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Biology subjects

Moreno, C. S.

Publications and source records attributed to Moreno, C. S..

4 recordsLinked to original sources

Cell jamming transitions shape regulatory protein gradients and prime evolutionary divergence

A long-standing goal of evolutionary developmental biology is to identify the mechanisms underlying criticality of developmental transitions that allow processes governing individual cells scale up to the organism-level patterning. The viscoelastic properties of embryonic tissues imply collective cell behaviors, leading to the expectation that signaling networks should capitalize on the material properties of tissues, structuring morphogenesis around the spatial and temporal transitions that they induce. Here, we show that this interaction is evident even prior to tissue differentiation and is traceable to behavior of individual cells. In avian beak primordia, we find that fields of mesenchymal cells undergo cycles of local jamming dynamically modulating coordination of cell shape and movement. These cycles progressively alter the spatial reach of regulatory proteins, strongly expanding or restricting their gradients based on tissue mechanical state. Tissue-level gradients of proteins most sensitive to local cell jamming transitions also diverge the most across populations, priming tissue compartmentalization. These findings suggest that the material state transition is an effective interface for integration of stochastic physical processes and genetic regulation and is well placed to underlie criticality of developmental systems allowing local rules governing cell-state transitions scale up to tissue-level patterning. More broadly, our findings reveal how transient material transitions reset developmental trajectories and promote diversification while preserving robustness.

evolutionary biology↗

Drivers of mangrove vulnerability and resilience to tropical cyclones in the North Atlantic Basin

The North Atlantic Basin (NAB) is seeing a significant increase in the frequency and intensity of tropical cyclones since the 1980s, with record-breaking seasons such as 2017 and 2020. However, little is known about how coastal ecosystems, particularly mangroves in the Gulf of Mexico and the Caribbean, are responding to these new "climate normals" at regional and subregional scales. Wind speed, rainfall, pre-cyclone forest structure, and hydro-geomorphology are known to influence mangrove damage and recovery following cyclones in the NAB. However, these studies have focused on site-specific responses and individual cyclonic events. Here, we analyze 25 years (1996-2020) of mangrove vulnerability (damage after a cyclone) and short-term resilience (recovery after damage) for the entire NAB and its subregions, using multi-annual, remote sensing-derived databases. We applied machine learning to characterize the influence of 22 potential drivers that include previously researched variables and new ones such as human development and long-term climate trends. The characteristics of the cyclones mainly drive vulnerability at the regional level, while resilience is largely driven by site-specific conditions. These include long-term climate conditions, such as air temperature and drought trends, pre-cyclone habitat conditions, such as canopy cover and height and soil organic carbon stock, and human interventions on the land. Rates and drivers of mangrove vulnerability and resilience vary across subregions in the NAB, and hotspots for restoration and conservation actions are highlighted within subregions. The impacts of increasing cyclone activity need to be framed in the context of climate change compound effects and heavy human influences in the region. There is an urgent need to value the restoration and conservation of mangroves as fundamental Nature-based Solutions against cyclone impacts in the NAB.

ecology↗

Systematic discovery of mutation-directed neo-protein-protein interactions in cancer

Comprehensive sequencing of patient tumors reveals numerous genomic mutations across tumor types that enable tumorigenesis and progression. A subset of oncogenic driver mutations results in neomorphic activity where the mutant protein mediates functions not engaged by the parental molecule. Here, we identify prevalent variant-enabled neomorph-protein-protein interactions (neoPPI) with a quantitative High Throughput differential Screening (qHT-dS) platform. Coupling of highly sensitive BRET biosensors with miniaturized co-expression in an ultra-HTS format allows large-scale monitoring of interactions of wild-type and mutant variant counterparts with a library of cancer-associated proteins in live cells. Screening of 13,392 interactions with 1,474,560 data points revealed a landscape of gain-of-interactions encompassing both oncogenic and tumor suppressor mutations. For example, the recurrent BRAF V600E lesion mediates KEAP1 neoPPI, rewiring a BRAFV600E-KEAP1 signaling axis and creating collateral vulnerability to NQO1 substrates, offering a combination therapeutic strategy. Thus, cancer genomic alterations can create neo-interactions, informing variant-directed therapeutic approaches for precision medicine.

cancer biology↗

Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions

Exosomes are extracellular vesicles that mediate transport of nucleic acids, proteins, and other molecules. Prior work has implicated exosomes in the transmission of radiation nontargeted effects. Here we investigate the ability of energetic heavy ions, representative of species found in galactic cosmic rays, to stimulate exosome release from human bronchial epithelial cells in vitro. Immortalized human bronchial epithelial cells (HBEC3-KT F25F) were irradiated with 1.0 Gy of high linear energy transfer (LET) 48Ti, 28Si, or 16O ions, or with 10 Gy of low-LET reference {gamma}-rays, and extracellular vesicles were collected from conditioned media. Preparations were characterized by single particle tracking analysis, transmission electron microscopy, and immunoblotting for the exosomal marker, TSG101. Irradiation with high-LET ions, but not {gamma}-rays, stimulated exosome release by about 3-fold, relative to mock-irradiated controls. The exosome-enriched vesicle preparations contained pro-inflammatory damage-associated molecular patterns, including HSP70 and calreticulin. Additionally, miRNA profiling was performed for vesicular RNAs using NanoString technology. The miRNA profile was skewed toward a small number of species that have previously been shown to be involved in cancer initiation and progression, including miR-1246, miR-1290, miR-23a, and miR-205. Additionally, a set of 24 miRNAs was defined as modestly over-represented in preparations from HZE ion-irradiated versus other cells. Gene set enrichment analysis based on the over-represented miRNAs showed highly significant association with nonsmall cell lung and other cancers.

molecular biology↗