Biology subjects

Vidal, N.

Publications and source records attributed to Vidal, N..

6 recordsLinked to original sources

bioRxiv2026

Morphologic intratumoral heterogeneity from routine whole-slide histopathology is prognostic for survival in primary central nervous system lymphoma: development in the LOC Network and international external validation

Background: Clinical scores incompletely capture outcomes in primary central nervous system lymphoma (PCNSL). We quantified morphologic heterogeneity in pretreatment hematoxylin and eosin (H\&E) whole slides. Patients and methods: Three independent cohorts of immunocompetent, HIV- and EBV-negative patients treated recently were analyzed: LOC 2023 (122 slides), phase III BLOCAGE-01 (245 slides; NCT02313389), and external Barcelona (BCN; 41 slides). UNI embeddings, prototype learning, spatial metrics, and elastic-net Cox regression defined ITH-C. Results: Models achieved bootstrap-corrected concordance of 0.797--0.834. Age-, sex-, and KPS-adjusted ITH-C HRs were 1.29 (95\% CI 1.01--1.64), 1.27 (1.07--1.51), and 2.13 (1.35--3.37), respectively. Adding ITH-C increased MSKCC C-index from 0.671 to 0.717, 0.560 to 0.593, and 0.588 to 0.706. Spatial transcriptomics linked ITH-C to immune programs. Conclusions: Routine H\&E encodes prognostic spatial heterogeneity in PCNSL. ITH-C complements clinical scores, supporting prospective risk stratification.

bioinformatics↗

bioRxiv2026

Periplasmic detoxification of urate hydroperoxide underpins E. coli survival in the inflamed gut

Uric acid, the final product of purine metabolism in humans, accumulates in blood and tissues at relatively high concentrations1 as humans lack the enzyme uricase2,3. Under inflammatory conditions, uric acid can be oxidised to yield reactive intermediates4. In activated neutrophils, myeloperoxidase (MPO) catalyses the oxidation of uric acid by hydrogen peroxide, leading to the formation of urate hydroperoxide (UH)5,6. While recent studies have shown that UH is toxic to bacteria lacking peroxiredoxins7, its precise mechanism of toxicity and the existence of dedicated bacterial defence systems remain unknown. Here, we identify HiuH as a periplasmic enzyme, conserved across E. coli strains, that specifically degrades UH. Our findings reveal that UH selectively induces the expression of hiuH and that HiuH efficiently detoxifies UH both in vitro and in bacterial cells. HiuH cooperates with MsrP, a periplasmic methionine sulfoxide reductase that repairs UH-induced protein-bound methionine oxidation. This combined defence offering both direct detoxification and damage repair, is essential for bacterial survival under UH stress, and confers a competitive fitness advantage in a DSS-induced mouse model of colitis. Although UH is chemically transient, our work shows that it imposes durable biological consequences and a sufficient fitness cost in the in vivo niches occupied by E. coli to favour the evolution of a dedicated detoxification pathway beyond general oxidative-stress responses, defining a key adaptation to periods of gut inflammation.

microbiology↗

bioRxiv2025

CRISPR screening reveals SYCP3 as a key driver of metastasis in prostate cancer

Prostate cancer (PCa) is a prevalent male cancer with high survival rates, except in advanced or metastatic stages, for which effective treatments are lacking. Metastatic PCa involves complex mechanisms including loss of tumor suppressor genes and DNA repair molecules, which impacts therapy responses. We have reanalyzed data from a CRISPR/Cas9 genome wide screening previously performed to identify essential regulators of invasive abilities of the metastatic cell line DU145 identifying SYCP3 as a regulator of metastatic invasion. Subsequent analyses of tumor samples demonstrated that SYCP3 expression is frequently upregulated in PCa tumors from patients in advanced stages. Furthermore, SYCP3 genetic depletion significantly reduced the invasive and migratory abilities of DU145 cells and increased their adhesion capacity. Additionally, and due to the implication of SYCP3 on DNA repair processes, we have analyzed the role of SYCP3 on the cellular response to radiotherapy (RT) and found that its depletion induced RT resistance, suggesting a role for SYCP3 in DNA damage response and genomic instability. All these data support a role for SYCP3 in PCa metastasis and provides opportunities for personalized medicine.

cancer biology↗

bioRxiv2025

Cell-type specific profiling of human entorhinal cortex at the onset of Alzheimer's disease neuropathology

Neurons located in layer II of the entorhinal cortex (ECII) are the primary site of pathological tau accumulation and neurodegeneration at preclinical stages of Alzheimers disease (AD). Exploring the alterations that underlie the early degeneration of these cells is essential to develop therapies that curb the disease before symptom onset. Here we performed cell-type specific profiling of human EC at the onset of AD neuropathology. We identify an early response to amyloid pathology by microglia and oligodendrocytes. Importantly, we provide the first insight into neuronal alterations that coincide with incipient tau pathology: the signaling pathway for Reelin, recently shown to be a major AD resilience gene is dysregulated in ECII neurons, while the secreted synaptic organizer molecules NPTX2 and CBLN4, emerging AD biomarkers, are downregulated in surrounding neurons. By uncovering the complex multicellular landscape of EC at these early AD stages, this study paves the way for detailed characterization of the mechanisms governing NFT formation and opens long-needed novel therapeutic avenues.

neuroscience↗

bioRxiv2023

The dynamics of oligodendrocyte populations following permanent ischemia promotes long-term spontaneous remyelination of damaged area.

Stroke is a major public health concern, whit limited clinically approved interventions available to enhance sensorimotor recovery beyond reperfusion. Remarkably, spontaneous recovery is observed in certain stroke patients, suggesting the existence of a self-brain repair mechanism not yet fully understood. In a rat model of permanent cerebral ischemia, we described an increase in oligodendrocytes expressing 3RTau in damaged area. Considering that restoration of myelin integrity ameliorates symptoms in many neurodegenerative diseases, here we hypothesize that this cellular response could trigger remyelination. Our results revealed after ischemia an early recruitment of OPCs to damaged area, followed by their differentiation into 3RTau+ pre-myelinating cells and subsequent into remyelinating oligodendrocytes. Using rat brain slices and mouse primary culture we confirmed the presence of 3RTau in pre-myelinating oligodendrocytes and a subset of mature. The myelin status analysis confirmed long-term remyelination in the damaged area. Postmortem samples from stroke subjects showed a reduction in oligodendrocytes, 3RTau+ cells, and myelin complexity in subcortical white matter. In conclusion, the dynamics of oligodendrocytes populations after ischemia reveals a spontaneous brain self-repair mechanism which restores the functionality of neuronal circuits long-term by remyelination of damage area. This is evidenced by the improvement of sensorimotor functions in ischemic rats. A deep understanding of this mechanism could be valuable in the search for alternative oligodendrocyte-based, therapeutic interventions to reduce the effects of stroke.

neuroscience↗

bioRxiv2023

CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel driver of metastasis in prostate cancer

Owing to the inefficacy of available treatments, the survival rate of patients with metastatic prostate cancer (mPCa) is severely decreased. Therefore, it is crucial to identify new therapeutic targets to increase their survival. This study aim was to identify the most relevant regulators of mPCa onset by performing two high-throughput CRISPR/Cas9 screenings. Furthermore, some of the top hits were validated using small interfering RNA (siRNA) technology, with protein arginine methyltransferase 7 (PRMT7) being the best candidate. Its inhibition or depletion via CRISPR significantly reduced mPCa cell capacities in vitro. Moreover, PRMT7 ablation reduced mPCa appearance in chicken chorioallantoic membrane and mouse xenograft assays. Molecularly, PRMT7 reprograms the expression of several adhesion molecules through methylation of several transcription factors, such as FoxK1 or NR1H2, which results in primary tumor PCa cell adhesion loss and motility gain. Importantly, PRMT7 is upregulated in advanced stages of Spanish PCa tumor samples and PRMT7 pharmacological inhibition reduces the dissemination of mPCa cells. Thus, here is shown that PRMT7 is a potential therapeutic target and biomarker of mPCa.

cancer biology↗