Biology subjects

Grove, S.

Publications and source records attributed to Grove, S..

3 recordsLinked to original sources

bioRxiv2024

PIKfyve controls dendritic cell function and tumor immunity

The modern armamentarium for cancer treatment includes immunotherapy and targeted therapy, such as protein kinase inhibitors. However, the mechanisms that allow cancer-targeting drugs to effectively mobilize dendritic cells (DCs) and affect immunotherapy are poorly understood. Here, we report that among shared gene targets of clinically relevant protein kinase inhibitors, high PIKFYVE expression was least predictive of complete response in patients who received immune checkpoint blockade (ICB). In immune cells, high PIKFYVE expression in DCs was associated with worse response to ICB. Genetic and pharmacological studies demonstrated that PIKfyve ablation enhanced DC function via selectively altering the alternate/non-canonical NF-{kappa}B pathway. Both loss of Pikfyve in DCs and treatment with apilimod, a potent and specific PIKfyve inhibitor, restrained tumor growth, enhanced DC-dependent T cell immunity, and potentiated ICB efficacy in tumor-bearing mouse models. Furthermore, the combination of a vaccine adjuvant and apilimod reduced tumor progression in vivo. Thus, PIKfyve negatively controls DCs, and PIKfyve inhibition has promise for cancer immunotherapy and vaccine treatment strategies.

cancer biology↗

bioRxiv2022

Strain and serovar variants of Salmonella enterica exhibit diverse tolerance to food chain-related stress

Non-Typhoidal Salmonella (NTS) continues to be a leading cause of foodborne illness worldwide. Food manufacturers implement hurdle technology by combining more than one approach to control food safety and quality, including preservatives such as organic acids, refrigeration, and heating. We assessed the variation in survival in stresses of genotypically diverse isolates of Salmonella enterica to identify genotypes with potential elevated risk to sub-optimal processing or cooking. Sub-lethal heat treatment, survival in desiccated conditions and growth in the presence of NaCl or organic acids were investigated. S. Gallinarum strain 287/91 was most sensitive to all stress conditions. While none of the strains replicated in a food matrix at 4{degrees}C, S. Infantis strain S1326/28 retained the greatest viability, and six strains exhibited a significantly reduced viability. A S. Kedougou strain exhibited the greatest resistance to incubation at 60{degrees}C in a food matrix that was significantly greater than S. Typhimurium U288, S Heidelberg, S. Kentucky, S. Schwarzengrund and S. Gallinarum strains. Two isolates of monophasic S. Typhimurium, S04698-09 and B54 Col9 exhibited the greatest tolerance to desiccation that was significantly more than for the S. Kentucky and S. Typhimurium U288 strains. In general, the presence of 12mM acetic acid or 14mM citric acid resulted in a similar pattern of decreased growth in broth, but this was not observed for S. Enteritidis, and S. Typhimurium strains ST4/74 and U288 S01960-05. Acetic acid had a moderately greater effect on growth despite the lower concentration tested. A similar pattern of decreased growth was observed in the presence of 6% NaCl, with the notable exception that S. Typhimurium strain U288 S01960-05 exhibited enhanced growth in elevated NaCl concentrations. An understanding of the molecular basis of phenotypic variation in response to stress has the potential to improve process validation during food challenge tests, improve processing, and result in more reliable risk assessments in the food industry.

microbiology↗

bioRxiv2020

Are fleas highly modified Mecoptera? Phylogenomic resolution of Antliophora (Insecta: Holometabola)

Insect orders have been defined and stable for decades, with few notable exceptions (e.g., Blattodea and Psocoptera). One of the few remaining questions of order-level monophyly is that of Mecoptera in respect to the phylogenetic placement of Siphonaptera (fleas). We used a large set of transcriptomic nucleotide sequence data representing 56 species and more than 3,000 single-copy genes to resolve the evolutionary history of Antliophora, including fleas (Siphonaptera), scorpionflies and relatives (Mecoptera), and true flies (Diptera). We find that fleas and mecopterans together are the sister group of flies. However, our data and/or analyses are unable to distinguish whether fleas are sister to a monophyletic Mecoptera, or whether they arose from within extant mecopteran families, rendering Mecoptera paraphyletic. We did not detect parameter bias in our dataset after applying a broad range of detection methods. Counter to a previous hypothesis that placed fleas within Mecoptera as the sister group to wingless boreids (snow fleas), we found a potential sister group relationship between fleas and the enigmatic family Nannochoristidae. Although we lack conclusive evidence, it seems possible that fleas represent the most-species rich group of modern mecopterans and that their parasitic lifestyle and morphological adaptations have simply made them unrecognizable in respect to their order-level classification.

evolutionary biology↗