Production of a polyunsaturated isoprenoid wax ester during aerobic metabolism of squalene by Marinobacter squalenivorans sp. nov

This paper describes the production of 5,9,13-trimethyltetradeca-4E,8E,12-trienyl-5,9,13-trimethyltetradeca-4E,8E,12-trienoate during the aerobic degradation of squalene by a Marinobacter strain, 2Asq64, isolated from the marine environment. A pathway involving initial cleavage of the C(10)-C(11) or C(14)-C(15) double bonds of the squalene molecule is proposed to explain the formation of this polyunsaturated isoprenoid wax ester. The isoprenoid wax ester content reached 1.1% of the degraded squalene at the mid-exponential growth phase and then decreased during the stationary phase. The wax ester content increased by approximately threefold in N-limited cultures, in which the ammonium concentration corresponds to conditions often found in marine sediments. This suggests that the bacterial formation of isoprenoid wax esters might be favored in such environments. The bacterial strain is then characterized as a member of a new species, for which we propose the name Marinobacter squalenivorans sp. nov.     

DNAJB3/HSP-40 Cochaperone Is Downregulated in Obese Humans and Is Restored by Physical Exercise

Obesity is a major risk factor for a myriad of disorders such as insulin resistance and diabetes. The mechanisms underlying these chronic conditions are complex but low grade inflammation and alteration of the endogenous stress defense system are well established. Previous studies indicated that impairment of HSP-25 and HSP-72 was linked to obesity, insulin resistance and diabetes in humans and animals while their induction was associated with improved clinical outcomes. In an attempt to identify additional components of the heat shock response that may be dysregulated by obesity, we used the RT²-Profiler PCR heat shock array, complemented with RT-PCR and validated by Western blot and immunohistochemistry. Using adipose tissue biopsies and PBMC of non-diabetic lean and obese subjects, we report the downregulation of DNAJB3 cochaperone mRNA and protein in obese that negatively correlated with percent body fat (P = 0.0001), triglycerides (P = 0.035) and the inflammatory chemokines IP-10 and RANTES (P = 0.036 and P = 0.02, respectively). DNAJB positively correlated with maximum oxygen consumption (P = 0.031). Based on the beneficial effect of physical exercise, we investigated its possible impact on DNAJB3 expression and indeed, we found that exercise restored the expression of DNAJB3 in obese subjects with a concomitant decrease of phosphorylated JNK. Using cell lines, DNAJB3 protein was reduced following treatment with palmitate and tunicamycin which is suggestive of the link between the expression of DNAJB3 and the activation of the endoplasmic reticulum stress. DNAJB3 was also shown to coimmunoprecipiate with JNK and IKKβ stress kinases along with HSP-72 and thus, suggesting its potential role in modulating their activities. Taken together, these data suggest that DNAJB3 can potentially play a protective role against obesity.     

Identification of Four New Chemical Series of Small Drug-Like Natural Products as Potential Neuropilin-1 Inhibitors by Structure-Based Virtual Screening: Pharmacophore-Based Molecular Docking and Dynamics Simulation

Neuropilin-1 (NRP-1), a surface transmembrane glycoprotein, is one of the most important co-receptors of VEGF-A165 (vascular endothelial growth factor) responsible for pathological angiogenesis. In general, NRP-1 overexpression in cancer correlates with poor prognosis and more tumor aggressiveness. NRP-1 role in cancer has been mainly explained by mediating VEGF-A165-induced effects on tumor angiogenesis. NRP-1 was recently identified as a co-receptor and an independent gateway for SARS-CoV-2 through binding subunit S2 of Spike protein in the same way as VEGF-A165. Thus, NRP-1 is of particular value as a target for cancer therapy and other angiogenesis-dependent diseases as well as for SARS-CoV-2 antiviral intervention. Herein, The Super Natural II, the largest available database of natural products (∼0.33 M), pre-filtered with drug-likeness criteria (absorption, distribution, metabolism and excretion/toxicity), was screened against NRP-1. NRP-1/VEGF-A165 interaction is one of protein-protein interfaces (PPIs) known to be challenging when approached in-silico. Thus, a PPI-suited multi-step virtual screening protocol, incorporating a derived pharmacophore with molecular docking and followed by MD (molecular dynamics) simulation, was designed. Two stages of pharmacophorically constrained molecular docking (standard and extra precisions), a mixed Torsional/Low-mode conformational search and MM-GBSA ΔG binding affinities calculation, resulted in the selection of 100 hits. These 100 hits were subjected to 20 ns MD simulation, that was extended to 100 ns for top hits (20) and followed by post-dynamics analysis (atomic ligand-protein contacts, RMSD, RMSF, MM-GBSA ΔG, Rg, SASA and H-bonds). Post-MD analysis showed that 19 small drug-like nonpeptide natural molecules, grouped in four chemical scaffolds (purine, thiazole, tetrahydropyrimidine and dihydroxyphenyl), well verified the derived pharmacophore and formed stable and compact complexes with NRP-1. The discovered molecules are promising and can serve as a base for further development of new NRP-1 inhibitors.     

In Silico Design of Novel Tetra-Substituted Pyridinylimidazoles Derivatives as c-Jun N-Terminal Kinase-3 Inhibitors,Using 2D/3D-QSAR Studies,Molecular Docking and ADMET Prediction

The c-Jun N-terminal Kinase 3 (JNK3) is a family of protein kinases that plays an important role in the neurodegenerative diseases such as Alzheimer’     

Essential oils from wild populations of Algerian Lavandula stoechas L.: composition, chemical variability, and in vitro biological properties

In an effort to develop local productions of aromatic and medicinal plants, a comprehensive assessment of the composition and biological activities of the essential oils (EOs) extracted from the aerial flowering parts of wild growing Lavandula stoechas L. collected from eleven different locations in northern Algeria was performed. The oils were characterized by GC‐FID and GC/MS analyses, and 121 compounds were identified, accounting for 69.88–91.2% of the total oil compositions. The eleven oils greatly differed in their compositions, since only 66 compounds were common to all oils. Major EO components were fenchone ( 2 ; 11.27–37.48%), camphor ( 3 , 1.94–21.8%), 1,8‐cineole ( 1 ; 0.16–8.71%), and viridiflorol ( 10 ; 2.89–7.38%). The assessed in vitro biological properties demonstrated that the DPPH‐based radical‐scavenging activities and the inhibition of the β‐carotene/linoleic acid‐based lipid oxidation differed by an eight‐fold factor between the most and the least active oils and were linked to different sets of molecules in the different EOs. The eleven EOs exhibited good antimicrobial activities against most of the 16 tested strains of bacteria, filamentous fungi, and yeasts, with minimum inhibitory concentrations (MICs) ranging from 0.16 to 11.90 mg/ml.     

Luminescence Study of Silver Nanoparticles Obtained by Annealed Ionic Exchange Silicate Glasses

The photoluminescence of silver nanoparticles glasses obtained by ionic exchange and annealing is investigated for various ionic exchange times. These glasses are prepared by immersion of silicate glass samples in a molten salt bath of molar concentration 10% AgNO₃ in NaNO₃ at T = 320 °C. Scanning electron microscopy measurement in electron diffraction scattering (EDS) configuration confirms the silver presence in the various glasses, and the UV/visible absorption gives the evolution of the spectra after ionic exchange and plasmon resonance apparition after annealing. After annealing at 450 °C, both diagnostics inform us about the particles’ formation and the silver rediffusion. Silver nanoparticle growth after annealing prior leads to photoluminescence exaltation and quenching for the longest exchange samples. Subsequently, we propose potential mechanisms of the nanoparticle formation with an initial depolymerization of the silicate network during the ionic exchange and repolymerization during annealing.     

DFT/TDDFT computational study of the structural,electronic and optical properties of rhodium (III) and iridium (III) complexes based on tris-picolinate bidentate ligands

The electronic structures and spectroscopic properties of two complexes [M(pic)₃] (M = Ir, Rh) containing picolinate as bidentate ligands have been calculated by means density functional theory (DFT) and time-dependent DFT/TD-DFT using three hybrid functionals B3LYP, PBE0 and mPW1PW91. The PBE0 and mPW1PW91 functionals, which have the same HF exchange fraction (25%), give similar results and do not differ drastically from B3LYP results. Calculated geometric parameters of the complexes are in good agreement with the available experimental data. The UV absorptions observed in acetonitrile were assigned on the basis of singlet state transitions. The most intense band observed in the UV-C region corresponds to ligand-to-ligand charge transfer states (LLCT) in both complexes. The theoretical spectrum of the rhodium complex is characterized by a large degree of mixing between metal-to-ligand-charge-transfer (MLCT), LLCT and metal centered (MC) states in the UV-A region. The presence of low-lying excited states with MC character affects the absorption spectrum under spin-orbit coupling (SOC) effects and play important roles in the photochemical properties.

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Graphical abstract Frontier molecular orbital diagram of mer-M(pic)₃ (M=Ir, Rh).

     

North African hybrid sparrows (Passer domesticus,P. hispaniolensis) back from oblivion – ecological segregation and asymmetric mitochondrial introgression between parental species

A stabilized hybrid form of the house sparrow (Passer domesticus) and the Spanish sparrow (P. hispaniolensis) is known as Passer italiae from the Italian Peninsula and a few Mediterranean islands. The growing attention for the Italian hybrid sparrow and increasing knowledge on its biology and genetic constitution greatly contrast the complete lack of knowledge of the long‐known phenotypical hybrid sparrow populations from North Africa. Our study provides new data on the breeding biology and variation of mitochondrial DNA in three Algerian populations of house sparrows, Spanish sparrows, and phenotypical hybrids. In two field seasons, the two species occupied different breeding habitats: Spanish sparrows were only found in rural areas outside the cities and bred in open‐cup nests built in large jujube bushes. In contrast, house sparrows bred only in the town centers and occupied nesting holes in walls of buildings. Phenotypical hybrids were always associated with house sparrow populations. House sparrows and phenotypical hybrids started breeding mid of March, and most pairs had three successive clutches, whereas Spanish sparrows started breeding almost one month later and had only two successive clutches. Mitochondrial introgression is strongly asymmetric because about 75% of the rural Spanish sparrow population carried house sparrow haplotypes. In contrast, populations of the Italian hybrid form, P. italiae, were genetically least diverse among all study populations and showed a near‐fixation of house sparrow haplotypes that elsewhere were extremely rare or that were even unique for the Italian Peninsula. Such differences between mitochondrial gene pools of Italian and North African hybrid sparrow populations provide first evidence that different demographic histories have shaped the extant genetic diversity observed on both continents.     

Diagnosis on the state of healthiness,quality of the coast and biological resources 'case of the Moroccan Atlantic coast' (City of El Jadida)

In this study, we present a diagnosis concerning the state of healthiness of the coast of the city of El Jadida by: characterisation of the various collectors rejected in sea without any preliminary treatment, measure of the physicochemical parameters of seawater from sampling stations, evaluation of the concentration of certain heavy metals (Cd, Cu, Zn, Fe and Mn) in four species of algae, which shows that metal contents vary according to the species and the sampling stations, measure of the metal content in mussels, which varies according to the site. A comparative study with the data of the literature shows that algae and mussels generally present values that are weaker than those coming from other geographical areas.     

Chromosome mapping in Alealigenes eutrophus CH34

Mutants and mobilizing plasmids were developed as genetic tools in Alcaligenes eutrophus CH34. In order to map the chromosome, spontaneous and ethyl methane sulphonate (EMS)-induced mutants (mostly auxotrophs) were isolated. Another source of mutants was provided by the phenomenon of temperature-induced mortality and mutagenesis that is observed at 37° C and is characteristic of many metallotolerant strains of A. eutrophus. Plasmid pULB113 (RP4::miniMu) was used to map the available mutations. Twenty-five loci were ordered in a circular map. pMOL50, a rearranged derivative of plasmid pMOL28, which was obtained in a survivor at 37° C and displayed chromosome mobilizing activity (Cma+), was also used to mobilize chromosomal markers: resulting linkages were stronger than with pULB113, allowing confirmation of the circularity of the A. eutrophus CH34 chromosome with a small number of crosses.