2,045 research outputs found

    The mucin-degradation strategy of Ruminococcus gnavus:The importance of intramolecular trans-sialidases

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    We previously identified and characterized an intramolecular trans-sialidase (IT-sialidase) in the gut symbiont Ruminococcus gnavus ATCC 29149, which is associated to the ability of the strain to grow on mucins. In this work we have obtained and analyzed the draft genome sequence of another R. gnavus mucin-degrader, ATCC 35913, isolated from a healthy individual. Transcriptomics analyses of both ATCC 29149 and ATCC 35913 strains confirmed that the strategy utilized by R. gnavus for mucin-degradation is focused on the utilization of terminal mucin glycans. R. gnavus ATCC 35913 also encodes a predicted IT-sialidase and harbors a Nan cluster dedicated to sialic acid utilization. We showed that the Nan cluster was upregulated when the strains were grown in presence of mucin. In addition we demonstrated that both R. gnavus strains were able to grow on 2,7-anyhydro-Neu5Ac, the IT-sialidase transglycosylation product, as a sole carbon source. Taken together these data further support the hypothesis that IT-sialidase expressing gut microbes, provide commensal bacteria such as R. gnavus with a nutritional competitive advantage, by accessing and transforming a source of nutrient to their own benefit

    Study of charge-charge coupling effects on dipole emitter relaxation within a classical electron-ion plasma description

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    Studies of charge-charge (ion-ion, ion-electron, and electron-electron) coupling properties for ion impurities in an electron gas and for a two component plasma are carried out on the basis of a regularized electron-ion potential without short-range Coulomb divergence. This work is motivated in part by questions arising from recent spectroscopic measurements revealing discrepancies with present theoretical descriptions. Many of the current radiative property models for plasmas include only single electron-emitter collisions and neglect some or all charge-charge interactions. A molecular dynamics simulation of dipole relaxation is proposed here to allow proper account of many electron-emitter interactions and all charge-charge couplings. As illustrations, molecular dynamics simulations are reported for the cases of a single ion imbedded in an electron plasma and for a two-component ion-electron plasma. Ion-ion, electron-ion, and electron-electron coupling effects are discussed for hydrogen-like Balmer alpha lines.Comment: 13 figures, submitted to Phys. Rev.

    www.fevertravel.ch: an online study prototype to evaluate the safety and feasibility of computerized guidelines for fever in returning travellers and migrants

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    Following the paper publication of practice guidelines for the management of febrile patients returning from the tropics, we constructed a consultation website that comprises a decision chart and specific diagnostic features providing medical diagnostic assistance to primary care physicians. We then integrated a research component to evaluate the implementation of these computerized guidelines. This study website has the same interface as the consultation website. In addition, one is able to record: (i) the pathway followed by the physician through the decision chart, (ii) the diagnostic tests performed, (iii) the initial and final diagnoses as well as outcome and (iv) reasons for non-adherence when the physician diverges from the proposed attitude. We believe that Internet technology is a powerful medium to reach physicians of different horizons in their own environment, and could prove to be an effective research tool to disseminate practice guidelines and evaluate their appropriateness. Here we describe the design, content, architecture and system implementation of this interactive study prototype aimed at integrating operational research in primary care practice. [Authors]]]> Emigration and Immigration; Fever; Guidelines as Topic; Internet; Travel eng oai:serval.unil.ch:BIB_4BBC99034368 2022-05-07T01:17:24Z ehelvetica openaire documents phdthesis urnserval <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_4BBC99034368 Usage conditionnel et inconditionnel des droits humains dans la vie quotidienne Anex, Emmanuelle Université de Lausanne, Faculté des sciences sociales et politiques info:eu-repo/semantics/doctoralThesis phdthesis 2018 fre https://serval.unil.ch/resource/serval:BIB_4BBC99034368.P001/REF.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_4BBC990343683 info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_4BBC990343683 info:eu-repo/semantics/openAccess Copying allowed only for non-profit organizations https://serval.unil.ch/disclaimer application/pdf oai:serval.unil.ch:BIB_4BA5F44A285D 2022-05-07T01:17:24Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_4BA5F44A285D A double-blind, placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: a clinical, pharmacokinetic, and pharmacogenetic investigation Baumann, Pierre Nil, Rico Souche, Alain Montaldi, Stefano Baettig, Dominique Lambert, Susanne Uehlinger, Claude Kasas, Anton Amey, Marlyse Jonzier-Perey, Michèle info:eu-repo/semantics/article article 1996 Journal of Clinical Psychopharmacology, vol. 16, pp. 307-314 one$; TBOK eng oai:serval.unil.ch:BIB_4BA60F08CDFC 2022-05-07T01:17:24Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_4BA60F08CDFC Busulfan Pharmacokinetics in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Gene Therapy. info:doi:10.1016/j.bbmt.2020.07.004 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbmt.2020.07.004 info:eu-repo/semantics/altIdentifier/pmid/32653625 Bradford, K.L. Liu, S. Krajinovic, M. Ansari, M. Garabedian, E. Tse, J. Wang, X. Shaw, K.L. Gaspar, H.B. Candotti, F. Kohn, D.B. info:eu-repo/semantics/article article 2020-10 Biology of blood and marrow transplantation, vol. 26, no. 10, pp. 1819-1827 info:eu-repo/semantics/altIdentifier/eissn/1523-6536 urn:issn:1083-8791 <![CDATA[The pharmacokinetics of low-dose busulfan (BU) were investigated as a nonmyeloablative conditioning regimen for autologous gene therapy (GT) in pediatric subjects with adenosine deaminase-deficient severe combined immunodeficiency disease (ADA SCID). In 3 successive clinical trials, which included either γ-retroviral (γ-RV) or lentiviral (LV) vectors, subjects were conditioned with BU using different dosing nomograms. The first cohort received BU doses based on body surface area (BSA), the second cohort received doses based on actual body weight (ABW), and in the third cohort, therapeutic drug monitoring (TDM) was used to target a specific area under the concentration-time curve (AUC). Neither BSA-based nor ABW-based dosing achieved a consistent cumulative BU AUC; in contrast, TDM-based dosing led to more consistent AUC. BU clearance increased as subject age increased from birth to 18 months. However, weight and age alone were insufficient to accurately predict the dose that would consistently achieve a target AUC. Furthermore, various clinical, laboratory, and genetic factors (eg, genotypes for glutathione-S-transferase isozymes known to participate in BU metabolism) were analyzed, but no single finding predicted subjects with rapid versus slow clearance. Analysis of BU AUC and the postengraftment vector copy number (VCN) in granulocytes, a surrogate marker of the level of engrafted gene-modified hematopoietic stem and progenitor cells (HSPCs), demonstrated gene marking at levels sufficient for therapeutic benefit in the subjects who had achieved the target BU AUC. Although many factors determine the ultimate engraftment following GT, this work demonstrates that the BU AUC correlated with the eventual level of engrafted gene-modified HSPCs within a vector group (γ-RV versus LV), with significantly higher levels of granulocyte VCN in the recipients of LV-modified grafts compared to recipients of γ-RV-transduced grafts. Taken together, these findings provide insight into low-dose BU pharmacokinetics in the unique setting of autologous GT for ADA SCID, and these dosing principles may be applied to future GT trials using low-dose BU to open the bone marrow niche

    At the nexus of three kingdoms: the genome of the mycorrhizal fungus Gigaspora margarita provides insights into plant, endobacterial and fungal interactions.

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    As members of the plant microbiota, arbuscular mycorrhizal fungi (AMF, Glomeromycotina) symbiotically colonize plant roots. AMF also possess their own microbiota, hosting some uncultivable endobacteria. Ongoing research has revealed the genetics underlying plant responses to colonization by AMF, but the fungal side of the relationship remains in the dark. Here, we sequenced the genome of Gigaspora margarita, a member of the Gigasporaceae in an early diverging group of the Glomeromycotina. In contrast to other AMF, G. margarita may host distinct endobacterial populations and possesses the largest fungal genome so far annotated (773.104 Mbp), with more than 64% transposable elements. Other unique traits of the G. margarita genome include the expansion of genes for inorganic phosphate metabolism, the presence of genes for production of secondary metabolites and a considerable number of potential horizontal gene transfer events. The sequencing of G. margarita genome reveals the importance of its immune system, shedding light on the evolutionary pathways that allowed early diverging fungi to interact with both plants and bacteria

    Myths and lessons of liberal intervention: The British campaign for the abolition of the Atlantic slave trade to Brazil

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    This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2012 Martinus NijhoffThis article takes issue with recent references to the British nineteenth century campaign for the abolition of the trans-Atlantic slave trade to Brazil that serve to bolster interventionist or imperialist agendas. In particular, such accounts reproduce two and a half myths about the campaign: that it can serve as a model for the present age; that the success of the campaign can be explained through the actions of the intervening party alone (with a corresponding neglect of those of the ‘target’ state); and the half-myth that the campaign’s success was due to military action (at the expense of institutional (legal) and normative factors and the capacity of the target state). I argue instead that this case – and interventions more generally – would benefit from an analysis that considers the role of force in relation to a series of residual institutional and cultural constraints within the liberal state and to political conditions in the target state. In light of the complexities and contingencies that these factors present the underlying lesson is that military force should be used sparingly, if at all

    Développer le pouvoir d’apprendre : pour une critique de la transmission en éducation et en formation

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    Researchers of the TAO Research Programs and the Centre de Recherche sur le Travail et le Développement (Research Center on Work and Development) at the Conservatoire National des Arts et Métiers, Paris, illustrate critical reflections on education and training. These collected papers, stemming from different disciplinary frameworks and approaches, share the theoretical work and the epistemological orientation. With particular reference to the teachings of Weber, Vygotskij and Bakhtin, they focus on learning, conceived as social action, on the development of learning activity, and on the development of thought in professional dialogues. Along this line, the idea according to which education and training realize the “transmission” of knowledge, capacity, competence, values, practices, gestures, etc., is questioned and discussed

    Fungal ecological strategies reflected in gene transcription - a case study of two litter decomposers.

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    Microbial communities interplay with their environment through their functional traits that can be a response or an effect on the environment. Here, we explore how a functional trait-the decomposition of organic matter, can be addressed based on genetic markers and how the expression of these markers reflect ecological strategies of two fungal litter decomposer Gymnopus androsaceus and Chalara longipes. We sequenced the genomes of these two fungi, as well as their transcriptomes at different steps of Pinus sylvestris needles decomposition in microcosms. Our results highlighted that if the gene content of the two species could indicate similar potential decomposition abilities, the expression levels of specific gene families belonging to the glycoside hydrolase category reflected contrasting ecological strategies. Actually, C. longipes, the weaker decomposer in this experiment, turned out to have a high content of genes involved in cell wall polysaccharides decomposition but low expression levels, reflecting a versatile ecology compare to the more competitive G. androsaceus with high expression levels of keystone functional genes. Thus, we established that sequential expression of genes coding for different components of the decomposer machinery indicated adaptation to chemical changes in the substrate as decomposition progressed

    Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region

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    In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity
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