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Biology subjects

Soldano, A.

Publications and source records attributed to Soldano, A..

5 recordsLinked to original sources

Range wide analysis of genetic diversity and structure gives insights into Rosa gallica L. evolutionary history

Rosa gallica L., the French rose, is a perennial, tetraploid, heterozygous species that naturally propagates by seed and sucker. It occurs in the wild, primarily in Europe, and also exists as cultivated varieties. R. gallica cultivars were extensively bred and cultivated in France at the beginning of the 19th century. Although several hypotheses have been proposed regarding the species expansion based on historical records, none have been assessed using molecular data. Indeed, its genetic diversity has so far been investigated only at local or regional scales, hindering the identification of the evolutionary factors shaping its present-day distribution. Using 29 sequenced microsatellites, we genotyped a comprehensive sample of 1618 individuals, including wild R. gallica from 219 sites across the species range, rose cultivars, and specimens from other Rosa species. We then detected clonal lineages and characterized the range-wide genetic diversity and structure, aiming to disentangle the roles of natural and human factors in shaping the distribution of R. gallica, with particular focus on France. French diversity appears particularly structured compared to the rest of the range, suggesting multiple origins within France. Populations in South Alps, Central Eastern Europe, and Eastern France appear to have recolonized naturally from a single southern glacial refugium. In contrast, populations in the western part of France likely resulted from more recent natural or human-mediated dispersal. Finally, clonal lineages containing both wild and cultivated individuals were predominantly found in France, highlighting the role of human-mediated dispersal in 28 of the 98 French sites studied. These findings show that the present-day natural range of R. gallica was shaped primarily by post-glacial recolonization, but also reveal a contribution of human activities to its recent dispersal, particularly in France, where cultivated varieties were intensively bred and exchanged.

genetics↗

Unveiling Oligodendrocyte-Lineage Differentiation in the Glioblastoma Infiltrative Zone Through Spatial Transcriptomics

IDH-wildtype glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by limited therapeutic options and inevitable recurrence. This recurrence is driven by the highly infiltrative behavior of GBM cells, which prevents complete resection. Here, we performed spatially resolved transcriptomic profiling of four surgically defined GBM regions to characterize the infiltrative tumor compartment. Across multiple datasets and profiling approaches, the infiltrative zone showed reduced cellular heterogeneity compared with the tumor core. By comparison with an integrated reference of single-cell RNA sequencing data, we revealed that this reduction reflects a preferential differentiation of infiltrative GBM cells toward an oligodendrocyte-like lineage, accompanied by attenuated inflammatory signaling. In contrast, necrotic and proliferative regions display pronounced astrocyte-like and mesenchymal-like programs. Combined immunohistochemistry and fluorescence in situ hybridization confirmed the enrichment of oligodendrocyte-like tumor cells in the infiltrative area. Together, these findings identify the oligodendrocyte-like state as a defining feature and potential therapeutic vulnerability of infiltrative GBM driving brain invasion and relapse.

cancer biology↗

Optimization of host cell-compatible, antimicrobial peptides effective against biofilms and clinical isolates of drug-resistant bacteria.

Here, we describe the continued synthetic molecular evolution of a lineage of host-compatible antimicrobial peptides (AMP) intended for the treatment of wounds infected with drug-resistant, biofilm-forming bacteria. The peptides tested are variants of an evolved AMP called D-CONGA, which has excellent antimicrobial activities in vitro and in vivo. In this newest generation of rational D-CONGA variants, we tested multiple sequence-structure-function hypotheses that had not been tested in previous generations. Many of the peptide variants have lower antibacterial activity against Gram-positive or Gram-negative pathogens, especially variants that have altered hydrophobicity, secondary structure potential, or spatial distribution of charged and hydrophobic residues. Thus, D-CONGA is generally well tuned for antimicrobial activity. However, we identified a variant, D-CONGA-Q7, with a polar glutamine inserted into the middle of the sequence, that has higher activity against both planktonic and biofilm-forming bacteria as well as lower cytotoxicity against human fibroblasts. Against clinical isolates of K. pneumoniae, innate resistance to D-CONGA was surprisingly common despite a lack of inducible resistance in P. aeruginosa reported previously. Yet, these same isolates were susceptible to D-CONGA-Q7. D-CONGA-Q7 is much less vulnerable to AMP resistance in Gram-negative bacteria than its predecessor. Consistent with the spirit of synthetic molecular evolution, D-CONGA-Q7 achieved a critical gain-of-function and has a significantly better activity profile.

biochemistry↗

The Amyloid Precursor Protein is a conserved Wnt receptor

The Amyloid Precursor Protein (APP) and its homologues are transmembrane proteins required for various aspects of neuronal development and activity, whose molecular function is unknown. Specifically, it is unclear whether APP acts as a receptor, and if so what its ligand(s) may be. We show that APP binds the Wnt ligands Wnt3a and Wnt5a and that this binding regulates APP protein levels. Wnt3a binding promotes full length APP (flAPP) recycling and stability. In contrast, Wnt5a promotes APP targeting to lysosomal compartments and reduces flAPP levels. A conserved Cysteine Rich Domain (CRD) in the extracellular portion of APP is required for Wnt binding, and deletion of the CRD abrogates the effects of Wnts on flAPP levels and trafficking. Finally, loss of APP results in increased axonal and reduced dendritic growth of mouse embryonic primary cortical neurons. This phenotype can be cell-autonomously rescued by full length, but not CRD-deleted, APP.

cell biology↗

The m6A reader Ythdf restricts axonal growth in Drosophila through target selection modulation of the Fragile X mental retardation protein

N6-methyladenosine (m6A) regulates a variety of physiological processes through modulation of RNA metabolism. The modification is particularly enriched in the nervous system of several species, and its dysregulation has been associated with neurodevelopmental defects and neural dysfunctions. In Drosophila, loss of m6A alters fly behavior albeit the underlying mechanism and the role of m6A during nervous system development have remained elusive. Here we find that impairment of the m6A pathway leads to axonal overgrowth and misguidance at larval neuromuscular junctions as well as in the adult mushroom bodies. We identify Ythdf as the main m6A reader in the nervous system being required for limiting axonal growth. Mechanistically, we show that Ythdf directly interacts with Fragile X mental retardation protein to inhibit the translation of key transcripts involved in axonal growth regulation. Altogether, this study demonstrates that the m6A pathway controls development of the nervous system by modulating Fmr1 target selection.

molecular biology↗