Analogs of α-conotoxin PnIC selectively inhibit α7ß2- over α7-only subtype nicotinic acetylcholine receptors via a novel allosteric mechanism.

This study was undertaken to identify and characterize the first ligands capable of selectively identifying nicotinic acetylcholine receptors containing α7 and ß2 subunits (α7ß2-nAChR subtype). Basal forebrain cholinergic neurons express α7ß2-nAChR. Here, they appear to mediate neuronal dysfunction induced by the elevated levels of oligomeric amyloid-ß associated with early Alzheimer's disease. Additional work indicates that α7ß2-nAChR are expressed across several further critically important cholinergic and GABAergic neuronal circuits within the central nervous system. Further studies, however, are significantly hindered by the inability of currently available ligands to distinguish heteromeric α7ß2-nAChR from the closely related and more widespread homomeric α7-only-nAChR subtype. Functional screening using two-electrode voltage-clamp electrophysiology identified a family of α7ß2-nAChR-selective analogs of α-conotoxin PnIC (α-CtxPnIC). A combined electrophysiology, functional kinetics, site-directed mutagenesis, and molecular dynamics approach was used to further characterize the α7ß2-nAChR selectivity and site of action of these α-CtxPnIC analogs. We determined that α7ß2-nAChR selectivity of α-CtxPnIC analogs arises from interactions at a site distinct from the orthosteric agonist-binding site shared between α7ß2- and α7-only-nAChR. As numerous previously identified α-Ctx ligands are competitive antagonists of orthosteric agonist-binding sites, this study profoundly expands the scope of use of α-Ctx ligands (which have already provided important nAChR research and translational breakthroughs). More immediately, analogs of α-CtxPnIC promise to enable, for the first time, both comprehensive mapping of the distribution of α7ß2-nAChR and detailed investigations of their physiological roles.

Sediment-associated microplastics in Chilika lake, India: Highlighting their prevalence, polymer types, possible sources, and ecological risks.

The primary objective of this research was to assess microplastics (MPs) in the sediments of Chilika lake. MPs were extracted from 22 sediment samples using the density separation method combined with vacuum pump filtration. A stereo-zoom microscope and Raman spectroscopy were employed to identify the sediment-associated MPs. The total MPs collected from all 22 sites was 440 ± 3.53 particles kg-1 wet sediments, with sizes ranging between 50 and 500 µm. In terms of morphology, fibers and fragments emerged as the dominant MP types, with counts of 210 ± 1.66 and 175 ± 1.76 particles kg-1 wet sediments, respectively. Raman spectroscopy verified the presence of various MP polymers in the sediments, predominantly HDPE (37 %), followed by PS (20 %), PET (18 %), PA (11 %), PP (7 %), and PC (7 %). A notable color variation was observed in MPs; black being the most prevalent (38.8 %), succeeded by blue (19.5 %), green (11.8 %), white (11.5 %), red (10.6 %), and transparent (7.5 %). ANOVA results indicated significant (p > 0.05) variations in MP abundance across the 22 sampling locations. However, principal component analysis (PCA) and multiple regression analysis indicated that water quality parameters did not significantly influence MP abundance, yet it was found that MP retention was higher in fine-grained sediments like clay and silt. The leading sources of MPs in Chilika lake were found to be aquafarming, trailed by river and sewage discharges, fishing activities, antifouling coatings and tourism. Additionally, the pollution load index (PLI) was employed to gauge the ecological risks, categorizing the lake under risk category 1, which implies a minimal level of MPs pollution. This research aims to serve as an early warning system for MPs pollution in productive brackish water habitats globally, including Chilika lake, guiding policymakers towards appropriate management strategies and preventive measures.

Bioactive extracts from berry byproducts on the pathogenicity of Salmonella Typhimurium.

The aim of this study was to evaluate the phenotypic and genotypic properties of Salmonella enterica serovar Typhimurium (ST) in the presence of lethal and sublethal concentrations (SLC2LOG) of blackberry (Rubus fruticosus) and blueberry (Vaccinium corymbosum) pomace extracts. Antimicrobial susceptibility, physicochemical properties, motility, biofilm formation ability, virulence gene expression patterns, and the ability of ST to colonize in chick cecum were evaluated in the presence of these bioactive extracts. HPLC-MS analysis indicated that the phenolics in the berry pomace extracts consisted, but not limited to, flavan, flavanone, flavones, glucuronides, glucosides, quinolones, catechol, coumarin, phenols, luteolines, tannins, quercetin, chlorogenic acid, ellagic acid, gallic acid, and xanthoxic acid. The SLC2LOG of both berry pomace extracts increased the rates of injured ST by ~50%; significantly decreased the hydrophobicity, auto-aggregation, cellular motility, and invasion into cultured INT407, HD11, and DF1 cells. The relative expression of type III secretion system regulated genes, hilA, hilC, invA, invF, sirA, and sirB was significantly downregulated in ST. In addition, natural colonization ability of Salmonella in chick cecum was reduced by more than two logs in the presence of 0.5 and 1.0gGallicAcidEquivalent/L berry pomace extracts when provided as water supplement. Findings from this study reveal the high potential of phenolic extracts from berry pomaces as a green antimicrobial against enteric pathogen Salmonella and application in the reduction of pre-harvest colonization level of Salmonella in poultry gut.