Jean-Jacques Rousseau : le dernier état de la Lettre à D’Alembert sur les spectacles (1758)

La Lettre à D’Alembert sur les spectacles fut écrite par Rousseau dans le feu d’une polémique avec D’Alembert, contre l’idée de l’installation d’un théâtre à Genève que ce dernier venait d’avancer dans l’article « Genève » de l’Encyclopédie. Sa genèse commence donc par la lecture d’un article de l’Encyclopédie – faite par Rousseau à la fin de l’année 1757 ; elle s’achèvera à une date indéterminée, après plusieurs étapes, dans les marges d’un exemplaire de l’édition originale de 1758 (fig. 1) ..

Un voyage au long cours dans l’écriture de Rousseau

La plongée dans les manuscrits de Rousseau est un voyage au long cours. Il faut du temps au chercheur pour parcourir et explorer un continent de plus de sept mille pages manuscrites qui restent à bien des égards mal connues – et là est peut-être la chose la plus étonnante. Voyage dépaysant, tant la forme de textualité à laquelle le lecteur se trouve confronté est différente de celle accoutumée. À partir d’une lettre de La Nouvelle Héloïse (IV, 3) qui a pour sujet le voyage autour du monde de St. Preux, on se propose de faire une lecture génétique – c’est-à-dire comprise dans le flux des états successifs connus – et interprétative de quelques pages de ce roman, dont on dispose de cinq états manuscrits. Cette observation en transparence du texte permet-elle de percevoir des significations qui nous échappaient ? On cherchera à montrer l’intérêt de la démarche génétique en termes d’interprétation, de connaissance et de compréhension d’une œuvre apparemment si bien connue.Delving into Rousseau’s manuscripts is a long-distance journey. The researcher needs time to browse through and explore a continent of more than seven thousand manuscript pages that remain in many ways poorly known, which is perhaps the biggest surprise. A disorientating journey, so unusual is the type of textuality to which the reader is confronted. With a letter of La Nouvelle Héloïse (IV, 3), about the St. Preux’s trip around the world, we will present a genetic reading – including the known successive versions – and interpretative of several pages of the novel of which five manuscript versions are available to us. Does this see-through observation of the text allow us to discover meanings that we had overlooked? We will try to show how very worthwhile this genetic approach is in terms of interpretation, knowledge and comprehension of a work supposedly so well-known.Das Eintauchen in die Manuskripte Rousseaus ist eine lange Reise. Der Forscher benötigt Zeit, um einen Kontinent von mehr als siebentausend Manuskriptseiten abzuschreiten und zu erforschen – Manuskripte, die in vielerlei Hinsicht immer noch wenig bekannt sind, und das ist vielleicht das Erstaunlichste. Es ist eine verunsichernde Reise: so groß ist nämlich der Unterschied zwischen der Textsubstanz, mit der sich der Leser dabei konfrontiert sieht, und dem ihm bislang vertrauten Text. Ausgehend von einem Brief der Nouvelle Héloïse (IV, 3), der die Weltumsegelung des St. Preux zum Gegenstand hat, nehmen wir uns eine genetische Lektüre vor – das heißt eine Lektüre, die den sukzessiven Entwurfsstadien Rechnung trägt –, aber auch eine interpretierende Lektüre einiger Seiten jenes Briefromans, von welchem fünf Manuskriptfassungen erhalten sind. Lernen wir aus dieser Art der Lektüre etwas, das uns bisher entging? Wir versuchen zu zeigen, was die genetische Herangehensweise an Interessantem für Interpretation, Kenntnis und Verständnis eines scheinbar so gut bekannten Werkes mit sich bringt.L’immersione nei manoscritti di Rousseau è un viaggio di lungo corso. Il ricercatore ha bisogno di tempo per percorrere ed esplorare un continente di più di settemila pagine manoscritte che rimangono, per molti aspetti, semisconosciuti – e questa è forse la cosa più stupefacente. Un viaggio “spaesante”, tanto la forma di testualità alla quale il lettore si trova confrontato è diversa da quella a cui è abituato. Partendo da una lettera della Nouvelle Héloïse (IV, 3) che ha per oggetto il giro del mondo di St. Preux, svilupperemo una lettura genetica – che attraversa cioè il flusso delle versioni successive – e interpretativa di alcune pagine di questo romanzo, del quale possediamo cinque versioni manoscritte. Quest’osservazione in trasparenza del testo ci permetterà di cogliere nuovi significati? Cercheremo di dimostrare l’importanza dell’approccio genetico in termini d’interpretazione, di conoscenza e comprensione di un’opera, in apparenza molto ben conosciuta.Mergulhar nos manuscritos de Rousseau é o mesmo que fazer uma viagem de longo curso. Leva tempo para que o pesquisador percorra e explore um continente de mais de sete mil páginas manuscritas, que, por incrível que seja, permanecem a muitos títulos mal conhecidas. Viagem por estranhas paragens, tão desusada é a forma de textualidade com que o leitor se confronta. A partir de uma carta de La Nouvelle Héloïse (IV, 3), que tem por tema a volta ao mundo de St. Preux, é empreendida uma leitura genética (enquadrada no fluxo dos estados sucessivos conhecidos) e interpretativa de algumas páginas do romance, que existe em cinco estados manuscritos. Permitirá esta observação do texto à transparência alcançar significações que de outro modo escapariam? Será demonstrado o interesse da abordagem genética para fins de interpretação, conhecimento e compreensão de uma obra aparentemente tão bem conhecida.La inmersión en los manuscritos de Rousseau es una navegación de altura. Le toma tiempo al investigador recorrer ese continente de más de siete mil páginas manuscritas, en muchos de sus aspectos poco conocidas -lo que sin duda resulta lo más asombroso. Viaje extraño, pues la forma de textualidad a la que el lector se ve confrontado difiere de la usual. A partir de una carta de La nueva Eloísa (IV, 3), cuyo tema es el viaje alrededor del mundo de St. Preux, nos proponemos efectuar una lectura genética -es decir, comprendida en el flujo de los estados sucesivos conocidos- e interpretativa de algunas páginas de esta novela, de la que existen cinco estados manuscritos. ¿Esta observación a contraluz del texto permite percibir significaciones ignoradas? Trataremos de demostrar el interés del procedimiento genético en términos de interpretación, de conocimiento y de comprensión de una obra aparentemente bien conocida

Les rosiéristes de la région lyonnaise : élaboration des variétés, étude des marchés (1873-1939)

Lyon se caractérise par une incontestable domination en matière de production et de création de rosiers, et ce dès la seconde moitié du 19e siècle. Une politique commerciale dynamique, le souci d’étendre les commandes et de rester compétitif sur tous les créneaux du métier, conduisent les rosiéristes lyonnais à conserver pendant tout le Second Empire et jusqu’aux années 1920, une position de leader sur le marché national et international en matière de création de roses nouvelles. L’étude entreprise grâce aux archives commerciales – catalogues, registres de commandes – recueillies auprès des exploitations Guillot et Laperrière – établies depuis plusieurs générations – révèle une croissance marquée de l’activité rosicole, entre 1860 et 1914, comparable à celle d’un marché du luxe parce qu’elle évolue en fonction des modes. Si les sources utilisées sont biaisées, elles permettent toutefois de distinguer le principal caractère du commerce rosicole : celui d’un marché étroit intégralement dominé par des professionnels confirmés pour qui l’activité de revente représente l’essentiel des revenus. On gagne sa vie par le commerce mais l’amour du métier s’exprime dans les pratiques de l’obtention. L’ensemble des procédés mis en œuvre dans la création de variétés nouvelles témoigne de la complexité que présente le travail du rosiériste. En dépit des progrès techniques accomplis par l’utilisation progressive de la génétique, le savoir-faire demeure la clef d’une production innovante capable de s’affirmer sur le marché. Entreprenante et volontariste, la politique de ces établissements s’appuie sur la connaissance exacte des débouchés potentiels et leur essor dépend de leur capacité à choisir les marchés les plus porteurs. Quant à l’étude de la consommation, elle met en évidence l’évolution des goûts et des modes en matière de roses, tandis que la périodisation des ventes confirme la prédominance d’une clientèle aisée, qui en achetant des roses, a la sensation d’intégrer un mode de consommation sélectif associé à une forme de distinction.Nathalie FERRAND, Roses growers from Lyon and its area: varieties processing and market development (1873-1939) Since the middle of the 19th century, Lyon can be considered as one of the main centres for rose creation and production in Europe. From the Second Empire to the 1920’s, a dynamic commercial strategy, aiming at the expansion of orders and a constant effort of competitiveness in all areas of trade, allows the rose growers of Lyon to keep the leadership in the creation of new rose-bushes both on the domestic and the international market. Our analysis, based on commercial archives – catalogues, orders books… – from the Guillot and Laperrière company, an agricultural holding active from generation to generation on the rose market –, puts emphasis on the growth of rose growing activity from 1860 to 1914, in relation with the luxury trade and the evolution of its tendencies. Even if our archives give a biased sight on this market, they allow us to perceive the logics of rose business: a narrow market, dominated by skilled professionals. The resale constitutes the main part of their income. They earn their living by trading, but passion is a key element in rose cultivation. The modus operandi, carried out to create new rose-bushes varieties, underlines the complexity of rose growers’ job. Despite technical improvements performed by the gradual use of genetics, the ability remains the key of an innovative production, condition of the commercial leadership. The entrepreneurial policy of these companies is based on the accurate knowledge of the potential outlet. Their expansion depends on their capacity to understand the evolution of the taste of consumers. Our study of the consumption of rose-bushes sets light on the rapid change of tastes and tendencies, in a context of hegemony of a wealthy clientele, led by the feeling of getting into a selective consumption associated with social distinction

The old and new regime in manuscript research

The article attempts to outline the history of French genetic research upon 18th-century manuscript collections. Contrary to the stereotypical view of the 18th century as a period when manuscripts were allegedly destroyed in order to hide evidence of the painstaking execution of the fi nal version of a work, this epoch did leave us manuscripts, frequently full of corrections, which suggest that the Enlightenment thought and literature kept searching and experimenting. The Enlightenment philosophical and political concepts had undergone many stages before they adopted the shape we are familiar with. Thanks to the existence of their preliminary, draft versions, enlightenment novels, theatrical plays and poems provide an opportunity to observe the whole process of creation. The fascinating workshop of enlightenment drafts and subsequent versions of written works shows an area of literary and philosophical work marked by aesthetic and ideological confl icts, which shook the authors in their process of artistic creation

Evolutionary dynamics of glucose-deprived cancer cells: insights from experimentally-informed mathematical modelling

Glucose is a primary energy source for cancer cells. Several lines of evidence support the idea that monocarboxylate transporters, such as MCT1, elicit metabolic reprogramming of cancer cells in glucose-poor environments, allowing them to reuse lactate, a byproduct of glucose metabolism, as an alternative energy source with serious consequences for disease progression. We employ a synergistic experimental and mathematical modelling approach to explore the evolutionary processes at the root of cancer cell adaptation to glucose deprivation, with particular focus on the mechanisms underlying the increase in MCT1 expression observed in glucose-deprived aggressive cancer cells. Data from in vitro experiments on breast cancer cells are used to inform and calibrate a mathematical model that comprises a partial integro-differential equation for the dynamics of a population of cancer cells structured by the level of MCT1 expression. Analytical and numerical results of this model suggest that environment-induced changes in MCT1 expression mediated by lactate-associated signalling pathways enable a prompt adaptive response of glucose-deprived cancer cells, whilst fluctuations in MCT1 expression due to epigenetic changes create the substrate for environmental selection to act upon, speeding up the selective sweep underlying cancer cell adaptation to glucose deprivation, and may constitute a long-term bet-hedging mechanism.Comment: Main manuscript: 14 pages, 4 figures. Supplementary material: 29 pages, 11 figures, 2 table

Dysfonctionnement systémique de la différenciation ostéoblastique des cellules souches adipeuses des patients atteints de myélome multiple

International audienceMultiple myeloma is characterized by bone lesions linked to increased osteoclast and decreased osteoblast activities. In particular, the osteoblast differentiation of bone marrow-derived stem cells (MSC) is impaired. Among the potential therapeutic tools for counteracting bone lesions, adipose-derived stem cells (ASC) could represent an appealing source for regenerative medicine due to their similar characteristics with MSC. Our study is among the first giving detailed insights into the osteoblastogenic capacities of ASC isolated by fat aspiration from myeloma patients (MM-ASC) compared to healthy subjects (HD-ASC). We showed that MM-ASC and HD-ASC exhibited comparable morphology, proliferative capacity, and immunophenotype. Unexpectedly, although normal in adipocyte differentiation, MM-ASC present a defective osteoblast differentiation, as indicated by less calcium deposition, decreased alkaline phosphatase activity, and downregulation of RUNX2 and osteocalcin. Furthermore, these ASC-derived osteoblasts displayed enhanced senescence, as shown by an increased β-galactosidase activity and cell cycle inhibitors expression (p16 INK4A , p21 WAF1/CIP1 .), associated with a markedly increased expression of DKK1, a major inhibitor of osteoblastogenesis in multiple myeloma. Interestingly, inhibition of DKK1 attenuated senescence and rescued osteoblast differentiation, highlighting its key role. Our findings show, for the first time, Cells 2019, 8, 441 2 of 16 that multiple myeloma is a systemic disease and suggest that ASC from patients would be unsuitable for tissue engineering designed to treat myeloma-associated bone disease.Le myélome multiple est caractérisé par des lésions osseuses liées à une augmentation de l'activité ostéoclastique et à une diminution de l'activité ostéoblastique. En particulier, la différenciation ostéoblastique des cellules souches issues de la moelle osseuse (CSM) est altérée. Parmi les outils thérapeutiques potentiels pour contrer les lésions osseuses, les cellules souches dérivées de l'adipeux (CSA) pourraient représenter une source intéressante pour la médecine régénérative en raison de leurs caractéristiques similaires à celles des cellules MSC. Notre étude est l'une des premières à donner un aperçu détaillé des capacités ostéoblastogènes de l'ASC isolée par aspiration graisseuse chez les patients atteints de myélome (MM-ASC) par rapport aux sujets sains (HD-ASC). Nous avons montré que le MM-ASC et le HD-ASC présentaient une morphologie, une capacité proliférative et un immunophénotype comparables. De façon inattendue, bien que normal dans la différenciation adipocytaire, le MM-ASC présente une différenciation ostéoblastique défectueuse, comme l'indiquent la diminution des dépôts de calcium, la diminution de l'activité des phosphatases alcalines et la régulation négative de RUNX2 et de l'ostéocalcine. De plus, ces ostéoblastes dérivés de l'ASC présentaient une sénescence accrue, comme en témoigne l'augmentation de l'activité de la β-galactosidase et de l'expression des inhibiteurs du cycle cellulaire (p16 INK4A, p21 WAF1/CIP1 .), associée à une expression nettement accrue du DKK1, un inhibiteur majeur de l'ostéoblastogenèse dans les myélomes multiples. Il est intéressant de noter que l'inhibition du DKK1 a atténué la sénescence et sauvé la différenciation des ostéoblastes, soulignant son rôle clé. Nos résultats montrent, pour la première fois, que le myélome multiple est une maladie systémique et suggèrent que les cellules 2019, 8, 441 2 sur 16 ne conviennent pas au génie tissulaire conçu pour traiter les maladies osseuses associées au myélome

Thrombin modifies growth, proliferation and apoptosis of human colon organoids: a protease-activated receptor 1- and protease-activated receptor 4-dependent mechanism

International audienceExperimental Approach: Crypts were isolated from human colonic resections and cultured for 6 days, forming human colon organoids. Cultured organoids were exposed to 10 and 50 mU·mL−1 of thrombin, in the presence or not of protease‐activated receptor (PAR) antagonists. Organoid morphology, metabolism, proliferation and apoptosis were followed.Key Results: Thrombin favoured organoid maturation leading to a decreased number of immature cystic structures and a concomitant increased number of larger structures releasing cell debris and apoptotic cells. The size of budding structures, metabolic activity and proliferation were significantly reduced in organoid cultures exposed to thrombin, while apoptosis was dramatically increased. Both PAR1 and PAR4 antagonists inhibited apoptosis regardless of thrombin doses. Thrombin‐induced inhibition of proliferation and metabolic activity were reversed by PAR4 antagonist for thrombin's lowest dose and by PAR1 antagonist for thrombin's highest dose.Conclusions and Implications: Overall, our data suggest that the presence of thrombin in the vicinity of human colon epithelial cells favours their maturation at the expense of their regenerative capacities. Our data point to thrombin and its two receptors PAR1 and PAR4 as potential molecular targets for epithelial repair therapies

Intracardiac electrophysiology to characterize susceptibility to ventricular arrhythmias in murine models

Introduction: Sudden cardiac death (SCD) and ventricular fibrillation are rare but severe complications of many cardiovascular diseases and represent a major health issue worldwide. Although the primary causes are often acute or chronic coronary diseases, genetic conditions, such as inherited channelopathies or non-ischemic cardiomyopathies are leading causes of SCD among the young. However, relevant experimental models to study the underlying mechanisms of arrhythmias and develop new therapies are still needed. The number of genetically engineered mouse models with cardiac phenotype is growing, making electrophysiological studies in mice essential tools to study arrhythmogenicity and arrhythmia mechanisms and to test novel treatments. Recently, intracardiac catheterization via the jugular vein was described to induce and record ventricular arrhythmias in living anesthetized mice. Several strategies have been reported, developed in healthy wild-type animals and based on aggressive right ventricular stimulation.Methods: Here, we report a protocol based on programmed electrical stimulation (PES) performed in clinical practice in patients with cardiac rhythm disorders, adapted to two transgenic mice models of arrhythmia - Brugada syndrome and cardiolaminopathy.Results: We show that this progressive protocol, based on a limited number of right ventricular extrastimuli, enables to reveal different rhythmic phenotypes between control and diseased mice. In this study, we provide detailed information on PES in mice, including catheter positioning, stimulation protocols, intracardiac and surface ECG interpretation and we reveal a higher susceptibility of two mouse lines to experience triggered ventricular arrhythmias, when compared to control mice.Discussion: Overall, this technique allows to characterize arrhythmias and provides results in phenotyping 2 arrhythmogenic-disease murine models

Prediction Of Beef Fatty Acid Composition Using Near Infrared Spectroscopy: Effects Of Tissue And Sample Preparations

International audienceThe aims of the study were to determine the best site of bovine carcass for predicting fatty acid (FA) composition using a NIRS (near infrared spectroscopy) portable equipment and to study the effect of different methods of sample preparation. 78 animals were sampled from different types and rearing systems. Seven tissues (Longissimus thoracis, Infraspinatus, Diaphragma, Rectus abdominis, shoulder subcutaneous adipose tissue (SAT), intercostal SAT and intermuscular fat at the 5th rib) were measured after sampling and grinding in liquid nitrogen. The effect of samples preparation were measured on carcass (C0), muscle without grinding (B0), ground with a meat chopper (B1), ground with a knife mill (B2) on RA muscle. FA composition was assessed using gas chromatograph and the spectra were measured at wavelengths between 350 and 2500 nm. For adipose tissue, FA were not correctly predicted from NIRS. However, predictions were more satisfactory for the major FA (C16:0, C18:0, C18:1d9c), total saturated and monounsaturated FA of muscles. The results show a better prediction of FA composition concomitant with an increased gradient of sample homogenization. For other FA and especially polyunsaturated fatty acids, the performances were not satisfactory for quantitative purposes whatever the grinding method