Biology subjects

Nathan, S.

Publications and source records attributed to Nathan, S..

7 recordsLinked to original sources

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↗

bioRxiv2024

hAMRonization: Enhancing antimicrobial resistance prediction using the PHA4GE AMR detection specification and tooling

The detection of antimicrobial resistance (AMR) markers directly from genomic or metagenomic data is becoming a standard clinical and public health procedure. This has resulted in the development of a number of different bioinformatic AMR prediction tools. Although many may implement similar principles, these tools differ significantly in their supported inputs, search algorithms, parameterisation, and underlying reference databases. Each of these tools generates a report of detected AMR genes or variants in a distinct, non-standard, format. This presents a huge barrier to the comparison of results and to the modularity of tools for AMR gene prediction within bioinformatic workflows. In collaboration with 17 public health laboratories across 10 countries, the Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) data structures working group has developed and piloted a standardized output specification for the bioinformatic detection of AMR from microbial genomes. In this report, we discuss hAMRonization, a python package and command-line utility, which implements PHA4GEs AMR specification to combine the outputs of disparate antimicrobial resistance gene detection tools into a single unified format. hAMRonization can be easily extended and currently supports 18 different tools (both species-agnostic and species-specific) for the detection of genes and/or variants conferring AMR. The harmonized reports are available in tabular form, JSON format or through an interactive HTML file (e.g., https://maguire-lab.github.io/assets/interactive_report_demo.html) that can be opened within the browser for navigable data exploration. As of 2024-03-07 hAMRonization has been downloaded [~]12,500 times, incorporated into >9 public bioinformatic tools and workflows, and been internally adopted by several national and international public health groups. The hAMRonization tool and underlying specification are open-source and freely available through PyPI, conda and GitHub (https://github.com/pha4ge/hAMRonization).

bioinformatics↗

bioRxiv2023

A Novel Amino Acid Deletion and Substitution in amrB Gene Associated with Gentamicin Susceptibility in Burkholderia pseudomallei from Malaysian Borneo

Burkholderia pseudomallei is a highly pathogenic saprophyte that is intrinsically resistant to a wide variety of antibiotics. Resistance to gentamicin is considered as an earmark of B. pseudomallei. However, rare susceptible strains have been isolated in certain regions due to gene mutations. Currently, data on the susceptible strains prevalence and the actual causal mutations are still scarce, particularly in Malaysian Borneo. A pool of B. pseudomallei isolates (n = 46) were screened for gentamicin susceptibility and phenotypically confirmed using the gradient minimum inhibitory concentration method. Three isolates were gentamicin-susceptible strains and were identified as having originated from Bintulu, Sarawak, Malaysian Borneo. The amrB gene mutation in these mutant strains was analysed, and the effect of amino acid substitution on the stability of the amrB protein was determined by using in silico analysis. The mutagenesis analysis identified a polymorphism-associated mutation, g.1056T>G, and two susceptible-associated mutations identified as novel in-frame amino acid deletion p.Val412del and amino acid substitution p.Thr368Arg that compromised gentamicin resistance. In silico analysis using amrB homology-modelled and AlphaFold-solved structures proposed the role of p.Thr368Arg amino acid substitution in conferring GEN susceptibility by other mechanisms than destabilising the structure of amrB protein, which is most probably due to the mutations location in the highly conserved region. The findings have shed light on the phenotypic characteristics and mutations involved in the amrB gene of the gentamicin-susceptible B. pseudomallei.

microbiology↗

bioRxiv2020

Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture

In an effort to identify therapeutic intervention strategies for the treatment of COVID-19, we have investigated a selection of FDA-approved small molecules and biologics that are commonly used to treat other human diseases. A investigation into 18 small molecules and 3 biologics was conducted in cell culture and the impact of treatment on viral titer was quantified by plaque assay. The investigation identified 4 FDA-approved small molecules, Maraviroc, FTY720 (Fingolimod), Atorvastatin and Nitazoxanide that were able to inhibit SARS-CoV-2 infection. Confocal microscopy with over expressed S-protein demonstrated that Maraviroc reduced the extent of S-protein mediated cell fusion as observed by fewer multinucleate cells in the context of drugtreatment. Mathematical modeling of drug-dependent viral multiplication dynamics revealed that prolonged drug treatment will exert an exponential decrease in viral load in a multicellular/tissue environment. Taken together, the data demonstrate that Maraviroc, Fingolimod, Atorvastatin and Nitazoxanide inhibit SARS-CoV-2 in cell culture.

microbiology↗

bioRxiv2020

Functional specialization of human salivary glands and origins of proteins intrinsic to human saliva

Salivary proteins are essential for maintaining health in the oral cavity and proximal digestive tract and serve as a diagnostic window into human disease. However, their precise organ origins remain unclear. Through transcriptomic analysis of major adult and fetal salivary glands, and integration with the saliva proteome and transcriptomes of 28+ organs, we linked human saliva proteins to their source, identified salivary gland-specific genes, and uncovered fetal- and adult-specific gene repertoires. Our results also provide new insights into the degree of gene retention during maturation and suggest that functional diversity between adult gland-types is driven by specific dosage combinations of hundreds of transcriptional regulators rather than a few gland-specific factors. Finally, we demonstrate the hitherto unrecognized heterogeneity of the human acinar cell lineage. Our results pave the way for future investigations into glandular biology and pathology, as well as salivas use as a diagnostic fluid.

developmental biology↗

bioRxiv2018

Monocyte and Macrophage Subtypes as Paired Cell Biomarkers for Coronary Artery Disease

Background: Monocytes and macrophages are central to atherosclerosis, but how they mark progression of human coronary artery disease (CAD) is unclear. We tested whether patients monocyte subtypes paired with their derived macrophage profiles correlate with extent of CAD.\n\nMethods: Peripheral blood was collected from 30 patients undergoing cardiac catheterization, and patients were categorized as having no significant CAD, single vessel disease, or multivessel disease according to the number of affected coronary arteries. Mononuclear cells were measured for monocyte markers CD14 and CD16 by flow cytometry, and separate monocytes were cultured into macrophages over 7 days and measured for polarization markers CD86 and CD206.\n\nResults: At baseline, patients with greater CAD burden were older with higher rates of statin use, whereas all other characteristics were similar across the spectrum of coronary disease. Non-classical (CD14loCD16hi) and all CD16+ monocytes were elevated in patients with single vessel and multivessel disease compared to those without significant CAD (8.6% and 10.5% vs. 2.8%, p < 0.05), whereas regulatory M2 macrophages (CD206+) were decreased in patients with single vessel and multivessel disease (0.34% and 0.34% vs. 1.4%, p < 0.05). An inverse relationship between paired CD16+ monocytes and M2 macrophages marked CAD severity. CAD was also found to be more tightly associated with CD16+ cells than age or traditional cardiovascular risk factors on multiple regression analysis of these patients.\n\nConclusions: CAD extent is correlated directly with CD16+ monocytes and inversely with M2 (CD206+) macrophages, suggesting circulating monocytes may influence downstream polarization of lesional macrophages. These measures of monocyte and macrophage subtypes hold potential as biomarkers in CAD.

physiology↗

bioRxiv2018

Diverse progenitor cells preserve salivary gland ductal architecture after radiation induced damage

The ductal system of the salivary gland has long been postulated to be resistant to radiation-induced damage, a common outcome incurred by head and neck cancer patients receiving radiotherapy. Yet, whether the ducts are capable of regenerating after genotoxic injury, or if damage to ductal cells induces lineage plasticity, as has been reported in other organ systems, remains unknown. Here, we show that two ductal progenitor populations marked by KRT14 and KIT exclusively maintain non-overlapping ductal compartments after radiation exposure but do so through distinct cellular mechanisms. KRT14+ progenitor cells are fast cycling cells that proliferate in response to radiation-induced damage in a sustained manner and divide asymmetrically to produce differentiated cells of the larger granulated ducts. Conversely, KIT+ cells are long lived progenitors for the intercalated ducts that undergo few cell divisions either during homeostasis or after gamma radiation, thus maintaining ductal architecture in the near absence of cell turnover. Together, these data illustrate the regenerative capacity of the salivary ducts and highlight the heterogeneity in the damage responses used by salivary progenitor cells to maintain tissue architecture.\n\nSummary StatementThe salivary gland ductal network is maintained during homeostasis and after genotoxic injury by diverse progenitors that respond differentially to radiation induced damage.

developmental biology↗