Lead in the marine environment: concentrations and effects on invertebrates

Lead (Pb) is a non-essential metal naturally present in the environment and often complexed with other elements (e.g., copper, selenium, zinc). This metal has been used since ancient Egypt and its extraction has grown in the last centuries. It has been used until recently as a fuel additive and is currently used in the production of vehicle batteries, paint, and plumbing. Marine ecosystems are sinks of terrestrial contaminations; consequently, lead is detected in oceans and seas. Furthermore, lead is not biodegradable. It remains in soil, atmosphere, and water inducing multiple negative impacts on marine invertebrates (key species in trophic chain) disturbing ecological ecosystems. This review established our knowledge on lead accumulation and its effects on marine invertebrates (Annelida, Cnidaria, Crustacea, Echinodermata, and Mollusca). Lead may affect different stages of development from fertilization to larval development and can also lead to disturbance in reproduction and mortality. Furthermore, we discussed changes in the seawater chemistry due to Ocean Acidification, which can affect the solubility, speciation, and distribution of the lead, increasing potentially its toxicity to marine invertebrates

Discovery of Inhibitors of Leishmania β-1,2-Mannosyltransferases Using a Click-Chemistry-Derived Guanosine Monophosphate Library

Leishmania spp. are a medically important group of protozoan parasites that synthesize a novel intracellular carbohydrate reserve polymer termed mannogen. Mannogen is a soluble homopolymer of β-1,2-linked mannose residues that accumulates in the major pathogenic stages in the sandfly vector and mammalian host. While several steps in mannogen biosynthesis have been defined, none of the enzymes have been isolated or characterized. We report the development of a simple assay for the GDP-mannose–dependent β-1,2-mannosyltransferases involved in mannogen synthesis. This assay utilizes octyl α-d-mannopyranoside to prime the formation of short mannogen oligomers up to 5 mannose residues. This assay was used to screen a focussed library of 44 GMP-triazole adducts for inhibitors. Several compounds provided effective inhibition of mannogen β-1,2-mannosyltransferases in a cell-free membrane preparation. This assay and inhibitor compounds will be useful for dissecting the role of different mannosyltransferases in regulating de novo biosynthesis and elongation reactions in mannogen metabolism

Approachability in Stackelberg Stochastic Games with Vector Costs

The notion of approachability was introduced by Blackwell [1] in the context of vector-valued repeated games. The famous Blackwell's approachability theorem prescribes a strategy for approachability, i.e., for `steering' the average cost of a given agent towards a given target set, irrespective of the strategies of the other agents. In this paper, motivated by the multi-objective optimization/decision making problems in dynamically changing environments, we address the approachability problem in Stackelberg stochastic games with vector valued cost functions. We make two main contributions. Firstly, we give a simple and computationally tractable strategy for approachability for Stackelberg stochastic games along the lines of Blackwell's. Secondly, we give a reinforcement learning algorithm for learning the approachable strategy when the transition kernel is unknown. We also recover as a by-product Blackwell's necessary and sufficient condition for approachability for convex sets in this set up and thus a complete characterization. We also give sufficient conditions for non-convex sets.Comment: 18 Pages, Submitted to Dynamic Games and Application

Role of phosphatidic acid in plant galactolipid synthesis

Phosphatidic acid (PA) is a precursor metabolite for phosphoglycerolipids and also for galactoglycerolipids, which are essential lipids for formation of plant membranes. PA has in addition a main regulatory role in a number of developmental processes notably in the response of the plant to environmental stresses. We review here the different pools of PA dispatched at different locations in the plant cell and how these pools are modified in different growth conditions, particularly during plastid membrane biogenesis and when the plant is exposed to phosphate deprivation. We analyze how these modifications can affect galactolipid synthesis by tuning the activity of MGD1 enzyme allowing a coupling of phospho- and galactolipid metabolisms. Some mechanisms are considered to explain how physicochemical properties of PA allow this lipid to act as a central internal sensor in plant physiology

CRISPR Screens Identify Toxoplasma Genes That Determine Parasite Fitness in Interferon Gamma-Stimulated Human Cells

Toxoplasma virulence depends on its ability to evade or survive the toxoplasmacidal mechanisms induced by interferon gamma (IFNγ). While many Toxoplasma genes involved in the evasion of the murine IFNγ response have been identified, genes required to survive the human IFNγ response are largely unknown. In this study, we used a genome-wide loss-of-function screen to identify Toxoplasma genes important for parasite fitness in IFNγ-stimulated primary human fibroblasts. We generated gene knockouts for the top six hits from the screen and confirmed their importance for parasite growth in IFNγ-stimulated human fibroblasts. Of these six genes, three have homology to GRA32, localize to dense granules, and coimmunoprecipitate with each other and GRA32, suggesting they might form a complex. Deletion of individual members of this complex leads to early parasite egress in IFNγ-stimulated cells. Thus, prevention of early egress is an important Toxoplasma fitness determinant in IFNγ-stimulated human cells. IMPORTANCE Toxoplasma infection causes serious complications in immunocompromised individuals and in the developing fetus. During infection, certain immune cells release a protein called interferon gamma that activates cells to destroy the parasite or inhibit its growth. While most Toxoplasma parasites are cleared by this immune response, some can survive by blocking or evading the IFNγ-induced restrictive environment. Many Toxoplasma genes that determine parasite survival in IFNγ-activated murine cells are known but parasite genes conferring fitness in IFNγ-activated human cells are largely unknown. Using a Toxoplasma adapted genome-wide loss-of-function screen, we identified many Toxoplasma genes that determine parasite fitness in IFNγ-activated human cells. The gene products of four top hits play a role in preventing early parasite egress in IFNγ-stimulated human cells. Understanding how IFNγ-stimulated human cells inhibit Toxoplasma growth and how Toxoplasma counteracts this, could lead to the development of novel therapeutics

Galvestine-1, a novel chemical probe for the study of the glycerolipid homeostasis system in plant cells.

International audiencePlant cells are characterized by the presence of chloroplasts, membrane lipids of which contain up to ∼80% mono- and digalactosyldiacylglycerol (MGDG and DGDG). The synthesis of MGDG in the chloroplast envelope is essential for the biogenesis and function of photosynthetic membranes, is coordinated with lipid metabolism in other cell compartments and is regulated in response to environmental factors. Phenotypic analyses of Arabidopsis using the recently developed specific inhibitor called galvestine-1 complete previous analyses performed using various approaches, from enzymology, cell biology to genetics. This review details how this probe could be beneficial to study the lipid homeostasis system at the whole cell level and highlights connections between MGDG synthesis and Arabidopsis flower development

Atypical lipid composition in the purified relict plastid (apicoplast) of malaria parasites.

International audienceThe human malaria parasite Plasmodium falciparum harbors a relict, nonphotosynthetic plastid of algal origin termed the apicoplast. Although considerable progress has been made in defining the metabolic functions of the apicoplast, information on the composition and biogenesis of the four delimiting membranes of this organelle is limited. Here, we report an efficient method for preparing highly purified apicoplasts from red blood cell parasite stages and the comprehensive lipidomic analysis of this organelle. Apicoplasts were prepared from transgenic parasites expressing an epitope-tagged triosephosphate transporter and immunopurified on magnetic beads. Gas and liquid chromatography MS analyses of isolated apicoplast lipids indicated significant differences compared with total parasite lipids. In particular, apicoplasts were highly enriched in phosphatidylinositol, consistent with a suggested role for phosphoinositides in targeting membrane vesicles to apicoplasts. Apicoplast phosphatidylinositol and other phospholipids were also enriched in saturated fatty acids, which could reflect limited acyl exchange with other membrane phospholipids and/or a requirement for specific physical properties. Lipids atypical for plastids (sphingomyelins, ceramides, and cholesterol) were detected in apicoplasts. The presence of cholesterol in apicoplast membranes was supported by filipin staining of isolated apicoplasts. Galactoglycerolipids, dominant in plant and algal plastids, were not detected in P. falciparum apicoplasts, suggesting that these glycolipids are a hallmark of photosynthetic plastids and were lost when these organisms assumed a parasitic lifestyle. Apicoplasts thus contain an atypical melange of lipids scavenged from the human host alongside lipids remodeled by the parasite cytoplasm, and stable isotope labeling shows some apicoplast lipids are generated de novo by the organelle itself