Multisubstrate adduct inhibitors: Drug design and biological tools

In drug discovery, different methods exist to create new inhibitors possessing satisfactory biological activity. The multisubstrate adduct inhibitor (MAI) approach is one of these methods, which consists of a covalent combination between analogs of the substrate and the cofactor or of the multiple substrates used by the target enzyme. Adopted as the first line of investigation for many enzymes, this method has brought insights into the enzymatic mechanism, structure, and inhibitory requirements. In this review, the MAI approach, applied to different classes of enzyme, is reported from the point of view of biological activity.

Aligning conservation priorities across taxa in Madagascar with high-resolution planning tools

Globally, priority areas for biodiversity are relatively well known, yet few detailed plans exist to direct conservation action within them, despite urgent need. Madagascar, like other globally recognized biodiversity hot spots, has complex spatial patterns of endemism that differ among taxonomic groups, creating challenges for the selection of within-country priorities. We show, in an analysis of wide taxonomic and geographic breadth and high spatial resolution, that multitaxonomic rather than single-taxon approaches are critical for identifying areas likely to promote the persistence of most species. Our conservation prioritization, facilitated by newly available techniques, identifies optimal expansion sites for the Madagascar government's current goal of tripling the land area under protection. Our findings further suggest that high-resolution multitaxonomic approaches to prioritization may be necessary to ensure protection for biodiversity in other global hot spots.

Enforcing Member State Compliance with EU Environmental Law: A Critical Evaulation of the Use of Financial Penalties

The 1993 Treaty on European Union finally closed a legal vacuum in
EU law, by giving the Court the power to impose financial penalties to
enforce compliance with its judgments. Today, this power is found
within Article 260(2) of the Treaty on the Functioning of the
European Union. Drawing upon case law, this article examines the
role that the Court’s enforcement powers have played in relation to
EU environmental law. It argues that EU law has yet to make full use
of their potential. The article commences with the Commission and
questions whether it has sufficient resources to carry out its functions
under Article 260(2). The article also examines the ongoing problem of
Member State delay in complying with Court judgments and the
weight given to environmental considerations in the Court’s decision
making on financial penalties. The article concludes by examining the
implications of the Lisbon Treaty.