Biology subjects

Baxter, D.

Publications and source records attributed to Baxter, D..

3 recordsLinked to original sources

bioRxiv2026

Integrated molecular and functional profiling identifies E0771 as a basal-like triple-negative breast cancer model

Breast cancer is a heterogeneous disease whose clinical management relies heavily on accurate molecular subtyping. The murine E0771 mammary carcinoma cell line is widely used in preclinical studies, yet its molecular identity remains controversial, with reports variably classifying it as luminal B or triple-negative. In this study, we performed an integrated molecular and functional characterization of two independently sourced E0771 cell line stocks to resolve this discrepancy. Both stocks were genetically authenticated and exhibited concordant phenotypes. Immunohistochemical and molecular analyses demonstrated absence of oestrogen and progesterone receptors, classifying E0771 as triple-negative. Functionally, E0771 cells showed no transcriptional response to oestrogen and displayed resistance to endocrine therapy both in vitro and in vivo. Collectively, our results establish E0771 as an oestrogen-independent, basal-like triple-negative breast cancer model, supporting its appropriate use in studies of hormone-resistant breast cancer biology.

cancer biology↗

bioRxiv2020

Cobalt(III) Schiff Base complexes stabilize non-fibrillar amyloid-β aggregates with reduced toxicity

The aggregation of A{beta} is believed to be foundational to the pathogenesis of Alzheimers disease (AD). In vitro aggregation kinetics have been shown to correlate with rates of disease progression in both AD patients and animal models, thus proving to be a useful metric for testing A{beta}-targeted therapeutics. Here we present evidence of Cobalt(III) Schiff base complex (Co(III)-sb) modulation of A{beta} aggregation kinetics by a variety of complementary techniques. These include Thioflavin T (ThT) fluorescence, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), and atomic force microscopy (AFM). Our data was fitted to kinetic rate laws using a mathematical model developed by Knowles et al. in order to extract mechanistic information about the effect of Co(III)-sb on aggregation kinetics. Our analysis revealed that Co(III)-sb significantly decreases the kinetic parameter k+, and significantly increases the polymerization rate kn, suggesting that Co(III)-sb causes A{beta} to rapidly form stable oligomeric species that are unable to elongate into mature fibrils. This result was corroborated by TEM and AFM of A{beta} aggregates in vitro. We also demonstrate that A{beta} aggregate mixtures produced in the presence of Co(III)-sb exhibit decreased cytotoxicity compared to untreated samples. Statement of SignificanceAmyloid-{beta} is thought to be a key mediator in the pathology of Alzheimers disease, yet its precise mechanisms of toxicity are poorly understood. The interaction of A{beta} with endogenous metal ions via its N terminal Histidine residues has been shown to alter the peptides aggregation and toxicity. As such, metal-based complexes have been developed both as therapeutic agents as well as tools for investigating the role of metal binding in the pathogenesis of AD. This work expands on our previous studies developing Cobalt(III) Schiff base complexes as amyloid inhibitors. Here we demonstrate effective inhibition of aggregation by various complementary modalities. Additionally we show that Co(III)-sb reduces the toxicity of A{beta} aggregates to cells in culture.

neuroscience↗

bioRxiv2017

Accuracy, Reproducibility And Bias Of Next Generation Sequencing For Quantitative Small RNA Profiling: A Multiple Protocol Study Across Multiple Laboratories

Small RNA-seq is increasingly being used for profiling of small RNAs. Quantitative characteristics of long RNA-seq have been extensively described, but small RNA-seq involves fundamentally different methods for library preparation, with distinct protocols and technical variations that have not been fully and systematically studied. We report here the results of a study using common references (synthetic RNA pools of defined composition, as well as plasma-derived RNA) to evaluate the accuracy, reproducibility and bias of small RNA-seq library preparation for five distinct protocols and across nine different laboratories. We observed protocol-specific and sequence-specific bias, which was ameliorated using adapters for ligation with randomized end-nucleotides, and computational correction factors. Despite this technical bias, relative quantification using small RNA-seq was remarkably accurate and reproducible, even across multiple laboratories using different methods. These results provide strong evidence for the feasibility of reproducible cross-laboratory small RNA-seq studies, even those involving analysis of data generated using different protocols.

genomics↗