Bruguiera gymnorhiza (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective

The recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and effective antibiotics on the market triggers the need to search for safe therapeutics from medicinal plants to fight viral and microbial infections. In the present study, we investigated whether a mangrove plant, Bruguiera gymnorhiza (L.) Lam. (B. gymnorhiza) collected in Mauritius, possesses antimicrobial and antibiotic potentiating abilities and exerts anti-ZIKV activity at non-cytotoxic doses. Microorganisms Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70603, methicillin-resistant Staphylococcus aureus ATCC 43300 (MRSA), Salmonella enteritidis ATCC 13076, Sarcina lutea ATCC 9341, Proteus mirabilis ATCC 25933, Bacillus cereus ATCC 11778 and Candida albicans ATCC 26555 were used to evaluate the antimicrobial properties. Ciprofloxacin, chloramphenicol and streptomycin antibiotics were used for assessing antibiotic potentiating activity. ZIKV^MC-MR766NIID (ZIKV^GFP) was used for assessing anti-ZIKV activity. In silico docking (Autodock 4) and ADME (SwissADME) analyses were performed on collected data. Antimicrobial results revealed that Bruguiera twig ethyl acetate (BTE) was the most potent extract inhibiting the growth of all nine microbes tested, with minimum inhibitory concentrations ranging from 0.19–0.39 mg/mL. BTE showed partial synergy effects against MRSA and Pseudomonas aeruginosa when applied in combination with streptomycin and ciprofloxacin, respectively. By using a recombinant ZIKV-expressing reporter GFP protein, we identified both Bruguiera root aqueous and Bruguiera fruit aqueous extracts as potent inhibitors of ZIKV infection in human epithelial A549 cells. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to bind to the host cell surface. In silico docking showed that ZIKV E protein, which is involved in cell receptor binding, could be a target for cryptochlorogenic acid, a chemical compound identified in B. gymnorhiza. From ADME results, cryptochlorogenic acid is predicted to be not orally bioavailable because it is too polar. Scientific data collected in this present work can open a new avenue for the development of potential inhibitors from B. gymnorhiza to fight ZIKV and microbial infections in the future.     

Siderophores and Iron‐Transport in Microorganisms

Iron is an essential element in many biological systems, and in spite of its abundance (5% of the earth crust), its availability is dramatically limited by the very high insolubility of iron(III) at physiological pHs where the concentration of free iron(III) is less than 10^?17 M, a value which is much too low to allow any possible growth to aerobic microorganisms. Iron metabolization by the microorganisms necessitates generally the biosynthesis of low molecular weight compounds (300 to 2000 Da) called siderophores. These molecules which are generally excreted into the culture medium, chelate very strongly iron(III), solubilize it and transport it into the cells using an ATP‐dependent high affinity transport system. For nearly fourty years, the structural studies on siderophores have shown a great diversity of structures for these iron‐chelating molecules synthesized by microorganisms. These structures are characterized by the presence of one, two and in most cases, three bidentate chelating groups, generally oxygenated, necessary for the formation of very stable hexacoordinated octahedric complexes between the siderophores and iron(III). These groups are generally either catecholates, or hydroxamates or hydroxyacids, but can be any other bidentate groups In what follows several typical examples of siderophores belonging to each of these categories are given. It is clear that considering the very high number of siderophores having so many different structures so far isolated and characterized (more than 200), we have restricted this report to the most representative structures of each category, with a special emphasis to pyoverdins, the fluorescent peptidic siderophores of the fluorescent pseudomonads. Similarly the siderophore‐mediated iron‐transport mechanisms of Gram‐negative bacteria described therafter will report mainly on those of Escherichia coli with a special emphasis to Pseudomonas when information is available. The pyoverdin‐mediated iron‐transport in fluorescent pseudomonads implies biochemical mechanisms which involve signal and energy exchanges between the two membranes across the periplasmic space. The energy transduction mechanism in the case of the pyoverdin‐mediated active transport in P. aeruginosa has not been completely elucidated so far. Nevertheless from the data obtained for ferric enterobactin and ferrichrome in E. coli, it is plausible that a common mechanism of transport can take place for all the enterobacteria. The key element of this mechanism is protein TonB in E. coli, head of a series of TonB proteins having a very close structure and characterized in P. putida WCS358 and P. aeruginosa ATCC 156942. The striking similarities existing between the various iron‐transport steps in these different bacterial species is highly in favour of a common energy‐dependent siderophore‐mediated iron‐transport mechanism in microorganisms.     

Jacobian of meromorphic curves

The contact structure of two meromorphic curves gives a factorization of their jacobian. Abhyankar’s work was partly supported by NSF Grant DMS 91-01424 and NSA grant MDA 904-97-1-0010.     

Influence of ultrashort laser pulse duration on the X-ray emission spectrum of plasma produced in cluster target

Line emission spectrum of a laser plasma produced in an argon cluster jet target was measured on the n ¹ P1?1¹ S ₀ (n=5–9) transitions of the helium-like Ar XVII ion for a pulse duration varying from 45 fs to 1.1 ps and a constant fluence of ～10⁵ J/cm². The independent modeling of the relative intensities of the transitions from the n=5,..., 10 levels, as well as of the 2¹ P ₁? 1² S ₀ and 2³ P ₁?1² S ₀ lines and dielectronic satellites indicates that the electron temperature is anomalously low and that the electron density in emitting plasma increases with shortening the laser pulse. The excitation from the ground state by a small fraction of hot electrons is expected to be the main channel of populating the Ar XVII levels.     

A Hybrid Kinetic-Quantum Model for Stationary Electron Transport

Interface conditions between a classical transport model described by the Boltzmann equation and a quantum model described by a set of Schrödinger equations are presented in the one-dimensional stationary setting. These interface conditions, derived thanks to an asymptotic analysis of the Wigner transform, are shown to be flux-preserving and are used to build a hybrid model consisting of a quantum zone surrounded by two classical ones. The hybrid model is shown to be well posed when the potential is either prescribed or computed self-consistently, and the semiclassical limit of the problem is shown to give the right interface conditions between two kinetic regions (the electrostatic potential being fixed). This model can be used to describe far-from-equilibrium electron transport in a resonant tunneling diode.     

Étude spectrométrique d'un plasma induit par haute fréquence : Partie I: Performances analytiques

A new design of inductively coupled plasma generator operating at 40 MHz is described. Data are presented to show that the generator gives satisfactory performance when used in both atomic emission and absorption spectrometry, although the former has the advantage of simplicity of operation.     

Some chain conditions in pullbacks

The main purpose of this paper is to study when a (T, I, D) construction ring is a C-ring in the sense of Echi (Port Math 50:277–295, 1993) where I is not necessarily a maximal ideal of T. This study allows us to generalize some results proved in Echi (Port Math 50:13–23, 1994) and to give new examples of C-rings.     

Kinetics and Mechanism of the Isomerisation of 2,4,6-Triphenyl-4H-Thiopyran

Isomerisation of 2,4,6-triphenyl-4H-thiopyran into 2,4,6-triphenyl-2H-thiopyran has been studied kinetically and the rate of the reaction was determined in dimethylformamide. The first order rate constant could be expressed in terms of the Arrhenius parameters by the equation k_t = 2.85 × 10⁷ e^{?15820±110/RT}.     

Solid phase synthesis of mono- or disubstituted arginine containing peptides from an isothiocitrulline precursor

A method for the solid phase synthesis of substituted arginine containing peptides starting from an isothiocitrulline precursor is described. In this procedure, a peptide containing one or more protected ornithine residue(s) was assembled on a solid support. Following selective deprotection, ornithine residue(s) was (were) converted into S-methyl-isothiocitrulline in three steps. Subsequent reaction with primary or secondary amines afforded mono and disubstituted arginine-containing derivatives, respectively. Using lysine instead of ornithine afforded substituted homoarginine-containing derivatives.