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Biology subjects

Catalano, I.

Publications and source records attributed to Catalano, I..

3 recordsLinked to original sources

Early auditory and adult mating experiences interact with singer identity to shape neural responses to song in female zebra finches

Social and sensory experiences across the lifespan can shape social interactions, however, experience-dependent plasticity is widely studied within discrete life stages. In the socially monogamous zebra finch, in which females use learned vocal signals to identify individuals and form long-lasting pair bonds, developmental exposure to song is key for females to show species-typical song perception and preferences. While adult mating experience can still lead to pair-bonding and song preference learning even in birds with limited previous song exposure ("song-naive"), whether similarities in adult behavioral plasticity between normally-reared and song-naive females reflect convergent patterns of neural activity is unknown. We investigated this using expression of a marker of neural activity and plasticity (phosphorylated S6) in mated normally-reared and song-naive females in response to song from either their mate, a neighbor, or an unfamiliar male. We found that, in portions of a secondary auditory region (the caudomedial nidopallium NCM) and in dopaminergic neurons of the caudal ventral tegmental area, hearing the mates song significantly increased pS6 expression in females from both rearing conditions. In contrast, within other NCM subregions, song-identity drove different patterns of pS6 expression depending on the rearing condition. These data suggest that developmental experiences can have long-lasting impacts on the neural signatures of behaviors acquired in adulthood and that socially-driven behavioral plasticity in adults may arise through both shared and divergent neural circuits depending on an individuals developmental experiences.

neuroscience↗

Heterogeneity and evolution of DNA mutation rates in microsatellite stable colorectal cancer

DNA sequence mutability in tumors with chromosomal instability is conventionally believed to remain uniform, constant, and low, based on the assumption that further mutational accrual in a context of marked aneuploidy is evolutionarily disadvantageous. However, this concept lacks robust experimental verification. We adapted the principles of mutation accumulation experiments, traditionally performed in lower organisms, to clonal populations of patient-derived tumoroids and empirically measured the spontaneous rates of accumulation of new DNA sequence variations in seven chromosomally unstable, microsatellite stable colorectal cancers (CRCs) and one microsatellite unstable CRC. Our findings revealed heterogeneous mutation rates (MRs) across different tumors, with variations in magnitude within microsatellite stable tumors as prominent as those distinguishing them from microsatellite unstable tumors. Moreover, comparative assessment of microsatellite stable primary tumors and matched synchronous metastases consistently documented a pattern of MR intensification during tumor progression. Therefore, wide-range diversity and progression-associated evolvability of DNA sequence mutational instability emerge as unforeseen hallmarks of microsatellite stable CRC, complementing karyotype alterations as selectable traits to increase genetic variation. One sentence summaryTumors with chromosomal instability accrue DNA sequence mutations at highly variable rates, which increase during metastatic progression.

cancer biology↗

XENTURION, a multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients for population-level translational oncology

The breadth and depth at which cancer models are interrogated contribute to successful translation of drug discovery efforts to the clinic. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, the setting where experimental therapies are typically tested. XENTURION is a unique open-science resource that combines a platform of 129 PDX models and a sister platform of 129 matched PDX-derived tumoroids (PDXTs) from patients with metastatic CRC, with accompanying multidimensional molecular and therapeutic characterization. A PDXT-based population trial with the anti-EGFR antibody cetuximab revealed variable sensitivities that were consistent with clinical response biomarkers, mirrored tumor growth changes in matched PDXs, and recapitulated the outcome of EGFR genetic deletion. Adaptive signals upregulated by EGFR blockade were computationally and functionally prioritized, and inhibition of top candidates increased the magnitude of response to cetuximab. These findings illustrate the probative value and accuracy of large ex vivo and in vivo living biobanks, highlight the importance of cross-platform and cross-methodology systematic validation, and offer avenues for molecularly informed preclinical research.

cancer biology↗