La végétation du mont Ventoux au cours des derniers millénaires.

Grâce à l'analyse des charbons de bois récoltés dans des avens du versant nord ou extraits des sols du mont Ventoux, il est possible d'avoir un aperçu de la végétation qu'abritait ce massif depuis environ 4000 ans. Ainsi, la calotte sommitale était colonisée par des peuplements mixtes de sapin, d'érable à feuille d'obier et de pins. La chênaie caducifoliée occupait les régions de plus basse altitude. Ces peuplements ont progressivement été détruits par, entre autre, les activités pastorales à partir du Néolithique, pour aboutir au déboisement presque total du XIXe siècle

Global Analysis of Protein N-Myristoylation and Exploration of N-Myristoyltransferase as a Drug Target in the Neglected Human Pathogen Leishmania donovani

N-Myristoyltransferase (NMT) modulates protein function through the attachment of the lipid myristate to the N terminus of target proteins, and is a promising drug target in eukaryotic parasites such as Leishmania donovani. Only a small number of NMT substrates have been characterized in Leishmania, and a global picture of N-myristoylation is lacking. Here, we use metabolic tagging with an alkyne-functionalized myristic acid mimetic in live parasites followed by downstream click chemistry and analysis to identify lipidated proteins in both the promastigote (extracellular) and amastigote (intracellular) life stages. Quantitative chemical proteomics is used to profile target engagement by NMT inhibitors, and to define the complement of N-myristoylated proteins. Our results provide new insight into the multiple pathways modulated by NMT and the pleiotropic effects of NMT inhibition. This work constitutes the first global experimental analysis of protein lipidation in Leishmania, and reveals the extent of NMT-related biology yet to be explored for this neglected human pathogen

Targeting N-myristoylation for therapy of B-cell lymphomas

N-myristoyltransferases (NMTs) target many signaling proteins to membranes. Here the authors show an NMT inhibitor named PCLX-001 selectively kills lymphoma cells by shutting down their main survival signaling pathway and offers an additional treatment strategy for lymphoma patients

Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus

Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharmacological inhibition of host-cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity. The identification of cooperative binding between weak-binding fragments led to rapid inhibitor optimization through fragment reconstruction, structure-guided fragment linking and conformational control over linker geometry. We show that inhibition of the co-translational myristoylation of a specific virus-encoded protein (VP0) by IMP-1088 potently blocks a key step in viral capsid assembly, to deliver a low nanomolar antiviral activity against multiple RV strains, poliovirus and foot and-mouth disease virus, and protection of cells against virus-induced killing, highlighting the potential of host myristoylation as a drug target in picornaviral infections

Seismic images and magnetic signature of the Late Jurassic to Early Cretaceous Africa-Eurasia plate boundary off SW Iberia

Over the last two decades numerous studies have investigated the structure of the west Iberia continental margin, a non-volcanic margin characterized by a broad continent–ocean transition (COT). However, the nature and structure of the crust of the segment of the margin off SW Iberia is still poorly understood, because of sparse geophysical and geological data coverage. Here we present a 275-km-long multichannel seismic reflection (MCS) profile, line AR01, acquired in E–W direction across the Horseshoe Abyssal Plain, to partially fill the gap of information along the SW Iberia margin. Line AR01 runs across the inferred plate boundary between the Iberian and the African plates during the opening of the Central Atlantic ocean. The boundary separates crust formed during or soon after continental rifting of the SW Iberian margin from normal seafloor spreading oceanic crust of the Central Atlantic ocean. Line AR01 has been processed and pre-stack depth migrated to show the tectonic structure of the crust across the palaeo plate boundary. This boundary is characterized by a 30–40-km-wide zone of large basements highs related to landward-dipping reflections, which penetrate to depths of 13–15 km, and it marks a change in the character of the basement structure and relief from east to west. In this study, we have used pre-stack depth migrated images, the velocity model of line AR01 and magnetic data available in the area to show that the change in basement structure occurs across the fossil plate boundary, separating African oceanic crust of the M series (M21–M16) to the west from the transitional crust of the Iberian margin to the east

Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation

A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. Although these regulatory modules are physicochemically distinct, they share an evolutionary plasticity that has facilitated a rapid growth of their use and resulted in their ubiquity in complex organisms. The ease of motif acquisition simplifies access to basal housekeeping functions, facilitates the co-regulation of multiple biomolecules allowing them to respond in a coordinated manner to changes in the cell state, and supports the integration of multiple signals for combinatorial decision-making. Consequently, motifs are indispensable for temporal, spatial, conditional and basal regulation at the transcriptional, post-transcriptional and post-translational level. In this review, we highlight that many of the key regulatory pathways of the cell are recruited by motifs and that the ease of motif acquisition has resulted in large networks of co-regulated biomolecules. We discuss how co-operativity allows simple static motifs to perform the conditional regulation that underlies decision-making in higher eukaryotic biological systems. We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. Finally, we contrast the regulatory properties of protein motifs and the regulatory elements of DNA and (pre-)mRNAs, advocating that co-regulation, co-operativity, and motif-driven regulatory programs are common mechanisms that emerge from the use of simple, evolutionarily plastic regulatory modules

Contribution \ue0 l\u27\ue9tude morpho-anatomique, biom\ue9trique et biochimique des caryopses de Gramin\ue9es du genre Stipagrostis Nees

Volume: 16Start Page: 283End Page: 29