Biology subjects

Bauer, A. J.

Publications and source records attributed to Bauer, A. J..

5 recordsLinked to original sources

bioRxiv2025

The role of container periphyton as an oviposition attractant for female Aedes aegypti

BackgroundAedes aegypti mosquitoes use diverse chemosensory cues to select an oviposition site. These cues are thought to provide information on factors such as food availability, predators, pathogens, and competitors. Most research on the stimuli attracting female Ae. aegypti to oviposit in natural or artificial containers has focused on the properties of the vessel and water, such as size, color, water quality, concentration of dissolved organic matter, and microorganisms. One understudied aspect of oviposition containers is periphyton, the complex community of microorganisms that can grow on the inner walls of containers where gravid Ae. aegypti females lay their eggs. Periphyton can potentially act as an indicator of the containers suitability for females looking for an oviposition site, and as a source of food for future mosquito larvae. We were interested in understanding if container periphyton attracts gravid Ae. aegypti females for oviposition and to assess the microbial composition of the periphyton community. MethodsTo answer these questions, we conducted a series of attraction and oviposition assays and collected samples from the periphyton used in these assays for 16s rRNA fingerprinting. ResultsWe demonstrated that periphyton promotes oviposition by Ae. aegypti. Results from 16s rRNA fingerprinting of periphyton specimens revealed that these communities exhibit high complexity and contain microbial taxa from several classes, including Cyanobacteria, Proteobacteria, Anaerolineae, and Cytophagia. ConclusionsUnderstanding the chemosensory interactions between mosquitoes and periphyton involved in egg laying could prompt the development and formulation of novel attractants useful in mosquito control.

ecology↗

bioRxiv2025

Single-cell analysis reveals the cellular and transcriptional diversity of thyrocytes in the normal pediatric thyroid

To enhance the understanding of cellular heterogeneity within the pediatric thyroid, single-nuclei RNA sequencing was used to recover 38,069 non-pathogenic cells from thyroid tissue of three pediatric patients. The recovered cells were analyzed using the SWANS (Single Entity Workflow ANalysiS) pipeline (version 1.0). Analysis revealed seven major cell types: thyrocytes, endothelial cells, fibroblasts, C cells, T cells, B cells, and myeloid cells. Thyrocytes were the most prominent and heterogeneous cell type. Initially, two dominant thyrocyte subsets were identified based on transcriptional activity, which were subsequently subdivided into seven subclusters. Differentially expressed genes within each cluster support distinct cellular functions, including a metabolically active subset which may be involved in hormone synthesis and a subset involved in the transport of thyroid hormone into circulation. We identified an immune subpopulation originating predominantly from a single sample that was histologically and morphologically similar to the other two samples. This supports that transcriptional changes can be detected and used to identify populations of cells, even in the absence of histologically observable changes. This characterization represents the first comprehensive portraiture of pediatric thyroid gland cells and the first description of normal patient thyrocyte and stromal cell heterogeneity in the absence of adjacent malignancy.

cell biology↗

bioRxiv2025

KEAP1 mutations activate the NRF2 pathway to drive cell growth and migration, and attenuate drug response in thyroid cancer

The KEAP1/NRF2 pathway, a major regulator of the cellular oxidative stress response, is frequently activated in human cancers. Often mediated by loss-of-function mutations in KEAP1, this activation causes increased NRF2 transcriptional activity and constitutive activation of the antioxidant response. While KEAP1 mutations have been well documented in various cancers, their presence and role in thyroid carcinoma have remained largely unexplored. In this study, we sequenced pediatric thyroid tumors and analyzed publicly available datasets, identifying 81 KEAP1 mutations in tumors across a range of histologies. In these tumors, we further identified frequent biallelic loss of KEAP1 via 19p13.2 loss of heterozygosity (LOH). MAPK-activating alterations were found in a subset of KEAP1-mutant cases, but they were mutually exclusive with 19p13.2 LOH. Transcriptome analysis also revealed significant activation of the NRF2 pathway in KEAP1-mutant tumors. Four additional cases with similar transcriptional profiles but lacking mutational data were identified, likely representing putative KEAP1 mutants. Using in vitro cell line models, we then profiled the functional consequences of KEAP1 knockout in cells with and without known driver alterations. In these models, we show that KEAP1 loss leads to an NRF2-dependent upregulation of AKR1C3, GCLC, NQO1, along with increased proliferation and migration, irrespective of MAPK mutational status. We also demonstrate that loss of KEAP1 reduced sensitivity of RET fusion-positive cells to selpercatinib, consistent with previous reports that these alterations promote drug resistance in other malignancies. In this report, we comprehensively profile KEAP1 mutations in thyroid tumors, showing they are more prevalent and functionally significant than previously recognized. These findings position KEAP1 mutations as potential novel oncogenic drivers in thyroid cancer and support the integration of KEAP1/NRF2 pathway profiling into future studies and clinical frameworks.

cancer biology↗

bioRxiv2024

A conserved function of corepressors is to nucleate assembly of the transcriptional preinitiation complex.

The plant corepressor TPL is recruited to diverse chromatin contexts, yet its mechanism of repression remains unclear. Previously, we have leveraged the fact that TPL retains its function in a synthetic transcriptional circuit in the yeast model Saccharomyces cerevisiae to localize repressive function to two distinct domains. Here, we employed two unbiased whole genome approaches to map the physical and genetic interactions of TPL at a repressed locus. We identified SPT4, SPT5 and SPT6 as necessary for repression with the SPT4 subunit acting as a bridge connecting TPL to SPT5 and SPT6. We also discovered the association of multiple additional constituents of the transcriptional preinitiation complex at TPL-repressed promoters, specifically those involved in early transcription initiation events. These findings were validated in yeast and plants through multiple assays, including a novel method to analyze conditional loss of function of essential genes in plants. Our findings support a model where TPL nucleates preassembly of the transcription activation machinery to facilitate rapid onset of transcription once repression is relieved.

molecular biology↗

bioRxiv2021

Fusion-oncogenes are associated with increased metastatic capacity and persistent disease in pediatric thyroid cancers

BackgroundIn 2014, data from a comprehensive multiplatform analysis of 496 adult papillary thyroid cancer samples reported by The Cancer Genome Atlas project suggested that reclassification of thyroid cancer into molecular subtypes, RAS-like and BRAF-like, better reflects clinical behavior than sole reliance on pathological classification. The aim of this study was to categorize the common oncogenic variants in pediatric differentiated thyroid cancer and investigate if mutation subtype classification correlated with the risk of metastasis and response to initial therapy in pediatric DTC. MethodsSomatic cancer gene panel analysis was completed on DTC from 131 pediatric patients. DTC were categorized into RAS-mutant (H-K-NRAS), BRAF-mutant (BRAF p.V600E) and RET/NTRK fusion (RET, NTRK1 and NTRK3 fusions) to determine differences between subtype classification in regard to pathological data (AJCC TNM) as well as response to therapy 1-year after initial treatment had been completed. ResultsMutation-based subtype categories were significant in most variables, including age at diagnosis, metastatic behavior, and the likelihood of remission at 1-year. Patients with RET/NTRK fusions were significantly more likely to have advanced lymph node and distant metastasis and less likely to achieve remission at one year than patients within RAS- or BRAF-mut subgroups. ConclusionsOur data supports that genetic subtyping of pediatric DTC more accurately reflects clinical behavior than sole reliance on pathological classification with patients with RET/NTRK fusions having worse outcomes than those with BRAF-mutant disease. Future trials should consider inclusion of molecular subtype into risk stratification.

genetics↗