Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death.

Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism. Under conditions of treatment with paclitaxel, non-cell-autonomous and cell-autonomous death were both detected in the treated cell population, while untreated neighboring cells exhibited features of apoptotic demise. The transcriptional activity of p53 tumor-suppressor protein contributed to the execution of cell-autonomous death, yet failed to affect the non-cell-autonomous death by cannibalism for the majority of tested anticancer agents, indicating that the induction of non-cell-autonomous death can occur under conditions in which cell-autonomous death was impaired. Altogether, these results reveal that chemotherapy and radiotherapy can induce both non-cell-autonomous and cell-autonomous death of cancer cells, highlighting the heterogeneity of cell death responses to anticancer treatments and the unsuspected potential contribution of non-cell-autonomous death to the global effects of anticancer treatment

Innovation et développement dans les systèmes agricoles et alimentaires

L’innovation est souvent présentée comme l’un des principaux leviers pour promouvoir un développement plus durable et plus inclusif. Dans les domaines de l’agriculture et de l’alimentation, l’innovation est marquée par des spécificités liées à sa relation à la nature, mais aussi à la grande diversité d’acteurs concernés, depuis les agriculteurs jusqu’aux consommateurs, en passant par les services de recherche et de développement. L’innovation émerge des interactions entre ces acteurs, qui mobilisent des ressources et produisent des connaissances dans des dispositifs collaboratifs, afin de générer des changements. Elle recouvre des domaines aussi variés que les pratiques de production, l’organisation des marchés, ou les pratiques alimentaires. L’innovation est reliée aux grands enjeux de développement : innovation agro-écologique, innovation sociale, innovation territoriale, etc. Cet ouvrage porte un regard sur l’innovation dans les systèmes agricoles et alimentaires. Il met un accent particulier sur l’accompagnement de l’innovation, en interrogeant les méthodes et les organisations, et sur l’évaluation de l’innovation au regard de différents critères. Il s’appuie sur des réflexions portées par différentes disciplines scientifiques, sur des travaux de terrain conduits tant en France que dans de nombreux pays du Sud, et enfin sur les expériences acquises en accompagnant des acteurs qui innovent. Il combine des synthèses sur l’innovation et des études de cas emblématiques pour illustrer les propos. L’ouvrage est destiné aux enseignants, professionnels, étudiants et chercheurs

The response of weed and crop species to shading. How to predict their morphology and plasticity from species traits and ecological indexes?

National audienceTo assess the competitive ability of plant species, ecologists describe many species from contrasting habitats with traits that are proxies of ecophysiological functions whereas agronomists describe few species from similar habitats with process-based parameters. Here, we combined both approaches and compared many contrasting crop and weed species of temperate European arable crops in terms of competition for light, to understand weed response to shading by crop canopies and to choose light-competitive crop species and varieties. We (1) measured species parameters that drive light-competition processes in 26 crop and 35 weed species of temperate European arable cropping systems, (2) related the parameter values to species features that are easier to measure or available in databases. Early plant-growth parameters (relative growth rate RGR, initial leaf area) were measured in optimal light and nutrient conditions in a greenhouse with automatic non-destructive measurements. Potential plant morphology in unshaded conditions (specific leaf area SLA, leaf biomass ratio LBR, plant height and width per unit biomass HM and WM, vertical leaf distribution) was measured in garden plots in optimal light and nutrient conditions and harvested at 4–5 stages. Shading response was measured by comparing potential morphology to that of plants grown under shading nets. We confirmed well-known relationships (lower SLA and LBR in legumes vs non-legumes…), included new species features (base temperature, photosynthetic pathway…), and established relationships for the new shading-response parameters (weeds respond more to shade than crops, by increasing LBR, SLA, HM and WM…). Some correlations reported in ecology (RGR vs SLA…) were not verified on our species pool from arable temperate fields. Shade-response parameters explained species responses to habitat described by Ellenberg indexes, e.g., when shaded, shade-loving species (low Ellenberg-L values) increased SLA and HM to increase light interception

1H-NMR-Based Analysis for Exploring Knee Synovial Fluid Metabolite Changes after Local Cryotherapy in Knee Arthritis Patients

International audienceRehabilitation using cryotherapy has widely been used in inflammatory diseases to relieve pain and decrease the disease activity. The aim of this study was to explore the metabolite changes in inflammatory knee-joint synovial fluids following local cryotherapy treatment (ice or cold CO2). We used proton nuclear magnetic resonance (1H NMR) spectroscopy to assess the metabolite patterns in synovial fluid (SF) in patients with knee arthritis (n = 46) before (D0) and after (D1, 24 h later) two applications of local cryotherapy. Spectra from aqueous samples and organic extracts were obtained with an 11.75 Tesla spectrometer. The metabolite concentrations within the SF were compared between D1 and D0 using multiple comparisons with the application of a false discovery rate (FDR) adjusted at 10% for each metabolite. A total of 32 metabolites/chemical structures were identified including amino acids, organic acids, fatty acids or sugars. Pyruvate, alanine, citrate, threonine was significantly higher at D1 vs D0 (p 0.05). The present study provides new insight into a short-term effect of cold stimulus in synovial fluid from patients with knee arthritis. Our observations suggest that the increased level of metabolites involved in energy metabolism may explain the underlying molecular pathways that mediate the antioxidant and anti-inflammatory capacities of cryotherapy

1H NMR Urinary Metabolomic Analysis in Older Adults after Hip Fracture Surgery May Provide Valuable Information for Patient Profiling : A Preliminary Investigation

In these times of precision and personalized medicine, profiling patients to identify their needs is crucial to providing the best and most cost-effective treatment. In this study, we used urine metabolomics to explore the characterization of older adults with hip fractures and to explore the forecasting of patient outcomes. Overnight urine specimens were collected from 33 patients (mean age 80 ± 8 years) after hip fracture surgery during their stay at a rehabilitation hospital. The specimens were analyzed with 1H NMR spectroscopy. We performed a metabolomics study regarding assessments of frailty status, Functional Independence Measure (FIM), and Short Physical Performance Battery (SPPB). The main metabolic variations concerned 10 identified metabolites: paracetamol derivatives (4 peaks: 2.15 ppm; 2.16 ppm; 7.13 ppm and 7.15 ppm); hippuric acid; acetate; acetone; dimethylamine; glycine; alanine; lactate; valine; TMAO. At baseline, the urinary levels of these metabolites were significantly higher (i) in frail compared with non-frail patients, (ii) in persons with poorer FIM scores, and (iii) in persons with poorer compared SPPB scores. Our findings suggested that patients with increased levels of urine metabolites associated with metabolic, inflammatory, and renal disorders presented clear signs of frailty, impaired functional independence, and poor physical performance. Metabolomics could be a valuable tool to further characterize older adults, especially after major medical events.peerReviewe

Compte-rendu de fin de projet - Projet ANR-07-JCJC-0081 IP4 (Interaction Privé-Public dans la Production des espaces Périurbains): Programme Jeunes Chercheurs 2007

The production of suburban areas: an international analysis of complex processes Does suburbanization yield to new models in the production of urban space ? The issue raised connects to the genesis of urban edges' areas, and of the underlying forces that structure them. Indeed, private actors contribute to the production of space (professional territorial management, real-estate developers...) ; local public authorities have key strategies (control on land-use, social selection of residents, urban sprawl or slow-growth policies) ; and publicly-owned and managed areas tend to disappear, yielding to a private urbanism in which planned-unit developments are key features. By the means of a comparative study of Paris-Ile-de-France and Los Angeles metropolitan regions, the study aims at investigating both contextual effects and interactions between public and private actors, in producing suburban developments. The project also aims at reinforcing the interactions between academic research and planning, by the means of a partnership with the IAU-IDF. A quantitative and theoretical approach Spatial analysis has been heavily used to characterize the dynamics on the suburban edges. The team, composed by geographers and planners has relied on quantitative methodologies (spatial analysis of road networks, geostatistics) and qualitative interviews ; the fields of economy and sociology have also been covered by the means of interactions with the international research network Private Urban Governance (http://www.gated-communities.de). On the one hand, theories of actors and systems have been mobilized to analyze the qualitative materials (interviews). On the other hand, the analysis of house prices have been instrumental in assessing the effects of local contexts, either because of the static effects of site and location rental ; but also dynamically, with an analysis of market local variations. The implementation of spatial databases (GIS) covering a large sample of surveyed subdivisions and planned communities covers both quantitative information on urban environment and qualitative data acquired during field surveys. Data collected therefore cover two fields, very different in terms of legal, urban and cultural contexts. Major results Multiple actors operate at different levels, according to their own strategies. Nevertheless, the different levels of public bodies of governments are preeminent in shaping the morphologies of suburban developments. Indeed, if residential enclaves clearly derive from the street patterns morphologies, produced by subdividers and developers, the local actors highly contribute to shaping the significance of the phenomenon (isolation, enclosure and gating, dedication of streets, renewal) - by the means of their decisional capacity in terms of local management. Scientific production Besides regular publication output (papers and conferences) and other means of promotion (reports, websites, press and TV interviews), two doctorate thesis will result from the project. Databases created will be distributed by the means of a web-based open access GIS (Mapserver) (http://gated.parisgeo.cnrs.fr). Factual informations The project IP4: (ANR-07-JCJC-0081 CSD9) is a fundamental and applied research project coordinated par Renaud LE GOIX, Associate Prof., University Paris 1 Panthéon-Sorbonne. The consortium is structured by a partnership between the UMR 8504 Géographie-Cités and IAU-Ile-de-France, with other contributing partners : Cardiff University (Dept. CPLAN), ENSG (IGN) and IFU. The project started in 2007, for a total of 36 month. It has received 79159 € of direct funding by the ANR, for a total cost of 114 000 €.La production du périurbain : analyse internationale d'un processus complexe La périurbanisation contribue-t-elle à inventer de nouveaux modèles de production de l'espace ? Le programme de recherche IP4 vise à expliciter la genèse des espaces résidentiels de front d'urbanisation ainsi que les forces qui les structurent. Le paysage périurbain est modelé tant par les acteurs privés, qui contribuent à sa production (gestionnaires d'espaces commerciaux, promoteurs), que par les collectivités locales qui en définissent les usages (restriction de l'offre foncière, sélection sociale des résidants, éparpillement du front urbain). Une des conséquences actuelle étant la tendance à la disparition des espaces de droit public au profit d'un urbanisme privé, dont les lotissements résidentiels représentent la figure dominante. Il s'agit donc de porter au travers de l'étude de deux grandes métropoles, Paris Île-de-France et Los Angeles, un double questionnement à la fois sur l'impact des effets de contexte et les interactions entre les acteurs privés et publics, dans la production de l'espace périurbain. Le projet a pour principale retombée d'accroître les interactions entre le champ de la recherche et celui de la planification opérationnelle, dans un partenariat Université - IAU-IDF. Une approche croisant analyse quantitative et théorique de la production du périurbain résidentiel L'analyse spatiale représente l'approche privilégiée afin de caractériser les transformations qui s'opèrent sur les franges périurbaines. Pour ce faire l'équipe de recherche composée de géographes et d'urbanistes-aménageurs a recouru à ses compétences techniques (analyse spatiale des réseaux routiers, traitements géo-statistiques, entretiens qualitatifs) mais également ouvert aux champs de l'économie et de la sociologie, au travers de la mobilisation d'un vaste réseau international de chercheurs et d'opérateurs (réseau international Private Urban Governance http://www.gated-communities.de). D'une part, la théorie des acteurs et des systèmes a été mobilisée pour le dépouillement des enquêtes. D'autre part l'analyse des prix immobiliers permet de mesurer les effets de contextes locaux, liés de manière statique aux effets de rente de site et de situation, mais également de manière dynamique des évolutions locales du marché. Dans cette optique, la construction de bases de données géo-référencées (SIG) sur les lotissements enquêtés a permis de croiser des données quantitatives sur l'environnement urbain et des connaissances qualitatives acquises sur le terrain. Les données ainsi collectées portent sur des terrains et des contextes juridiques, urbains et culturels différents (Californie, Île-de-France). Résultats majeurs du projet Si les acteurs sont multiples et opèrent à différents échelons et selon des stratégies qui leur sont propres, il apparaît que ce sont les différents échelons des pouvoirs publics qui déterminent les morphologies des ensembles résidentiels. En effet si l'enclavement résidentiel est avant tout perceptible de part sa morphologie viaire, produite par les opérateurs et les promoteurs immobilier, ce sont en définitif les acteurs locaux qui, au travers de leurs compétences décisionnelles en matière de gestion locales lui confèrent sa portée (enclavement, fermeture, rétrocession, rénovation). Production scientifique Outre les publications (articles et colloques) et éléments de valorisation (rapports, site internet, presse et TV), deux thèses sont en cours. Les bases de données créées sont pérennisées et seront rendues disponibles par le biais d'une interface cartographique en ligne en libre-accès (Mapserver) (http://gated.parisgeo.cnrs.fr). Informations factuelles Le projet ANR-07-JCJC-0081 CSD9 - IP4:Interaction Privé-Public dans la Production des espaces Périurbains est un projet de recherche fondamentale et appliquée coordonné par Renaud LE GOIX, Maître de conférences à l'Université Paris 1 Panthéon-Sorbonne. Il associe le laboratoire UMR 8504 Géographie-cités et l'IAU-Ile-de-France, ainsi que des contributeurs de l'Université de Cardiff (Dept. CPLAN), l'ENSG, ainsi que l'IFU. Le projet a commencé en novembre 2007 et a duré 36 mois. Il a bénéficié d'une aide ANR de 79159 € pour un coût global de l'ordre de 114 000 €

Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab

In 1989 Maine enacted the Comprehensive Planning and Land Use Regulation Act. The Act\u27s legislative findings declared that “ the State has a vital interest in ensuring that a comprehensive system of land-use planning and growth management is established as quickly as possible.” However, whenever the state exercises its police power to regulate private land use, it faces a constitutional limit as to how far it can go. When the land-use restriction exceeds that limit, a regulatory taking occurs. This Comment argues that the Comprehensive Planning and Land Use Regulation Act, as it is being interpreted and implemented by state and local officials across the state, encourages growth management regulation that goes too far. When regulation under the Act is applied too aggressively, it violates the Taking Clause of the Maine Constitution. This argument is based upon the premise that there exists in Maine law a standard for determining when a regulatory taking occurs. The problem, however, is that taking decisions by the Law Court have been fact-specific and seemingly unrelated. All but one of Maine\u27s taking cases have involved an as-applied challenge to the land-use restriction rather than a facial challenge to the statute. Consequently, “the principal focus of the Law Court in ‘taking’ cases has become a factual inquiry” into the unique facts of each case. Because of this ad hoc approach, it is difficult “to develop any ‘set formula’ for determining when ‘justice and fairness\u27 require that economic injuries caused by public action be compensated by the government, rather than remain disproportionately concentrated on a few persons.” This does not mean, however, that one is precluded from deriving a general rule regarding the taking issue in Maine. This Comment will demonstrate that upon comprehensive examination, a coherent test for resolving the taking question emerges from the Maine case law