Action of Patulin on Yeast

The action of patulin on Saccharomyces cerevisiae was studied. At weak doses, the drug inhibited growth, but inhibition was transient. After 10 min, syntheses of rRNA, tRNA, and probably mRNA were blocked; this was shown by radioactive precursor incorporation assays and gel electrophoresis of RNAs. After recovery of growth, patulin disappeared from the medium. It seemed that this degradation resulted from the activity of an inducible enzymatic system. Induced cells resisted very high patulin concentrations

Elasticity of Ingestive Behaviour and Intake in Sheep Associated with Food Diversity on Plurispecific Swards

Animals on heterogeneous swards generally opt for a varied diet. This may stimulate their intake, unless searching constraints limit intake rate (Champion et al., 1998). However the management of plurispecific swards presents a risk of overgrazing the preferred species and undergrazing the less-preferred species. This study aimed to test the effect of type of diversity and type of management on the elasticity of ingestive behaviour and intake in sheep

Finding undetected protein associations in cell signaling by belief propagation

External information propagates in the cell mainly through signaling cascades and transcriptional activation, allowing it to react to a wide spectrum of environmental changes. High throughput experiments identify numerous molecular components of such cascades that may, however, interact through unknown partners. Some of them may be detected using data coming from the integration of a protein-protein interaction network and mRNA expression profiles. This inference problem can be mapped onto the problem of finding appropriate optimal connected subgraphs of a network defined by these datasets. The optimization procedure turns out to be computationally intractable in general. Here we present a new distributed algorithm for this task, inspired from statistical physics, and apply this scheme to alpha factor and drug perturbations data in yeast. We identify the role of the COS8 protein, a member of a gene family of previously unknown function, and validate the results by genetic experiments. The algorithm we present is specially suited for very large datasets, can run in parallel, and can be adapted to other problems in systems biology. On renowned benchmarks it outperforms other algorithms in the field.Comment: 6 pages, 3 figures, 1 table, Supporting Informatio

First astronomical unit scale image of the GW Ori triple. Direct detection of a new stellar companion

Young and close multiple systems are unique laboratories to probe the initial dynamical interactions between forming stellar systems and their dust and gas environment. Their study is a key building block to understanding the high frequency of main-sequence multiple systems. However, the number of detected spectroscopic young multiple systems that allow dynamical studies is limited. GW Orionis is one such system. It is one of the brightest young T Tauri stars and is surrounded by a massive disk. Our goal is to probe the GW Orionis multiplicity at angular scales at which we can spatially resolve the orbit. We used the IOTA/IONIC3 interferometer to probe the environment of GW Orionis with an astronomical unit resolution in 2003, 2004, and 2005. By measuring squared visibilities and closure phases with a good UV coverage we carry out the first image reconstruction of GW Ori from infrared long-baseline interferometry. We obtain the first infrared image of a T Tauri multiple system with astronomical unit resolution. We show that GW Orionis is a triple system, resolve for the first time the previously known inner pair (separation $\rho\sim$1.4 AU) and reveal a new more distant component (GW Ori C) with a projected separation of $\sim$8 AU with direct evidence of motion. Furthermore, the nearly equal (2:1) H-band flux ratio of the inner components suggests that either GW Ori B is undergoing a preferential accretion event that increases its disk luminosity or that the estimate of the masses has to be revisited in favour of a more equal mass-ratio system that is seen at lower inclination. Accretion disk models of GW Ori will need to be completely reconsidered because of this outer companion C and the unexpected brightness of companion B.Comment: 5 pages, 9 figures, accepted Astronomy and Astrophysics Letters. 201

Inference algorithms for gene networks: a statistical mechanics analysis

The inference of gene regulatory networks from high throughput gene expression data is one of the major challenges in systems biology. This paper aims at analysing and comparing two different algorithmic approaches. The first approach uses pairwise correlations between regulated and regulating genes; the second one uses message-passing techniques for inferring activating and inhibiting regulatory interactions. The performance of these two algorithms can be analysed theoretically on well-defined test sets, using tools from the statistical physics of disordered systems like the replica method. We find that the second algorithm outperforms the first one since it takes into account collective effects of multiple regulators

Cancer targeting with biomolecules: a comparative study of photodynamic therapy efficacy using antibody or lectin conjugated phthalocyanine-PEG gold nanoparticles

The functionalisation of therapeutic nanoparticle constructs with cancer-specific biomolecules can enable selective tumour accumulation and targeted treatment. Water soluble gold nanoparticles (ca. 4 nm) stabilised by a mixed monolayer of a hydrophobic zinc phthalocyanine photosensitiser (C11Pc) and hydrophilic polyethylene glycol (PEG) have been prepared. The C11Pc-PEG gold nanoparticle constructs were further functionalised with jacalin, a lectin specific for the cancer-associated Thomsen–Friedenreich (T) carbohydrate antigen, or with monoclonal antibodies specific for the human epidermal growth factor receptor-2 (HER-2). The two biofunctionalised nanoparticle conjugates produced similar levels of singlet oxygen upon irradiation at 633 nm. Importantly, both nanoparticle conjugates demonstrated extensive, yet comparable, phototoxicity in HT-29 colorectal adenocarcinoma cells (80–90%) and in SK-BR-3 breast adenocarcinoma cells (>99%). Non-conjugated C11Pc-PEG gold nanoparticles were only minimally phototoxic. Lysosomal colocalisation studies performed with the HT-29 colon cancer cells and the SK-BR-3 breast cancer cells revealed that both nanoparticle conjugates were partially localised within acidic organelles, which is typical of receptor-mediated endocytosis. The similarity of the targeted PDT efficacy of the two biofunctionalised C11Pc-PEG gold nanoparticles is discussed with respect to targeting ligand binding affinity and cell surface antigen density as key determinants of targeting efficiency. This study highlights how targeting small cell-surface molecules, such as the T antigen, can mediate a selective photodynamic treatment response which is similar to that achieved when targeting overexpressed protein receptors, such as HER-2. The high prevalence of the T antigen present on the cellular surface of primary tumours emphasises the broad potential applications for lectin-targeted therapies

Effets du dérangement par la chasse sur les oiseaux d'eau : revue de littérature

La chasse aux oiseaux d'eau, activité humaine largement pratiquée sur les zones humides du continent eurasiatique, présente deux composantes pouvant affecter la dynamique des populations de ces espèces migratrices : le prélèvement (qui concerne la mortalité) et le dérangement. Ce dernier aspect fait l'objet d'études de plus en plus nombreuses et détaillées, ici synthétisées, incluant des protocoles expérimentaux et des approches conceptuelles. Le dérangement par la chasse est considéré comme important pour une espèce lorsque les modifications qu'il induit ont un effet sur la « fitness » des individus de cette espèce (diminution de la survie et/ou du succès reproducteur). Les études montrent que le dérangement modifie presque toujours la distribution géographique des oiseaux en favorisant leur regroupement (5 à 50 fois plus) sur des espaces non chassés, induisant une sous-exploitation des ressources trophiques présentes sur les espaces chassés. Le dérangement peut aussi provoquer un accroissement du taux de renouvellement (« turnover ») des individus sur leur étape migratoire. Ces transferts d'oiseaux, bien quantifiés localement, ont un impact encore inconnu sur la taille des populations concernées, la large distribution de ces populations sur plusieurs continents rendant cette évaluation difficile. Le dérangement provoque une modification comportementale soit en favorisant des activités plus coûteuses que celles pratiquées sans dérangement, soit en diminuant le temps passé à des activités qui permettent d'acquérir de l'énergie. Les estimations ou simulations de ces pertes peuvent atteindre 25 % de la dépense énergétique journalière. Les oiseaux dérangés développent des capacités d'adaptation physiologique face aux contraintes associées au dérangement, par exemple une augmentation de la prise alimentaire, une augmentation du rendement de l'assimilation énergétique ou une augmentation de la sécrétion de corticostérone qui stimule l'activité de recherche de nourriture. L'évaluation directe du bilan énergétique de ces adaptations n'a pas encore été réalisée et l'on peut admettre qu'elles permettent à l'oiseau de maintenir un apport énergétique analogue à celui obtenu sans dérangement; mais le coût à terme de cette acquisition est élevé. Ainsi, une étude récente sur la Grande Oie des neiges Anser caerules-cens atlantica au Canada révèle que lorsque les individus sont dérangés par la chasse sur leur étape migratoire de printemps, ils sont contraints d'exploiter des sites moins riches que s'il n'y avait pas de chasse; ils sont alors dans de moins bonnes conditions corporelles (lipidiques et protéiniques) lors du départ vers leurs lieux de reproduction et ils ont finalement un moindre succès de reproduction que les individus n'ayant pas subi le dérangement par la chasse. Certes, des lacunes et des incertitudes persistent, par exemple au niveau spécifique (peu d'études sur les limicoles), mais tous les auteurs qui les ont mises en évidence s'accordent aussi pour reconnaître que, pour contrebalancer les effets du dérangement par la chasse, des mesures de protection doivent être prises.Waterbird hunting is a widespread human activity over wetlands of the Eurasian continent. It has two components that can influence the population dynamics of migratory species : mortality and disturbance. Disturbance is the focus of an increasing number of detailed studies, using both experimental and theoretical approaches. They are synthesized herein. Disturbance is considered important when induced changes influence the fitness of the individuals of a species (decrease in survival or breeding success). Studies show that disturbance almost always change the geographical distribution of birds, conducting to an under-exploitation of food resources available in hunting areas. Disturbance can also favour an increase in the turnover rate of individuals on their migratory stopover. These changes in bird distribution, although precisely quantified at a local scale, have an unknown impact on the population size of the concerned species. The wide distribution of several of these species ranging over several continents makes the precise evaluation of this impact difficult. Disturbance changes behaviour either by increasing time spent in activities more costly than those done without disturbance or by decreasing time spent gaining energy. Estimation or simulation of these lost can reach 25% of the daily energy expenses. Facing disturbance, birds can develop several physiological adaptations, for instance an increased food intake, an increased efficiency of energy assimilation or an augmentation of corticosterone secretion stimulating food searching. The direct evaluation of the energy balance of these adaptations has not been made yet and it can be acknowledged that they allow birds to maintain energy gains similar to those obtained without disturbance. However, the long-term cost of this compensation is high. A recent study of the Greater Snow Goose Anser caerulescens atlantica on their spring stopover in Canada indicates that hunting disturbance makes geese use lower quality habitats, decreases their body condition (fat and protein) when they depart to the breeding sites and decreases their breeding success relative to individuals that have not experienced hunting. Uncertainties remain, for instance at the species level (few studies on waders), but all authors that emphasized them also agree to acknowledge that protection measures must be taken to counter-balance the effects of hunting disturbance. They recommend the increase of protected areas (hunt-free areas), the elaboration of a network of reserves and the establishment of non hunted zones around existing reserves to reduce to the minimum the negative effects of disturbance on birds that use these reserves. The implementation of these management actions must favour the widening of the distribution of these populations and facilitate the local and regional increase of their numbers. These protection measures are positive responses to the recommendations of the European Union birds and habitats directives

Environmental assessment of the behavior of a BOF steel slag used in road construction : the PRECODD-ECLAIR research program

International audienceSteel production generate great amounts of by-products as steel slags. The use of Basic Oxygen Furnace slags (BOF slags) has been restrained due to insufficient volume stability, and due to the lack of environmental regulations. The purpose of the PRECODD-ECLAIR research program is to develop a behavior model based on a multi-scale physico-chemical, mechanical, hydrodynamic and ecotoxicological characterizations of a BOF slag used in a public works scenario. This paper aims at presenting the overall ECLAIR research program, the equipped experimental platform constructed using a BOF steel slag, and the first results of the slag characterization

Evaluation of a novel antibody to define histone 3.3 G34R mutant brain tumours

Missense somatic mutations affecting histone H3.1 and H3.3 proteins are now accepted as the hallmark of paediatric diffuse intrinsic pontine gliomas (DIPG), non-brain stem paediatric high grade gliomas (pHGG) as well as a subset of adult glioblastoma multiforme (GBM). Different mutations give rise to one of three amino acid substitutions at two critical positions within the histone tails, K27M, G34R/V. Several studies have highlighted gene expression and epigenetic changes associated with histone H3 mutations; however their precise roles in tumourigenesis remain incompletely understood. Determining how such amino acid substitutions in a protein affect its properties can be challenging because of difficulties in detecting and tracking mutant proteins within cells and tissues. Here we describe a strategy for the generation of antibodies to discriminate G34R and G34V mutant histone H3 proteins from their wild-type counterparts. Antibodies were validated by western blotting and immunocytochemistry, using recombinant H3.3 proteins and paediatric GBM cell lines. The H3-G34R antibody demonstrated a high degree of selectivity towards its target sequence. Accordingly, immunostaining on a cohort of 22 formalin-fixed paraffin embedded tumours with a previously known H3.3 G34R mutation status, detected successfully the corresponding mutant protein in 11/11 G34R cases. Since there was a high concordance between genotype and immunohistochemical analysis of G34R mutant tumour samples, we analysed a series of tissue microarrays (TMAs) to assess the specificity of the antibody in a range of paediatric brain tumours, and noted immunoreactivity in 2/634 cases. Importantly, we describe the generation and validation of highly specific antibodies for G34 mutations. Overall our work adds to an extremely valuable portfolio of antibodies, not only for histopathologic detection of tumour-associated mutant histone sequences, but also facilitating the study of spatial/anatomical aspects of tumour formation and the identification of downstream targets and pathways in malignant glioma progression