Biology subjects

Eapen, A.

Publications and source records attributed to Eapen, A..

3 recordsLinked to original sources

bioRxiv2026

Effects of neem extract on Artemia franciscana: insights from high-throughput transcriptomics and phenotypic analysis

Neem-derived biopesticides are increasingly applied in agriculture and have been tested in aquaculture research, yet their effects on non-target aquatic invertebrates remain insufficiently characterized. We evaluated the effect of neem extract on the brine shrimp Artemia franciscana using an integrated ecotoxicological approach combining phenotypic, transcriptomic, and histological analyses. Juvenile A. franciscana exhibited dose-dependent mortality and sublethal abnormalities, with a 24 h median lethal concentration of 292.48 mg/L (95% confidence interval, 257.75- 331.89) for mortality and a median effective concentration of 146.36 mg/L (95% confidence interval, 113.04-189.50) for the combined endpoint "abnormal + dead". In adults, males showed greater mortality than females after extended exposure. High-throughput RNA sequencing revealed broad treatment-associated differences in transcript abundance, with juveniles displaying downregulation of detoxification enzymes and chitin biosynthesis genes, alongside enrichment of immune- and cuticle-related gene ontologies. Adults showed transcriptional signatures of stress, including upregulation of heat shock proteins and cytoskeletal components, and suppression of genes involved in energy metabolism. Chitin precursor enzymes were selectively downregulated in males, and altered carbohydrate metabolism was observed in females. Histological analyses revealed structural deterioration of the brood sac cuticle and reduced ovarian area in treated females, consistent with transcriptomic evidence of impaired exoskeletal and reproductive processes. Overall, neem exposure was associated with phenotypic, histological, and transcriptomic changes in A. franciscana. These results support the use of combined transcriptomic and histopathological endpoints to characterize responses to plant-derived biopesticides in aquatic arthropods.

pharmacology and toxicology↗

bioRxiv2025

A unified genetic perturbation language for human cellular programming

Evolution simultaneously and combinatorially explores complex genetic changes across perturbation classes, including gene knockouts, knockdowns, overexpression, and the creation of new genes from existing domains. Separate technologies are capable of genetic perturbations at scale in human cells, but these methods are largely mutually incompatible. Here we present CRISPR-All, a unified genetic perturbation language for programming of any major type of genetic perturbation simultaneously, in any combination, at genome scale, in primary human cells. This is enabled by a standardized molecular architecture for each major perturbation class, development of a functional syntax for combining arbitrary numbers of elements across classes, and linkage to unique single cell compatible barcodes. To facilitate use, CRISPR-All converts high level descriptions of desired complex genetic changes into a single DNA sequence that can rewire genomic programs within a cell. Using the CRISPR-All language allowed for head-to-head functional comparisons across perturbation types in a comprehensive analysis of all previously identified genetic enhancements of human CAR-T cells. Combining CRISPR-All programs with single cell RNA sequencing revealed a greater diversity of phenotypic states, including improved functional performance, only accessible through distinct perturbation classes. Finally, CRISPR-All combinatorial genome scale screening of up to four distinct perturbations simultaneously revealed additive functional improvements in human T cells accessible only through iterative multiplexing of modifications across perturbation classes. CRISPR-All enables exploration of a combinatorial genetic perturbation space, which may be impactful for biological and clinical applications.

genetics↗

bioRxiv2021

Epigenetic and Transcriptional Dysregulation in CD4+ T cells of Patients with Atopic Dermatitis

Atopic dermatitis (AD) is one of the most common skin disorders in children. Disease etiology involves genetic and environmental factors, with the 29 independent AD risk loci enriched for risk allele-dependent gene expression in the skin and CD4+ T cell compartments. We investigated epigenetic mechanisms that may account for genetic susceptibility in CD4+ T cells. To understand gene regulatory activity differences in peripheral blood T cells in AD, we measured chromatin accessibility (ATAC-seq), NFKB1 binding (ChIP-seq), and gene expression (RNA-seq) in stimulated CD4+ T cells from subjects with active moderate-to-severe AD and age-matched, non-allergic controls. Open chromatin regions in stimulated CD4+ T cells were highly enriched for AD genetic risk variants, with almost half of AD risk loci overlapping with AD-dependent ATAC-seq peaks. AD-specific open chromatin regions were strongly enriched for NF{kappa}B DNA binding motifs. ChIP-seq identified hundreds of NFKB1-occupied genomic loci that were AD-specific or Control-specific. As expected, the AD-specific ChIP-seq peaks were strongly enriched for NF{kappa}B DNA binding motifs. Surprisingly, Control-specific NKFB1 ChIP-seq peaks were not enriched for NFKB1 motifs, instead containing motifs for other classes of human TFs, suggesting a mechanism involving altered indirect NFKB1 binding. Using DNA sequencing data, we identified 63 instances of genotype-dependent chromatin accessibility at 36 AD risk variants (30% of AD risk loci) that could lead to genotype-dependent expression at these loci. We propose that CD4+ T cells respond to stimulation in an AD-specific manner, resulting in disease and genotype-dependent chromatin accessibility involving NFKB binding. AUTHOR SUMMARYStimulated CD4+ T cells from patients with atopic dermatitis have disease-dependent regulation of how gene expression is regulated. This regulation is disease dependent and the way the DNA is accessible and the transcription factor NFKB1 binds is enriched for genetic risk variants. Clinically, the CD4+ T cells in the peripheral blood of patients with AD respond to stimulation in a disease and genotype-dependent manner.

genomics↗