposés fait comprendre que Perronneau avait de son vivant la faveur des artistes et du public. Il permet de mesurer les effets de la rivalité avec le peintre de Cour sur sa carrière. Delatour faisait exposer en 1750 son autoportrait à côté de son portrait demandé à Perronneau. Les qualités des deux peintres étaient comparées par la nouvelle critique. Notre étude s'attache à ce qui les rapproche comme à ce qui les sépare. Dans la deuxième partie, les peintres des milieux artistiques qu'il fréquente, Louis Tocqué, Jean-Baptiste Oudry, Charles Nicolas Cochin, pour citer les principaux, sont convoqués pour évaluer l'art de Perronneau dans ce que Cochin appelle la « ressemblance savante ». Les peintres les plus ambitieux s'attachent à son interprétation malgré les difficultés dues aux réactions de leur clientèle. La façon dont procède Perronneau est ici envisagée suivant deux aspects : d'une part, la composition du portrait selon une idée du naturel qui détermine l'attitude et une certaine imitation des défauts ; d'autre part, l'imitation de la nature qui réside dans les qualités de l'art, et donc picturales, appréciées des amateurs avertis. La façon qui lui est propre est de composer un naturel selon des poses variées, fondé sur la noblesse de l'attitude conjuguée à la simplicité, conformément à l'idéal courtois en vigueur depuis le XVIe siècle ; elle reste immuable au long de sa carrière. Dans l'imitation de la nature, sont mis en évidence des aspects cachés du faire lors de la mise en place du relief de la figure, les références aux maîtres anciens, Rembrandt, Van Dyck, la conscience de la distance à laquelle le tableau doit être vu, qui atténue la vigueur de la touche, comme le fait le verre qui sert aussi de vernis au pastel. L'idée de sprezzatura qui régit la distinction légère de la pose se décèle à la surface de ses portraits à travers l'apparence de facilité qu'il s'attache à leur donner, et jusque dans l'inimitable retouche finale. Grâce à la qualité de sa retouche, Perronneau accroît sensiblement dans certaines oeuvres à partir de 1768 l'expression savante et inventive de son sentiment. Afin de peindre comme il l'entend tout en gagnant sa vie et celle de sa famille, le peintre prend le parti de voyager comme l'y autorisait la libéralité de son statut. Dans la troisième partie est étudiée la trame de ses voyages que constituent les recommandations dont il bénéficie. Les identités des quatre cent dix modèles peints en France et en Europe de 1740 à 1782 sont systématiquement étudiées dans le catalogue ainsi que les conditions de leur rencontre avec le peintre. Elles décrivent une clientèle variée représentative de la mobilité des statuts dans l'Europe d'ancien Régime dont la composante nouvelle est la clientèle du monde de la banque internationale et du grand commerce. Leurs portraits peints à l'étranger ou dans les villes de Province que Perronneau présente au Salon irritent et inquiètent l'élite parisienne et donne lieu à de nouvelles tensions avec l'éternel rival, Delatour, au Salon de 1767. Perronneau se sent à juste titre évincé de Paris. Alors que l'on avait pu penser qu'il avait peu souffert des critiques du philosophe qui ne furent publiées qu'après sa mort, il apparaît que sa réputation pâtit de ses jugements diffusés par les nouvelles à la main au-delà des frontières et jusqu'auprès de la prestigieuse clientèle qui lui était acquise. Le travail sur son la carrière et l'oeuvre de Perronneau permet surtout une compréhension nouvelle de l'art du portrait au milieu du siècle, au moment où la représentation individuelle n'a jamais encore touché un aussi large public et où l'Académie ambitionne d'élever cet art au plus haut degré.

Influence of Gilbert's syndrome on the formation of ethyl glucuronide.

A drinking experiment with participants suffering from Gilbert's syndrome was performed to study the possible influence of this glucuronidation disorder on the formation of ethyl glucuronide (EtG). Gilbert's syndrome is a rather common and, in most cases, asymptomatic congenital metabolic aberration with a prevalence of about 5 %. It is characterized by a reduction of the enzyme activity of the uridine diphosphate glucuronosyltransferase (UGT) isoform 1A1 up to 80 %. One of the glucuronidation products is EtG, which is formed in the organism following exposure to ethanol. EtG is used as a short-term marker for ethyl alcohol consumption to prove abstinence in various settings. After 2 days of abstinence from ethanol and giving a void urine sample, 30 study participants drank 0.1 L of sparkling wine (9 g ethanol). 3, 6, 12, and 24 h after drinking, urine samples were collected. 3 hours after drinking, an additional blood sample was taken, in which liver enzyme activities, ethanol, hematological parameters, and bilirubin were measured. EtG and ethyl sulfate (EtS), another short-term marker of ethanol consumption, were determined in the urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS); creatinine was measured photometrically. In all participants, EtG and EtS were detected in concentrations showing a wide range (EtG: 3 h sample 0.5-18.43 mg/L and 6 h sample 0.67-13.8 mg/L; EtS: 3 h sample 0.87-6.87 mg/L and 6 h sample 0.29-4.48 mg/L). No evidence of impaired EtG formation was found. Thus, EtG seems to be a suitable marker for ethanol consumption even in individuals with Gilbert's syndrome.

Genome of an arbuscular mycorrhizal fungus provides insight into the oldest plant symbiosis.

The mutualistic symbiosis involving Glomeromycota, a distinctive phylum of early diverging Fungi, is widely hypothesized to have promoted the evolution of land plants during the middle Paleozoic. These arbuscular mycorrhizal fungi (AMF) perform vital functions in the phosphorus cycle that are fundamental to sustainable crop plant productivity. The unusual biological features of AMF have long fascinated evolutionary biologists. The coenocytic hyphae host a community of hundreds of nuclei and reproduce clonally through large multinucleated spores. It has been suggested that the AMF maintain a stable assemblage of several different genomes during the life cycle, but this genomic organization has been questioned. Here we introduce the 153-Mb haploid genome of Rhizophagus irregularis and its repertoire of 28,232 genes. The observed low level of genome polymorphism (0.43 SNP per kb) is not consistent with the occurrence of multiple, highly diverged genomes. The expansion of mating-related genes suggests the existence of cryptic sex-related processes. A comparison of gene categories confirms that R. irregularis is close to the Mucoromycotina. The AMF obligate biotrophy is not explained by genome erosion or any related loss of metabolic complexity in central metabolism, but is marked by a lack of genes encoding plant cell wall-degrading enzymes and of genes involved in toxin and thiamine synthesis. A battery of mycorrhiza-induced secreted proteins is expressed in symbiotic tissues. The present comprehensive repertoire of R. irregularis genes provides a basis for future research on symbiosis-related mechanisms in Glomeromycota.

Toward interoperable bioscience data.

To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry for direct bacterial identification from positive blood culture pellets.

An ammonium chloride erythrocyte-lysing procedure was used to prepare a bacterial pellet from positive blood cultures for direct matrix-assisted laser desorption-ionization time of flight (MALDI-TOF) mass spectrometry analysis. Identification was obtained for 78.7% of the pellets tested. Moreover, 99% of the MALDI-TOF identifications were congruent at the species level when considering valid scores. This fast and accurate method is promising.

In vivo conditional Pax4 overexpression in mature islet β-cells prevents stress-induced hyperglycemia in mice.

OBJECTIVE To establish the role of the transcription factor Pax4 in pancreatic islet expansion and survival in response to physiological stress and its impact on glucose metabolism, we generated transgenic mice conditionally and selectively overexpressing Pax4 or a diabetes-linked mutant variant (Pax4R129 W) in β-cells. RESEARCH DESIGN AND METHODS Glucose homeostasis and β-cell death and proliferation were assessed in Pax4- or Pax4R129 W-overexpressing transgenic animals challenged with or without streptozotocin. Isolated transgenic islets were also exposed to cytokines, and apoptosis was evaluated by DNA fragmentation or cytochrome C release. The expression profiles of proliferation and apoptotic genes and β-cell markers were studied by immunohistochemistry and quantitative RT-PCR. RESULTS Pax4 but not Pax4R129 W protected animals against streptozotocin-induced hyperglycemia and isolated islets from cytokine-mediated β-cell apoptosis. Cytochrome C release was abrogated in Pax4 islets treated with cytokines. Interleukin-1β transcript levels were suppressed in Pax4 islets, whereas they were increased along with NOS2 in Pax4R129 W islets. Bcl-2, Cdk4, and c-myc expression levels were increased in Pax4 islets while MafA, insulin, and GLUT2 transcript levels were suppressed in both animal models. Long-term Pax4 expression promoted proliferation of a Pdx1-positive cell subpopulation while impeding insulin secretion. Suppression of Pax4 rescued this defect with a concomitant increase in pancreatic insulin content. CONCLUSIONS Pax4 protects adult islets from stress-induced apoptosis by suppressing selective nuclear factor-κB target genes while increasing Bcl-2 levels. Furthermore, it promotes dedifferentiation and proliferation of β-cells through MafA repression, with a concomitant increase in Cdk4 and c-myc expression.

NYVAC immunization induces polyfunctional HIV-specific T-cell responses in chronically-infected, ART-treated HIV patients.

We report the results of the Theravac-01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus-based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC-B vaccine was injected intra-muscularly into ten HIV-infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV-specific T-cell responses following immunization were quantitatively analyzed using an IFN-γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC-B vaccine is safe and highly immunogenic, as indicated by increased HIV-specific T-cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T-cell responses, and the appearance of newly detected HIV-specific CD4(+) and CD8(+) T-cell responses were observed. Furthermore, immunization mostly induced an increase in Gag-specific T-cell responses. In conclusion, NYVAC-B immunization induces broad, vigorous, and polyfunctional HIV-specific T-cell responses, suggesting that poxvirus-based vaccine regimens may be instrumental in the therapeutic HIV vaccine field.

Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group.

Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.