Biology subjects

Batten, S.

Publications and source records attributed to Batten, S..

3 recordsLinked to original sources

bioRxiv2026

Dual inhibition of p38α MAPK and Casein kinase δ/ϵ as a novel treatment strategy for AR-independent and taxane-resistant advanced prostate cancer

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death among US men. Metastatic castration-resistant PCa (mCRPC) is a clinically advanced form of PCa, often associated with increased aggressiveness, metastatic potential, morbidity, and a higher risk of developing resistance to taxanes (TX), the first-line chemotherapy for mCRPC. Furthermore, cancer stemness and epithelial to mesenchymal trans-differentiation (EMT) potentially contribute to aggressiveness and the development of drug resistance in mCRPC. Here, we applied our drug development pipeline, secDrug, which utilizes a pharmacogenomics data-driven computational algorithm, to demonstrate that TAK-715 - a dual inhibitor of p38 MAPK and Casein kinase {delta}/{epsilon}, is a promising treatment for these advanced/lethal variants of PCa. Using in vitro cytotoxicity assays followed by cell-based functional assays in a panel of mCRPC cell lines representing TX-sensitive mCRPC, clonally derived TX-resistant lines, and a highly aggressive metastatic variant of mCRPC, we demonstrated the efficacy of TAK-715 treatment as a single agent and in combination with TX, including cancer stem-like cells. Further, we showed that the apoptotic effects of TAK-715 occur via a mitochondrial-mediated pathway. Bulk tumor RNA sequencing followed by pathway analysis identified genes associated with mitochondrial dysfunction and cell cycle arrest as the top molecular networks associated with TAK-715 single-treatment. HES1, a gene associated with nodal metastasis and PCa progression, was the top differentially expressed gene. Single-cell transcriptomics analysis revealed that TAK-715 treatment erodes the subclonal populations responsible for cancer stemness, metastasis, and drug resistance. The clinical significance of these findings was validated in silico using multiple patient datasets. Our results suggest that TAK-715 treatment has the potential to decrease oncogenic progression and cancer stem cell-like activity in drug-resistant, aggressive, and stem-like mCRPC cells.

cancer biology↗

bioRxiv2026

Dopamine dynamics in human anterior cingulate cortex during Pavlovian-instrumental conflict

Dopamine is believed to modulate not only instrumental learning about the link between states, actions, and outcomes but also reflexive behaviours, such as a Pavlovian bias to approach in rewarding states and freeze in aversive ones. We studied these dual roles in the human brain, by combining intracranial dopamine recordings from the anterior cingulate cortex (ACC)-- a region implicated in behavioural and cognitive control -- with a motivational Go/NoGo task involving conflict between instrumental and Pavlovian action selection. We found evidence that dopamine in the ACC is involved in evaluating whether Pavlovian responding should guide behaviour. This computational motif was observed across multiple task events, including in response to rewards and punishments, and in analyses based on a reinforcement learning model. Our results indicate that dopamine supports learning at the more abstract level of behavioural policies in addition to the more concrete levels of states and actions.

neuroscience↗

bioRxiv2021

Food or physics: plankton communities structured across Gulf of Alaska eddies

Oceanic features, such as mesoscale eddies that entrap and transport water masses, create heterogeneous seascapes to which biological communities may respond. To date, however, our understanding of how internal eddy dynamics influence plankton community structuring is limited by sparse sampling of eddies and their associated biotic communities. In this paper, we used 10 years of archived Continuous Plankton Recorder (CPR) data (2002-2013) associated with 9 mesoscale eddies in the Northeast Pacific/Gulf of Alaska to test the hypothesis that eddy origin and rotational direction determines the structure and dynamics of entrained plankton communities. Using generalized additive models and accounting for confounding factors (e.g., timing of sampling), we found peak diatom abundance within both cyclonic and anticyclonic eddies near the eddy edge. Zooplankton abundances, however, varied with distance to the eddy center/edge by rotational type and eddy life stage, and differed by taxonomic group. For example, the greatest abundance of small copepods was found near the center of anticyclonic eddies during eddy maturation and decay, but near the edge of cyclonic eddies during eddy formation and intensification. Distributions of copepod abundances across eddy surfaces were not mediated by phytoplankton distribution. Our results therefore suggest that physical mechanisms such as internal eddy dynamics exert a direct impact on the structure of zooplankton communities rather than indirect mechanisms involving potential food resources.

ecology↗