Distinct Mycobacterium marinum phosphatases determine pathogen vacuole phosphoinositide pattern,phagosome maturation,and escape to the cytosol

The causative agent of tuberculosis, Mycobacterium tuberculosis, and its close relative Mycobacterium marinum manipulate phagocytic host cells, thereby creating a replication‐permissive compartment termed the Mycobacterium‐containing vacuole (MCV). The phosphoinositide (PI) lipid pattern is a crucial determinant of MCV formation and is targeted by mycobacterial PI phosphatases. In this study, we establish an efficient phage transduction protocol to construct defined M. marinum deletion mutants lacking one or three phosphatases, PtpA, PtpB, and/or SapM. These strains were defective for intracellular replication in macrophages and amoebae, and the growth defect was complemented by the corresponding plasmid‐borne genes. Fluorescence microscopy of M. marinum‐infected Dictyostelium discoideum revealed that MCVs harbouring mycobacteria lacking PtpA, SapM, or all three phosphatases accumulate significantly more phosphatidylinositol‐3‐phosphate (PtdIns3P) compared with MCVs containing the parental strain. Moreover, PtpA reduced MCV acidification by blocking the recruitment of the V‐ATPase, and all three phosphatases promoted bacterial escape from the pathogen vacuole to the cytoplasm. In summary, the secreted M. marinum phosphatases PtpA, PtpB, and SapM determine the MCV PI pattern, compartment acidification, and phagosomal escape.     

Evidence of high Ca uptake by cyanobacteria forming intracellular CaCO3 and impact on their growth

Several species of cyanobacteria biomineralizing intracellular amorphous calcium carbonates (ACC) were recently discovered. However, the mechanisms involved in this biomineralization process and the determinants discriminating species forming intracellular ACC from those not forming intracellular ACC remain unknown. Recently, it was hypothesized that the intensity of Ca uptake (i.e., how much Ca was scavenged from the extracellular solution) might be a major parameter controlling the capability of a cyanobacterium to form intracellular ACC. Here, we tested this hypothesis by systematically measuring the Ca uptake by a set of 52 cyanobacterial strains cultured in the same growth medium. The results evidenced a dichotomy among cyanobacteria regarding Ca sequestration capabilities, with all strains forming intracellular ACC incorporating significantly more calcium than strains not forming ACC. Moreover, Ca provided at a concentration of 50 μM in BG‐11 was shown to be limiting for the growth of some of the strains forming intracellular ACC, suggesting an overlooked quantitative role of Ca for these strains. All cyanobacteria forming intracellular ACC contained at least one gene coding for a mechanosensitive channel, which might be involved in Ca influx, as well as at least one gene coding for a Ca²⁺/H⁺ exchanger and membrane proteins of the UPF0016 family, which might be involved in active Ca transport either from the cytosol to the extracellular solution or the cytosol toward an intracellular compartment. Overall, massive Ca sequestration may have an indirect role by allowing the formation of intracellular ACC. The latter may be beneficial to the growth of the cells as a storage of inorganic C and/or a buffer of intracellular pH. Moreover, high Ca scavenging by cyanobacteria biomineralizing intracellular ACC, a trait shared with endolithic cyanobacteria, suggests that these cyanobacteria should be considered as potentially significant geochemical reservoirs of Ca.     

Knockout of receptor for advanced glycation end‐products attenuates age‐related renal lesions

Pro‐aging effects of endogenous advanced glycation end‐products (AGEs) have been reported, and there is increasing interest in the pro‐inflammatory and ‐fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill‐defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML‐enriched diet on renal aging. Two‐month‐old male, wild‐type (WT) and RAGE^?/? C57Bl/6 mice were fed a control or a CML‐enriched diet (200 μg CML/g_food) for 18 months. Compared to controls, we observed higher CML levels in the kidneys of both CML WT and CML RAGE^?/? mice, with a predominantly tubular localization. The CML‐rich diet had no significant impact on the studied renal parameters, whereby only a trend to worsening glomerular sclerosis was detected. Irrespective of diet, RAGE^?/? mice were significantly protected against nephrosclerosis lesions (hyalinosis, tubular atrophy, fibrosis and glomerular sclerosis) and renal senile apolipoprotein A‐II (ApoA‐II) amyloidosis (p < 0.001). A positive linear correlation between sclerosis score and ApoA‐II amyloidosis score (r = 0.92) was observed. Compared with old WT mice, old RAGE^?/? mice exhibited lower expression of inflammation markers and activation of AKT, and greater expression of Sod2 and SIRT1. Overall, nephrosclerosis lesions and senile amyloidosis were significantly reduced in RAGE^?/? mice, indicating a protective effect of RAGE deletion with respect to renal aging. This could be due to reduced inflammation and oxidative stress in RAGE^?/? mice, suggesting RAGE is an important receptor in so‐called inflamm‐aging.     

Chelate-assisted phytoextraction of lead using Fagopyrum esculentum: laboratory vs. field experiments

Abstract

The development of more sustainable remediation techniques has been receiving greater attention, as an alternative to soil excavation plan in urban gardens. An in situ phytoextraction experiment with buckwheat (Fagopyrum esculentum) was performed with a 5?mmol kg^?1 citric acid (CA) application. Joint experiments under laboratory conditions were conducted using various cultivars of F. esculentum in two soils with a Pb contamination of either geogenic or anthropogenic origin and various chelate concentrations. Results show that a minimum dose of 50?mmol kg^?1 of CA is required to lower soil pH and raise the concentration of mobile Pb–CaCl₂ for both soils. Consequently, Pb shoot uptake is increased from 6.3 to 8.9 times depending on soil type. Phytoextraction efficiency is found to be 1.3 to 2.0 times higher in the anthropogenic contaminated soil than in the soil with geogenic Pb. A scale effect has also been identified since Pb root accumulation under laboratory conditions was 2.4 times higher than in the field experiment. Despite an increase in the Pb extraction rate with CA, buckwheat appears to lack the efficiency needed to remove Pb in moderately contaminated soils. The calculated remediation period would last 166?years to remove the mobile Pb fraction.     

Cascade‐Type Prelithiation Approach for Li‐Ion Capacitors

An industry‐relevant method for pre‐lithiation of lithium‐ion capacitors to balance the first charge irreversibility is demonstrated, which addresses the prime bottleneck for their market integration. Based on a composite positive electrode that integrates pyrene monomers and an insoluble lithiated base, Li₃PO₄, a “cascade‐type” process involving two consecutive irreversible reactions is proposed: i) oxidative electropolymerization of the pyrene moieties releases electrons and protons; ii) protons are captured by Li₃PO₄ and exchanged for a stoichiometric amount of Li⁺ into the electrolyte. (¹H, ¹⁹F, and ³¹P) NMR spectroscopy, operando X‐ray diffraction, and Raman spectroscopy support this mechanism. By decoupling the irreversible source of lithium ions from electrons, the cascade‐type pre‐lithiation allows the simultaneous enhancement of the capacity of the positive electrode, thanks to p‐doping of the resulting polymer. Remarkably, the proton scavenging properties of Li₃PO₄ also boost the polymerization process, which enables a 16% increase in capacity without detrimental effect on power properties and cyclability. Full cells integrating a cheap carbon black based negative electrode, show much‐improved capacity of 17 mAh g^‐1_electrodes (44 F g^‐1_electrodes, 3–4.4 V) and excellent stability over 2200 cycles at 1 A g^‐1. Thanks to its versatile chemistry and flexibility this approach in principle can be applied to any kind of ion‐battery.     

Synthesis and biological evaluation of 3-amino-, 3-alkoxy- and 3-aryloxy-6-(hetero)arylpyridazines as potent antitumor agents

Various 3-amino-, 3-aryloxy- and alkoxy-6-arylpyridazines have been synthesized by an electrochemical reductive cross-coupling between 3-amino-, 3-aryloxy- or 3-alkoxy-6-chloropyridazines and aryl or heteroaryl halides. In vitro antiproliferative activity of these products was evaluated against a representative panel of cancer cell lines (HuH7, CaCo-2, MDA-MB-231, HCT116, PC3, NCI-H727, HaCaT) and oncogenicity prevention of the more efficient derivatives was highlighted on human breast cancer cell line MDA-MB 468-Luc prior establishing their interaction with p44/42 and Akt-dependent signaling pathways.     

Predicting the success of an invader: Niche shift versus niche conservatism

Invasive species can encounter environments different from their source populations, which may trigger rapid adaptive changes after introduction (niche shift hypothesis). To test this hypothesis, we investigated whether postintroduction evolution is correlated with contrasting environmental conditions between the European invasive and source ranges in the Asian tiger mosquito Aedes albopictus. The comparison of environmental niches occupied in European and source population ranges revealed more than 96% overlap between invasive and source niches, supporting niche conservatism. However, we found evidence for postintroduction genetic evolution by reanalyzing a published ddRADseq genomic dataset from 90 European invasive populations using genotype–environment association (GEA) methods and generalized dissimilarity modeling (GDM). Three loci, among which a putative heat‐shock protein, exhibited significant allelic turnover along the gradient of winter precipitation that could be associated with ongoing range expansion. Wing morphometric traits weakly correlated with environmental gradients within Europe, but wing size differed between invasive and source populations located in different climatic areas. Niche similarities between source and invasive ranges might have facilitated the establishment of populations. Nonetheless, we found evidence for environmental‐induced adaptive changes after introduction. The ability to rapidly evolve observed in invasive populations (genetic shift) together with a large proportion of unfilled potential suitable areas (80%) pave the way to further spread of Ae. albopictus in Europe.