Defining the Kv2.1-syntaxin molecular interaction identifies a first-in-class small molecule neuroprotectant.

The neuronal cell death-promoting loss of cytoplasmic K+ following injury is mediated by an increase in Kv2.1 potassium channels in the plasma membrane. This phenomenon relies on Kv2.1 binding to syntaxin 1A via 9 amino acids within the channel intrinsically disordered C terminus. Preventing this interaction with a cell and blood-brain barrier-permeant peptide is neuroprotective in an in vivo stroke model. Here a rational approach was applied to define the key molecular interactions between syntaxin and Kv2.1, some of which are shared with mammalian uncoordinated-18 (munc18). Armed with this information, we found a small molecule Kv2.1-syntaxin-binding inhibitor (cpd5) that improves cortical neuron survival by suppressing SNARE-dependent enhancement of Kv2.1-mediated currents following excitotoxic injury. We validated that cpd5 selectively displaces Kv2.1-syntaxin-binding peptides from syntaxin and, at higher concentrations, munc18, but without affecting either synaptic or neuronal intrinsic properties in brain tissue slices at neuroprotective concentrations. Collectively, our findings provide insight into the role of syntaxin in neuronal cell death and validate an important target for neuroprotection.

Untargeted metabolite profiling of Enterococcus villorum SB2, isolated from the vagina of pregnant women, by HR-LCMS.

Enterococcus bacteria are studied in various sectors including fermentation, food and dairy industries,as well as studied for their probiotic properties but have limited use due to their possible pathogenic behavior. The present report talks about the metabolites produced, by the previously isolated Enterococcus strain, E.villorum SB2 (accession number KX830968), from the vaginal source. The growth of the bacteria in three types of media (M17, MRS and LAPTg) was compared, where the M17 media gave better bacterial colonies, also maximum growth rate was observed in M17 media (Td = 1.6 h & k = 0.4 h-1), and thus was selected as the metabolite production media. Further, the studied bacteria did not show any hemolytic activity, making it safe for industrial applications. The HR-LCMS results showed the production of various amino acids, organic acids, peptides, and other metabolites like flavonoids (Quercetin 3-O-Manoglucoside), terpenoids (7',8',Dihydro-8'-hydroxycitraniaxanthin, O-Methylganoderic acid O, Thalicsessine, Austinol, Valdiate), indole derivatives produced by tryptophan metabolism (5-hydroxykynurenamine, 2S,4R)-4-(9H-Pyrido[3,4-b]indol-1-yl)-1,2,4-butanetriol, Indoleacrylic acid), antimicrobial compounds (Fortimicin A) and fatty acids (Stearic acid, Myristic acid), which were earlier unreported form Enterococcus species opening new scope for discovering new industrial applications of the strain. As the studied bacteria has been reported to be a potential probiotic, the detection of these industrially important metabolites can be studied further in future studies to reveal the potential industrial applications of the strain.

Removal and degradation of mixed dye pollutants by integrated adsorption-photocatalysis technique using 2-D MoS2/TiO2 nanocomposite.

Two-dimensional (2D) Molybdenum disulfide (MoS2) has become one of the most exciting areas of research for adsorbents due to its high surface area and abundant active sites. Mainly, 2D MoS2 show promising removal of textile dye pollutants by adsorption process, but it show high affinity for anionic type of dyes, that limits its performance in mixed dye pollutants treatment. Herein, we demonstrate an integrated approach to remove mixed dye pollutants (anionic and cationic) concurrently by combining adsorption and photocatalysis process. We synthesize MoS2/TiO2 nanocomposites for different weight percentages 2.5, 5, 10, 20, 30 and 50 wt% of pre-synthesized flower-like MoS2 nanoparticle by a two-step hydrothermal method. We demonstrate a new process of two-stage adsorption/photocatalysis using high wt% of MoS2 (Stage-I) and low wt% of MoS2 (Stage-II) nanocomposites. The proposed two-stage integrated adsorption and photocatalysis process using 50% and 2.5% of MoS2 coated TiO2, respectively showed complete removal of methylene blue dye ∼5 times faster than conventional single-stage (adsorption or photocatalysis) water treatment process. Furthermore, the feasibility of the proposed two-stage method in mixed dye pollutants removal (anionic and cationic) testified, which showed excellent performance even in doubling the dye pollutant concentration. This work brings a deeper insight into understanding the morphology and concentration of 2-D MoS2 in MoS2/TiO2 nanocomposite in tackling mixed dye pollutants and the possibilities of applying in textile dyeing industries wastewater treatment plants.