Dynamic RNA profiling in Plasmodium falciparum synchronized blood stages exposed to lethal doses of artesunate

<p>Abstract</p> <p>Background</p> <p>Translation of the genome sequence of <it>Plasmodium sp</it>. into biologically relevant information relies on high through-put genomics technology which includes transcriptome analysis. However, few studies to date have used this powerful approach to explore transcriptome alterations of <it>P. falciparum </it>parasites exposed to antimalarial drugs.</p> <p>Results</p> <p>The rapid action of artesunate allowed us to study dynamic changes of the parasite transcriptome in synchronous parasite cultures exposed to the drug for 90 minutes and 3 hours. Developmentally regulated genes were filtered out, leaving 398 genes which presented altered transcript levels reflecting drug-exposure. Few genes related to metabolic pathways, most encoded chaperones, transporters, kinases, Zn-finger proteins, transcription activating proteins, proteins involved in proteasome degradation, in oxidative stress and in cell cycle regulation. A positive bias was observed for over-expressed genes presenting a subtelomeric location, allelic polymorphism and encoding proteins with potential export sequences, which often belonged to subtelomeric multi-gene families. This pointed to the mobilization of processes shaping the interface between the parasite and its environment. In parallel, pathways were engaged which could lead to parasite death, such as interference with purine/pyrimidine metabolism, the mitochondrial electron transport chain, proteasome-dependent protein degradation or the integrity of the food vacuole.</p> <p>Conclusion</p> <p>The high proportion of over-expressed genes encoding proteins exported from the parasite highlight the importance of extra-parasitic compartments as fields for exploration in drug research which, to date, has mostly focused on the parasite itself rather than on its intra and extra erythrocytic environment. Further work is needed to clarify which transcriptome alterations observed reflect a specific response to overcome artesunate toxicity or more general perturbations on the path to cellular death.</p

Bidirectional intraflagellar transport is restricted to two sets of microtubule doublets in the trypanosome flagellum

Intraflagellar transport (IFT) is the rapid bidirectional movement of large protein complexes driven by kinesin and dynein motors along microtubule doublets of cilia and flagella. In this study, we used a combination of high-resolution electron and light microscopy to investigate how and where these IFT trains move within the flagellum of the protist Trypanosoma brucei. Focused ion beam scanning electron microscopy (FIB-SEM) analysis of trypanosomes showed that trains are found almost exclusively along two sets of doublets (3–4 and 7–8) and distribute in two categories according to their length. High-resolution live imaging of cells expressing mNeonGreen::IFT81 or GFP::IFT52 revealed for the first time IFT trafficking on two parallel lines within the flagellum. Anterograde and retrograde IFT occurs on each of these lines. At the distal end, a large individual anterograde IFT train is converted in several smaller retrograde trains in the space of 3–4 s while remaining on the same side of the axoneme

Discovery of a low-mass companion inside the debris ring surrounding the F5V star HD 206893

Aims: Uncovering the ingredients and the architecture of planetary systems is a very active field of research that has fuelled many new theories on giant planet formation, migration, composition, and interaction with the circumstellar environment. We aim at discovering and studying new such systems, to further expand our knowledge of how low-mass companions form and evolve. Methods: We obtained high-contrast H-band images of the circumstellar environment of the F5V star HD 206893, known to host a debris disc never detected in scattered light. These observations are part of the SPHERE High Angular Resolution Debris Disc Survey (SHARDDS) using the InfraRed Dual-band Imager and Spectrograph (IRDIS) installed on VLT/SPHERE. Results: We report the detection of a source with a contrast of 3.6 × 10[SUP]-5[/SUP] in the H-band, orbiting at a projected separation of 270 milliarcsec or 10 au, corresponding to a mass in the range 24 to 73 M[SUB]Jup[/SUB] for an age of the system in the range 0.2 to 2 Gyr. The detection was confirmed ten months later with VLT/NaCo, ruling out a background object with no proper motion. A faint extended emission compatible with the disc scattered light signal is also observed. Conclusions: The detection of a low-mass companion inside a massive debris disc makes this system an analog of other young planetary systems such as β Pictoris, HR 8799 or HD 95086 and requires now further characterisation of both components to understand their interactions.Peer reviewe

Ville et agriculture périubaine: la trajectoire française

The paper aims at retracing the steps of peri-urban agriculture in France. Starting from the history of dualism between Town and Country, and highlighting the periurban agriculture’s phases of politicization, it deals with the issue of development of agglomeration policies in which the agriculture topic is embedded, leading to the emergence of five different types of agricultural agglomeration policies. It describes the great movements which, today, are deeply renewing peri-urban agriculture policies: the identification of sustainable cities (together with the fight against urban sprawl), the food issue (with the enhancement of the production function of agriculture) and the return to a territorial economy. The focus is then placed on the uncertainty of the argument and its exploitation by different policies.Il saggio si pone l’obiettivo di ripercorrere le tappe dell’agricoltura periurbana in Francia. Partendo dalla storia del dualismo “Città-Campagna” ed evidenziando le fasi di politicizzazione dell’agricoltura periurbana, affronta l’argomento dello sviluppo delle politiche di agglomerazione in cui viene integrato il tema dell’agricoltura, portando alla nascita di cinque diversi tipi di “Politique agricoles périurbaine d’agglomération”. Vengono spiegati i grandi movimenti che, oggi, rinnovano profondamente le politiche agricole periurbane: l’indicazione della città durevole (con la lotta contro l’espansione della città), la questione alimentare (con la rivalorizzazione della funzione di produzione dell’agricoltura) e il ritorno all’economia territoriale. Viene quindi posta l’attenzione sull’incertezza dell’argomento e sulla sua strumentalizzazione da parte di altre politiche

L'alimentation des sociétés urbaines : une cure de jouvence pour l'agriculture des territoires métropolitains ?

International audienceThis paper intends to tackle the issue of the urban and peri-urban agriculture in relation to the emergent social demand concerning food. We question ourselves about the potential link the supply of food for urban societies could be for the relations between the city and its agricultural periphery. Since the Second World War, the food of industrialized societies has evolved deeply and rapidly, changing the relationship with the territory. We can observe a kind of swing between the deterritorialized and reterritorialized processes which seems currently to tilt towards the latter. We study the way food gets into the local governments agenda through the periurban agricultural policies of the cities members of the Terres en Villes network. If this introduction of food in the public agenda is usually set up by an agricultural entry, we put forward the way food could be a lever of questioning for the planning policies concerning urban regions "to live in". Thus, we observe the very beginning of food policies which go beyond the alternative food systems policies, and create links with stakeholders other than the agricultural stakeholders that could meet around the food issue to get involved into the building of metropolitan territories.Cet article se propose d'aborder la question du rôle de l'agriculture urbaine et périurbaine par rapport à l'émergence d'une nouvelle demande sociale concernant l'alimentation. Nous nous interrogeons sur le nouveau liant que l'alimentation des sociétés urbaines pourrait constituer dans le cadre des rapports entre ville et agriculture. Depuis la Seconde Guerre mondiale, l'alimentation des sociétés des pays industrialisés a connu des évolutions profondes et rapides qui ont reconfiguré les rapports au territoire. On observe ainsi un mouvement de balancier entre déterritorialisation et reterritorialisation qui semble actuellement se faire au profit du second. Face à une demande sociale en émergence qui se traduit dans la métropole par un mélange complexe de saveurs territoriales, nous étudions comment la question alimentaire se hisse à l'agenda des collectivités territoriales dans les politiques agricoles périurbaines des agglomérations membres du réseau Terres en Villes. Si cette mise à l'agenda se fait essentiellement pour l'instant par une entrée agricole, nous mettons en avant la façon dont l'alimentation pourrait constituer un levier d'interpellation des politiques d'aménagement dans le cadre de la gestion territoriale de régions urbaines " à vivre ". Ainsi, on observe les prémices d'une émergence de politiques alimentaires, dépassant les seules politiques de circuit-court, créant des liens avec des sphères d'acteurs autres que celles du monde agricole, pouvant se retrouver autour de la question alimentaire pour s'engager dans la construction de territoires métropolitains

Régulation politique et territorialisation du fait alimentaire : de l’agriculture à l’agri-alimentaire

National audienceThis paper deals with the political regulation of food supply (voir commentaire au-dessus) in France through a comparative analysis between international and national policies and the peri-urban agricultural policies of the territorial authorities who are members of the ‘Terres en Villes’ network. As food is emerging as an issue for metropolitan areas, the main question is focused on the articulations between the various conceptions of this issue held at the different levels of intervention.By looking back to the first international and national policies focused on food security using a quantitative approach, and to the history of short food supply networks being taken into account in public agricultural policy in peri-urban areas, it is shown how the agricultural and economic prism has shaped the treatment of this issue from the very beginning. Around this original prism, a normative and health-based approach was developed, whereas peri-urban agricultural policies were looking in more depth at a multifunctional approach to this question and at short food supply networks. If the hybridization of these two approaches is difficult, the article shows that at the present time the different fields and scales of approach and stakeholders’ interests are beginning to converge and, as a result, a less sectoral treatment of the food supply question is emerging.As a sign of this evolution, it is shown that the peri-urban agricultural policies have entered a period of transition leading them from the agricultural to the agri-food field. This approach reveals the socio-spatial tensions and points out to the difficulties of formulating a global territorial food policy, integrating the various sectors and scales implied in metropolitan development projects.Cet article se propose d’analyser la régulation politique du fait alimentaire en France en mettant en regard les politiques internationales et nationales et les politiques agricoles périurbaines des agglomérations membres du réseau Terres en Villes. Nous nous interrogeons sur les articulations des différentes conceptions du fait alimentaire portées par ces différentes échelles d’action face au nouvel enjeu territorial en émergence que constitue l’alimentation pour les territoires métropolitains.En revenant aux premières politiques internationales et nationales focalisées sur la sécurité alimentaire dans une approche quantitative et à l’histoire de la prise en compte des circuits courts dans l’action publique agricole périurbaine, nous montrons le prisme agricole et économique qui structure le traitement politique du fait alimentaire. Autour de ce prisme originel s’est ensuite développée une approche normative et sanitaire de l’alimentation tandis que les politiques agricoles périurbaines approfondissaient une approche multifonctionnelle de l’agriculture périurbaine et des circuits courts. Si ces deux chemins d’appréhension du fait alimentaire semblent difficiles à hybrider, l’article montre que la période actuelle engage des rapprochements entre champs, acteurs et échelles et donc des constructions moins sectorielles du traitement du fait alimentaire. Signe de cette évolution, nous montrons que les politiques agricoles périurbaines sont entrées dans une transition les faisant évoluer du champ agricole au champ agri-alimentaire. Mais cette approche révèle les tensions socio-spatiales à l’œuvre et souligne les difficultés de la formulation d’une politique alimentaire territoriale transversale aux différents champs et intégrée au projet d’agglomération

L’alimentation des sociétés urbaines : une cure de jouvence pour l’agriculture des territoires métropolitains ?

This paper intends to tackle the issue of the urban and peri-urban agriculture in relation to the emergent social demand concerning food. We question ourselves about the potential link the supply of food for urban societies could be for the relations between the city and its agricultural periphery.Since the Second World War, the food of industrialized societies has evolved deeply and rapidly, changing the relationship with the territory. We can observe a kind of swing between the deterritorialized and reterritorialized processes which seems currently to tilt towards the latter. We study the way food gets into the local governments agenda through the periurban agricultural policies of the cities members of the Terres en Villes network. If this introduction of food in the public agenda is usually set up by an agricultural entry, we put forward the way food could be a lever of questioning for the planning policies concerning urban regions “to live in”. Thus, we observe the very beginning of food policies which go beyond the alternative food systems policies, and create links with stakeholders other than the agricultural stakeholders that could meet around the food issue to get involved into the building of metropolitan territories

Compréhension des mécanismes de formation des adduits exocycliques à l'ADN par les dérivés aromatiques nitrés

Les adduits exocycliques à l ADN paraissent être la conséquence indirecte, sous la médiation de la peroxydation lipidique, du stress oxydant cellulaire induit par les composés aromatiques nitrés (CANs) de l environnement. Ces derniers, formés le plus souvent in situ dans les environnements complexes sont un sujet de préoccupation croissante en santé environnementale. Le but étant de comprendre les mécanismes de formation et de dégradation de ces adduits afin d en apprécier leur place dans la toxicité des CANs et leur intérêt en tant que biomarqueurs du stress oxydant induit par l environnement.Nous avons réalisé la synthèse de deux adduits exocycliques : le 1,N -éthéno-2 -déoxyguanosine ( dG) et le 1,N -propano-2 -déoxyguanosine (pdG-HNE) et étudié leurstabilité en présence d une oxydation radicalaire. Il est apparu que le pdG-HNE semble être lemeilleur candidat en tant que biomarqueur du stress oxydant.Pour approcher au mieux la chimie du vivant, nous nous sommes posés la question dela stabilité de ces adduits en milieu cellulaire. Une étude préliminaire de génotoxicité a étéréalisée et montre que seuls les hydrocarbures aromatiques polycycliques nitrés présententune potentialité mutagène significative. Nous avons donc étudié le pyrène et ses dérivés nitrés(1-Nitropyrène/1,3-Dinitropyrène/1,6-Dinitropyrène/1,8-Dinitropyrène) afin d étudier leurcapacité à générer des adduits dans les lymphocytes humains.Nos résultats montrent que le 1-Nitropyrène génère in vitro des adduits stables dans letemps ; ce qui pose la question de leur réparabilité par les systèmes cellulaires et de leurspotentialités cancérogènes pour l homme.Exocyclic DNA adducts seem to be the indirect consequence, mediated by lipidperoxidation, of oxidative stress induced by nitro aromatic compounds (NACs). The latterusually formed in situ in environmental complex mixtures are a matter of concern inenvironmental health. The aim is to understand the mechanisms of formation and degradationof these adducts to assess their place in toxicity of NACs and their importance as oxidativestress biomarkers induced by the environment.We synthesized two exocylic adducts: 1, N -etheno-2 -deoxyguanosine ( dG) and 1,N -propano-2'-deoxyguanosine (pdG-HNE) and studied their stability when a radicaloxidation is present. It appeared that pdG-HNE seems a suitable biomarker of oxidative stress.To come close to life chemistry, we were wondering whether these adducts are stablein cellular environment. A preliminary study of genotoxicity was carried out and showed thatonly nitro polycyclic aromatic hydrocarbons have a significant mutagenic potency. Thereforewe studied pyrene and nitropyrenes (1-Nitropyrene/1,3-Dinitropyrene/1,6-Dinitropyrene/1,8-Dinitropyrene) to examine their ability to produce adducts in human lymphocytes.Our results show that 1-Nitropyrene give rise to stable adducts in vitro, which raisesthe question of their repairability by cellular systems and their potential carcinogenic tohumans.AIX-MARSEILLE2-Bib.electronique (130559901) / SudocSudocFranceF

Intraflagellar transport is required for the maintenance of the trypanosome flagellum composition but not its length.

International audienceIntraflagellar transport (IFT) is required for construction of most cilia and flagella. Here, we used electron microscopy, immunofluorescence and live video microscopy to show that IFT is absent or arrested in the mature flagellum of Trypanosoma brucei upon RNA interference (RNAi)-mediated knockdown of IFT88 and IFT140, respectively. Flagella assembled prior to RNAi did not shorten, showing that IFT is not essential for the maintenance of flagella length. Although the ultrastructure of the axoneme was not visibly affected, flagellar beating was strongly reduced and the distribution of several flagellar components was drastically modified. The R subunit of the protein kinase A was no longer concentrated in the flagellum but was largely found in the cell body whereas the kinesin 9B motor was accumulating at the distal tip of the flagellum. In contrast, the distal tip protein FLAM8 was dispersed along the flagellum. This reveals that IFT also functions in maintaining the distribution of some flagellar proteins after construction of the organelle is completed