El significat de les activitats aquàtiques del nadó des d'una perspectiva evolutiva

Aquest article pretén d’aprofundir des d’una perspectiva evolutiva en l’estudi i l’anàlisi de les activitats aquàtiques del nadó. A partir d’aquí, l’article interpreta des de l’òptica filogenètica i ontogenètica de les activitats aquàtiques dels nadons, quin significat tindran aquestes activitats en el seu desenvolupament general. Per assolir els objectius fixats, l’article utilitza un enfocament fenomenològic (Husserl, 1996) que se sustentarà conceptualment en l’abordatge filogenètic del desenvolupament psicomotriu de Fonseca (1998). Partint d’aquesta estructura, s’estudiaran les raons filogenètiques i ontogenètiques que ens poden significar les activitats aquàtiques del nadó per tal que, en última instància, i des de la línia més existencial de la fenomenologia (Sartre, 1999; Merleau-Ponty, 2000), puguem argumentar la significació evolutiva d’aquestes activitats.

Self-Expanding Versus Balloon-Expandable Stents in Acute Myocardial Infarction: Results From the APPOSITION II Study: Self-Expanding Stents in ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: This study sought to investigate whether self-expanding stents are more effective than balloon-expandable stents for reducing stent malapposition at 3 days after implantation in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. BACKGROUND: Acute myocardial infarction is associated with vasoconstriction and large thrombus burden. Resolution of vasoconstriction and thrombus load during the first hours to days after primary percutaneous coronary intervention may lead to stent undersizing and malapposition, which may subsequently lead to stent thrombosis or restenosis. In addition, aggressive stent deployment may cause distal embolization. METHODS: Eighty patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomized to receive a self-expanding stent (STENTYS, STENTYS SA, Paris, France) (n = 43) or a balloon-expandable stent (VISION, Abbott Vascular, Santa Clara, California; or Driver, Medtronic, Minneapolis, Minnesota) (n = 37) at 9 European centers. The primary endpoint was the proportion of stent strut malapposition at 3 days after implantation measured by optical coherence tomography. Secondary endpoints included major adverse cardiac events (cardiac death, recurrent myocardial infarction, emergent bypass surgery, or clinically driven target lesion revascularization). RESULTS: At 3 days after implantation, on a per-strut basis, a lower rate of malapposed stent struts was observed by optical coherence tomography in the self-expanding stent group than in the balloon-expandable group (0.58% vs. 5.46%, p < 0.001). On a per-patient basis, none of the patients in the self-expanding stent group versus 28% in the balloon-expandable group presented ≥5% malapposed struts (p < 0.001). At 6 months, major adverse cardiac events were 2.3% versus 0% in the self-expanding and balloon-expandable groups, respectively (p = NS). CONCLUSIONS: Strut malapposition at 3 days is significantly lower in ST-segment elevation myocardial infarction patients allocated to self-expanding stents when than in those allocated to balloon-expandable stents. The impact of this difference on clinical outcome and the risk of late stent thrombosis need to be evaluated further. (Randomized Comparison Between the STENTYS Self-expanding Coronary Stent and a Balloon-expandable Stent in Acute Myocardial Infarction [APPOSITION II]; NCT01008085).

Integrated Analysis of High-Resolution Gene Expression and Copy Number Profiling Identified Biallelic Deletion of CDKN2A/2B Tumor Suppressor Locus As the Most Frequent and Unique Genomic Abnormality in Diffuse Large B-Cell Lymphoma (DLBCL) with Strong Prognostic Value in Both GCB and ABC Subtypes and Not Overcome by a Dose-Intensive Immunochemotherapy Regimen Plus Rituximab. Results of a Prospective GELA Clinical Trial Program

Background and aim of the study: Genomic gains and losses play a crucial role in the development and progression of DLBCL and are closely related to gene expression profiles (GEP), including the germinal center B-cell like (GCB) and activated B-cell like (ABC) cell of origin (COO) molecular signatures. To identify new oncogenes or tumor suppressor genes (TSG) involved in DLBCL pathogenesis and to determine their prognostic values, an integrated analysis of high-resolution gene expression and copy number profiling was performed. Patients and methods: Two hundred and eight adult patients with de novo CD20+ DLBCL enrolled in the prospective multicentric randomized LNH-03 GELA trials (LNH03-1B, -2B, -3B, 39B, -5B, -6B, -7B) with available frozen tumour samples, centralized reviewing and adequate DNA/RNA quality were selected. 116 patients were treated by Rituximab(R)-CHOP/R-miniCHOP and 92 patients were treated by the high dose (R)-ACVBP regimen dedicated to patients younger than 60 years (y) in frontline. Tumour samples were simultaneously analysed by high resolution comparative genomic hybridization (CGH, Agilent, 144K) and gene expression arrays (Affymetrix, U133+2). Minimal common regions (MCR), as defined by segments that affect the same chromosomal region in different cases, were delineated. Gene expression and MCR data sets were merged using Gene expression and dosage integrator algorithm (GEDI, Lenz et al. PNAS 2008) to identify new potential driver genes. Results: A total of 1363 recurrent (defined by a penetrance > 5%) MCRs within the DLBCL data set, ranging in size from 386 bp, affecting a single gene, to more than 24 Mb were identified by CGH. Of these MCRs, 756 (55%) showed a significant association with gene expression: 396 (59%) gains, 354 (52%) single-copy deletions, and 6 (67%) homozygous deletions. By this integrated approach, in addition to previously reported genes (CDKN2A/2B, PTEN, DLEU2, TNFAIP3, B2M, CD58, TNFRSF14, FOXP1, REL...), several genes targeted by gene copy abnormalities with a dosage effect and potential physiopathological impact were identified, including genes with TSG activity involved in cell cycle (HACE1, CDKN2C) immune response (CD68, CD177, CD70, TNFSF9, IRAK2), DNA integrity (XRCC2, BRCA1, NCOR1, NF1, FHIT) or oncogenic functions (CD79b, PTPRT, MALT1, AUTS2, MCL1, PTTG1...) with distinct distribution according to COO signature. The CDKN2A/2B tumor suppressor locus (9p21) was deleted homozygously in 27% of cases and hemizygously in 9% of cases. Biallelic loss was observed in 49% of ABC DLBCL and in 10% of GCB DLBCL. This deletion was strongly correlated to age and associated to a limited number of additional genetic abnormalities including trisomy 3, 18 and short gains/losses of Chr. 1, 2, 19 regions (FDR < 0.01), allowing to identify genes that may have synergistic effects with CDKN2A/2B inactivation. With a median follow-up of 42.9 months, only CDKN2A/2B biallelic deletion strongly correlates (FDR p.value < 0.01) to a poor outcome in the entire cohort (4y PFS = 44% [32-61] respectively vs. 74% [66-82] for patients in germline configuration; 4y OS = 53% [39-72] vs 83% [76-90]). In a Cox proportional hazard prediction of the PFS, CDKN2A/2B deletion remains predictive (HR = 1.9 [1.1-3.2], p = 0.02) when combined with IPI (HR = 2.4 [1.4-4.1], p = 0.001) and GCB status (HR = 1.3 [0.8-2.3], p = 0.31). This difference remains predictive in the subgroup of patients treated by R-CHOP (4y PFS = 43% [29-63] vs. 66% [55-78], p=0.02), in patients treated by R-ACVBP (4y PFS = 49% [28-84] vs. 83% [74-92], p=0.003), and in GCB (4y PFS = 50% [27-93] vs. 81% [73-90], p=0.02), or ABC/unclassified (5y PFS = 42% [28-61] vs. 67% [55-82] p = 0.009) molecular subtypes (Figure 1). Conclusion: We report for the first time an integrated genetic analysis of a large cohort of DLBCL patients included in a prospective multicentric clinical trial program allowing identifying new potential driver genes with pathogenic impact. However CDKN2A/2B deletion constitutes the strongest and unique prognostic factor of chemoresistance to R-CHOP, regardless the COO signature, which is not overcome by a more intensified immunochemotherapy. Patients displaying this frequent genomic abnormality warrant new and dedicated therapeutic approaches.

Pollution stress on aquatic microbial communities

Thousands of chemical compounds enter the natural environment but many have unknown effects and consequences, in particular at low concentrations. This thesis work contributes to our understanding of pollution effects by using bacteria as test organisms. Bacteria are important for this question because some of them degrade and transform pollutants into less harmful compounds, but secondly because they themselves can be inhibited in their reproduction by exposure to toxic compounds. When inhibitory effects occur this may change the composition of the microbial com¬munity in the long run, leading to altered or diminished ecosystem services by those communities. As a result chemicals of anthropogenic origin may accumulate and per¬sist in the environment, and finally, affect higher organisms as well. In addition to acquiring basic understanding of pollutant effects at low concentrations on bacterial communities an applied goal of this thesis work was to develop bacteria-based tests to screen new organic chemicals for toxicity and biodégradation. In the first part of this work we developed a flow cytometry-based assay on SYT09 plus ethidium-bromide or propidium-iodide stained cells of Pseudomonas ûuorescens exposed or not to a variety of pollutants under oligotrophic growth conditions. Flow cytometry (FC) allows fast and accurate counting of bacterial cells under simul¬taneous assessment of their physiological state, in particular in combination with different fluorescent dyes. Here we employed FC and fluorescent dyes to monitor the effect that pollutants may exert on Pseudomonas ûuorescens SV3. First we designed an oligotrophic growth test, which enabled us to follow population growth at low densities (104 - 10 7 cells per ml) using 0.1 mM sodium acetate as carbon source. Cells in the oligotrophic milieu were then exposed or not to a variety of common pollutants, such as 2-chlorobiphenyl (2CBP), naphthalene (NAH), 4-chlorophenol (4CP), tetradecane (TD), mercury chloride (HgCl2) or benzene, in different dosages. Exposed culture samples were stained with SYT09 (green fluorescent dye binding nucleic acids, generally staining all cells) in combination with propidium iodide (PI) or ethidium bromide (EB), both dyes being membrane integrity indicators. We ob- served that most of the tested compounds decreased population growth in a dosage- dependent manner. SYT09/PI or SYT09/EB staining then revealed that chemical exposure led to arisal of subpopulations of live and injured or dead cells. By modeling population growth on the total cell numbers in population or only the subpopulation of live cells we inferred that even in stressed populations live cells multiply at rates no different to unexposed controls. The net decrease in population growth would thus be a consequence of more and more cells being not able to multiply at all, rather than all cells multiplying at slower rates. In addition, the proportion of injured cells correlated to the compound dosage. We concluded that the oligotrophic test may be useful to asses toxicity of unknown chemicals on a variety of model bacteria. Mul¬tiple tests can be run in parallel and effects are rapidly measured within a period of 8 hours. Interestingly, in the same exposure tests with P. fluorescens SV3 we observed that some chemicals which did not lead to a reduction of net population growth rates did cause measurable effects on live cells. This was mainly observed in cells within the live subpopulation as an increase of the EB fluorescence signal. We showed that SYT09/EB is a more useful combination of dyes than SYT09/PI because PI fluorescence tend to increase only when cells are effectively dead, but not so much in live cells (less then twofold). In contrast, EB geometric mean fluorescence in live cells increased up to eightfold after exposure to toxic compounds. All compounds even at the lowest concentration caused a measurable increase in EB geometric mean fluorescence especially after 2 h incubation time. This effect was found to be transient for cells exposed to 2CBP and 4CP, but chronic for cells incubated with TD and NAH (ultimately leading to cell death). In order to understand the mechanism underlying the observed effects we used known membrane or energy uncouplers. The pattern of EB signal increase in chemical-exposed populations resembled mostly that of EDTA, although EB fluorescence in EDTA-treated or pasteurized cells was even higher than after exposure to the four test chemicals. We conclude that the ability of cells to efflux EB under equilibrium conditions is an appropriate measure for the potential of a chemical to exert toxicity. Since most bacterial species possess efflux systems for EB that all require cellular energy, our test should be more widely relevant to infer toxicity effects of chemical exposure on the physiological status of the bacterial cell. To better understand the effect of toxicant exposure on efflux defense systems, we studied 2-hydroxybiphenyl toxicity to Pseudomonas azeiaica HBP1. We showed that 2-HBP exerts toxicity even to P. azelaica HBP1, but only at concentrations higher than 0.5 mM. Above this concentration transient loss of membrane polarization and integrity occurred, which we conclude from staining of growing cells with fluorescent dyes. Cells finally recover and resume growth on 2HBP. The high resistance of P. azelaica HBP1 to 2-HBP was found to be the result of an efficient MexABOprM- type efflux pump system counteracting passive influx of this compound into the membrane and cellular interior. Mutants with disrupted mexA, mexB and oprM genes did no longer grow on 2-HBP at concentrations above 100 μΜ, whereas below this concentration we found 2-HBP-concentration dependent decrease of growth rate. The MexAB-OprM system in P. azeiaica HBP1 is indeed an efflux pump for ethidium bromide as well. By introducing gfp reporter fusions responsive to intracellular 2- HBP concentrations into HBP1 wild-type or the mutants we demonstrated that 2HBP enters into the cells in a similar way. In contrast, the reporter system in the wild-type cells does not react to 2-HBP at an outside concentration of 2.4 μΜ, whereas in mutant cells it does. This suggests that wild-type cells pump 2-HBP to the outside very effectively preventing accumulation of 2-HBP. 2HBP metabolism, therefore, is not efficient enough to lower the intracellular concentration and prevent toxicity. We conclude that P. azelaica HBP1 resistance to 2-HBP is mainly due to an efficient efflux system and that 2HBP in high concentrations exerts narcotic effects on the bacterial membrane. In the part of this thesis, we investigated the possibilities of bacteria to degrade pollutants at low concentrations (1 mg per L and below). As test components we used 2-hydroxybiphenyl, antibiotics and a variety of fragrances, many of which are known to be difficult to biodegrade. By using accurate counting of low numbers of bacterial cells we could demonstrate that specific growth on these compounds is possible. We demonstrated the accuracy of FC counting at low cell numbers (down to 103 bacterial cells per ml). Then we tested whether bacterial population growth could be specifically monitored at the expense of low substrate concentrations, us¬ing P. azelaica HBP1. A perfect relationship was found between growth rate, yield and 2-HBP concentrations in the range of 0.1 up to 5 mg per L. Mixing P. azelaica within sludge, however, suggested that growth yields in a mixed community can be much lower than in pure culture, perhaps because of loss of metabolic intermediates. We then isolated new strains from activated sludge using 2-HBP or antibiotics (Nal, AMP, SMX) at low concentrations (0.1-1 mg per L) as sole carbon and energy sub¬strate and PAO microdishes. The purified strains were then examined for growth on their respective substrate, which interestingly, showed that all strains can not with¬stand higher than 1 or 10 mg per L concentrations of target substrate. Thus, bacteria must exist that contribute to compound degradation at low pollutant concentrations but are inhibited at higher concentrations. Finally we tested whether specific biomass growth (in number of cells) at the expense of pollutants can also be detected with communities as starting material. Hereto, we focused on a number of fragrance chemicals and measured community biomass increase by flow cytometry cell counting on two distinct starter communities: (i) diluted Lake Geneva water, and dilute activated sludge from a wastewater treatment plant. We observed that most of the test compounds indeed resulted in significant biomass increase in the starter community compared to a no-carbon added control, but activated sludge and lake Geneva water strongly differed (almost mutually ex¬clusive) in their capacity to degrade the test chemicals. In two cases for activated sludge the same type of microbial community developed upon compound exposure, as concluded from transcription fragment length polymorphism analysis on community purified and PCR amplified 16S rRNA gene fragments. To properly test compound biodegradability it is thus important to use starter communities of different origin. We conclude that FC counting can be a valuable tool to screen chemicals for their biodegradability and toxicity. - Des milliers de produits chimiques sont libérés dans l'environnement mais beaucoup ont des effets inconnus, en particulier à basses concentrations. Ce travail de thèse contribue à notre comprehension des effets de la pollution en utilisant des bacteries comme des organismes-tests. Les bacteries sont importantes pour etudier cette ques¬tion car certaines d'entre elles peuvent degrader ou transformer les polluants, mais également parce qu'elles-mmes peuvent tre inhibees dans leur reproduction après avoit ete exposees à ces composes toxiques. Quand des effets inhibiteurs ont lieu, la composition de la communauté microbienne peut tre changee à long terme, ce qui mène à une reduction du service d'ecosystème offert par ces communautés. En consequence, après leur liberation dans l'environnement, les produits chimiques d'origine anthropogenique peuvent soit s'y accumuler et per¬sister, exerant ainsi des effets encore inconnus sur les organismes vivants. En plus d'acquérir des connaissances de base sur les effets des polluants à basses concentra¬tions sur les communautés microbiennes, un but applique de cette thèse était de développer des tests bases sur les bacteries afin d'identifier de nouveau composes pour leur toxicité ou leur biodégradation. Dans la première partie de ce travail, nous avons developpe un test base sur la cytometrie de flux (FC) sur des cellules de Pseudomonas fluorescens colorees par du bromure d'ethidium ou de l'iodure de propidium et exposees ou non à une palette de polluants sous des conditions de croissance oligotrophique. La cytometrie de flux est une technique qui connaît de nombreuses applications dans la microbiologie environ¬nementale. Cela est principalement du au fait qu'elle permet un comptage rapide et precis ainsi que l'évaluation de l'état physiologique, en particulier lorsqu'elle est combinée h des colorations fluorescentes. Ici, nous avons utilise la technique FC et des colorants fluorescents afin de mesurer l'effet que peuvent exercer certains pollu¬ants sur Pseudomonas ûuorescens SV3 . D'abord nous avons conu des tests oligo- trophiques qui nous permettent de suivre la croissance complète de cellules en culture h des densites faibles (104 -10 7 cellules par ml), sur de l'acetate de sodium à 0.1 mM, en presence ou absence de produits chimiques (2-chlorobiphenyl (2CBP), naphthalène (NAH), 4-chlorophenol (4CP), tetradecane (TD), chlorure de mercure(II) (HgCl2)) à différentes concentrations. Afin de montrer le devenir des bacteries tant au niveau de la cellule individuelle que celui de la population globale, après exposition à des series de composes chimiques, nous avons compte les cellules colorees avec du SYT09 (col¬orant fluorescent vert des acides nucléiques pour la discrimination des cellules par rapport au bruit de fond) en combinaison avec l'iodure de propidium (PI) ou le bromure d'ethidium (EB), indicateurs de l'intégrité de la membrane cellulaire avec FC. Nous avons observe que de nombreux composes testes avaient un effet sur la croissance bacterienne, resultant en une baisse du taux de reproduction de la pop¬ulation. En outre, la double coloration que nous avons utilisee dans cette etude SYT09/PI ou SYT09/EB a montre que les produits chimiques testes induisaient une reponse heterogène des cellules dans la population, divisant celle-ci en sous- populations "saine", "endommagee" ou "morte". Les nombres de cellules à partir du comptage et de la proportion de celles "saines" et "endommagees/mortes" ont ensuite ete utilises pour modeliser la croissance de P. ûuorescens SV3 exposee aux produits chimiques. La reduction nette dans la croissance de population est une consequence du fait que de plus en plus de cellules sont incapables de se reproduire, plutt que du fait d'une croissance plus lente de l'ensemble de la population. De plus, la proportion de cellules endommagees est correllee au dosage du compose chimique. Les résultats obtenus nous ont permis de conclure que le test oligotrophique que nous avons developpe peut tre utilise pour l'évaluation de la toxicité de produits chimiques sur différents modèles bacteriens. Des tests multiples peuvent tre lances en parallèle et les effets sont mesures en l'espace de huit heures. Par ailleurs, nous en déduisons que les produits chimiques exercént un effet sur la croissance des cellules de P. ûuorescens SV3, qui est heterogène parmi les cellules dans la population et depend du produit chimique. Il est intéressant de noter que dans les mmes tests d'exposition avec P. ûuorescens SV3, nous avons observe que certains composes qui n'ont pas conduit à une reduction du taux de la croissance nette de la population, ont cause des effets mesurables sur les cellule saines. Ceci a ete essentiellement observe dans la portion "saine" des cellules en tant qu'augmentation du signal de la fluorescence de 1ΈΒ. D'abord nous avons montre que SYT09/EB était une com¬binaison de colorants plus utile que celle de SYT09/PI parce que la fluorescence du PI a tendance à augmenter uniquement lorsque les cellules sont effectivement mortes, et non pas dans les cellules saines (moins de deux fois plus). Par opposi¬tion, la fluorescence moyenne de l'EB dans les cellules saines augmente jusqu'à huit fois plus après exposition aux composes toxiques. Tous les composes, mme aux plus basses concentrations, induisent une augmentation mesurable de la fluorescence moy¬enne de 1ΈΒ, plus particulièrement après deux heures d'incubation. Cet effet s'est revele tre transitoire pour les cellules exposees aux 2CNP et 4CP, mais est chro¬nique pour les cellules incubees avec le TD et le NAH (entranant la mort cellulaire). Afin de comprendre les mécanismes qui sous-tendent les effets observes, nous avons utilise des decoupleurs d'energie ou de membrane. L'augmentation du signal EB dans les populations causee par des produits chimiques ressemblait à celle exerce par le chelateur des ions divalents EDTA. Cependant, les intensités du signal EB des cellules exposees aux produits chimiques testees n'ont jamais atteint les valeurs des cellules traitees avec l'EDTA ou pasteurises. Nous en concluons que le test oli- gotrophique utilisant la coloration (SYT09/)EB des cellules exposees ou non à un produit chimique est utile afin d'evaluer l'effet toxique exerce par les polluants sur la physiologie bacterienne. Afin de mieux comprendre la reaction d'un système de defense par pompe à efflux après exposition à une toxine, nous avons étudié la toxicité du 2-hydroxybiphenyl (2-HBP) sur Pseudomonas azeiaica HBP1. Nous avons montre que le 2-HBP exerce une toxicité mme sur HBP1, mais uniquement à des concentrations supérieures à 0.5 mM. Au-dessus de cette concentration, des pertes transitoires d'intégrité et de polarization membranaire ont lieu, comme cela nous a ete montre par coloration des cellules en croissance. Les cellules sont finalement capables de se rétablir et de reprendre leur croissance sur 2-HBP. La forte resistance de P. azeiaica HBP1 h 2-HBP physiologie bacterienne s'est revele tre le résultat d'un système de pompe h efflux de type MexABOprM qui contre-balance l'influx passif de ce compose h travers la membrane. Nous avons montre, en construisant des mutants avec des insertions dans les gènes mexA, mexB and oprM et des fusions avec le gène rapporteur gfp, que l'altération de n'importe quelle partie du système d'efflux conduisait à accroître l'accumulation de 2-HBP dans la cellule, en comparaison avec la souche sauvage HBP1, provoquant une diminution de la resistance au 2-HBP ainsi qu'une baisse du taux de reproduction des cellules. Des systèmes d'efflux similaires sont répandus chez de nombreuses espèces bactériennes. Ils seraient responsables de la resistance aux produits chimiques tels que les colorants fluorescents (bromure d'ethidium) et des antibiotiques. Nous concluons que la resistance de P. azelaica HBP1 à 2-HBP est principalement due à un système d'efflux efficace et que 2-HBP, à des concentrations elevees, exerce un effet deletère sur la membrane bacterienne. En se basant sur le comptage des cellules avec la FC, nous avons developpe ensuite une methode pour evaluer la biodegradabilite de polluants tels que le 2-HBP ainsi que les antibiotiques (acide nalidixique (Nal), ampicilline (AMP) ou sulfamethoxazole (SMX)) à de faibles concentrations lmg par L et moins), par le suivi de la croissance spécifique sur le compose de cultures microbiennes pures et mixtes. En utilisant un comptage precis de faibles quantités de cellules nous avons pu demontrer que la croissance spécifique sur ces composes est possible. Nous avons pu illustrer la precision du comptage par cytometrie de flux à faible quantité de cellules (jusqu'à 10 3 cellules par ml). Ensuite, nous avons teste s'il était possible de suivre dynamiquement la croissance de la population de cellules sur faibles concentrations de substrats, en utilisant P. azelaica HBP1. Une relation parfaite a ete trouvee entre le taux de croissance, le rendement et les concentrations de 2-HBP (entre 0.1 et 5 mg par L). En mélangeant HBP1 à de la boue active, nous avons pu montrer que le rendement en communauté mixtes pouvait tre bien inférieur qu'en culture pure. Ceci étant peut tre le résultat d'une perte d'intermédiaires métaboliques. Nous avons ensuite isole de nouvelles souches à partir de la boue active en utilisant le 2-HBP ou des antibiotiques (Nal, AMP, SMX) h basses concentrations (0.1-1 mg par L) comme seules sources de carbone et d'energie. En combinaison avec ceci, nous avons également utilise des microplaques PAO. Les souches purifiees ont ensuite ete examinees pour leurs croissances sur leurs substrats respectifs. De faon intéressante, toutes ces souches ont montre qu'elles ne pouvaient pas survivre à des concentrations de substrats supérieures à 1 ou 10 mg par L. Ainsi, il existe des bacteries qui contribuent à la degradation de composes à basses concentrations de polluant mais sont inhibes lorsque ces concentrations deviennent plus hautes. Finalement, nous avons cherche à savoir s'il est possible de detecter une croissance spécifique à une biomasse au depend d'un polluant, en partant d'une communauté microbienne. Ainsi, nous nous sommes concentre sur certains composes et avons mesure l'augmentation de la biomasse d'une communauté grce à la cytometrie de flux. Nous avons compte deux communautés de depart distinctes: (i) une dilution d'eau du Lac Léman, et une dilution de boue active d'une station d'épuration. Nous avons observe que la plupart des composes testes ont entrane une augmentation de la biomasse de depart par rapport au control sans addition de source de carbone. Néanmoins, les échantillons du lac Léman et de la station d'épuration différaient largement (s'excluant mutuellement l'un l'autre) dans leur capacité à degrader les composes chimiques. Dans deux cas provenant de la station d'épuration, le mme type de communauté microbienne s'est developpe après exposition aux composes, comme l'a démontré l'analyse TRFLP sur les fragments d'ARN 16S purifie de la communauté et amplifie par PCR. Afin de tester correctement la biodegradabilite d'un compose, il est donc important d'utiliser des communautés de depart de différentes origines Nous en concluons que le comptage par cytometrie de flux peut tre un outil de grande utilité pour mettre en valeur la biodegradabillite et la toxicité des composes chimiques.

Backseat drivers: the hidden influence of microbial viruses on disease.

Because viral replication depends on the vigour of its host, many viruses have evolved incentives of fitness to pay their keep. When the viral host is a human pathogen, these fitness factors can surface as virulence: creating a Russian doll of pathogenesis where pathogens within pathogens complicate the disease process. Microbial viruses can even be independently immunogenic, as we recently reported for leishmania-virus. Thus, the incidence of this 'hyperpathogenism' is becoming an important clinical consideration and by appreciating the microbial-virus as a backseat driver of human disease, we could exploit its presence as a diagnostic biomarker and molecular target for therapeutic intervention. Here we discuss the prevalence of clinically relevant hyperpathogenism as well as the environmental sanctuaries that breed it.

Visual activity predicts auditory recovery from deafness after adult cochlear implantation.

Modern cochlear implantation technologies allow deaf patients to understand auditory speech; however, the implants deliver only a coarse auditory input and patients must use long-term adaptive processes to achieve coherent percepts. In adults with post-lingual deafness, the high progress of speech recovery is observed during the first year after cochlear implantation, but there is a large range of variability in the level of cochlear implant outcomes and the temporal evolution of recovery. It has been proposed that when profoundly deaf subjects receive a cochlear implant, the visual cross-modal reorganization of the brain is deleterious for auditory speech recovery. We tested this hypothesis in post-lingually deaf adults by analysing whether brain activity shortly after implantation correlated with the level of auditory recovery 6 months later. Based on brain activity induced by a speech-processing task, we found strong positive correlations in areas outside the auditory cortex. The highest positive correlations were found in the occipital cortex involved in visual processing, as well as in the posterior-temporal cortex known for audio-visual integration. The other area, which positively correlated with auditory speech recovery, was localized in the left inferior frontal area known for speech processing. Our results demonstrate that the visual modality's functional level is related to the proficiency level of auditory recovery. Based on the positive correlation of visual activity with auditory speech recovery, we suggest that visual modality may facilitate the perception of the word's auditory counterpart in communicative situations. The link demonstrated between visual activity and auditory speech perception indicates that visuoauditory synergy is crucial for cross-modal plasticity and fostering speech-comprehension recovery in adult cochlear-implanted deaf patients.

The situation of open access institutional repositories in Spain: 2009 report

Introduction. The DRIVER I project drew up a detailed report of European repositories based on data gathered in a survey in which Spain's participation was very low. This created a highly distorted image of the implementation of repositories in Spain. This study aims to analyse the current state of Spanish open-access institutional repositories and to describe their characteristics. Method. The data were gathered through a Web survey. The questionnaire was based on that used by DRIVER I: coverage; technical infrastructure and technical issues; institutional policies; services created; and stimulators and inhibitors for establishing, filling and maintaining their digital institutional repositories. Analysis. Data were tabulated and analysed systematically according responses obtained from the questionnaire and grouped by coverage. Results. Responses were obtained from 38 of the 104 institutions contacted, which had 29 institutional repositories. This represents 78.3% of the Spanish repositories according to the BuscaRepositorios directory. Spanish repositories contained mainly full-text materials (journal articles and doctoral theses) together with metadata. The software most used was DSpace, followed by EPrints. The metadata standard most used was Dublin Core. Spanish repositories offered more usage statistics and fewer author-oriented services than the European average. The priorities for the future development of the repositories are the need for clear policies on access to scientific production based on public funding and the need for quality control indicators. Conclusions.This is the first detailed study of Spanish institutional repositories. The key stimulants for establishing, filling and maintaining were, in order of importance, the increase of visibility and citation, the interest of decision-makers, simplicity of use and search services. On the other hand the main inhibitors identified were the absence of policies, the lack of integration with other national and international systems and the lack of awareness efforts among academia.

The Sensation of colour

The figurative painter accesses very complex levels of knowledge. To produce a painting requires, first, a deep analysis of the image of the reality and, afterwards, the study of the reconstruction of this reality. This is not about a process of copying, but a process of the comprehension of the concepts that appear in the representation. The drawing guides us in the process of the production of the surface and in the distribution of the colours that, after all, are the data with which the vision mechanism builds the visual reality. Knowing the colour and its behaviour have always been a requirement for the figurative painter. From that knowledge we can draw wider conclusions.

Molecular Proxies for Climate Maladaptation in a Long-Lived Tree (Pinus pinaster Aiton, Pinaceae).

Understanding adaptive genetic responses to climate change is a main challenge for preserving biological diversity. Successful predictive models for climate-driven range shifts of species depend on the integration of information on adaptation, including that derived from genomic studies. Long-lived forest trees can experience substantial environmental change across generations, which results in a much more prominent adaptation lag than in annual species. Here, we show that candidate-gene SNPs (single nucleotide polymorphisms) can be used as predictors of maladaptation to climate in maritime pine (Pinus pinaster Aiton), an outcrossing long-lived keystone tree. A set of 18 SNPs potentially associated with climate, 5 of them involving amino acid-changing variants, were retained after performing logistic regression, latent factor mixed models, and Bayesian analyses of SNP-climate correlations. These relationships identified temperature as an important adaptive driver in maritime pine and highlighted that selective forces are operating differentially in geographically discrete gene pools. The frequency of the locally advantageous alleles at these selected loci was strongly correlated with survival in a common garden under extreme (hot and dry) climate conditions, which suggests that candidate-gene SNPs can be used to forecast the likely destiny of natural forest ecosystems under climate change scenarios. Differential levels of forest decline are anticipated for distinct maritime pine gene pools. Geographically defined molecular proxies for climate adaptation will thus critically enhance the predictive power of range-shift models and help establish mitigation measures for long-lived keystone forest trees in the face of impending climate change.

A prospective study of predictors of poststroke depression.

OBJECTIVE: To investigate the association between early depressive behavior after stroke onset and occurrence of poststroke depression (PSD) at 3- and 12-month follow-up evaluations. METHODS: The study prospectively included 273 patients with first-ever single uncomplicated ischemic stroke. In the stroke unit, nurses scored crying, overt sadness, and apathy daily using an observational method to include patients with comprehension deficits. The Barthel Index was used to assess disability. Follow-up evaluation at months 3 and 12 included psychiatric assessment based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. RESULTS: Crying (19.8%), overt sadness (50.5%), and apathy (47.6%) were observed. Of the patients observed crying, 4 showed pathologic crying, 19 emotionalism, and 12 catastrophic reactions. Crying and overt sadness, but not apathy, were associated with a subjective experience of depression (p < 0.05). Thirty of 52 (58%) patients observed crying, 12 of 19 (63%) patients with emotionalism, and 5 of 12 (41%) patients with catastrophic reactions developed PSD within the first year. Multiple logistic regression analysis showed that only severe functional disability (odds ratio [OR], 4.31; 95% CI, 2.41 to 7.69), crying behaviors (OR, 2.66; 95% CI, 1.35 to 5.27), and an age <68 years (OR, 2.32; 95% CI, 1.30 to 4.13) were (p < 0.05) predictors of late PSD development (13% of the variance). CONCLUSIONS: In the stroke unit, crying and overt sadness are more reliable indicators of depressed mood than apathy. In patients with first-ever stroke, crying behaviors soon after stroke, a younger age, and severe disability are predictors of poststroke depression occurrence within the first year after stroke onset.

Speed Limit Questions? Here’s Your Answer, February 8, 2010

Iowa’s speed regulations are based on the same basic speed law that is used in all 50 states: “Any person driving a motor vehicle on a highway shall drive the same at a careful and prudent speed not greater than nor less than is reasonable and proper, having due regard to the traffic, surface, and width of the highway and of any other conditions then existing, and no person shall drive any vehicle upon a highway at a speed greater than will permit the person to bring it to a stop within the assured clear distance ahead, such driver having the right to assume, however, that all persons using said highway will observe the law.” Statutory limits are based on the concept that uniform categories of highways can be traveled safely at certain preset maximum speeds under ideal conditions. Whether the speed limit is posted or unposted, drivers should reduce their speed below these values in poor weather, heavy traffic, and under other potentially hazardous conditions.

Médecine génomique et oncologie [Genomics medicine and oncology].

Progress in genomics with, in particular, high throughput next generation sequencing is revolutionizing oncology. The impact of these techniques is seen on the one hand the identification of germline mutations that predispose to a given type of cancer, allowing for a personalized care of patients or healthy carriers and, on the other hand, the characterization of all acquired somatic mutation of the tumor cell, opening the door to personalized treatment targeting the driver oncogenes. In both cases, next generation sequencing techniques allow a global approach whereby the integrality of the genome mutations is analyzed and correlated with the clinical data. The benefits on the quality of care delivered to our patients are extremely impressive.

Unusual concentration of Early Albian arthropod-bearing amber in the Basque-Cantabrian Basin (El Soplao, Cantabria, Spain): Palaeoenvironmental and paleobiological implications.

The El Soplao site is a recently-discovered Early Albian locality of the Basque-Cantabrian Basin (northern Spain) that has yielded a number of amber pieces with abundant bioinclusions. The amber-bearing deposit occurs in a non-marine to transitional marine siliciclastic unit (Las Peñosas Formation) that is interleaved within a regressive-transgressive, carbonate-dominated Lower Aptian-Upper Albian marine sequence. The Las Peñosas Formation corresponds to the regressive stage of this sequence and in its turn it splits into two smaller regressive-transgressive cycles. The coal and amber-bearing deposits occur in deltaic-estuarine environments developed during the maximum regressive episodes of these smaller regressive-transgressive cycles. The El Soplao amber shows Fourier Transform Infrared Spectroscopy spectra similar to other Spanish Cretaceous ambers and it is characterized by the profusion of sub-aerial, stalactite-like flows. Well-preserved plant cuticles assigned to the conifer genera Frenelopsis and Mirovia are abundant in the beds associated with amber. Leaves of the ginkgoalean genera Nehvizdya and Pseudotorellia also occur occasionally. Bioinclusions mainly consist of fossil insects of the orders Blattaria, Hemiptera, Thysanoptera, Raphidioptera, Neuroptera, Coleoptera, Hymenoptera and Diptera, although some spiders and spider webs have been observed as well. Some insects belong to groups scarce in the fossil record, such as a new morphotype of the wasp Archaeromma (of the family Mymarommatidae) and the biting midge Lebanoculicoides (of the monogeneric subfamily Lebanoculicoidinae). This new amber locality constitutes a very significant finding that will contribute to improving the knowledge and comprehension of the Albian non-marine paleoarthropod fauna.

Characterization of gravitational rock slope deformations at different spatial scales based on field, remote sensing and numerical approaches

Rock slope instabilities such as rock slides, rock avalanche or deep-seated gravitational slope deformations are widespread in Alpine valleys. These phenomena represent at the same time a main factor that control the mountain belts erosion and also a significant natural hazard that creates important losses to the mountain communities. However, the potential geometrical and dynamic connections linking outcrop and slope-scale instabilities are often unknown. A more detailed definition of the potential links will be essential to improve the comprehension of the destabilization processes and to dispose of a more complete hazard characterization of the rock instabilities at different spatial scales. In order to propose an integrated approach in the study of the rock slope instabilities, three main themes were analysed in this PhD thesis: (1) the inventory and the spatial distribution of rock slope deformations at regional scale and their influence on the landscape evolution, (2) the influence of brittle and ductile tectonic structures on rock slope instabilities development and (3) the characterization of hazard posed by potential rock slope instabilities through the development of conceptual instability models. To prose and integrated approach for the analyses of these topics, several techniques were adopted. In particular, high resolution digital elevation models revealed to be fundamental tools that were employed during the different stages of the rock slope instability assessment. A special attention was spent in the application of digital elevation model for detailed geometrical modelling of past and potential instabilities and for the rock slope monitoring at different spatial scales. Detailed field analyses and numerical models were performed to complete and verify the remote sensing approach. In the first part of this thesis, large slope instabilities in Rhone valley (Switzerland) were mapped in order to dispose of a first overview of tectonic and climatic factors influencing their distribution and their characteristics. Our analyses demonstrate the key influence of neotectonic activity and the glacial conditioning on the spatial distribution of the rock slope deformations. Besides, the volumes of rock instabilities identified along the main Rhone valley, were then used to propose the first estimate of the postglacial denudation and filling of the Rhone valley associated to large gravitational movements. In the second part of the thesis, detailed structural analyses of the Frank slide and the Sierre rock avalanche were performed to characterize the influence of brittle and ductile tectonic structures on the geometry and on the failure mechanism of large instabilities. Our observations indicated that the geometric characteristics and the variation of the rock mass quality associated to ductile tectonic structures, that are often ignored landslide study, represent important factors that can drastically influence the extension and the failure mechanism of rock slope instabilities. In the last part of the thesis, the failure mechanisms and the hazard associated to five potential instabilities were analysed in detail. These case studies clearly highlighted the importance to incorporate different analyses and monitoring techniques to dispose of reliable and hazard scenarios. This information associated to the development of a conceptual instability model represents the primary data for an integrated risk management of rock slope instabilities. - Les mouvements de versant tels que les chutes de blocs, les éboulements ou encore les phénomènes plus lents comme les déformations gravitaires profondes de versant représentent des manifestations courantes en régions montagneuses. Les mouvements de versant sont à la fois un des facteurs principaux contrôlant la destruction progressive des chaines orogéniques mais aussi un danger naturel concret qui peut provoquer des dommages importants. Pourtant, les phénomènes gravitaires sont rarement analysés dans leur globalité et les rapports géométriques et mécaniques qui lient les instabilités à l'échelle du versant aux instabilités locales restent encore mal définis. Une meilleure caractérisation de ces liens pourrait pourtant représenter un apport substantiel dans la compréhension des processus de déstabilisation des versants et améliorer la caractérisation des dangers gravitaires à toutes les échelles spatiales. Dans le but de proposer un approche plus globale à la problématique des mouvements gravitaires, ce travail de thèse propose trois axes de recherche principaux: (1) l'inventaire et l'analyse de la distribution spatiale des grandes instabilités rocheuses à l'échelle régionale, (2) l'analyse des structures tectoniques cassantes et ductiles en relation avec les mécanismes de rupture des grandes instabilités rocheuses et (3) la caractérisation des aléas rocheux par une approche multidisciplinaire visant à développer un modèle conceptuel de l'instabilité et une meilleure appréciation du danger . Pour analyser les différentes problématiques traitées dans cette thèse, différentes techniques ont été utilisées. En particulier, le modèle numérique de terrain s'est révélé être un outil indispensable pour la majorité des analyses effectuées, en partant de l'identification de l'instabilité jusqu'au suivi des mouvements. Les analyses de terrain et des modélisations numériques ont ensuite permis de compléter les informations issues du modèle numérique de terrain. Dans la première partie de cette thèse, les mouvements gravitaires rocheux dans la vallée du Rhône (Suisse) ont été cartographiés pour étudier leur répartition en fonction des variables géologiques et morphologiques régionales. En particulier, les analyses ont mis en évidence l'influence de l'activité néotectonique et des phases glaciaires sur la distribution des zones à forte densité d'instabilités rocheuses. Les volumes des instabilités rocheuses identifiées le long de la vallée principale ont été ensuite utilisés pour estimer le taux de dénudations postglaciaire et le remplissage de la vallée du Rhône lié aux grands mouvements gravitaires. Dans la deuxième partie, l'étude de l'agencement structural des avalanches rocheuses de Sierre (Suisse) et de Frank (Canada) a permis de mieux caractériser l'influence passive des structures tectoniques sur la géométrie des instabilités. En particulier, les structures issues d'une tectonique ductile, souvent ignorées dans l'étude des instabilités gravitaires, ont été identifiées comme des structures très importantes qui contrôlent les mécanismes de rupture des instabilités à différentes échelles. Dans la dernière partie de la thèse, cinq instabilités rocheuses différentes ont été étudiées par une approche multidisciplinaire visant à mieux caractériser l'aléa et à développer un modèle conceptuel trois dimensionnel de ces instabilités. A l'aide de ces analyses on a pu mettre en évidence la nécessité d'incorporer différentes techniques d'analyses et de surveillance pour une gestion plus objective du risque associée aux grandes instabilités rocheuses.

Pavement Markings and Safety Final Report, November 2010

Previous research on pavement markings from a safety perspective tackled various issues such as pavement marking retroreflectivity variability, relationship between pavement marking retroreflectivity and driver visibility, or pavement marking improvements and safety. A recent research interest in this area has been to find a correlation between retroreflectivity and crashes, but a significant statistical relationship has not yet been found. This study investigates such a possible statistical relationship by analyzing five years of pavement marking retroreflectivity data collected by the Iowa Department of Transportation (DOT) on all state primary roads and corresponding crash and traffic data. This study developed a spatial-temporal database using measured retroreflectivity data to account for the deterioration of pavement markings over time along with statewide crash data to attempt to quantify a relationship between crash occurrence probability and pavement marking retroreflectivity. First, logistic regression analyses were done for the whole data set to find a statistical relationship between crash occurrence probability and identified variables, which are road type, line type, retroreflectivity, and traffic (vehicle miles traveled). The analysis looked into subsets of the data set such as road type, retroreflectivity measurement source, high crash routes, retroreflectivity range, and line types. Retroreflectivity was found to have a significant effect in crash occurrence probability for four data subsets—interstate, white edge line, yellow edge line, and yellow center line data. For white edge line and yellow center line data, crash occurrence probability was found to increase by decreasing values of retroreflectivity.