Biology subjects

Gallo, R.

Publications and source records attributed to Gallo, R..

3 recordsLinked to original sources

bioRxiv2026

ClonoDynamics enables replicate-resolved inference of longitudinal T cell receptor repertoire dynamics

Longitudinal T cell receptor repertoire analysis can confound biological change with measurement noise and estimator-induced structure. We developed ClonoDynamics, a framework integrating latent abundance inference with replicate-decoupled estimates of directional change and cross-replicate displacement covariance. Pseudo longitudinal series assembled from 12 independently processed technical measurements of one biological sample revealed apparent restoring dynamics caused by reusing measurements for conditioning and change estimation. Separating these roles between replicates largely removed this artifact. Synthetic controls preserving empirical detection patterns showed dose-dependent recovery of temporal accumulation, resolving the two larger imposed effects but not the smallest. Applied to TCR{beta} repertoires from ten healthy adults sampled weekly for six weeks, ClonoDynamics identified abundance-dependent directional change and shared fluctuations exceeding the technical reference. Within the analyzed abundance domain, these fluctuations showed no consistent positive accumulation over 1 to 5 weeks. ClonoDynamics provides an experimentally benchmarked framework for distinguishing estimator-induced patterns, replicate-consistent longitudinal variation, and temporal accumulation.

immunology↗

bioRxiv2026

Extracellular DNASE1L3 dysfunction fuels obesity-driven inflammation and metabolic syndrome

Obesity, a global health crisis affecting 16% of the world population, is characterized by chronic inflammation that contributes to health complications such as type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Emerging evidence suggests that self-DNA released from dying cells aberrantly activates inflammatory responses during obesity. However, the role of extracellular deoxyribonucleases (DNASEs), which at steady state regulate abundance of extracellular self-DNA, remains poorly understood in this context. Here, we show that individuals with obesity exhibit elevated levels of circulating cell-free DNA (cfDNA) with a distinctive end-motif signature, anti-DNASE1L3 autoantibodies and a reduction in circulating DNASE activity. These cfDNA alterations correlate with the severity of obesity and can be corrected by therapeutic intervention such as bariatric surgery. Similarly, mice fed a high-fat diet (HFD) displayed increased cfDNA levels and decreased DNASE activity. Genetic deficiency of the extracellular nuclease DNASE1L3 in mice worsened HFD-induced metabolic complications, including glucose intolerance, insulin resistance, MASLD, and metabolic tissue inflammation. Conversely, targeted supplementation of DNASE1L3 in the liver using adeno-associated viral vectors protected obese mice from developing MASLD and liver inflammation. These findings uncover a novel role of DNASE1L3 in controlling obesity-associated inflammation and its potential therapeutic use for preventing metabolic disease.

pathology↗

bioRxiv2020

DYRK3-Controlled Phase Separation Organizes the Early Secretory Pathway

The dual-specificity kinase DYRK3 controls formation and dissolution of several intracellular condensates thereby regulating various cell physiological processes. Here we report that DYRK3 establishes a dynamic equilibrium between condensation and dissolution of proteins associated with membranous structures of the early secretory pathway to organize membrane traffic between the ER and the Golgi complex in mammalian cells. This depends on the peripheral membrane protein Sec16A, whose N-terminal disordered region forms DYRK3-controlled liquid-like condensates on the surface of the ER and co-phase separates with multiple ER exit site components and a subset of matrix proteins specifically associated with ERGIC and cis-Golgi. Our findings support a mechanism whereby multiple interacting and differentially regulated intracellular condensates create favorable environments for directional membrane traffic in eukaryotic cells.

cell biology↗