Biology subjects

Ravindra, V.

Publications and source records attributed to Ravindra, V..

3 recordsLinked to original sources

bioRxiv2026

Normative brain-state trajectories reveal deviation from healthy aging in Alzheimer's disease

INTRODUCTIONDistinguishing healthy brain aging from early neurodegenerative disruption remains a major challenge in Alzheimers disease. METHODSUsing resting-state fMRI from the Alzheimers Disease Neuroimaging Initiative (357 participants; cognitively normal, mild cognitive impairment, Alzheimers disease), we trained a Hidden Markov Model exclusively on cognitively normal adults to define latent connectivity states. A generalized additive model estimated an age-adjusted reference trajectory of transition entropy, and subject-specific deviations from this trajectory were quantified. RESULTSMild cognitive impairment and Alzheimers disease showed progressively greater deviation from the normative reference, with the strongest disruption in Alzheimers disease. A single absolute-deviation score retained much of the predictive information contained in higher-dimensional dynamic features. DISCUSSIONThese findings suggest Alzheimers disease is associated with measurable departure from healthy dynamic brain aging, providing an interpretable framework for future longitudinal and clinically validated studies.

neuroscience↗

bioRxiv2026

Prenatal corticosteroid exposure disrupts vascular-immune interactions and impairs steroidogenesis in the fetal testis

Antenatal corticosteroid (ACS) therapy, typically using dexamethasone (Dex), is a cornerstone of improving preterm infant survival by accelerating lung maturation. However, its systemic effects on other developing organs remain poorly understood. Here, we reveal a previously unrecognized impact of prenatal Dex exposure on fetal testis development, with implications for long-term male reproductive health. Analysis of fetal testes from a Dex-based ACS mouse model revealed that Dex suppressed androgen synthesis by reducing Leydig cell number and downregulating steroidogenic pathways. Dex also activated immune programs, inducing CD163 M2 macrophages and IL10 signaling, which promoted endothelial expansion. Despite these pro-angiogenic signals, vascular architecture was disrupted: capillary density and pericyte coverage declined, while blood vessel diameter increased. Transcriptomic analyses revealed downregulation of androgen response and cholesterol metabolism pathways, alongside upregulation of immune and coagulation signatures. Analyses of fetal ovaries revealed a sexually dimorphic and organ-specific effect of ACS therapy, in which ovarian gene expression remained unaffected. Our findings uncover an immune-vascular mechanism linking prenatal Dex exposure to impaired steroidogenesis, providing new insight into potentially broad effects of ACS therapy. One Sentence SummaryPrenatal corticosteroid exposure disturbs immune-vascular interactions and suppresses androgen synthesis in the fetal testis, revealing potentially widespread effects of a commonly used therapy.

developmental biology↗

bioRxiv2016

Take ACTION to identify high-resolution cell types and associated transcriptional pathways

Single-cell transcriptomic data has the potential to radically redefine our view of cell type identity. Cells that were previously believed to be homogeneous are now clearly distinguishable in terms of their expression phenotype. Methods for automatically characterizing the functional identity of cells, and their associated properties, can be used to uncover processes involved in lineage differentiation as well as sub-typing cancer cells. They can also be used to suggest personalized therapies based on molecular signatures associated with pathology. We develop a new method, called ACTION, to infer the functional identity of cells from their transcriptional profile, classify them based on their dominant function, and reconstruct regulatory networks that are responsible for mediating their identity. Using ACTION, we identify novel Melanoma sub-types with differential survival rates and therapeutic responses, for which we provide biomarkers along with their underlying regulatory networks.

bioinformatics↗