Botany, Genetics and Ethnobotany: A Crossed Investigation on the Elusive Tapir's Diet in French Guiana

While the populations of large herbivores are being depleted in many tropical rainforests, the importance of their trophic role in the ecological functioning and biodiversity of these ecosystems is still not well evaluated. This is due to the outstanding plant diversity that they feed upon and the inherent difficulties involved in observing their elusive behaviour. Classically, the diet of elusive tropical herbivores is studied through the observation of browsing signs and macroscopic analysis of faeces or stomach contents. In this study, we illustrate that the original coupling of classic methods with genetic and ethnobotanical approaches yields information both about the diet diversity, the foraging modalities and the potential impact on vegetation of the largest terrestrial mammal of Amazonia, the lowland tapir. The study was conducted in the Guianan shield, where the ecology of tapirs has been less investigated. We identified 92 new species, 51 new genera and 13 new families of plants eaten by tapirs. We discuss the relative contribution of our different approaches, notably the contribution of genetic barcoding, used for the first time to investigate the diet of a large tropical mammal, and how local traditional ecological knowledge is accredited and valuable for research on the ecology of elusive animals

Diastereoselective Synthesis of Novel Aza-diketopiperazines via a Domino Cyclohydrocarbonylation/Addition Process

Herein, we report an unprecedented, short and diastereo-selective synthesis of newly reported aza-diketopiperazine (aza-DKP) scaffolds starting from amino acids. The strategy is based on a Rh(I)-catalyzed hydroformylative cyclohydrocarbonylation of allyl-substituted aza-DKP, followed by a diastereoselective functionalization of the platform. This methodology allows the synthesis of novel bicyclic and tricyclic aza-DKP scaffolds incorporating six- or seven-membered rings, with potential applications in medicinal chemistry

A step-economical multicomponent synthesis of 3D-shaped aza-diketopiperazines and their drug-like chemical space analysis

A rapid and atom economical multicomponent synthesis of complex aza-diketopiperazines (aza-DKPs) driven by Rh(I)-catalyzed hydroformylation of alkenylsemicarbazides is described. Combined with catalytic amounts of acid and the presence of nucleophilic species, this unprecedented multicomponent reaction (MCR) enabled the formation of six bonds and a controlled stereocenter from simple substrates. The efficacy of the strategy was demonstrated with a series of various allyl-substituted semicarbazides and nucleophiles leading to the preparation of 3D-shaped bicyclic aza-DKPs. Moreover, an analysis of their 3D molecular descriptors and “drug-likeness” properties highlights not only their originality in the chemical space of aza-heterocycles but also their great potential for medicinal chemistry

Near-Infrared Laser Adjuvant for Influenza Vaccine

Safe and effective immunologic adjuvants are often essential for vaccines. However, the choice of adjuvant for licensed vaccines is limited, especially for those that are administered intradermally. We show that non-tissue damaging, near-infrared (NIR) laser light given in short exposures to small areas of skin, without the use of additional chemical or biological agents, significantly increases immune responses to intradermal influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We show that NIR laser treatment induces the expression of specific chemokines in the skin resulting in recruitment and activation of dendritic cells and is safe to use in both mice and humans. The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use, potentially broadly applicable and clinically feasible approach to enhancing vaccine efficacy as an alternative to chemical and biological adjuvants

Limitations in a frataxin knockdown cell model for Friedreich ataxia in a high-throughput drug screen

<p>Abstract</p> <p>Background</p> <p>Pharmacological high-throughput screening (HTS) represents a powerful strategy for drug discovery in genetic diseases, particularly when the full spectrum of pathological dysfunctions remains unclear, such as in Friedreich ataxia (FRDA). FRDA, the most common recessive ataxia, results from a generalized deficiency of mitochondrial and cytosolic iron-sulfur cluster (ISC) proteins activity, due to a partial loss of frataxin function, a mitochondrial protein proposed to function as an iron-chaperone for ISC biosynthesis. In the absence of measurable catalytic function for frataxin, a cell-based assay is required for HTS assay.</p> <p>Methods</p> <p>Using a targeted ribozyme strategy in murine fibroblasts, we have developed a cellular model with strongly reduced levels of frataxin. We have used this model to screen the Prestwick Chemical Library, a collection of one thousand off-patent drugs, for potential molecules for FRDA.</p> <p>Results</p> <p>The frataxin deficient cell lines exhibit a proliferation defect, associated with an ISC enzyme deficit. Using the growth defect as end-point criteria, we screened the Prestwick Chemical Library. However no molecule presented a significant and reproducible effect on the proliferation rate of frataxin deficient cells. Moreover over numerous passages, the antisense ribozyme fibroblast cell lines revealed an increase in frataxin residual level associated with the normalization of ISC enzyme activities. However, the ribozyme cell lines and FRDA patient cells presented an increase in Mthfd2 transcript, a mitochondrial enzyme that was previously shown to be upregulated at very early stages of the pathogenesis in the cardiac mouse model.</p> <p>Conclusion</p> <p>Although no active hit has been identified, the present study demonstrates the feasibility of using a cell-based approach to HTS for FRDA. Furthermore, it highlights the difficulty in the development of a stable frataxin-deficient cell model, an essential condition for productive HTS in the future.</p

Recherche de facteurs circulants impliqués dans la cardioprotection ischémique à distance par une approche protéomique

Early reperfusion of occluded coronary artery significantly improves outcomes in patients with myocardial infarction. Unfortunately, this reperfusion can be the cause of irreversible myocardial damage, called reperfusion injuries. Remote ischemic preconditioning (RIPreC) is a simple and attractive strategy to reduce these myocardial injuries. Despite convincing evidence of the critical role played by circulating humoral mediators in RIPreC-induced cardioprotection, their actual identities remain unknown. Therefore, in this study we aimed to identify RIPreC-induced humoral mediators. In the first part of the study, we performed a proteomic analysis on rat plasma using SELDI-TOF-MStechnique. We thus related RIPreC to highly proteomic modulation. Overall, the proteins identified were inaccordance with a protective role of RIPreC. Some ofthem play a role in anti-oxidative stress, tissue repair, and anti-inflammatory process. In particular, apolipoprotein A-I (ApoA-I), significantly increased in rat plasma following RIPreC stimulus, has strong cytoprotective effects against ischemia-reperfusioninjury. It could then be a potential blood-borne factor of RIPreC. In the second part of the study we tried to demonstrate the cardioprotective properties of ApoA-I ina myocardial infarction model in vivo. ApoA-I injected before myocardial ischemia in rats significantly reduced myocardial infarct size. Taken together, our data indicated that RIPreC induces significant modifications of plasmatic proteome in vivo, notably ApoA-I increase.Furthermore, ApoA-I injection before myocardial ischemia-reperfusion was able to recapitulate RIPreC induced cardioprotection. ApoA-I may then be aprotective blood-borne factor involved in the RIPreC mechanism.La désobstruction coronaire précoce améliore considérablement le pronostic des patients atteints d’infarctus du myocarde, mais elle est à l’origine de lésions myocardiques irréversibles. Une technique simple et efficace pour lutter contre ces lésions de reperfusion est le préconditionnement ischémique à distance (RIPreC). De nombreuses études suggèrent un rôle majeur des facteurs humoraux transportés par la circulation, dans la cardioprotection induite par le RIPreC, mais leurs identités restent encore inconnues.L’objectif de notre travail était donc d’identifier un ou des facteurs circulants du RIPreC. Dans la première partie de l’étude nous avons réalisé une analyse protéomique SELDI-TOF-MS sur des plasmas de rats. Nous avons ainsi démontré que le RIPreC était responsable de nombreuses modifications du protéome plasmatique.Dans l’ensemble les protéines identifiées étaient cohérentes avec un rôle protecteur du RIPreC.Certaines sont en effet impliquées dans la réponse antioxydative, la réparation tissulaire ou encore l’anti-inflammation.Les données de la littérature rapportant des propriétés de cytoprotection dans un contexte d'ischémie-reperfusion, l’apolipoprotéine A-I (ApoA-I),augmentée suite au RIPreC, était une bonne candidate pour être un facteur circulant du RIPreC. La seconde partie du projet consistait à valider in vivo l’action bénéfique de cette protéine, dans un modèle d’infarctus du myocarde. L’ApoA-I, injectée avant l’ischémie myocardique, était capable de réduire la taille de l’infarctus. Nous avons ainsi confirmé que le RIPreC était responsable de modifications significatives du protéome plasmatique in vivo, et en particulier de l’augmentation de l’ApoA-I. Cette protéine était capable d’induire une cardioprotection lorsqu’elle est injectée avant l’ischémie myocardique. L’ApoA-I pourrait donc être un facteur circulant impliqué dans le RIPreC

Morphological criteria to identify faecal pellets of sympatric ungulates in West African savanna and estimates of associated error

Les études indirectes peuvent compléter de façon intéressante les comptages directs classiquement utilisés pour le suivi des populations d'ongulés et pour mieux appréhender la structure et le fonctionnement des riches communautés d'ongulés des savanes africaines. Toutefois, dans les cas où plusieurs espèces coexistent, l'identification de leurs crottes peut s'avérer difficile. Cette étude propose des critères simples pour distinguer sur le terrain les crottes de dix espèces d'ongulés d'Afrique de l'Ouest. Les moyennes de différentes mesures sur les tas de crottes ont été analysées à l'aide d'une analyse discriminante afin d'identifier les meilleurs critères de distinction entre les espèces. Le diamètre moyen ainsi que la profondeur moyenne de la cupule des crottes d'un même tas, respectivement associés au premier et au second axe discriminants, se sont révélées les meilleures variables pour séparer les espèces. Les tas de crottes de six espèces parmi les dix étudiées ont pu être identifiées avec une faible erreur de classification. Néanmoins, aucun critère morphologique simple n'a pu être identifié pour distinguer les crottes du bubale de celles du damalisque, et les crottes du guib harnaché de celles du rédunca. Une fois que les tas de crottes sont identifiés, leur densité et leur distribution spatiale peuvent fournir une information intéressante sur l'utilisation de l'espace et des habitats par des espèces sympatriques pour des périodes données. (Résumé d'auteur

Data from: Unveiling the diet of elusive rainforest herbivores in next generation sequencing era? The tapir as a case study

Characterizing the trophic relationships between large herbivores and the outstanding plant diversity in rainforest is a major challenge because of their elusiveness. This is crucial to understand the role of these herbivores in the functioning of the rainforest ecosystems. We tested a non-invasive approach based on the high-throughput sequencing of environmental samples using small plant plastid sequences (the trnL P6 loop) and ribosomal ITS1 primers, referred to as DNA metabarcoding, to investigate the diet of the largest neotropical herbivore, the lowland tapir. Sequencing was performed on plant DNA extracted from tapir faeces collected at the Nouragues station, a protected area of French Guiana. In spite of a limited sampling, our approach reliably provided information about the lowland tapir's diet at this site. Indeed, 95.1% and 74.4% of the plant families and genera identified thanks to the trnL P6 loop, respectively, matched with taxa already known to be consumed by tapirs. With this approach we were able to show that two families and eight new genera are also consumed by the lowland tapir. The taxonomic resolution of this method is limited to the plant family and genera. Complementary barcodes, such as a small portion of ITS1, can be used to efficiently narrow identifications down to the species in some problematic families. We will discuss the remaining limitations of this approach and how useful it is at this stage to unravel the diet of elusive rainforest herbivores and better understand their role as engineers of the ecosystem

Comparative Study of the Synthesis and Structural and Physicochemical Properties of Diketopiperazines vs Aza-diketopiperazines

International audienc