Biology subjects

Flores, A. M.

Publications and source records attributed to Flores, A. M..

3 recordsLinked to original sources

bioRxiv2026

Deformability screening identifies NUDT5 as a mediator of cellular mechanobiology

How cells deform, sense, and respond to mechanical cues drives physiological and disease processes ranging from development to cancer metastasis; however, unbiased approaches to identify mechanical mediators are lacking. We screened 1280 compounds to identify modulators of cancer cell deformability using a cellular filtration assay and identified 92 compounds that significantly reduced deformability of ovarian cancer cells; top hits also reduced migration and invasion. Connectivity mapping of the top 21 compounds identified NUDT5 (Nudix hydrolase 5) as a predicted mechanical mediator; transcriptomic analyses implicated NUDT5 in mechanobiology and metabolic processes. We confirmed that NUDT5 mediates intracellular ATP and cellular mechanical behaviors, including morphology and deformability. In ovarian cancer, increased NUDT5 levels were associated with higher tumor stage and worse patient survival; NUDT5 inhibition reduced migration and colony formation in vitro and peritoneal tumor burden in mice. These findings establish deformability-based screening as a platform for discovering mechanical mediators and identify NUDT5 as a therapeutic target in ovarian cancer. TeaserScreening cells based on deformability provides an unbiased approach to identify NUDT5 as a mediator of cell mechanics

cell biology↗

bioRxiv2024

Connectivity of the neuronal network for contextual fear memory is disrupted in a mouse model of third-trimester binge-like ethanol exposure

BackgroundIn rodents, third-trimester equivalent alcohol exposure (TTAE) produces significant deficits in hippocampal-dependent memory processes such as contextual fear conditioning (CFC). The present study sought to characterize changes in both behavior and Fos+ neurons following CFC in ethanol (EtOH)-treated versus saline-treated mice using TRAP2:Ai14 mice that permanently label Fos+ neurons following a tamoxifen injection. We hypothesized that TTAE would produce long-lasting disruptions to the networks engaged following CFC with a particular emphasis on the limbic memory system. MethodsOn postnatal day 7, mice received either two injections of saline or 2.5 g/kg EtOH spaced 2 hours apart. The mice were left undisturbed until they reached adulthood, at which point they underwent CFC. After context exposure on day 2, mice received a tamoxifen injection. Brain tissue was harvested. Slides were automatically imaged using a Zeiss AxioScanner. Manual counts on a priori regions of interest were conducted. Automated counts were performed on the whole brain using the QUINT 2D stitching pipeline. Last, novel network analyses were applied to identify future regions of interest. ResultsTTAE reduced context recall on day 2 of CFC. Fos+ neural density increased in the CA1 and CA3. Fos+ counts were reduced in the anteroventral (AV) and anterodorsal thalamus. The limbic memory system showed significant hyperconnectivity in male TTAE mice and the AV shifted affinity towards hippocampal subregions. Last, novel regions such as a subparafascicular area and basomedial amygdalar nucleus were implicated as important mediators. DiscussionThese results suggest that CFC is mediated by the limbic memory system and is disrupted following TTAE. Given the increase in CA1 and CA3 activity, a potential hypothesis is that TTAE causes disruptions to memory encoding following day 1 conditioning. Future studies will aim to determine whether this disruption specifically affects the encoding or retrieval of fear memories.

neuroscience↗

bioRxiv2019

Leaf shape is a predictor of fruit quality and cultivar performance in tomato

O_LICommercial tomato (Solanum lycopersicum) is one of the most widely grown vegetable crops worldwide. Heirloom tomatoes retain extensive genetic diversity and a considerable range of fruit quality and leaf morphological traits.\nC_LIO_LIHere the role of leaf morphology was investigated for its impact on fruit quality. Heirloom cultivars were grown in field conditions and BRIX by Yield (BY) and other traits measured over a fourteen-week period. The complex relationships among these morphological and physiological traits were evaluated using PLS-Path Modeling, and a consensus model developed.\nC_LIO_LIPhotosynthesis contributed strongly to vegetative biomass and sugar content of fruits but had a negative impact on yield. Conversely leaf shape, specifically rounder leaves, had a strong positive impact on both fruit sugar content and yield. Cultivars such as Stupice and Glacier, with very round leaves, had the highest performance in both fruit sugar and yield. Our model accurately predicted BY for two commercial cultivars using leaf shape data as input.\nC_LIO_LIThis study revealed the importance of leaf shape to fruit quality in tomato, with rounder leaves having significantly improved fruit quality. This correlation was maintained across a range of diverse genetic backgrounds and shows the importance of leaf morphology in tomato crop improvement.\nC_LI

plant biology↗