Biology subjects

Raval, R.

Publications and source records attributed to Raval, R..

5 recordsLinked to original sources

bioRxiv2026

Dietary depletion of glutamine is atheroprotective

Heart attacks and strokes are late-stage complications of rupture of unstable atherosclerotic plaques. Stable plaques contain stabilizing matrix-producing fibrotic cells, largely smooth muscle cell (SMC)-derived. The molecular drivers of SMC phenotypic transitions to beneficial fibrotic or destabilizing inflammatory and calcifying phenotypes are unclear. Since atherosclerosis develops over decades, there is extensive interest in identifying dietary alterations that enhance plaque stability. We demonstrate that SMC acquire a fibrotic phenotype dependent on glutamine-derived metabolites supporting both catabolism and collagen synthesis. Moreover, dietary glutamine restriction decreases mortality of mice susceptible to atherosclerotic plaque rupture. Lesions from glutamine-restricted mice are smaller and have increased SMC investment. This study identifies dietary glutamine as a driver of cardiovascular mortality, suggesting a new strategy for reducing late-stage complications of atherosclerosis.

physiology↗

bioRxiv2025

Hyphal induction in Candida albicans: Optimizing medium parameters to accelerate hyphal growth enhanced by GlcNAc

Hyphal formation is a critical virulence trait in Candida species, contributing significantly to host tissue invasion, immune evasion, and disease progression. The morphological transition from yeast to hyphal form is therefore a key target for antifungal intervention. However, conventional hyphal induction media are often complex, expensive, and poorly standardized. In this study, we developed a simplified and cost-effective medium (MF8) containing peptone (0.16%), dextrose (0.4%), and bovine serum albumin (BSA; 0.25%), which supported moderate hyphal growth under nutrient-limited conditions. The addition of N-acetylglucosamine (GlcNAc) markedly enhanced filamentation. Using a Design of Experiments (DOE) approach via JMP software, we evaluated the effects of GlcNAc and magnesium sulfate (MgSO) on hyphal induction. GlcNAc was identified as a significant enhancer (p < 0.05; R{superscript 2} = 0.26), while MgSO had no significant impact (p > 0.05). Under optimized conditions (30 mM GlcNAc, 1 mM MgSO), RT-qPCR analysis revealed strong upregulation of HWP1 (100-fold at 4 h; 85-fold at 6 h) and HGC1 (>6-fold; p < 0.05). A concurrent pH shift from alkaline to acidic during 1-6 hours correlated with hyphal induction and gene activation, suggesting that acidification may serve as an additional cue regulating morphogenesis. IMPORTANCECandida species are highly adaptable opportunistic fungi that persist in diverse host niches due to numerous virulence factors. While typically commensal, they can transition to pathogenic forms, with hyphal formation being a key virulence trait. This yeast-to-hypha switch facilitates tissue invasion, immune evasion, and disease progression, making it a major target in antifungal research. Conventional hyphal induction media are often complex and costly. Developing a simplified, cost-effective, and reproducible medium would enhance studies on morphogenesis and pathogenesis, support drug screening, and potentially reveal novel virulence mechanisms under alternative environmental cues.

microbiology↗

bioRxiv2025

Anticancer synthetic arylsulfonamides with Wnt1-modulating activity

Dysregulation of the Wnt1/{beta}-catenin signaling pathway has been demonstrated to be a driving factor in the propagation of several human cancers. Previous studies have discovered methyl 3-{[(4-methylphenyl)sulfonyl]amino}benzoate (MSAB) as a selective inhibitor of the Wnt1/{beta}-catenin signaling pathway, which putatively functions through direct engagement of {beta}-catenin. To understand how changes to the identity and position of the methyl ester affect the in vitro potency of this compound in Wnt1-driven mammalian cell lines, we prepared and evaluated three analogs of MSAB with 3- and 4-substituted methyl and ethyl esters. In MTT assays, analogs with methyl esters showed significantly more activity than their ethyl ester counterparts and both 4-substituted esters exhibited significantly attenuated antiproliferative activity, with MSAB exhibiting dose-dependent activity across cancerous cell lines. Further analysis by flow cytometry reveals low-Annexin V signal, suggesting that these compounds do not function via a pro-apoptotic pathway. Additionally, through a TCF/LEF-activated luciferase reporter cell assay, we observe that the 4-substituted methyl ester analogous to MSAB exhibits slightly diminished Wnt1-inhibitory activity, while 3- and 4-substituted ethyl esters exhibit minimal Wnt1-inhibitory activity. This difference in potency with a simple ester substitution might be attributed to several factors that ultimately drive antiproliferative activity, prompting the investigation of other potential substituents to further investigate the structure-activity relationship of these compounds as Wnt1-based antiproliferative agents.

cancer biology↗

bioRxiv2021

Synchronous seasonality in the gut microbiota of wild wood mouse populations

O_LIThe gut microbiome performs many important functions in mammalian hosts, with community composition shaping its functional role. However, what factors drive individual microbiota variation in wild animals and to what extent these are predictable or idiosyncratic across populations remains poorly understood. C_LIO_LIHere, we use a multi-population dataset from a common rodent species (the wood mouse, Apodemus sylvaticus), to test whether a consistent set of core gut microbes is identifiable in this species, and to what extent the predictors of microbiota variation are consistent across populations. C_LIO_LIBetween 2014 and 2018 we used capture-mark-recapture and 16S rRNA profiling to intensively monitor two wild UK mouse populations and their gut microbiota, as well as characterising the microbiota from a laboratory-housed colony of the same species. C_LIO_LIAlthough broadly similar at high taxonomic levels and despite being only 50km apart, the two wild populations did not share a single bacterial amplicon sequence variant (ASV). Meanwhile, the laboratory-housed colony shared many ASVs with one of the wild populations from which it is thought to have been founded decades ago. Despite strong taxonomic divergence in the microbiota, the factors predicting compositional variation in each wild population were remarkably similar. We identified a strong and consistent pattern of seasonal microbiota restructuring that occurred at both sites, in all years, and within individual mice. While the microbiota was highly individualised, seasonal convergence in the gut microbiota among individuals occurred in late winter/early spring. C_LIO_LIThese findings reveal highly repeatable seasonal gut microbiota dynamics across distinct populations of this species, despite divergent taxa being involved. Providing a platform for future work to understand the drivers and functional implications of such predictable seasonal microbiome restructuring, including whether it might provide the host with adaptive seasonal phenotypic plasticity. C_LI

ecology↗

bioRxiv2021

Identification and quantification of chimeric sequencing reads in a highly multiplexed RAD-seq protocol

Highly multiplexed approaches have become a common practice in genomic studies. They have improved the cost-effectiveness of genotyping hundreds of individuals by using combinatorially-barcoded adapters. These strategies, however, can potentially misassign reads to incorrect samples. Here we used a modified quaddRAD protocol to analyse the occurrence of index hopping and PCR chimeras in a series of experiments with up to a 100 multiplexed samples per sequencing lane (total n = 639). We created two types of sequencing libraries: four libraries of Type A, where PCR reactions were run on individual samples before multiplexing, and three libraries of Type B, where PCRs were run on pooled samples. We used fixed pairs of inner barcodes to identify chimeric reads. Type B libraries show a higher percentage of misassigned reads (1.15%) compared to Type A libraries (0.65%). We also quantify the commonly undetectable chimeric sequences that occur whenever multiplexed groups of samples with different outer barcodes are sequenced together on a single flow cell. Our results suggest that these types of chimeric sequences represent up to 1.56% and 1.29% of reads in Type A and B libraries, respectively. We review the source of such errors, provide recommendations for developing highly-multiplexed RAD-seq protocols and analysing the resulting data to minimise the generation of chimeric sequences, allow their quantification, and provide finer control over the number of PCR cycles necessary to generate enough input DNA for library preparation.

bioinformatics↗