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Clapp, A.

Publications and source records attributed to Clapp, A..

2 recordsLinked to original sources
bioRxiv2026

Oxylipins and Other Natural Products Produced by UV-sterilization Impact Commercial Oyster Larvae Production in a New England Estuary

Here, oyster larval developmental abnormalities within a New England hatchery were linked to a common UV sterilization technique that has been used for over 20 years. Because of the known link between phytoplankton oxylipins and egg mortality in copepods, we hypothesized that UV pretreatment of seawater results in the production of oxylipins that inhibit larval digestion of microalgae. We used lipidomics to observe changes in the organic compounds dissolved in estuarine seawater when filtered and when filtered and pretreated with UV. UV treatment resulted in an increase in the relative abundance of oxylipins associated with cyanobacteria, fungi, and macroalgae in 2020, whereas oxylipins typically produced by diatoms were more abundant in the UV treatments from 2021. Oxylipin concentrations were higher in 2020, when the hatchery reported the most severe problems with larval development. Removing the UV step allowed continued larval production in both years. However, the lack of UV sterilization led to an unidentified bacterial pathogen in 2021, which nearly decimated the overall seasonal production of oyster seed. To follow up in a more controlled environment, the larvae were exposed to exogenous oxidized lipids, which resulted in the same digestive syndrome and histological symptoms as the endogenous suite of compounds produced by UV. Further investigation of the lipidomes revealed that oxylipins were only one class of potentially harmful compounds linked to UV sterilization, and the dissolved concentrations of secondary metabolites associated with higher plants, a wide range of pharmaceuticals, and anthropogenic organic pollutants also increased under UV light. Future efforts will explore the sources of these compounds, the mechanisms by which they inhibit oysters, and whether this is an emerging environmental problem for other ecosystems and shellfish hatcheries. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/738347v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1427dc0org.highwire.dtl.DTLVardef@4dcbf9org.highwire.dtl.DTLVardef@18a57faorg.highwire.dtl.DTLVardef@195e0ed_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗
bioRxiv2018

Regulation of the error-prone DNA polymerase polκ by oncogenic signaling and its contribution to drug resistance

Mutations in the proofreading domains of the replicative DNA polymerases pol{delta} and pol{varepsilon} are associated with elevated mutation rates in cancer, but the roles of other DNA polymerases in tumorigenesis remain poorly understood. One such polymerase is pol{kappa}, an enzyme that plays a key role in translesion synthesis. pol{kappa} contributes to cell survival in the face of DNA damage but can be highly mutagenic due to lack of a proofreading domain. Here we demonstrate that cancer cells under stress from oncogene inhibition upregulate pol{kappa} and shift its localization from the cytoplasm to the nucleus. This effect can be phenocopied by mTOR inhibition or glucose deprivation, analogous to stress-induced mutagenesis in E. coli whereby cell stress and nutrient deprivation can upregulate and activate DinB/pol IV (the bacterial orthologue of pol{kappa}). We find that cancer cells normally sequester pol{kappa} in the cytoplasm via exportin-1, likely to prevent excess mutagenesis from the error-prone nature of this polymerase. Subverting the normal nuclear-cytoplasmic shuttling by forced overexpression of nuclear pol{kappa} increases resistance of melanoma cells to the BRAFV600E inhibitor vemurafenib. This data suggests a mechanism by which cancer cells regulate the expression and localization of the error-prone polymerase pol{kappa}, abrogation of which can contribute to drug resistance.\n\nOne Sentence Summary: Cancer cells under stress from oncogene or mTOR inhibition dysregulate the error-prone DNA polymerase pol{kappa}, which contributes to drug resistance in melanoma cells.

cancer biology↗