Jason A. Somarelli

Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) are crucial during metastasis and therapy resistance. While the dynamics and master regulators of EMT are well-studied, the transcription factors that can prevent EMT or promote MET are relatively less understood. Here, by integrating bulk and spatial transcriptomic data analysis from cell lines and patient samples with mechanism-based dynamical modelling we identify IRF6 as a factor that strongly associates with an epithelial phenotype and is often inhibited during EMT. In vitro experiments in multiple cancer cell lines demonstrate the progression to a mesenchymal phenotype upon IRF6 knockdown, suggesting a role as an inhibitor of EMT. Finally, we observe that IRF6 expression levels correlate with worse patient survival in a subset of solid tumour types. Our integrated computational-experimental, systems-level analysis suggests that IRF6 is frequently downregulated during EMT and can also prevent the progression towards a complete EMT, underscoring its role as an MET stabilizing factor.

Background: Epithelial-mesenchymal transition (EMT) and its reverse process Mesenchymal-Epithelial Transition (MET) are crucial during metastasis and therapy resistance. While the dynamics and master regulators of EMT are well-studied, the transcription factors that can prevent EMT or promote MET are relatively less understood. Results: Here, by integrating bulk and spatial transcriptomic data analysis from cell lines and patient samples, with mechanism-based dynamical modelling, we identify IRF6 as a factor that strongly associates with an epithelial phenotype and is often inhibited during EMT. In vitro experiments in multiple cancer cell lines demonstrate the progression to a mesenchymal phenotype upon IRF6 knock-down, suggesting a role as an inhibitor of EMT. Finally, we observe that IRF6 expression levels correlates with worse patient survival in a subset of solid tumour types. Conclusion: Our integrated computational-experimental systems-level analysis suggests that IRF6 is frequently downregulated during EMT and can also prevent the progression towards a complete EMT, underscoring its role as an MET stabilizing factor.

Local governments and environmental nonprofits are increasingly using trash traps to intercept and remove escaped plastics and other litter from stormwater systems and surface waters. In this paper, we demonstrate the utility of these devices for collecting data that provide insights into riverine litter sources and solutions. Between 2021 and 2024, seven Waterkeeper organizations in North Carolina maintained 21 in‐stream trash traps in watersheds across the state and trained staff and volunteers to record the types and quantities of litter during cleanouts. Over this period, Waterkeeper organizations and their volunteers documented 150,750 pieces of litter captured by traps. Captured litter overwhelmingly comprised plastic that floats and is resistant to biodegradation. Litter accumulation rates were moderately positively correlated with the percentages of developed land and impervious surface as well as road and ambient population density in the associated watershed. In some traps, litter accumulation rates were also positively correlated with precipitation rates. Beyond understanding riverine plastic pollution, this paper also provides insights on challenges and opportunities that arise from using trash traps to collect data on riverine litter.

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals extensively used as plastic additives. Their environmental persistence and potential for bioaccumulation have raised significant toxicological concerns. This study evaluates the cytotoxic and molecular effects of Perfluorooctanoic acid (PFOA) and its replacement compound, Perfluoro(2-methyl-3-oxohexanoic) acid (GenX), in human-derived skin (A375), liver (HepG2), kidney (SN12C), and colon (SW620) cell lines. The experimental design assessed cell viability, gene expression, and perturbations in key cellular stress pathways, with a particular focus on TGF-β/SMAD-mediated inflammation and the p53-driven DNA damage response. Our results demonstrate compound- and cell-type-specific toxicity, with GenX displaying reduced cytotoxicity compared to PFOA across all cell types. Molecular analyses revealed that both PFAS compounds induced alterations in the TGF-β/SMAD pathway, consistent with a pro-inflammatory cellular state. Additionally, we observed activation of the DNA damage response, as evidenced by increased expression of ATM, ATR, and p53, alongside ribosomal stress-related changes in RPL5 and RPL11. Notably, while skin and liver cells exhibited similar response profiles, kidney and colon cells showed divergent modulation of SMAD signaling, suggesting tissue-specific susceptibility and mechanistic differences. These findings contribute to a deeper understanding of the differential toxicological profiles of legacy and replacement PFAS, with implications for health risk assessment and regulatory policy. Graphical

We measured the BASAL breathing frequency following an overnight fast in adult, non‐pregnant/non‐lactating, inactive mammals ranging in body mass from 15 to 5520 kg. The data included results from 338 individual animals from 34 species that were divided into terrestrial, semi‐aquatic (Otariidae and Phocidae) and aquatic mammals. Following attempts to limit the collection of breathing frequency using a basal definition and to correct the analysis phylogenetically, our results suggest that there are differences in the allometric mass‐exponent between terrestrial and aquatic/semi‐aquatic mammals. An allometric regression model, whereby both body mass and breathing frequency were transformed using log₁₀, suggested that the allometric mass exponent for terrestrial mammals (−0.303) was different from both aquatic mammals (−0.124) and semi‐aquatic mammals (−0.091). For semi‐aquatic mammals, the breathing frequency was lower in water, but we detected no association between the breathing frequency and the temperature of the medium (water or air). We propose that allometric studies of cardiorespiratory function should, if possible, adhere to the basal definition during data collection, similar to that used for metabolic rate. Such data will provide valuable information for comparative medicine of large species that are difficult to study, for which controlled baseline data might be difficult to obtain.