Biology subjects

Basu, N.

Publications and source records attributed to Basu, N..

6 recordsLinked to original sources

bioRxiv2026

Neurostructural and molecular evidence of advanced brain aging in rheumatoid arthritis

Chronic systemic inflammation has been implicated in age-related neurodegeneration, but whether rheumatoid arthritis (RA) is associated with accelerated brain aging remains unclear. We combined structural magnetic resonance imaging (MRI), circulating neurodegeneration biomarkers, and peripheral monocyte transcriptomics to investigate brain aging in RA across two independent cohorts. A brain-age prediction model trained in healthy controls from the IXI imaging dataset was applied to RA patient cohorts from Gothenburg (n = 71) and Glasgow (n = 50). RA was associated with significantly elevated corrected brain-age gap relative to healthy controls (+6.5 years, 95% CI 4.2-8.8 years, p = 1.2 x 10-7), with substantially stronger effects in patients [≥]60 years. Older RA patients demonstrated a significant ventricular enlargement together with reduced frontal and parietal lobe volumes. Serum brain-derived tau and glial fibrillary acidic protein levels were elevated in RA. The increased brain-age gap was associated with altered myeloid transcriptional signatures. These findings demonstrate that RA is associated with age-related neurostructural alterations consistent with accelerated brain aging.

neuroscience↗

bioRxiv2026

Synovial lining expressed mechanosensor PIEZO1 drives inflammation-permissive macrophage phenotypes and joint inflammation

Synovial tissue-resident macrophages regulate immune homeostasis within the joint, but can adopt an inflammation-permissive phenotype that promotes immune cell infiltration in rheumatoid arthritis (RA). Understanding the factors that drive this phenotypic switch may help prevent the localisation of inflammation in the joints of individuals at-risk of RA. We identified the mechanosensitive ion channel PIEZO1 as a potential regulator of lining-layer synovial tissue macrophage (STM) function. PIEZO1 was highly expressed in homeostatic, tissue resident TREM2pos lining-layer STMs and in its pathogenic chemokine producing TREM2low phenotype that characterises the hyperplastic lining-layer in active RA. Intra-articular injection of a PIEZO1 agonist in mice induced neutrophil and monocyte infiltration, whereas inhibition of PIEZO1 signalling restored the protective macrophage phenotype. Thus, mechanosensing via PIEZO1 is a defining feature of the joint lining-layer, and its aberrant activation by mechanical stress may lead to the localisation of inflammation within the joint, facilitating a transition from asymptomatic autoimmunity of at-risk RA to clinical disease.

immunology↗

bioRxiv2025

A Versatile, Simple, and Rapid (VSR) method for generating gene clones, diverse mutants, and short gene fragments for molecular biology applications

Gene cloning, site-directed mutagenesis (SDM), and short gene synthesis are essential tools in molecular biology, yet existing approaches remain constrained by efficiency, flexibility, and cost. Here, we developed a versatile, simple, and rapid (VSR) 3-in-1 method that integrates seamless cloning, mutagenesis, and short gene assembly in a single platform. This approach works on the principles of overlap extension polymerase chain reaction (OPCR), uses high-fidelity DNA polymerase and short overlapping primers. Target genes can be directly amplified from genomic DNA or complementary DNA (cDNA) templates and cloned into vectors without intermediate purification, restriction enzyme digestion, or ligation. VSR supports the insertion of DNA fragments ranging from 80 bp to 33 kb at any plasmid locus while enabling the introduction of single or multiple nucleotide substitutions at one or more sites in a single reaction. Using this method, we cloned 35 genes of diverse lengths and two complete viral genomes with efficiencies ranging from 60-100% and introduced up to 17 substitutions in a single mutagenesis reaction. We further demonstrate efficient de novo synthesis of short genes from overlapping oligonucleotides. The VSR method is a reliable, rapid, and cost-effective approach with a wide range of applications for both routine and high-throughput workflows. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/682745v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1295a5aorg.highwire.dtl.DTLVardef@1eacb4eorg.highwire.dtl.DTLVardef@1c98fb1org.highwire.dtl.DTLVardef@1f8bcbe_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2024

A flavin-based extracellular electron transfer strategy in a novel gram-positive microbe Microbacterium deferre sp. nov. strain A1-JK, isolated from cable bacteria enrichments

Microbacterium deferre sp. nov. A1-JK is a metabolically versatile Gram-positive bacterium isolated from the oxic-anoxic interface of freshwater sediment, inhabited by cable bacteria. M. deferre A1-JK could simultaneously reduce oxygen and Fe(III), challenging the traditional view of microbial Fe(III)-reduction as a strictly anaerobic process. Electrochemical studies revealed extracellular electron transfer (EET) metabolism facilitated by soluble flavin shuttles, identified via HPLC. Genomic analyses uncovered EET pathways involving cytochrome FccA and flavin reductase FmnA. Its metabolic versatility also allowed for weak electroactivity in alkaline (pH 9-10) and saline conditions (0-4% NaCl). The ability to reduce Fe(III), in the presence of atmospheric oxygen highlights its adaptability to dynamic sediment environments with fluctuating oxygen and Fe(III) gradients. These findings underscore the metabolic versatility of M. deferre A1-JK at oxic-anoxic interfaces, providing insights into the coexistence of aerobic and anaerobic processes in a single cell. ImportanceMicrobacterium deferre A1-JK is a newly discovered gram-positive bacterium that employs flavin-mediated extracellular electron transfer to respire minerals and electrodes. Associated with cable bacteria in freshwater sediments, M. deferre A1-JK was able to simultaneously reduce oxygen and Fe(III). This makes it highly adaptable to changing environments, such as those found in (cable-bacteria-containing) sediments with fluctuating oxygen and Fe concentrations. The metabolic versatility of M. deferre A1-JK offers opportunities to fundamentally revise our understanding of microbial metabolism and nutrient cycling models that strictly separate aerobic and anaerobic metabolisms.

microbiology↗

bioRxiv2023

Towards establishing a 24-hour, microplate-based, transcriptomics assay for rainbow trout embryos

There is interest in the development of early-life stage (ELS) tests with fish embryo models that are high-throughput and can generate transcriptomics point of departure (tPOD) values. The objective of this study was to establish a method in rainbow trout (Oncorhynchus mykiss) hatchlings that could satisfy both of these interests. We based our pilot method on recent efforts by U.S. EPA researchers to establish a larval fathead minnow high throughput transcriptomics assay. Here, 1-2 day post hatch trout were assayed in 24-well plates in which they were exposed for 24 hours to 12 different concentrations of test chemicals, including a negative control (DMSO, culture water). Test concentrations were anchored with a chemicals LC50 data from the US EPA ECOTOX database and EnviroTox database, and from this, concentrations were spaced on a half-log basis that spanned 6-7 orders of magnitude. In pilot study 1 we tested 3,4-dichloroaniline, CuSO4 (0.34 mg/L), and ethinylestradiol. In pilot study 2 we tested 3,4-dichloroaniline (58.5 mg/L), CuSO4 (0.34 and 0.41 mg/L), ethinylestradiol (>10 {micro}g/L), permethrin (>10 {micro}g/L), malathion (0.61 mg/L), 6PPD quinone (5.6 {micro}g/L), acetaldehyde (41.2 mg/L), 4-fluoroaniline (242.7 mg/L), glyphosate ([~]150 mg/L), ethanol (>1 g/L), thiamethoxam (>300 mg/L), and allyl alcohol (>30 mg/L). In both pilot studies derived LC50 values are provided in parentheses. Repeated studies of CuSO4 yielded consistent LC50 values (0.34, 0.34, 0.41 mg/L). The correlation between LC50s from the current study for rainbow trout embryos versus those from the literature on adult rainbow trout for 7 chemicals was r2 = 0.91. Work is underway to optimize transcriptomics assays from these samples using EcoToxChips and UPXome, with the ultimate goal to be able to derive transcriptomics points of departure. Taken together these results provide a foundation towards establishing a novel testing platform for chemical and environmental risk assessment that is much quicker (24 hrs), ethical (non-protected life stages), resource efficient (e.g., microplate-based, small volumes of chemicals), and more informative (molecular clues into MOA) than traditional bioassay approaches.

pharmacology and toxicology↗

bioRxiv2022

Resource requirements for ecotoxicity testing: A comparison of traditional and new approach methods

Toxicity testing is under transformation as it aims to harness the potential of New Approach Methods (NAMs) as alternative test methods that may be less resource intensive (i.e., fewer animals, cheaper costs, quicker assays) than traditional approaches while also providing more data and information. While many stakeholders are of the opinion that this unfolding transformation holds significant promise as a more efficient and ethical way forward, few studies have compared the resources required for NAMs versus those needed for traditional animal-based toxicity tests, particularly in the field of ecotoxicology. The objective was to compare resources needed for traditional animal-based ecotoxicity tests versus alternative tests using emergent NAMs. From a bibliometric review, we estimate that traditional tests for a single chemical cost $118,000 USD, require 135 animals, and take 8 weeks. In comparison, alternative tests cost $2,600, require 20 animals (or none), and take up to 4 weeks to test 16 (to potentially hundreds of) chemicals. Based on our analysis we conclude that NAMs in ecotoxicology can be more advantageous than traditional methods in terms of resources required (i.e., monetary costs, number of animals needed, and testing times). We note, however, that the evidence underpinning these conclusions is relatively sparse. Moving forward, groups developing and applying NAMs should provide more detailed accounts of the resources required. In addition, there is also a need for carefully designed case studies that demonstrate the domain of applicability of NAMs (and make comparisons to traditional tests) to ultimately build confidence among the user community.

pharmacology and toxicology↗