Indoleamine 2,3-dioxygenesae-1 (IDO-1) catalyses the initial, rate-limiting step in tryptophan metabolism, thereby regulating tryptophan availability and the formation of downstream metabolites, including picolinic and quinolinic acid. We found that Mycobacterium tuberculosis infection induced marked upregulation of IDO-1 expression in both human and murine macrophages in vitro and in the lungs of mice following aerosol challenge with M. tuberculosis. The absence of IDO-1 in dendritic cells enhanced the activation of mycobacteria-specific T cells in vitro. Interestingly, IDO-1-deficiency during M. tuberculosis infection in mice was not associated with altered mycobacteria-specific T cell responses in vivo. The bacterial burden of infected organs, pulmonary inflammatory responses, and survival were also comparable in M. tuberculosis-infected IDO-1 deficient and wild type animals. Tryptophan is metabolised into either picolinic acid or quinolinic acid, but only picolinic acid inhibited the growth of M. tuberculosis in vitro. By contrast macrophages infected with pathogenic mycobacteria, produced quinolinic, rather than picolinic acid, which did not reduce M. tuberculosis growth in vitro. Therefore, although M. tuberculosis induces robust expression of IDO-1 and activation of tryptophan metabolism, IDO-1-deficiency fails to impact on the immune control and the outcome of the infection in the mouse model of tuberculosis.
Party autonomy is becoming more prevalent in substantive family law, and therefore private international law should find a method of incorporating party autonomy into family law. This should be done in a way that takes account of the specific characteristics of family life. Currently the EU Regulations take a disjointed and incoherent approach to party autonomy in family law, and do not consider specific issues relating to the family. There is no clear explanation of why this is and it appears to be related to the fragmented development of the EU family law instruments. This inconsistency is not only apparent across the instruments but also within the instruments, suggesting that the discrepancies are not context-specific. This article argues that it is possible to have a consistent approach to party autonomy across all areas of family law while catering for family specific issues. A consistent approach will allow families to resolve their disputes within one legal system, rather than the more complicated situation which confronts some families due to the fragmentation of jurisdiction required by the current legal rules.
Article 11(6)-(8) of the Brussels IIa Regulation for the courts of the habitual residence to insist on the return of a child that has been abducted after a court in the State where the child was abducted to has refused to return the child on the basis of one of the exceptions to the duty to return provided for in Article 13 of the Hague Child Abduction Convention 1980. It will reveal how infrequently used and largely ineffective the Article 11(6)- (8) system is and will make proposals for law reform in the current revision of the Brussels IIa Regulation.Keywords: international family law; child abduction; intra-EU cases; Brussels IIa Regulation; Hague Child Abduction Convention; gender of abducting parent; right of a child to be heard; right of parents to be heard; grave risk of harm; child's objections to return; consent; acquiescence.
This article examines how the European Court of Human Rights has clarified its jurisprudence on how the 1980 Hague Child Abduction Convention Article 13 exceptions are to be applied in a manner that is consistent with Article 8 of the European Convention on Human Rights. It also analyses recent case law of the European Court of Human Rights on how the courts in the EU are to handle child abduction cases where the courts of the habitual residence have made use of their power under Article 11 of Brussels IIa.
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