Characterization of SLC transporters in human skin

Most identified drug transporters belong to the ATP-binding Cassette (ABC) and Solute Carrier (SLC) families. Recent research indicates that some of these transporters play an important role in the absorption, distribution and excretion of drugs, and are involved in clinically relevant drug-drug interactions for systemic drugs. However, very little is known about the role of drug transporters in human skin in the disposition of topically applied drugs and their involvement in drug-drug interactions. The aim of this work was to compare the expression in human skin (vs human hepatocytes and kidney) of SLC transporters included in the EMA guidance as the most likely clinical sources of drug interactions. The expression of SLC transporters in human tissues was analyzed by quantitative RT-PCR. Modulation of SLC47A1 and SLC47A2 (MATE1 and MATE2) expression was analyzed after treatment of human skin in organ-culture with rifampicin and UV irradiation. The expression of SLCO2B1 (OATPB), SLCO3A1 (OATPD), SLCO4A1 (OATPE), SLC47A1 and SLC47A2 (MATE1 and MATE2) was detected in human skin, OATPE and MATE1 being the most expressed. OATPE is about 70 times more expressed in human skin than in human hepatocytes. Moreover, the expression of SLC47A1 and SLC47A2 was down-regulated after treatment with rifampicin or after exposure to UV light. The present findings demonstrate that SLCO4A1 (OATPE) and SLC47A1 (MATE1) are highly expressed in human skin and suggest the involvement of SLC transporters in the disposition of topically applied drugs

The GRAVITY+ Project: Towards All-sky, Faint-Science, High-Contrast Near-Infrared Interferometry at the VLTI

The GRAVITY instrument has been revolutionary for near-infrared interferometry by pushing sensitivity and precision to previously unknown limits. With the upgrade of GRAVITY and the Very Large Telescope Interferometer (VLTI) in GRAVITY+, these limits will be pushed even further, with vastly improved sky coverage, as well as faint-science and high-contrast capabilities. This upgrade includes the implementation of wide-field off-axis fringe-tracking, new adaptive optics systems on all Unit Telescopes, and laser guide stars in an upgraded facility. GRAVITY+ will open up the sky to the measurement of black hole masses across cosmic time in hundreds of active galactic nuclei, use the faint stars in the Galactic centre to probe General Relativity, and enable the characterisation of dozens of young exoplanets to study their formation, bearing the promise of another scientific revolution to come at the VLTI.Comment: Published in the ESO Messenge

Suivi 2011 des captures d'anguilles pour la DCF : analyse des otolithes

Ce rapport synthétise l'analyse des otolithes d'anguilles prélevés en 2011 dans le cadre du suivi des captures de cette espèce inscrite à la DCF (Data Collection Framework règlement CE n°199/2008 du conseil du 25 février 2008). 140 anguilles ont été prélevées entre fin juillet et fin octobre 2011 dans la Loire, la Dordogne et la Gironde. La relation entre la longueur totale (Lt) et le poids total (Wt) des anguilles prélevées en 2011 dans toute la France (Loire, Garonne et Dordogne) est du type Wt = 5.10-7.Lt3,21. Ainsi, les anguilles présentent une allométrie majorante (b=3.21) c’est-à-dire que le poids croit plus vite que la longueur. L'institut IFREMER à travers le pôle national de Sclérochronologie à Boulogne-sur-mer a préparé et interprété les otolithes, pièce calcifiée de l'oreille interne, permettant d'estimer l'âge de ces poissons. Pour chaque otolithe, une lame mince transversale polie a été réalisée pour permettre d'estimer l'âge de chaque individu à l'aide du logiciel TNPC (Traitement Numérique des Pièces Calcifiées, www.tnpc.fr). Parmi les 140 poissons échantillonnés, l'âge de 130 anguilles a pu être estimé. L'âge de 10 poissons n'a pas pu être réalisé car soit les otolithes étaient cassés donc inutilisables soit les coupes d'otolithes ne présentaient pas de structures interprétables. Les âges estimés étaient dans la Garonne et la Dordogne de 2 à 16 ans avec une moyenne de 7 ans et dans la Loire de 5 à 15 ans avec une moyenne de 11 ans. Parmi les classes d'âge observées de 2 à 16 ans, on observe que les intervalles de longueur pour les classes d'âge de 2 à 10 ans sont relativement faibles à l'inverse des groupes d'âge supérieurs à 10 ans (Fig. 8). Ainsi, pour les groupes d'âge supérieurs à 10 ans, les variations de croissance entre les individus sont très importantes et pour une taille donnée, il est très difficile d'estimer l'âge sans interpréter l'otolithe. Tous ces otolithes et données associées (taille, poids, date de capture, lieu...) sont stockés et gérés actuellement dans la base nationale d'archivage et de gestion des pièces calcifiées développée par l'IFREMER

Report of the Seabass (Dicentrarchus labrax) Otolith and Scale Exchange Scheme 2013

The ICES Planning Group on Commercial Catch, Discards and Biological Sampling (PGCCDBS) identified the need of a seabass Dicentrarchus labrax) otolith exchange to take place in 2013. It was the second exchange after that’s of 2011. The IFREMER institute coordinated this exchange. A total of 223 fish from the bay of Biscay (ICES area : VIII, N=29), the Eastern English Channel (ICES area : VIId, N=149) and the North Sea (ICES area : IV, N=45) was sampled onboard French research vessels (Gwen-Drez and Thalassa) during 3 international surveys (EVHOE, CGFS and IBTS). The length range of the fish was between 26 and 71 cm, with mean 42.3 cm. For each fish, the Sagittae otoliths and few scales were used to compare the age estimation between the both calcified pieces. Only 3 readers were participated from France (1 reader), Belgium (1 reader) and UK England (1 reader). During the first exchange in 2011, there were only 2 countries (France and UK England). Only images were used during this exchange. The analyses did not show a high mean precision of age estimate for individual fish with Coefficient of Variation (CV) of 9.4% and percent agreement to modal age of 68.6%. Among 223 fish, 84 were read with 100% agreement (37%) and thus a CV of 0%. During this exchange, 2 different calcified pieces (otolith and scale) from the same sampling were analysed. The results showed precision of age estimation from the scales (Agreement = 78.4%; CV=1.4) was better than that’s from the otoliths (Agreement = 55.7%; CV=13.4). However, the size of sampling for the otolith exercise (N=149) is twice as much as that’s of the scale exercise (N=74, Tab. 2). Moreover, 2 readers (France and Belgium) preferred to analyse otoliths and only 1 reader the otoliths of seabass

Prevalence of Parascaris equorum infection in foals on French stud farms and first report of ivermectin-resistant P. equorum populations in France

International audienc

Suivi 2013 des captures d'anguilles pour la DCF : analyse des otolithes

Ce rapport synthétise l'analyse des otolithes d'anguilles prélevés en 2013 dans le cadre du suivi des captures de cette espèce inscrite à la DCF (Data Collection Framework règlement CE n°199/2008 du conseil du 25 février 2008). 240 anguilles ont été prélevées en septembre/octobre 2013 dans le lac de Grand Lieu, la Dordogne et la Garonne. La relation entre la longueur totale (Lt) et le poids total (W) des anguilles prélevées en 2013 dans toute la France est du type W = 3.10-7.Lt3,273. Ainsi, les anguilles présentent une allométrie majorante (b=3,273) c’est-à-dire que le poids croit plus vite que la longueur. L'institut IFREMER à travers le pôle national de Sclérochronologie à Boulogne-sur-mer a préparé et interprété les otolithes, pièces calcifiées de l'oreille interne, permettant d'estimer l'âge de ces poissons. Pour chaque otolithe, une lame mince transversale polie a été réalisée pour permettre d'estimer l'âge de chaque individu à l'aide du logiciel TNPC (Traitement Numérique des Pièces Calcifiées, www.tnpc.fr). Tous ces otolithes et données associées (taille, poids, date de capture, lieu...) sont stockés et gérés actuellement dans la base nationale d'archivage et de gestion des pièces calcifiées développée par l'IFREMER

Characterization of SLC transporters in human skin

Most identified drug transporters belong to the ATP-binding Cassette (ABC) and Solute Carrier (SLC) families. Recent research indicates that some of these transporters play an important role in the absorption, distribution and excretion of drugs, and are involved in clinically relevant drug-drug interactions for systemic drugs. However, very little is known about the role of drug transporters in human skin in the disposition of topically applied drugs and their involvement in drug-drug interactions. The aim of this work was to compare the expression in human skin (vs human hepatocytes and kidney) of SLC transporters included in the EMA guidance as the most likely clinical sources of drug interactions. The expression of SLC transporters in human tissues was analyzed by quantitative RT-PCR. Modulation of SLC47A1 and SLC47A2 (MATE1 and MATE2) expression was analyzed after treatment of human skin in organ-culture with rifampicin and UV irradiation. The expression of SLCO2B1 (OATPB), SLCO3A1 (OATPD), SLCO4A1 (OATPE), SLC47A1 and SLC47A2 (MATE1 and MATE2) was detected in human skin, OATPE and MATE1 being the most expressed. OATPE is about 70 times more expressed in human skin than in human hepatocytes. Moreover, the expression of SLC47A1 and SLC47A2 was down-regulated after treatment with rifampicin or after exposure to UV light. The present findings demonstrate that SLCO4A1 (OATPE) and SLC47A1 (MATE1) are highly expressed in human skin and suggest the involvement of SLC transporters in the disposition of topically applied drugs

Políticas públicas de juventude : interfaces entre educação e formação profissional alguns apontamentos também sobre o programa de privação de liberdade

Este trabalho é o resultado de um processo de reflexões e estudos, desencadeado há mais de uma década a partir de minhas práticas profissionais e pesquisas acadêmicas sobre as políticas públicas como possibilidades de inserção social para a juventude brasileira desfavoreci da socioeconomicamente. A intenção de sistematizar a produção própria vem desde a atuação junto ao Programa Agent e Jovem de Desenvolvimento Social e Humano, na condição de Educadora Social, passando pela assessoria aos empreendimentos de Economia Popular Solidária, à Fundação de Atendimento Sócio- Educativo (FASE), e ainda pela prática docente da educação básica e técnica. De forma mais específica, revisitar esses estudos e práticas, complementando- os com a revisão bibliográfica de outras autorias, foi a estratégia metodológica que encontrei para f ocar as interfaces entre os aspectos educacionais e os da formação profissional em programas sociais para os jovens. Pela recorrência da práxis entre ação e reflexão no âmbito dessas políticas e pela relevância social do tema, que é cada vez mais atual, entendo ser razoável continuar problematizando. Também por se tratar de elemento fundamental no mosaico que constitui o processo de inserção social de jovens beneficiários das políticas públicas, com idade considerada pelas normativas trabalhistas como a fase de referência para a aprendizagem e iniciação profissional. Aborda ainda entraves à inserção social, como baixa escolaridade e precariedade na oferta de qualificação profissional, para aqueles que estiveram ou estão privados de liberdade por determinação judicial. Com efeito, cabe questionar em que medi da o Est ado vem cumprindo o que lhe é pressuposto junto às políticas sociais. Constatar as fragilidades dos programas que poderiam prevenir a vi a delituosa desses sujeitos e outorgar-lhes cidadania, como está constatado neste e em outros estudos, não seria um bom começo para propor estratégias de enfrentamento? Em que pese tratar-se de um segmento populacional que representa uma grande oportunidade para o país, também pelo seu volume numérico, o preconceito faz com que sejam vistos como problema, criando barreiras para o desenvolvimento pleno do seu potencial. Nesse sentido, o estudo é também propositivo quanto às alternativas para o enfrentamento das questões que são aqui abordadas e que afetam a vida desse segmento populacional que carece da ajuda do Estado.This work is the result of a process of reflection and study, initiated more than a decade from my professional practice and academic research on public policy and social inclusion opportunities for socioeconomically disadvantaged Brazilian youth. The aim of systematizing the production itself comes from the performance in the Young Agent Program for Social and Human Development, provided Social Educator, through assistance to enterprises of Popular Solidarity Economy, the Foundation for Social-Education ( FASE), and further the activities as a teacher of basic and technical education. More specifically, to revisit these studies and practices, complemented with a literature review, the methodological tools that were found to focus on the interfaces between the educational aspects of vocational training and social programs for youth. For the recurrence of praxis between action and reflection within these policies, I believe it is reasonable to continue questioning the subject, even by its social relevance that is more current. It should be clarified that this study restricts the sociohistorical aspects of the working world and t hose in the educational setting that points to emerge as a key element of the mosaic that constitutes the process of social inclusion of young beneficiaries of public policies, with age considered by regulations such as labor phase reference for learning and professional initiation. It also addresses barriers to social inclusion, such as low education and job insecurity in the provision of professional qualification for those who were or are deprived of t heir liberty by court order. Indeed, one must question t he extent to which the Stat e has complied with the assumption that it is close to social policies. See the weaknesses of the programs that could prevent these subjects through criminal and grant them citizenship, as is seen in this and other studies, there would be a good start t o propose coping strategies? Despite that this is a population segment that represents a great opportunity for the country, also by volume number, the bi as causes t hem to be seen as a problem by creating barriers to the full development potential. In this sense, the study is also purposeful about the alternatives for dealing with issues that are addressed here and that affect the lives of this population segment that needs the help of state

Variability of PCB burden in 5 fish and sharks species of the French Mediterranean continental slope

Despite being generally located far from contamination sources, deep marine ecosystems are impacted by chemicals like PCB. The PCB contamination in five fish and shark species collected in the continental slope of the Gulf of Lions (NW Mediterranean Sea) was measured, with a special focus on intra- and interspecific variability and on the driving factors. Significant differences occurred between species. Higher values were measured in Scyliorhinus canicula, Galeus melastomus and Helicolenus dactylopterus and lower values in Phycis blennoides and Lepidorhombus boscii. These differences might be explained by specific abilities to accumulate and eliminate contaminant, mostly through cytochrome P450 pathway. Interindividual variation was also high and no correlation was observed between contamination and length, age or trophic level. Despite its major importance, actual bioaccumulation of PCB in deep fish is not as documented as in other marine ecosystems, calling for a better assessment of the factors driving individual bioaccumulation mechanisms and originating high variability in PCB contamination

Antimicrobial resistance and genetic diversity of Klebsiella pneumoniae strains from different clinical sources in horses

International audienceIntroduction: Klebsiella pneumoniae is a major cause of infections and reproductive disorders among horses, ranked in recent French studies as the sixth most frequently isolated bacterial pathogen in equine clinical samples. The proportion of multidrug-resistant (MDR) K. pneumoniae is therefore significant in a context where MDR K. pneumoniae strains are considered a major global concern by the World Health Organization.Methods: In this study, we used a genomic approach to characterize a population of 119 equine K. pneumoniae strains collected by two laboratories specialized in animal health in Normandy (France). We describe the main antibiotic resistance profiles and acquired resistance genes, and specify the proportion of virulence-encoding genes carried by these strains. The originality of our panel of strains lies in the broad collection period covered, ranging from 1996 to 2020, and the variety of sample sources: necropsies, suspected bacterial infections (e.g., genital, wound, allantochorion, and umbilical artery samples), and contagious equine metritis analyses.Results: Our results reveal a remarkable level of genomic diversity among the strains studied and we report the presence of 39% MDR and 9% hypervirulent strains (including 5% that are both MDR and hypervirulent).Discussion: These findings clearly emphasize the importance of improving the surveillance of K. pneumoniae in routine equine diagnostic tests to detect high-risk MDR-hypervirulent Klebsiella pneumoniae strains. The circulation of these worrisome strains reveals that they are not being detected by the simple K1, K2, and K5 serotype approach currently implemented in the French horse-breeding sector