Biology subjects

J, A.

Publications and source records attributed to J, A..

5 recordsLinked to original sources

bioRxiv2024

Benzamidine-Mediated Inhibition of Human Lysozyme Aggregation: Differential Ligand Binding in Homologous Proteins

Amyloid fibril formation is a hallmark of several protein misfolding diseases, including systemic hereditary amyloidosis (SHA), in which lysozyme aggregates into plaques, causing inflammation in various tissues. SHA is a rare disease with no current drug treatment options. In our efforts to identify potential therapeutics for SHA, we investigated the inhibitory effects of benzamidine (BEN) on the fibrillation of human lysozyme (HL). Multiple biophysical assays demonstrated BENs ability to effectively prevent amyloid formation. Intrinsic fluorescence measurements highlighted BENs interaction with HL. We inferred the binding mode of BEN to HL through ITC experiments, molecular docking, and molecular dynamics simulations, confirmed BENs binding at the active site, particularly near stretch-2 (residues 52-64), a key region in its anti-amyloidogenic activity. This interaction differed from the previously reported interaction with HEWL. Further, microscopy analyses, including scanning electron microscopy (SEM) and transmission electron microscopy (TEM), further supported these findings by showing reduced fibril formation and alterations in fibril morphology in the presence of BEN. Importantly, BEN exhibited no cytotoxic effects in HEK-293 cells, reinforcing its potential as a therapeutic candidate for amyloidosis. These results provide strong evidence of BENs anti-amyloidogenic activity and offer a foundation for future drug development targeting lysozyme amyloidosis.

bioinformatics↗

bioRxiv2024

Sustainable and Ecofriendly Nanoparticle Synthesis Using Microbial Strains Isolated From Heavy Metal Rich Industrial Effluent

Given the enormous potential of metal nanomaterials, their sustainable production is of paramount importance and is a key area of focus worldwide. In this regard, bacteria are highly valued because of their potential for rapid, cost-effective and eco-friendly metal nanomaterial synthesis. In this study, culture supernatants of Bacillus cereus and Curvularia sp isolated from heavy metal rich Titanium industry effluent effectively synthesised cobalt and copper nanoparticles of narrow size range at room temperature, neutral pH and static conditions within 2-7 days. This was verified by visible colour changes, UV-Vis spectroscopy and FT-IR. The UV-Visible spectra of the biosynthesized cobalt and copper nanoparticles exhibited sharp narrow peaks at 341 and 342 nm. This suggested that the cobalt and copper nanoparticles were not only small but also had a narrow size distribution, a feature rarely reported in biosynthesis studies. Furthermore, our approach was conducted at room temperature using cell-free supernatant, eliminating the need for additional heating or cooling, and minimising processing thus making the process energy-efficient, cost effective and sustainable. This is a first report on the production of monodisperse cobalt and copper nanoparticles by microbes isolated from this novel extreme environment. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=59 SRC="FIGDIR/small/585342v2_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@28e945org.highwire.dtl.DTLVardef@1eaea8aorg.highwire.dtl.DTLVardef@1cc1129org.highwire.dtl.DTLVardef@7ab864_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Bacterial pore-forming toxin pneumolysin drives pathogenicity through shed toxin-loaded host extracellular vesicles

Streptococcus pneumoniae is a global priority respiratory pathogen that kills over a million people annually and produces the pore-forming cytotoxin, pneumolysin (PLY). Host cells expel membrane assembled toxin by shedding microvesicles, but the composition and pathophysiological sequelae of the toxin-induced host extracellular vesicles (EVs) are unknown. Here, we found that EVs shed from PLY-challenged monocytes (PLY-EVs) harbor membrane-bound toxin that induced cytotoxicity upon fusion with recipient cells. EVs from human monocytes challenged with recombinant PLY as well as PLY-expressing pneumococcal strains, but not the isogenic PLY mutant, primed dendritic cells and evoked higher pro-inflammatory cytokines upon infection. Proteomic analysis revealed that PLY-EVs are enriched for key antimicrobial and inflammatory host proteins such as IFI16, NLRC4, PTX3 and MMP9. In vivo, zebrafish and mice administered with PLY-EVs showed mortality, pericardial edema, tissue damage and inflammation. Our findings show that host EVs bearing the cytotoxin PLY constitute a previously unexplored mechanism of pneumococcal pathogenesis.

microbiology↗

bioRxiv2020

Characterization of Onion Seedlots into Different Storability Groups with 4 Parameter Hill Function (4-PHF)

Onion varieties were classified into different storability groups by comparing two approaches (i)germination and vigor indices (conventional germination parameters) (ii)variables extracted from 4 Parameter Hill Function (4-PHF), after mimicking ageing conditions with accelerated ageing (42 {degrees}C and 100% RH). The study revealed that in comparison to evaluation using conventional germination parameters, the parameters extracted using 4-PHF provided realistic characterization of varieties as good, medium and poor storers. Time related parameters like time to maximum germination rate (TMGR), time to 50% germination (T50), difference between time at germination onset (lag) and 50% germination (Dlag-50), uniformity (U) along with germination percent (a) and area under curve (AUC) were decisive in identification of the varieties to a storage category which was misinterpreted with exclusive use of conventional approach. The distinction between good and medium storers was not of much significance but shift of varieties like Bhima Super, Pusa Red and Agrifound Light Red from poor to good performance cluster could be detected exclusively through 4-PHF analysis. Curve fittings highlighted AUC as the most crucial parameter contributing towards clustering of the varieties in different storability groups. Our study is the first reported research of using 4-PHF mathematical function for seedlot characterization into different storability groups.

plant biology↗

bioRxiv2020

FRET based aptamer assay for sensitive detection of Salmonella paratyphi A and revealing its molecular interaction with DNA gyrase: An in silico accessment

Rapid pathogen detection and identification of its serovars are crucial to provide essential treatment during pandemic circumstances. Herein, we developed a facile and versatile FRET-based aptasensor for rapid Salmonella paratyphi A detection. The ssDNA aptamers specific towards pathogenic Salmonella paratyphi A were generated via whole-cell SELEX. The aptamer was conjugated onto quantum dot (QD) that served as the molecular beacon and graphene oxide (GO) was used as fluorescence quencher. The detection of Salmonella paratyphi A leads to the quenching of QD fluorescence due to the non-covalent interaction between GO and CdTe quantum dot. The assay shows a detection limit up to 10 cfu{middle dot}mL-1 with no cross-reactivity towards closely related species. The spiking analysis demonstrated an inter-assay coefficient of variance less than 8 % and recovery rate between 85%-102% mitigates assay reliability. Further analysis with commercially available ELISA kit validated the reliability of the developed aptasensor. Furthermore, molecular dynamics simulation was used to establish the mechanism of action of generated aptamer against bacterial DNA gyrase protein. The strong non-bonded interaction energies along with hydrogen bonds between the aptamer and protein inhibit the function of the bacteria.

synthetic biology↗