Biology subjects

Grande, A.

Publications and source records attributed to Grande, A..

3 recordsLinked to original sources

bioRxiv2026

Microhaplotypes Improve Kinship Estimation in Heterozygous, Mixed-Ploidy Populations of Actinidia

Over the past decade there has been increasing interest in the use of microhaplotype markers in autopolyploid taxa. This has been driven by theoretical and observed improvements in signals of allelic dosage, linkage, and heritability. Yet, to date there has been little investigation into the suitability of microhaplotype markers for estimating kinship. Here, we develop the theory of kinship estimation from microhaplotypes, introduce the MCHap microhaplotype caller for autopolyploid populations, and apply these methods to a highly diverse germplasm population of mixed-ploidy Actinidia (kiwifruit and relatives). We find that microhaplotype-based kinship estimates are generally superior to equivalent single nucleotide variant based estimates. This is because microhaplotypes minimize the coalescent signal among alleles which may bias estimates within the context of a recent reference population. Hence, kinship estimates from microhaplotypes more accurately capture the recent demographic history of a population. These findings are supported by both coalescent simulations and the analysis of real data. Our findings are relevant to organisms of any ploidy, but most actionable in highly heterozygous taxa such as Actinidia.

genetics↗

bioRxiv2025

Mycobacterium tuberculosis-infected macrophages accumulate more nanoparticles

In response to the escalating threat of infectious diseases and the widespread emergence of antimicrobial-resistant strains, novel therapeutic strategies are being actively developed. Nanoparticle-based delivery systems have emerged as promising tools to improve the targeted administration of antimicrobials directly to sites of infection. In the context of pulmonary infections, aerosolized nanocarriers can enhance local biodistribution while minimizing systemic exposure and associated side effects. In this study, we demonstrate that following pulmonary administration in Mycobacterium tuberculosis-infected mice, poly(lactic-co-glycolic acid) (PLGA) nanoparticles are broadly distributed throughout the lungs and preferentially interact with alveolar macrophages--the primary host cells of the pathogen. Remarkably, infected macrophages internalize significantly more nanoparticles than uninfected cells independently of the virulence and viability of the bacteria. Using transcriptomic analysis, we uncovered a list of 21 commonly modulated genes that may be responsible for this phenotype. Collectively, our findings reveal a striking feature of nanoparticles: their capacity to selectively accumulate in infected cells, offering a powerful mechanism to enhance antimicrobial delivery precisely where it is most needed.

cell biology↗

bioRxiv2022

Caveolae couple mechanical stress to integrin recycling and activation

Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts. This phenotype is Rho-independent and mainly derived from increased active {beta}1-integrin content on the surface of Cav1KO fibroblasts. FRAP analysis and endocytosis/recycling assays revealed that active {beta}1-integrin is mostly endocytosed through the CLIC/GEEC pathway and is more rapidly recycled to the PM in Cav1KO fibroblasts, in a Rab4-dependent manner. Moreover, the threshold for PM tension-driven {beta}1-integrin activation is lower in Cav1KO MEFs than in wild type MEFs, through a mechanism dependent on talin activity. Our findings suggest that caveolae couple mechanical stress to integrin cycling and activation, thereby regulating the early steps of the cellular mechanosensing response.

cell biology↗