Free exopolysaccharide from Mycoplasma mycoides subsp. mycoides possesses anti-inflammatory properties

In this study we explored the immunomodulatory properties of highly purified free galactan, the soluble exopolysaccharide secreted by Mycoplasma mycoides subsp. mycoides (Mmm). Galactan was shown to bind to TLR2 but not TLR4 using HEK293 reporter cells and to induce the production of the anti-inflammatory cytokine IL-10 in bovine macrophages, whereas low IL-12p40 and no TNF-α, both pro-inflammatory cytokines, were induced in these cells. In addition, pre-treatment of macrophages with galactan substantially reduced lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines TNF- and IL-12p40 while increasing LPS-induced secretion of immunosuppressive IL-10. Also, galactan did not activate naïve lymphocytes and induced only low production of the Th1 cytokine IFN-γ in Mmm-experienced lymphocytes. Finally, galactan triggered weak recall proliferation of CD4+ T lymphocytes from contagious bovine pleuropneumonia-infected animals despite having a positive effect on the expression of co-stimulatory molecules on macrophages. All together, these results suggest that galactan possesses anti-inflammatory properties and potentially provides Mmm with a mechanism to evade host innate and adaptive cell-mediated immune responses. (Résumé d'auteur

Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses

Nucleic acids are used in many therapeutic modalities, including gene therapy, but their ability to trigger host immune responses in vivo can lead to decreased safety and efficacy. In the case of adeno-associated viral (AAV) vectors, studies have shown that the genome of the vector activates Toll-like receptor 9 (TLR9), a pattern recognition receptor that senses foreign DNA. Here, we engineered AAV vectors to be intrinsically less immunogenic by incorporating short DNA oligonucleotides that antagonize TLR9 activation directly into the vector genome. The engineered vectors elicited markedly reduced innate immune and T cell responses and enhanced gene expression in clinically relevant mouse and pig models across different tissues, including liver, muscle, and retina. Subretinal administration of higher-dose AAV in pigs resulted in photoreceptor pathology with microglia and T cell infiltration. These adverse findings were avoided in the contralateral eyes of the same animals that were injected with the engineered vectors. However, intravitreal injection of higher-dose AAV in macaques, a more immunogenic route of administration, showed that the engineered vector delayed but did not prevent clinical uveitis, suggesting that other immune factors in addition to TLR9 may contribute to intraocular inflammation in this model. Our results demonstrate that linking specific immunomodulatory noncoding sequences to much longer therapeutic nucleic acids can “cloak” the vector from inducing unwanted immune responses in multiple, but not all, models. This “coupled immunomodulation” strategy may widen the therapeutic window for AAV therapies as well as other DNA-based gene transfer methods

Editors’ Introduction: An Overview of the Educational Administration and Leadership Curriculum: Traditions of Islamic Educational Administration and Leadership in Higher Education

This chapter provides an overview of several topics relevant to constructing an approach to teaching educational administration and leadership in Muslim countries. First, it places the topic in the context of the changing nature and critiques of the field that argue for a greater internationalisation to both resist some of the negative aspects of globalisation and to represent countries’ traditions in the professional curriculum. Then, it identifies literature that presents the underlying principles and values of Islamic education that guide curriculum and pedagogy and shape its administration and leadership including the Qur’an and Sunnah and the classical educational literature which focuses on aims, values and goals of education as well as character development upon which a ‘good’ society is built. This is followed by a section on the Islamic administration and leadership traditions that are relevant to education, including the values of educational organisations and how they should be administered, identifying literature on the distinctive Islamic traditions of leadership and administrator education and training as it applies to education from the establishment of Islam and early classical scholars and senior administrators in the medieval period who laid a strong foundation for a highly sophisticated preparation and practice of administration in philosophical writings and the Mirrors of Princes writings, and subsequent authors who have built upon it up to the contemporary period. The final section provides an overview of the chapters in this collection

Révision des autorisations de prélèvements d'eau pour l'irrigation sur le bassin Adour-Garonne. Rapport de phase II : Analyse de mesures d'accompagnement

Ce rapport présente la méthode mise en oeuvre pour évaluer l'impact économique associé à la réduction du volume prélevable par l'agriculture. La méthode est alors appliquée à 6 bassins pilotes et des mesures d'accompagnement permettant d'atténuer cet impact économique sont identifiées

Révision des autorisations de prélèvement d'eau pour l'irrigation sur le bassin Adour-Garonne Synthèse

Ce rapport présente une synthèse des trois phases de l'étude sur la révision des autorisations de prélèvement d'eau pour l'irrigation sur le bassin Adour Garonne: i) EVALUATION TERRITORIALISEE DE L'IMPACT SUR L'ECONOMIE AGRICOLE; ii) PROPOSITION DE MESURES D'ACCOMPAGNEMENT ET PASSAGE AU PV déf et iii) ESSAI D'EXTRAPOLATION A L'ECHELLE DU BASSIN ADOUR-GARONN

Révision des autorisations de prèlevement d'eau pour l'irrigation sur le bassin Adour-Garonne. Rapport de phase III : Extrapolation à l'ensemble du bassin Adour-Garonne et enseignements

Ce rapport présente la méthode mise en oeuvre pour évaluer, extrapoler les résultats d'évaluation de l'impact économique associé à la réduction du volume prélevable par l'agriculture obtenus au niveau de petits bassins versants à l'ensemble du bassin Adour Garonne

Révision des autorisations de prélèvement d'eau pour l'irrigation sur la bassin ADOUR-GARONNE. Rapport de phase I : Evaluation territorialisée de l'impact sur l'économie agricole

Ce rapport présente la méthode de mise en oeuvre pour évaluer l'impact économique associé à la réduction du volume prélevable par l'agriculture. La méthode est alors appliquée à 6 bassins pilotes