55 research outputs found

    Monophyletic group of unclassified γ-Proteobacteria dominates in mixed culture biofilm of high-performing oxygen reducing biocathode

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    International audienceSeveral mixed microbial communities have been reported to show robust bioelectrocatalysis of oxygen reduction over time at applicable operation conditions. However, clarification of electron transfer mechanism(s) and identification of essential micro-organisms have not been realised. Therefore, the objective of this study was to shape oxygen reducing biocathodes with different microbial communities by means of surface modification using the electrochemical reduction of two different diazonium salts in order to discuss the relation of microbial composition and performance. The resulting oxygen reducing mixed culture biocathodes had complex bacterial biofilms variable in size and shape as observed by confocal and electron microscopy. Sequence analysis of ribosomal 16S rDNA revealed a putative correlation between the abundance of certain microbiota and biocathode performance. The best performing biocathode developed on the unmodified graphite electrode and reached a high current density for oxygen reducing biocathodes at neutral pH (0.9A/m(2)). This correlated with the highest domination (60.7%) of a monophyletic group of unclassified γ-Proteobacteria. These results corroborate earlier reports by other groups, however, higher current densities and higher presence of these unclassified bacteria were observed in this work. Therefore, members of this group are likely key-players for highly performing oxygen reducing biocathodes.[on SciFinder (R)

    TRPV1 in Brain Is Involved in Acetaminophen-Induced Antinociception

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    Background: Acetaminophen, the major active metabolite of acetanilide in man, has become one of the most popular overthe- counter analgesic and antipyretic agents, consumed by millions of people daily. However, its mechanism of action is still a matter of debate. We have previously shown that acetaminophen is further metabolized to N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404) by fatty acid amide hydrolase (FAAH) in the rat and mouse brain and that this metabolite is a potent activator of transient receptor potential vanilloid 1 (TRPV1) in vitro. Pharmacological activation of TRPV1 in the midbrain periaqueductal gray elicits antinociception in rats. It is therefore possible that activation of TRPV1 in the brain contributes to the analgesic effect of acetaminophen. Methodology/Principal Findings: Here we show that the antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity is absent in FAAH and TRPV1 knockout mice in the formalin, tail immersion and von Frey tests. This dose of acetaminophen did not affect the global brain contents of prostaglandin E-2 (PGE(2)) and endocannabinoids. Intracerebroventricular injection of AM404 produced a TRPV1-mediated antinociceptive effect in the mouse formalin test. Pharmacological inhibition of TRPV1 in the brain by intracerebroventricular capsazepine injection abolished the antinociceptive effect of oral acetaminophen in the same test. Conclusions: This study shows that TRPV1 in brain is involved in the antinociceptive action of acetaminophen and provides a strategy for developing central nervous system active oral analgesics based on the coexpression of FAAH and TRPV1 in the brain

    Author Correction:A consensus protocol for functional connectivity analysis in the rat brain

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    Le paracétamol : un ancêtre plein d’avenir

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    Plus d’un siècle après sa synthèse, le paracétamol demeure l’antalgique le plus utilisé dans le monde. Malgré son grand âge, ses effets bénéfiques (antalgique, antipyrétique) autant qu’indésirables ainsi que sa toxicité sont une source intarissable de publications. En effet, les mécanismes sous-tendant ces différentes actions sont loin d’être élucidés. Nous pensons qu’une meilleure compréhension de son mécanisme d’action antalgique permettra d’identifier la ou les cible(s) moléculaire(s) à l’origine de son effet et ainsi de concevoir de nouveaux antalgiques plus efficaces présentant une tolérance au moins comparable à celle du paracétamol. Plusieurs systèmes semblent être impliqués dont le système sérotoninergique et celui des prostaglandines, auxquels s’ajoute désormais la participation des systèmes endogènes cannabinoïdergique et vanilloïdergique. Ainsi, de récentes études dévoilent une nouvelle vision du paracétamol : celle d’un pro-médicament qui nécessite d’être bio-transformé pour exercer son effet antalgique. Ces dernières données laissent présager que le paracétamol n’a pas fini de nous étonner

    Trends, stasis, and drift in the evolution of nematode vulva development.

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    International audienceBACKGROUND: A surprising amount of developmental variation has been observed for otherwise highly conserved features, a phenomenon known as developmental system drift. Either stochastic processes (e.g., drift and absence of selection-independent constraints) or deterministic processes (e.g., selection or constraints) could be the predominate mechanism for the evolution of such variation. We tested whether evolutionary patterns of change were unbiased or biased, as predicted by the stochastic or deterministic hypotheses, respectively. As a model, we used the nematode vulva, a highly conserved, essential organ, the development of which has been intensively studied in the model systems Caenorhabditis elegans and Pristionchus pacificus. RESULTS: For 51 rhabditid species, we analyzed more than 40 characteristics of vulva development, including cell fates, fate induction, cell competence, division patterns, morphogenesis, and related aspects of gonad development. We then defined individual characters and plotted their evolution on a phylogeny inferred for 65 species from three nuclear gene sequences. This taxon-dense phylogeny provides for the first time a highly resolved picture of rhabditid evolution and allows the reconstruction of the number and directionality of changes in the vulva development characters. We found an astonishing amount of variation and an even larger number of evolutionary changes, suggesting a high degree of homoplasy (convergences and reversals). Surprisingly, only two characters showed unbiased evolution. Evolution of all other characters was biased. CONCLUSIONS: We propose that developmental evolution is primarily governed by selection and/or selection-independent constraints, not stochastic processes such as drift in unconstrained phenotypic space

    Characterization of early white matter changes in CADASIL using microscopic diffusion imaging and relaxometry

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    Background and purpose Cerebral small vessel diseases (SVDs) are characterized by early white matter (WM) changes, whose pathological underpinnings are yet poorly understood. CADASIL is a monogenic and archetypal SVD, providing an ideal model for investigating these changes. Here, we used multicompartment microscopic diffusion imaging and relaxometry to elucidate microstructural changes underlying early WM abnormalities in CADASIL. Methods We acquired diffusion MRI data with a multiple-shell Q-space sampling strategy, and relaxometry T1 and T2 data, with a 160 and 80-μm isotropic resolution respectively, ex vivo , in CADASIL and control mice. Diffusion datasets were computed with the Neurite Orientation Dispersion and Density Imaging model to extract the neurite density index, the extracellular free water and the orientation dispersion index. Relaxometry datasets were computed with a 3-compartment myelin water imaging model to extract the myelin content. MRI metrics were compared between CADASIL and control mice using voxel and WM tract-based analyses and with electron microscopy analysis. Results WM in CADASIL mice displayed a widespread reduction in general fractional anisotropy, a large increase in extracellular free water, a reduction in the myelin content, but no reduction in neurite density. Electron microscopy analysis showed a ∽2-fold increase in the extracellular spaces and an elevation of the g-ratio indicative of myelin sheath thinning in CADASIL WM. Conclusion Our findings suggest that accumulation of interstitial fluid and myelin damage are 2 major factors underlying early WM changes in CADASIL. Advanced diffusion MRI and relaxometry are promising approaches to decipher the underpinnings of WM alterations in SVDs
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