Biology subjects

Fuentes, I.

Publications and source records attributed to Fuentes, I..

4 recordsLinked to original sources

bioRxiv2025

A Xanthomonas effector protein contributes quantitatively to virulence by inducing at least two minor Susceptibility genes

The transcription activator-like effector Tal12a is widely conserved among Xanthomonas campestris pv. campestris strains that cause black rot in Brassica crops. However, its role in disease remains unclear. To investigate how Tal12a contributes to pathogenesis, we combined transcriptomic profiling of cauliflower leaves infected with Tal12a-expressing strains, prediction of TALE-binding elements, and heterologous expression assays in Nicotiana benthamiana. The aim of this approach was to identify candidate susceptibility genes. Artificial TALEs were further employed to validate the contribution of these candidate targets to disease development. Tal12a enhanced both virulence and bacterial growth in cauliflower. Transcriptome analysis revealed 380 genes that were induced upon infection, nine of which were prioritised as candidates. Seven of these were confirmed as direct Tal12a targets, while the induction of the sugar transporter genes BoSWEET13 and BoSWEET14c likely occurred indirectly. Functional assays demonstrated that these two SWEET genes and the BoIAA7c gene, which encodes auxin-dependent transcriptional regulator, contribute to disease development. These findings identify the first susceptibility genes in cauliflower and reveal that Tal12a promotes disease through a complex transcriptional reprogramming, involving direct and indirect target induction, with several genes functioning as minor susceptibility factors.

plant biology↗

bioRxiv2025

Dietary lipids, not ketone body metabolites, influence intestinal tumorigenesis in a ketogenic diet

Diet composition shapes tissue function and disease risk by modulating nutrient availability, metabolic state, and cellular dynamics. In the gastrointestinal tract, obesogenic high-fat diets enhance intestinal stem cell activity and tumorigenesis. However, the impact of ketogenic diets (KD), which contain even higher lipid content but induce ketogenesis, remains poorly understood. This is particularly relevant for patients with familial adenomatous polyposis (FAP), who face a high risk of small intestinal tumours. Here, we combine dietary, genetic, and metabolic manipulations in mouse models of spontaneous intestinal adenoma formation to dissect the role of systemic and epithelial ketogenesis in intestinal cancer. We show that KD accelerates tumour burden and shortens survival, independent of ketone body production. Through genetic manipulation of the ketogenic pathway, we modulate local and systemic ketone body production; however, neither inhibition nor augmentation of the ketogenic enzyme HMGCS2 nor disruption of ketolysis altered tumour progression. In contrast, inhibition of fatty acid oxidation did limit adenomatous formation. These findings reveal that dietary lipid content, through FAO rather than ketone body metabolism, influences intestinal tumorigenesis and highlight the need for nuanced consideration of dietary strategies for cancer prevention in genetically susceptible populations.

cancer biology↗

bioRxiv2022

Viroscope: plant viral diagnosis from NGS data using biologically-informed genome assembly coverage

Next-generation sequencing (NGS) methods are transforming our capacity to detect pathogens and perform disease diagnosis. Although sequencing advances have enabled accessible and point-of-care NGS, data analysis pipelines have yet to provide robust tools for precise and certain diagnosis, particularly in cases of low sequencing coverage. Lack of standardized metrics and harmonized detection thresholds confound the problem further, impeding the adoption and implementation of these solutions in real-world applications. In this work, we tackle these issues and propose biologically-informed viral genome assembly coverage as a method to improve diagnostic certainty. We use the identification of viral replicases, an essential function of viral life cycles, to define genome coverage thresholds in which biological functions can be described. We validate the analysis pipeline, Viroscope, using field samples, synthetic and published datasets and demonstrate that it provides sensitive and specific viral detection. Furthermore, we developed Viroscope.io a web-service to provide on-demand NGS data viral diagnosis to facilitate adoption and implementation by phytosanitary agencies to enable precise viral diagnosis.

microbiology↗

bioRxiv2021

The gastrin-releasing peptide regulates stress-enhanced fear and dopamine signaling

Fear extinction is an adaptive behavioral process critical for organisms survival, but deficiency in extinction may lead to PTSD. While the amygdala and its neural circuits are critical for fear extinction, the molecular identity and organizational logic of cell types that lie at the core of these circuits remain unclear. Here we report that mice deficient for amygdala-enriched gastrin-releasing peptide gene (Grp-/-) exhibit enhanced neuronal activity in the basolateral amygdala (BLA) and stronger fear conditioning, as well as deficient extinction in stress-enhanced fear learning (SEFL). rAAV2-retro-based tracing combined with visualization of the GFP knocked in the Grp gene showed that BLA receives GRPergic or conditioned stimulus projections from the indirect auditory thalamus-to-auditory cortex pathway, ventral hippocampus and ventral tegmental area. Transcription of dopamine-related genes was decreased in BLA of Grp-/- mice following SEFL extinction recall, suggesting that the GRP may mediate fear extinction regulation by dopamine. Impact statementMice deficient for the amygdala-enriched gastrin-releasing peptide gene are susceptible to stress-enhanced fear, a behavioral protocol with relevance to PTSD, and show a decrease in dopamine-related gene transcription.

neuroscience↗