Biology subjects

Latour, D.

Publications and source records attributed to Latour, D..

3 recordsLinked to original sources

bioRxiv2025

Temperature dependent response of microcystin-LR in acclimated Microcystis aeruginosa: highest content expected near the growth optimum

As climate change raises global temperatures and increases the frequency of cyanobacterial blooms, understanding how rising mean temperatures affect cyanotoxin content is crucial. However, no clear consensus exists, and the use of different methodologies, including different units of measurement and experimental conditions could significantly alter the yield of the relationship between temperature and toxins content. In this study, we assessed free microcystin content and cell volume in Microcystis aeruginosa PCC 7806 acclimated to seven temperatures spanning its entire thermal niche. This experimental design firstly highlighted the significant reduction in cell volume with rising temperatures between 17{degrees}C and 29{degrees}C. As a result, when the microcystin concentration was normalized by its cell volume, its temperature response was transformed from a negative correlation to a bell-shaped curve, with higher free MC-LR content measured at an estimated optimum temperature of 26.2{degrees}C, close to the thermal growth optimum of Microcystis aeruginosa. These findings provide new insights into the effects of climate warming on microcystin content. ImportanceMicrocystin-LR is a widespread cyanotoxin, originally known for its liver toxicity. In freshwater environments, cyanotoxins are an increasing concern as harmful cyanobacterial blooms become more frequent with rising global temperatures. Microcystis aeruginosa, a common bloom-forming species found worldwide, is a major producer of microcystin-LR. Understanding how environmental factors such as temperature influence toxin content in this species is essential for predicting bloom toxicity under future climate scenarios. However, current knowledge remains fragmented due to numerous factors that can influence its production and also to different way of measuring toxins and expressing their concentrations (cell or {micro}m3). Confirming that temperature greatly modifies biovolume of M. aeruginosa, this study offers new insights by highlighting the importance of considering cell volume when evaluating toxin content. Integrating changes in cell size helps reconcile earlier conflicting results and contributes to a more accurate understanding of how temperature affects toxin production in cyanobacteria. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=176 HEIGHT=200 SRC="FIGDIR/small/660678v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@7a591org.highwire.dtl.DTLVardef@6eb39org.highwire.dtl.DTLVardef@3d0f19org.highwire.dtl.DTLVardef@aa6be0_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

TIAM1 signaling drives prostatic budding and branching phenotypes and is a potential therapeutic target for BPH

Benign prostatic hyperplasia (BPH) is the most prevalent urologic disease in men aged over 50 years. However, the molecular mechanisms that drive BPH pathophysiology remain elusive. In this study, we integrated bioinformatic and experimental analyses of human BPH to identify TIAM1-RAC1 signaling pathway as a promising candidate for a molecular-based approach for BPH therapy. First, elevated TIAM1 expression in a BPH transcriptomic signature that was generated from the analysis of RNA-seq data from three independent BPH patient cohorts was validated at the protein level in a fourth patient cohort. Additional bioinformatic analyses of the BPH transcriptomic signature pointed to TIAM1-RAC1 pathway as the potential lead therapeutic pathway; and NSC23766 - a small molecule inhibitor of TIAM1 signaling - as a developmental lead compound for BPH therapy. Next, a proof-of-concept pharmacological approach of TIAM1-RAC1 inhibition in human prostatic cells using NSC23766 resulted in attenuated organoid budding and branching - a developmental program associated with prostatic nodule formation and BPH pathogenesis. Finally, shRNA-based genetic knock-down of TIAM1 in human prostatic cells led to a reduction in budding and branching phenotypes thereby phenocopying the effects of NSC23766. Together, our observations implicate elevated TIAM1 as a driver of budding and branching in BPH, and our studies pave the way for TIAM1-RAC1 based targeted approach for the treatment of the disease.

cell biology↗

bioRxiv2023

TBX2 driven switch from Androgen Receptor to Glucocorticoid Receptor signaling confers therapeutic resistance in Prostate Cancer

Recent studies have highlighted that androgen receptor (AR) signaling can be bypassed via activation of the glucocorticoid receptor (GR), and that this bypass drives enzalutamide resistance in advanced prostate cancer (PCa). However, the molecular mechanism(s) that drive the switch from AR to GR signaling remain unknown. We have previously reported that TBX2, a developmental T-box transcription factor (TF), is over-expressed in castrate resistant prostate cancer (CRPC) and that TBX2 drives the CRPC phenotype via cell-intrinsic and exosome-mediated paracrine modes. Our current study demonstrates that TBX2, a TF with known repressor and activator functions, may be the molecular switch that represses AR on one hand while activating GR expression on the other to drive CRPC. Mechanistically, our studies revealed a two-tiered mechanism of AR repression by TBX2 wherein TBX2 directly binds to the promoters of AR and GATA2, an AR coregulator, thereby resulting in the repression of AR as well as GATA2. Conversely, our results demonstrate that TBX2 mediates increased expression of GR via directly binding to the GR promoter, and through TBX2-GR functional protein-protein interaction. Our results demonstrate that the TBX2 driven switch from AR to GR signaling results in enzalutamide resistance since GR inhibition in the context of TBX2 over-expression attenuates enzalutamide resistance. Further, we present evidence that SP2509 based allosteric inhibition of Lysine Specific Demethylase 1 (LSD1), a protein that interacts with TBX2 as part of the Co-repressor of RE1-Silencing Transcription Factor (COREST) complex, is able to disrupt TBX2-GR interaction. Taken together, our study has identified TBX2 as the molecular switch that drives AR to GR signaling and thereby confers enzalutamide resistance in CRPC. Furthermore, our study provides key insights into a potential therapeutic strategy of targeting the AR to GR switch wherein SP2509-based allosteric inhibition of TBX2-LSD1 could be harnessed to target the TBX2-GR interaction, thereby resulting in the inhibition of enzalutamide resistance in CRPC.

cancer biology↗