Biology subjects

Goswami, G.

Publications and source records attributed to Goswami, G..

3 recordsLinked to original sources

bioRxiv2026

Reversing Pathophysiology in Fragile X Syndrome Mice by Promoting PGC-1α and Mitochondrial Functions

Fragile X syndrome (FXS) is the leading cause of intellectual disabilities and autism, but a disease-modifying strategy remains unavailable. Recent studies have suggested reduced mitochondrial functions in FXS. However, the mechanisms underlying mitochondrial defects and their impact on FXS pathophysiology remain largely unclear. Here, we reveal a reduction in the mitochondrial master regulator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1) in the mouse model of FXS, the Fmr1 knockout (KO) mice. We show that this impairment is caused by the inactivity of the transcription factor cAMP-response element-binding protein (CREB) in Fmr1 KO mice. Using the small molecule ZLN005, which induces AMP-activated protein kinase (AMPK)- and CREB-dependent elevation of PGC-1 in Fmr1 KO mice, we observed significantly increased mitochondrial functions and dynamics in cultured neurons in vitro and in the hippocampus in vivo. Furthermore, ZLN005 elicited a wide range of beneficial effects in Fmr1 KO mice, including enhanced inhibitory synaptic transmission, reduced circuit hyperexcitability, improved hippocampal synaptic plasticity, reduced cortical gamma-band oscillations, and improved interhemispheric coherence. Most importantly, we observed improved cognition and reduced autism-like behaviors in ZLN005-treated Fmr1 KO mice. Together, our findings identify AMPK-CREB signaling and PGC-1 as promising and selective therapeutic targets for FXS and reveal the broad impact of restoring PGC-1 on FXS pathophysiology. One Sentence SummaryPromoting PGC-1 Reverses FXS Pathophysiology.

neuroscience↗

bioRxiv2026

Contrastive Alignment of Expression and Copy Number Highlights Dosage-Insensitive Genes in Cancer

Copy number variations (CNVs) are a hallmark of cancer genomes, yet the relationship between CNV and gene expression is not strictly deterministic. Some genes maintain stable expression despite copy number changes through regulatory compensation. Identifying these dosage-insensitive genes is challenging, requiring methods that distinguish true regulatory escape from technical noise in heterogeneous single-cell data. Here, we present a contrastive learning framework that learns a shared latent space aligning single-cell RNA-seq expression profiles with inferred CNV patterns. Our key innovation is hard negative mining: explicitly training on cell pairs with similar CNV but divergent expression patterns, which represent potential dosage insensitivity. By combining InfoNCE loss with hard negative triplet loss, we learn embeddings where expression-CNV distance quantifies regulatory concordance. We apply this framework to 10 lung adenocarcinoma patients (80k cells) from the GSE131907 atlas, classifying cancer cells as "concordant" (expression follows CNV) or "discordant" (expression escapes CNV). Differential expression analysis between these groups reveals two gene categories: escape genes upregulated in discordant cells despite CNV status, and compensation genes downregulated in discordant cells. Pooled analysis across 40,775 cancer cells identifies significant escape genes including VSIG4, FCGR1A, TREM2, and MARCO, as well as compensation genes such as MALAT1, CCL5, and CD8A. These genes represent candidate therapeutic targets and biomarker hypotheses for CNV-independent tumor behavior. Our approach provides a generalizable frame-work for discovering regulatory escape mechanisms in cancer using standard single-cell RNA-seq data.

genomics↗

bioRxiv2019

Mechanism of interaction of an endofungal bacterium Serratia marcescens D1 with its host and non-host fungi

Association of bacteria with fungi is a major area of research in infection biology, however, very few strains of bacteria have been reported that can invade and reside within fungal hyphae. Here, we report the characterization of an endofungal bacterium Serratia marcescens D1 from Mucor irregularis SS7 hyphae. Upon re-inoculation, colonization of the endobacterium S. marcescens D1 in the hyphae of Mucor irregularis SS7 was demonstrated using stereo microscopy. However, S. marcescens D1 failed to invade into the hyphae of the tested Ascomycetes (except Fusarium oxysporum) and Basidiomycetes. Remarkably, Serratia marcescens D1 could invade and spread over the culture of F. oxysporum that resulted in mycelial death. Prodigiosin, the red pigment produced by the Serratia marcescens D1, helps the bacterium to invade fungal hyphae as revealed by the increasing permeability in fungal cell membrane. On the other hand, genes encoding the type VI secretion system (T6SS) assembly protein TssJ and an outer membrane associated murein lipoprotein also showed significant up-regulation during the interaction process, suggesting the involvement of T6SS in the invasion process.

microbiology↗