Biology subjects

Ramasamy, A.

Publications and source records attributed to Ramasamy, A..

6 recordsLinked to original sources

bioRxiv2026

Asymmetric biparental but inefficient horizontal transmission of paralysis-causing sigmavirus in Queensland fruit fly

Insects are associated with diverse RNA viruses, including vertically transmitted viruses that form persistent infections without apparent symptoms. One of the first documented vertically transmitted viruses is sigmavirus (Rhabdoviridae) affecting fitness of Drosophila. Sigmaviruses and related rhabdoviruses have also been detected in pest fruit flies and other arthropods. However, their prevalence, transmission, tissue localisation and fitness effects remain poorly known, despite their potentially common infections in diverse hosts. We investigated Sigmavirus tryoni (BtSV) prevalence, load, transmission across multiple generations and host effects in Queensland fruit fly (Bactrocera tryoni), Australias most significant horticultural pest, which carries BtSV at low prevalence (13.7%) across field populations. We detected BtSV in 6 of 12 laboratory populations (prevalence 12.5% to 80.4%) where it was transmitted biparentally within embryos. Although incomplete, maternal transmission was more reliable and resulted in higher BtSV load than paternal transmission. Paternally transmitted BtSV was almost entirely lost after two generations. BtSV became detectable in most uninfected individuals cohabiting with infected flies, but this resulted in a low load that was subsequently transmitted to only few offspring. BtSV occurred across developmental stages, digestive and reproductive tissues, albeit its viral load was lower in reproductive tissues when received paternally than maternally, and lower in testes than ovaries. Furthermore, BtSV-infected individuals suffered paralysis and mortality when exposed to high CO2 concentrations, a Rhabdoviridae effect previously reported for several Drosophila species, a muscid fly and mosquitoes. Our study suggests that sigmavirus transmission dynamics and fitness effects may apply broadly to arthropod hosts and affect their management.

evolutionary biology↗

bioRxiv2024

Molecular Mimicry as a Mechanism of Viral Immune Evasion and Autoimmunity

Mimicry of host protein structures ("molecular mimicry") is a common mechanism employed by viruses to evade the hosts immune system. To date, studies have primarily evaluated molecular mimicry in the context of full protein structural mimics. However, recent work has demonstrated that short linear amino acid (AA) molecular mimics can elicit cross-reactive antibodies and T-cells from the host, which may contribute to development and progression of autoimmunity. Despite this, the prevalence of molecular mimics throughout the human virome has not been fully explored. In this study, we evaluate 134 human infecting viruses and find significant usage of linear mimicry across the virome, particularly those in the herpesviridae and poxviridae families. Furthermore, we identify that proteins involved in cellular replication and inflammation, those expressed from autosomes, the X chromosome, and in thymic cells are over-enriched in viral mimicry. Finally, we demonstrate that short linear mimicry from Epstein-Barr virus (EBV) is significantly higher in auto-antibodies found in multiple sclerosis patients to a greater degree than previously appreciated. Our results demonstrate that human-infecting viruses frequently leverage mimicry in the course of their infection, point to substantial evolutionary pressure for mimicry, and highlight mimicrys important role in human autoimmunity. Clinically, our findings could translate to development of novel therapeutic strategies that target viral infections linked to autoimmunity, with the goal of eliminating disease-associated latent viruses and preventing their reactivation.

microbiology↗

bioRxiv2023

Comparison of shear stress patterns by the established and advanced reconstruction method incorporating side branches to predict plaque progression

BackgroundComplete vessel reconstruction (CVR) with incorporation of side branches is essential for accurate evaluation of wall shear stress (WSS) distribution. However, CVR is time consuming and blood flow simulation is computationally expensive, while there is no evidence that WSS computed by CVR, enables better prediction of disease progression compared to WSS derived from the conventional single vessel reconstruction (SVR). We aim to compare the WSS in models reconstructed using the CVR and SVR methods and examine its ability to predict disease progression. MethodsPatients who had baseline and 13-months follow-up intravascular ultrasound (IVUS) imaging (n=19 vessels), and with neoatherosclerotic lesions (n=13 vessels) on optical coherence tomography (OCT) were included in the present analysis. All the studied vessels had at least one side branch with diameter >1mm. 3-dimensional (3D) CVR and SVR were performed and time averaged (TAWSS) and multidirectional WSS were computed using pulsatile blood flow simulation and the performance of both methods in predicting disease progression in IVUS and OCT models were assessed. ResultsThe incorporation of side branches in 3D geometry resulted in lower TAWSS in the IVUS (0.821 vs 1.698Pa, p<0.001) and OCT-based reconstructions (0.682 vs 1.325Pa, p<0.001) and influenced the multidirectional WSS distribution. In native segments, WSS metrics estimated by the CVR enabled better prediction of the lumen and plaque area and burden at follow-up than SVR and disease progression defined as decrease in lumen area and increase in plaque burden (AUC CVR 0.712 vs SVR 0.554). In stented segments, multidirectional WSS was associated with neointima area in both CVR and SVR methods, but TAWSS was only a predictor of neointima area in the CVR method. ConclusionsThe incorporation of side branches in vessel reconstruction influences WSS distribution and enables more accurate prediction of disease progression in native and stented segments than SVR modelling. HighlightsO_LIComplete vessel reconstruction (CVR) with incorporation of vessel side branches has been proposed for accurate evaluation of wall shear stress (WSS) distribution compared to the traditional single vessel reconstruction (SVR) method; however, there are no studies comparing the performance of the WSS metrics derived by these methods in predicting atherosclerotic evolution. C_LIO_LIIn vessels with large side branches, the incorporation of the side branches in the vessel geometry reconstructed from angiographic and intravascular imaging data resulted in lower time averaged wall shear stress (TAWSS) and influenced the multidirectional WSS estimations compared to the models reconstructed without the side branches. C_LIO_LIThe WSS metrics estimated in the CVR models enabled better prediction of atherosclerotic disease progression at 13-months follow-up on IVUS than the WSS derived by the SVR. C_LIO_LIIn stented vessels, all the WSS metrics in the CVR and the multidirectional WSS in SVR were associated with neointima tissue development; however, both approaches showed limited efficacy in predicting neointima proliferation. C_LI

bioengineering↗

bioRxiv2021

Developmental and Intergenerational Landscape of Human Circulatory Lipidome and its Association with Obesity Risk

Lipids play a vital role in human health and development, but changes to their circulatory levels during gestation and in early life are poorly understood. Here we present the first developmental and intergenerational landscape of the human circulatory lipidome, derived by profiling of 480 lipid species representing 25 lipid classes, in mothers and their offspring (n=2491). Levels of 66% of the profiled lipids increased in maternal circulation during gestation, while cord blood had higher concentrations of acylcarnitines and lysophospholipids. The offspring lipidome at age six years revealed striking similarities with postnatal maternal lipidome (adult) in its lipid composition and concentrations. Comparison of lipids associated with child and maternal adiposity identified a 92% overlap, implying intergenerational similarities in the lipid signatures of obesity risk. We also catalogued lipid signatures linked with maternal adiposity during gestation and offspring birthweight, and validated (>70% overlap) the findings in an independent birth-cohort (n=1935).

systems biology↗

bioRxiv2019

Regulatory sites for known and novel splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants that affect neurological and psychiatric disease risk. Given that many causal variants are likely to operate by regulating gene expression, an improved understanding of the genetic control of gene expression in human brain is vital. However, the difficulties of sampling human brain, and its complexity, has meant that brain-related expression quantitative trait loci (eQTL) and allele specific expression (ASE) signals have been more limited in their explanatory power than might otherwise be expected. To address this, we use paired genomic and transcriptomic data from putamen and substantia nigra dissected from 117 brains, combined with a comprehensive set of analyses, to interrogate regulation at different stages of RNA processing and uncover novel transcripts. We identify disease-relevant regulatory loci and reveal the types of analyses and regulatory positions yielding the most disease-specific information. We find that splicing eQTLs are enriched for neuron-specific regulatory information; that ASE analyses provide highly cell-specific regulatory information; and that incomplete annotation of the brain transcriptome limits the interpretation of risk loci for neuropsychiatric disease. We release this rich resource of regulatory data through a searchable webserver, http://braineacv2.inf.um.es/.

bioinformatics↗

bioRxiv2018

Type-2 CD8+ T lymphocytes responsive to PGD2 and LTE4 in severe eosinophilic asthma

The functions and in vivo roles of type-2 CD8+ T cells in humans have not been well defined and this cell type has been largely overlooked in models of disease. We investigated this in the context of severe asthma with persistent airway eosinophilia - a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+CRTH2+ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2 (PGD2) and cysteinyl leukotriene E4 (LTE4) are also increased in the airways of the same group of patients. In vitro PGD2 and LTE4 function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.

immunology↗