Road expansion and persistence in forests of the Congo Basin

ISSN:2398-962

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

Long-Term Vegetation Change in Central Africa: The Need for an Integrated Management Framework for Forests and Savannas

peer reviewedTropical forests and savannas are the main biomes in sub-Saharan Africa, covering most of the continent. Collectively they offer important habitat for biodiversity and provide multiple ecosystem services. Considering their global importance and the multiple sustainability challenges they face in the era of the Anthropocene, this chapter undertakes a comprehensive analysis of the past, present, and future vegetation patterns in central African forests and savannas. Past changes in climate, vegetation, land use, and human activity have affected the distribution of forests and savannas across central Africa. Currently, forests form a continuous block across the wet and moist areas of central Africa, and are characterized by high tree cover (>90% tree cover). Savannas and woodlands have lower tree cover (<40% tree cover), are found in drier sites in the north and south of the region, and are maintained by frequent fires. Recent tree cover loss (2000–2015) has been more important for forests than for savannas, which, however, reportedly experienced woody encroachment. Future cropland expansion is expected to have a strong impact on savannas, while the extent of climatic impacts depends on the actual scenario. We finally identify some of the policy implications for restoring ecosystems, expanding protected areas, and designing sustainable ecosystem management approaches in the region

The acidic domain of cytochrome c₁ in paracoccus denitrificans, analogous to the acidic subunits in eukaryotic bc₁ complexes, is not involved in the electron transfer reaction to its native substrate cytochrome c(552).

The cytochrome bc(1) complex is a key component in several respiratory pathways. One of the characteristics of the eukaryotic complex is the presence of a small acidic subunit, which is thought to guide the interaction of the complex with its electron acceptor and facilitate electron transfer. Paracoccus denitrificans represents the only example of a prokaryotic organism in which a highly acidic domain is covalently fused to the cytochrome c(1) subunit. In this work, a deletion variant lacking this acidic domain has been produced and purified by affinity chromatography. The complex is fully intact as shown by its X-ray structure, and is a dimer (Kleinschroth et al., subm.) compared to the tetrameric (dimer-of-dimer) state of the wild-type. The variant complex is studied by steady-state kinetics and flash photolysis, showing wild type turnover and a virtually identical interaction with its substrate cytochrome c(552). 2011 Elsevier B.V. All rights reserved

L’aménagement forestier au Congo engendre-t-il plus de déforestation ?

Un article publié dans Land Use Policy début 2016 arrive à la conclusion a priori étonnante que la déforestation serait, au Congo, plus élevée dans les concessions forestières avec des plans d’aménagement que dans celles qui n’en ont pas. L’analyse d’évaluation d’impact qui a conduit ces chercheurs à un tel résultat se base sur un appariement de parcelles sélectionnées aléatoirement dans des concessions avec et sans plans d’aménagement. Ces chercheurs indiquent que le réseau de routes forestières plus développé dans les concessions aménagées serait un des facteurs explicatifs. L’autre facteur serait le développement local lié aux cahiers des charges des plans d’aménagement, lequel conduirait à une augmentation de la population dans ces concessions et à une déforestation accrue. Notre groupe d’une vingtaine de chercheurs connaissant bien la problématique de l’aménagement forestier en Afrique centrale s’est penché à son tour sur cette question et a analysé la déforestation au niveau des concessions sur le même intervalle de temps. Nos résultats montrent, cette fois, que la déforestation est moins importante dans les concessions avec un plan d’aménagement que dans les autres. Et si l’on compare à production égale la déforestation dans des concessions avec et sans plan d’aménagement, il apparaît que les UFA aménagées sont environ deux fois plus « efficaces », c’est-à-dire qu’on observe deux fois moins de perte de couvert forestier par mètre-cube produit. Nous en concluons qu’il est nécessaire d’analyser précisément la dynamique des différents facteurs de déforestation, et éviter d’imputer mécaniquement à l’aménagement forestier un rôle excessif dans l’évolution dans un sens ou dans l’autre du taux de déboisement. Enfin, toute évaluation doit rappeler que les effets de l’aménagement forestier doivent être mesurés sur le long terme : l’objectif de l’aménagement est de permettre une mise en valeur forestière durable, en conservant l’essentiel du capital productif pour éviter, autant que possible, la conversion à d’autres usages après les cycles de coupe initiaux