Visualization of recombination intermediates produced by RAD52-mediated single-strand annealing.

Double-strand breaks (DSBs) occur frequently during DNA replication. They are also caused by ionizing radiation, chemical damage or as part of the series of programmed events that occur during meiosis. In yeast, DSB repair requires RAD52, a protein that plays a critical role in homologous recombination. Here we describe the actions of human RAD52 protein in a model system for single-strand annealing (SSA) using tailed (i.e. exonuclease resected) duplex DNA molecules. Purified human RAD52 protein binds resected DSBs and promotes associations between complementary DNA termini. Heteroduplex intermediates of these recombination reactions have been visualized by electron microscopy, revealing the specific binding of multiple rings of RAD52 to the resected termini and the formation of large protein complexes at heteroduplex joints formed by RAD52-mediated annealing.

The importance of root-produced volatiles as foraging cues for entomopathogenic nematodes

Background Entomopathogenic nematodes (EPNs) are tiny parasitic worms that parasitize insects, in which they reproduce. Their foraging behavior has been subject to numerous studies, most of which have proposed that, at short distances, EPNs use chemicals that are emitted directly from the host as host location cues. Carbon dioxide (CO2) in particular has been implicated as an important cue. Recent evidence shows that at longer distances several EPNs take advantage of volatiles that are specifically emitted by roots in response to insect attack. Studies that have revealed these plant-mediated interactions among three trophic levels have been met with some disbelief. Scope This review aims to take away this skepticism by summarizing the evidence for a role of root volatiles as foraging cues for EPNs. To reinforce our argument, we conducted olfactometer assays in which we directly compared the attraction of an EPN species to CO2 and two typical inducible root volatiles. Conclusions The combination of the ubiquitous gas and a more specific root volatile was found to be considerably more attractive than one of the two alone. Hence, future studies on EPN foraging behavior should take into account that CO2 and plant volatiles may work in synergy as attractants for EPNs. Recent research efforts also reveal prospects of exploiting plant-produced signals to improve the biological control of insect pests in the rhizosphere.

Effect of irrigation water and processing on the microbial quality of lettuces produced and sold on markets in Dakar (Senegal)

The aim of this survey is to assess the microbiological impact of irrigation water on lettuces produced on two urban agricultural sites and sold on markets; 6 and 7%, respectively, of lettuces coming from the sites of Pikine and Patte d'Oie were Salmonella spp. positive. Lettuces irrigated with shallow groundwater (''Ceanes'' water) were more contaminated (8% at both Pikine and Patte d'Oie sites) compared to those irrigated with wastewater (4% at Pikine) or well water (5% at Patte d'Oie). As for the lettuces in marketplaces, their contamination seems to depend on the type of treatment occurring before sale. Lettuces previously washed in the ``Ceanes'' were more contaminated than those rinsed with tap water at the marketplace. Salmonella spp. have been isolated from all marketplaces. However, the rates of contamination in markets surrounding Patte d'Oie are higher (9 and 11% at Grand Yoff and Dalifort) than those surrounding Pikine (4 and 2% at Zinc and Sham) or Rufisque, the control (2%). Our results confirm that the reuse of wastewater in irrigation is an alternative to animal manure. Its risk of microbial contamination can be significantly reduced by washing the vegetables with tap water before they are sold. Copyright (C) 2010 John Wiley & Sons, Ltd.

IL-4 rapidly produced by V beta 4 V alpha 8 CD4+ T cells instructs Th2 development and susceptibility to Leishmania major in BALB/c mice.

BALB/c mice develop aberrant T helper 2 (Th2) responses and suffer progressive disease after infection with Leishmania major. These outcomes depend on the production of interleukin-4 (IL-4) early after infection. Here we demonstrate that the burst of IL-4 mRNA, peaking in draining lymph nodes of BALB/c mice 16 hr after infection, occurs within CD4+ T cells that express V beta 4 V alpha 8 T cell receptors. In contrast to control and V beta 6-deficient BALB/c mice, V beta 4-deficient BALB/c mice were resistant to infection, demonstrating the role of these cells in Th2 development. The early IL-4 response was absent in these mice, and T helper 1 responses occurred following infection. Recombinant LACK antigen from L. major induced comparable IL-4 production in V beta 4 V alpha 8 CD4+ cells. Thus, the IL-4 required for Th2 development and susceptibility to L. major is produced by a restricted population of V beta 4 V alpha 8 CD4+ T cells after cognate interaction with a single antigen from this complex organism.

Cost-effectiveness analysis of the first-line therapies for nicotine dependence.

BACKGROUND: Nicotine dependence is the major obstacle for smokers who want to quit. Guidelines have identified five effective first-line therapies, four nicotine replacement therapies (NRTs)--gum, patch, nasal spray and inhaler--and bupropion. Studying the extent to which these various treatments are cost-effective requires additional research. OBJECTIVES: To determine cost-effectiveness (CE) ratios of pharmacotherapies for nicotine dependence provided by general practitioners (GPs) during routine visits as an adjunct to cessation counselling. METHODS: We used a Markov model to generate two cohorts of one-pack-a-day smokers: (1) the reference cohort received only cessation counselling from a GP during routine office visits; (2) the second cohort received the same counselling plus an offer to use a pharmacological treatment to help them quit smoking. The effectiveness of adjunctive therapy was expressed in terms of the resultant differential in mortality rate between the two cohorts. Data on the effectiveness of therapies came from meta-analyses, and we used odds ratio for quitting as the measure of effectiveness. The costs of pharmacotherapies were based on the cost of the additional time spent by GPs offering, prescribing and following-up treatment, and on the retail prices of the therapies. We used the third-party-payer perspective. Results are expressed as the incremental cost per life-year saved. RESULTS: The cost per life-year saved for only counselling ranged from Euro 385 to Euro 622 for men and from Euro 468 to Euro 796 for women. The CE ratios for the five pharmacological treatments varied from Euro 1768 to Euro 6879 for men, and from Euro 2146 to Euro 8799 for women. Significant variations in CE ratios among the five treatments were primarily due to differences in retail prices. The most cost-effective treatments were bupropion and the patch, and, then, in descending order, the spray, the inhaler and, lastly, gum. Differences in CE between men and women across treatments were due to the shape of their respective mortality curve. The lowest CE ratio in men was for the 45- to 49-year-old group and for women in the 50- to 54-year-old group. Sensitivity analysis showed that changes in treatment efficacy produced effects only for less-well proven treatments (spray, inhaler, and bupropion) and revealed a strong influence of the discount rate and natural quit rate on the CE of pharmacological treatments. CONCLUSION: The CE of first-line treatments for nicotine dependence varied widely with age and sex and was sensitive to the assumption for the natural quit rate. Bupropion and the nicotine patch were the two most cost-effective treatments.

Le filtre invisible : l'obstacle du Sujet (conflits implicites dans les transferts culturels de France en Russie en philosophie)

Cette thèse est un travail de comparaison qui essaie de s'affranchir des dogmes ambiants afin de trouver une nouvelle voie, une autre façon de comprendre la culture intellectuelle en Russie. La présente recherche s'inscrit dans le cadre de l'épistémologie comparée dont l'objectif principal est d'éviter un travail par oppositions et de mettre en évidence les différences et les ressemblances des systèmes de connaissances dans deux mondes intellectuels : la Russie et le monde francophone.La question posée dans ce travail concerne le Sujet en philosophie en Russie, plus précisément la façon dominante de le voir et de le théoriser, qui joue un rôle important dans la formation de l'horizon d'attente intellectuelle. On trouve l'impact de cette attente intellectuelle particulière lors des transferts « culturels » des théories et des idées quand certaines de ces dernières passent et d'autres provoquent des résistances. Qu'est-ce qui définit alors le seuil de passage et quel obstacle [invisible ?) est la cause des malentendus ?La réponse trouvée est simple dans sa complexité : le dispositif de la *personne intégrale. Il s'agit d'un ensemble de discours et de pratiques qui valorise et rend possible certains comportements mettant en avant les idées de fusion et de collectivisme à différents niveaux de la vie sociale, par rapport à l'homme et à ses relations dans la société, et décourageant les idées d'individualisme au sens large du terme.Le dispositif de la *personne intégrale nous a permis de constater et d'expliquer une certaine continuité des valeurs et de la doxa dans les théories du Sujet au XIXe siècle en Russie, à l'époque soviétique et après la dissolution de l'URSS, ce qui, à première vue, pouvait paraître paradoxal. Les ruptures idéologiques importantes qu'a connues la Russie auraient dû susciter des changements dans la vision du Sujet. Or, d'une façon étonnante, aussi bien les slavophiles, les anarchistes que les marxistes soviétiques cherchaient à construire une théorie du Sujet fondée sur les principes d'organicisme, d'intégralité et d'ontologisme. Autrement dit, la conception matérialiste du Sujet à l'époque soviétique n'était pas fondamentalement distincte de celle que le XIXe siècle lui avait léguée. C'est la raison pour laquelle la période postsoviétique manifeste autant d'intérêt pour les valeurs d'intégralité, d'organisme vivant et d'ontologisme, qui trouvent leur place dans une grande partie des critiques adressées aux idées « postmodernes » proclamant une tout autre façon de voir les choses : le décentrement, la déconstruction, le multiple et l'hétérogène, ce qui ne peut que provoquer un grave conflit de valeurs.Il y avait une énigme à résoudre : qu'est-ce qui fait obstacle à la réception des théories du Sujet divisé ? Cette énigme, nous avons essayé de l'élucider en rassemblant patiemment les bribes entrelacées d'un gigantesque tissu, en tentant d'en montrer la paradoxale cohérence. Un autre travail reste à faire, qui consisterait à construire une hypothèse autrement hardie, celle qui saurait expliquer pourquoi un tel dispositif s'est mis en place en Russie à cette époque et pas ailleurs.

Binding of low concentration of peptide to H-2Kd produced in insect cells requires mouse beta 2-microglobulin co-expression.

A recombinant baculovirus expressing the murine class I MHC heavy chain H-2Kd cDNA under the transcriptional control of Autografa californica nuclear polyhedrosis virus (AcNPV) polyhedrin promoter has been isolated and used to infect Sf9 lepidopteran cells either alone or in association with a previously isolated virus expressing mouse beta 2-microglobulina (beta 2-ma). When infected with the heavy chain-encoding virus alone, H-2Kd was produced in a beta 2-m-free conformation detected on the surface of infected cells by conformation-independent antibodies. When Sf9 cells were co-infected with both viruses, approximately 10% of the heavy chain pool was engaged in the formation of native heterodimeric MHC class I molecules, which were glycosylated and transported to the cell surface as demonstrated by radio-binding experiments and flow cytometry. The assembly of the recombinant class I molecule was dependent on peptide, since heterodimer formation was brought about by H-2Kd-specific peptide ligands both in vivo, upon incubation with dually infected cells, and in vitro, in cell-free detergent extracts. In addition, a change in heavy chain conformation was brought about upon incubation with high concentrations (100 microM) of an H-2Kd-restricted octapeptide epitope from Plasmodium berghei. Furthermore, using low concentrations (3 nM) of a photoaffinity label derivative of this peptide, we show direct binding to cells co-expressing class I heavy chain and mouse beta 2-m but not to cells expressing free heavy chain only.

Concise reviews: in vitro-produced pancreas organogenesis models in three dimensions: self-organization from few stem cells or progenitors.

Three-dimensional models of organ biogenesis have recently flourished. They promote a balance between stem/progenitor cell expansion and differentiation without the constraints of flat tissue culture vessels, allowing for autonomous self-organization of cells. Such models allow the formation of miniature organs in a dish and are emerging for the pancreas, starting from embryonic progenitors and adult cells. This review focuses on the currently available systems and how these allow new types of questions to be addressed. We discuss the expected advancements including their potential to study human pancreas development and function as well as to develop diabetes models and therapeutic cells.

Compétences en santé déficientes: obstacle à une prise en charge optimale [Low health literacy: barrier to optimal care].

Health literacy is defined as "the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions." Low health literacy mainly affects certain populations at risk limiting access to care, interaction with caregivers and self-management. If there are screening tests, their routine use is not advisable and recommended interventions in practice consist rather to reduce barriers to patient-caregiver communication. It is thus important to include not only population's health literacy but also communication skills of a health system wich tend to become more complex.

The In Vitro Mass-Produced Model Mycorrhizal Fungus, Rhizophagus irregularis, Significantly Increases Yields of the Globally Important Food Security Crop Cassava.

The arbuscular mycorrhizal symbiosis is formed between arbuscular mycorrhizal fungi (AMF) and plant roots. The fungi provide the plant with inorganic phosphate (P). The symbiosis can result in increased plant growth. Although most global food crops naturally form this symbiosis, very few studies have shown that their practical application can lead to large-scale increases in food production. Application of AMF to crops in the tropics is potentially effective for improving yields. However, a main problem of using AMF on a large-scale is producing cheap inoculum in a clean sterile carrier and sufficiently concentrated to cheaply transport. Recently, mass-produced in vitro inoculum of the model mycorrhizal fungus Rhizophagus irregularis became available, potentially making its use viable in tropical agriculture. One of the most globally important food plants in the tropics is cassava. We evaluated the effect of in vitro mass-produced R. irregularis inoculum on the yield of cassava crops at two locations in Colombia. A significant effect of R. irregularis inoculation on yield occurred at both sites. At one site, yield increases were observed irrespective of P fertilization. At the other site, inoculation with AMF and 50% of the normally applied P gave the highest yield. Despite that AMF inoculation resulted in greater food production, economic analyses revealed that AMF inoculation did not give greater return on investment than with conventional cultivation. However, the amount of AMF inoculum used was double the recommended dose and was calculated with European, not Colombian, inoculum prices. R. irregularis can also be manipulated genetically in vitro, leading to improved plant growth. We conclude that application of in vitro R. irregularis is currently a way of increasing cassava yields, that there is a strong potential for it to be economically profitable and that there is enormous potential to improve this efficiency further in the future.

Effect of irrigation water on the incidence of Salmonella spp. on lettuces produced by urban agriculture and sold on the markets in Dakar, Senegal

The aim of our survey was to assess the effect of irrigation water of the microbiological quality on the production chain of lettuce in the Dakar area. Microbiological analysis showed that 35% of irrigation water was contaminated by Salmonella spp. between the two water-types used for irrigation (groundwater and wastewater), no significant difference (p>0.05) in their degree of contamination was found. The incidence of different types of irrigation water on the contamination rate of lettuces from the farm (Pikine and Patte d'Oie) was not different either (p>0.05). However, the contamination rate of lettuce from markets of Dalifort and Grand-Yoff that were supplied by the area of Patte d'Oie was greater than those of Sham and Zinc supplied by Pikine (p<0.05). Comparison of serotypes of Salmonella isolated from irrigation water and lettuce showed that irrigation water may affect the microbiological quality of lettuce. Manures, frequently used as organic amendment in cultivating lettuce are another potential source of contamination. These results showed that lettuce may constitute effective vectors for the transmission of pathogens to consumers. Extensive treatment of the used wastewater and/or composting of manure could considerably reduce these risks.

Towards a global criteria based framework for the sustainability assessment of bioethanol supply chains: application to the Swiss dilemma : is local produced bioethanol more sustainable than bioethanol imported from Brazil?

Biofuels are considered as a promising substitute for fossil fuels when considering the possible reduction of greenhouse gases emissions. However limiting their impacts on potential benefits for reducing climate change is shortsighted. Global sustainability assessments are necessary to determine the sustainability of supply chains. We propose a new global criterion based framework enabling a comprehensive international comparison of bioethanol supply chains. The interest of this framework is that the selection of the sustainability indicators is qualified on three criterions: relevance, reliability and adaptability to the local context. Sustainability issues have been handled along environmental, social and economical issues. This new framework has been applied for a specific issue: from a Swiss perspective, is locally produced bioethanol in Switzerland more sustainable than imported from Brazil? Thanks to this framework integrating local context in its indicator definition, Brazilian production of bioethanol is shown as energy efficient and economically interesting for Brazil. From a strictly economic point of view, bioethanol production within Switzerland is not justified for Swiss consumption and questionable for the environmental issue. The social dimension is delicate to assess due to the lack of reliable data and is strongly linked to the agricultural policy in both countries. There is a need of establishing minimum sustainability criteria for imported bioethanol to avoid unwanted negative or leakage effects.