Biology subjects

Alonso, M.

Publications and source records attributed to Alonso, M..

7 recordsLinked to original sources

bioRxiv2025

CD44v6 Drives Tumor Aggressiveness and Chemoresistance in Bladder Cancer

Bladder cancer is a fast-moving and recurrent malignancy where survival hinges on early detection and precise risk stratification. The search for robust biomarkers is urgent, and CD44v6 has emerged as a compelling candidate. In this study, we reveal that CD44v6 is not merely a marker but a driver of urothelial carcinoma aggressiveness. Through integrated clinical and functional analyses, we show that high CD44v6 expression is strongly associated with poor patient outcomes. Mechanistic investigations demonstrate that CD44v6 amplifies the proliferative, migratory, and invasive potential of bladder cancer cells, while conferring marked resistance to cisplatin. These findings position CD44v6 at the intersection of tumor progression and therapeutic failure, underscoring its value as both a prognostic biomarker and a promising therapeutic target. Targeting CD44v6 could pave the way for strategies that curb disease aggressiveness and overcome chemoresistance in bladder cancer.

cancer biology↗

bioRxiv2025

Comparative microbiome analyses reveal differences between wild populations and captive groups of the Montseny Brook Newt (Calotriton arnoldi)

The Montseny brook newt, Calotriton arnoldi, is a Critically Endangered amphibian species endemic to the Montseny Massif in Catalonia, Northeastern Spain. Due to population declines and threats to its natural habitat, an ex-situ breeding program was initiated in 2007. A key goal of the program is to ensure the survival of captive-bred individuals after reintroduction, which in amphibians heavily relies on the specimens microbiome being capable of protecting them from environmental microorganisms, especially considering the global Chytridiomycosis pandemic caused by the fungi Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). This study aims to characterize the microbiome of wild and captive specimens of Calotriton arnoldi, to identify differences in microbiome composition, and to determine their potential impact on captive-bred individuals upon reintroduction. Up to 7,438 ASVs (Amplicon Sequence Variants) were identified from 138 samples from 21 and 61 wild and captive-bred individuals, respectively. Results indicate that wild populations from different subspecies have significantly different microbiome composition, as do wild and captive-bred groups from the same subspecies. Additionally, dissimilarities in microbiome variability were only found within each subspecies, between wild and captive-bred groups. In terms of composition, certain bacteria were identified as potential markers for both wild and captive environments. Enhancing microbiome variability might improve the survival prospects of reintroduced specimens. Thus, exposing captive specimens to a more natural environment while in captivity or a soft-release procedure could potentially mitigate the absence of exposure to other bacteria and potential pathogens from their native environment.

microbiology↗

bioRxiv2025

Molecular mechanisms underlying the determination of axillary bud fate and outgrowth into branch crown in strawberry

{blacksquare} In strawberry, the axillary bud (AXB) can produce either an elongated stem called stolon giving a daughter-plant (asexual reproduction) or an inflorescence-bearing branch crown (BC) (sexual reproduction). The fate of the AXB depends on node position on the axis and on genetic and environmental factors. Here, in Fragaria vesca, we addressed the largely unanswered question of how molecular factors determine AXB fate. {blacksquare}To get insights into the mechanisms already at play in a morphologically indistinguishable (undifferentiated) AXB, depending on its fate, we combined (1) the phenotypic characterization of AXB development throughout plant growth with (2) the RNA-seq analysis of undifferentiated AXBs, using three different genotypes producing either BCs or stolons (fvetfl1 and fvega20ox mutants, FveFT3 overexpressor). {blacksquare}Results allowed the identification of genes regulating AXB fate and outgrowth, among which FveBRC1. The analysis of FveBRC1 expression in genotypes combining various traits (perpetual/seasonal flowering; runnering/runneless) and the generation of CRISPR/Cas9 brc1 mutants further demonstrated that FveBRC1 plays a central role in the determination of AXB fate in strawberry, in addition to its well-known function in BC outgrowth. {blacksquare}These original results provide new insights into the determination of AXB fate and, consequently, the control of fruit yield in strawberry.

plant biology↗

bioRxiv2025

Structures of the 26S proteasome in complex with the Hsp70 cochaperone Bag1 reveal a novel mechanism of ubiquitin-independent proteasomal degradation

The 26S proteasome primarily degrades proteins marked by polyubiquitin chains. Although ubiquitin-independent pathways for proteasomal degradation exist, the mechanisms involved remain poorly understood. Bag1 links the Hsp70 chaperone to the 26S proteasome, recruiting Hsp70-bound aberrant proteins for degradation. Here, we present high-resolution cryo-EM structures of the Bag1-bound 26S proteasome, which reveal unprecedented conformational changes within the 19S regulatory particle. Bag1 binding to the Rpn1 subunit induces a dramatic reconfiguration of AAA+ ATPase subunits, disrupting the canonical spiral staircase conformation and remodeling the central channel architecture. This creates a large cavity above the substrate entry gate of the 20S core particle, enabling the direct entry of Hsp70 clients into the proteolytic chamber. Thus, in this ubiquitin-independent degradation pathway, unfolded proteins can bypass the need for both client ubiquitination and ATP hydrolysis for degradation.

molecular biology↗

bioRxiv2024

Targeting the tomato fruit cuticle by gene overexpression and editing with the fruit epidermis-preferential nsLTP promoter

The thick cuticle covering and embedding epidermal cells of tomato (Solanum lycopersicum) fruit, a model for cuticle studies, plays important roles in fruit protection and quality. To further our understanding of the influence of cuticle components on cuticle architecture and properties, the next step is to engineer cuticle composition. Ideally, to avoid indirect effects at whole-plant level, a fruit-and epidermis-specific promoter should be used. Here, to overexpress and edit target genes in tomato, we selected a non-specific Lipid Transfer Protein 2 promoter (pronsLTP) with preferential activity in fruit epidermis, as shown by NLS-GFP fluorescence analysis. Overexpression of SlMYB75 driven by pronsLTP induced anthocyanin accumulation specifically in the growing fruit epidermis, consistent with the cuticle deposition pattern. In keeping with changes in anthocyanins, the cuticle composition in flavonoids and phenolic acids was altered, as shown by Raman microspectroscopy, as were several cuticle properties. We then edited the carotenoid PSY1 gene with a pronsLTP-driven CRISPR/Cas9 system. Different PSY1 knock-out alleles were detected predominantly in fruit exocarp and mesocarp of color-impaired pronsLTP::Cas9-Psy1 mutants, and very little in the leaf. A mutant carrying a heritable knock-out mutation in both fruit and leaf was also detected, indicating that mutants obtained with pronsLTP may require screening before being studied. Altogether, our results indicate that pronsLTP2 can efficiently result in gene overexpression and editing in fruit epidermis. Implications of these findings are important for the functional analysis and genetic engineering of cuticle-related genes in tomato.

plant biology↗

bioRxiv2022

GSK2556286 is a novel antitubercular drug candidate effective in vivo with the potential to shorten tuberculosis treatment

As a result of a high-throughput compound screening campaign of Mycobacterium tuberculosis infected macrophages, a new preclinical drug candidate for the treatment of tuberculosis has been identified. GSK2556286 inhibits growth within human macrophages (IC50 = 0.07 {micro}M), is active against extracellular bacteria in cholesterol-containing culture media and exhibits no cross-resistance with known antitubercular drugs. In addition, it has shown efficacy in different mouse models of tuberculosis (TB) and has an adequate safety profile in two preclinical species. These features indicate a compound with a novel mode of action, although still not fully defined, that is effective against both multidrug or extensively-resistant (M/XDR) and drug-sensitive (DS) M. tuberculosis with the potential to shorten the duration of treatment in novel combination drug regimens. One Sentence SummaryGSK2556286 is a novel preclinical drug candidate for the treatment of tuberculosis with a new mode of action potentially able to contribute to the shortening of TB chemotherapy.

pharmacology and toxicology↗

bioRxiv2017

Leveraging heterogeneity across multiple data sets increases accuracy of cell-mixture deconvolution and reduces biological and technical biases

In silico quantification of cell proportions from mixed-cell transcriptomics data (deconvolution) requires a reference expression matrix, called basis matrix. We hypothesized that matrices created using only healthy samples from a single microarray platform would introduce biological and technical biases in deconvolution. We show presence of such biases in two existing matrices, IRIS and LM22, irrespective of the deconvolution method used. Here, we present immunoStates, a basis matrix built using 6160 samples with different disease states across 42 microarray platforms. We found that immunoStates significantly reduced biological and technical biases. We further show that cellular proportion estimates using immunoStates are consistently more correlated with measured proportions than IRIS and LM22, across all methods. Importantly, we found that different methods have virtually no effect once the basis matrix is chosen. Our results demonstrate the need and importance of incorporating biological and technical heterogeneity in a basis matrix for achieving consistently high accuracy.

bioinformatics↗