Emma Costa
Ph.D. Student in Neurosciences, admitted Autumn 2019
All Publications
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BayesAge 2.0: A Maximum Likelihood Algorithm to Predict Transcriptomic Age.
bioRxiv : the preprint server for biology
2024
Abstract
Aging is a complex biological process influenced by various factors, including genetic and environmental influences. In this study, we present BayesAge 2.0, an improved version of our maximum likelihood algorithm designed for predicting transcriptomic age (tAge) from RNA-seq data. Building on the original BayesAge framework, which was developed for epigenetic age prediction, BayesAge 2.0 integrates a Poisson distribution to model count-based gene expression data and employs LOWESS smoothing to capture non-linear gene-age relationships. BayesAge 2.0 provides significant improvements over traditional linear models, such as Elastic Net regression. Specifically, it addresses issues of age bias in predictions, with minimal age-associated bias observed in residuals. Its computational efficiency further distinguishes it from traditional models, as reference construction and cross-validation are completed more quickly compared to Elastic Net regression, which requires extensive hyperparameter tuning. Overall, BayesAge 2.0 represents a notable advance in transcriptomic age prediction, offering a robust, accurate, and efficient tool for aging research and biomarker development.
View details for DOI 10.1101/2024.09.16.613354
View details for PubMedID 39345375
View details for PubMedCentralID PMC11429879
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Publisher Correction: Age-related changes in the zebrafish and killifish inner ear and lateral line.
Scientific reports
2024; 14 (1): 9327
View details for DOI 10.1038/s41598-024-59895-7
View details for PubMedID 38654134
View details for PubMedCentralID PMC11039694
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Age-related changes in the zebrafish and killifish inner ear and lateral line.
Scientific reports
2024; 14 (1): 6670
Abstract
Age-related hearing loss (ARHL) is a debilitating disorder for millions worldwide. While there are multiple underlying causes of ARHL, one common factor is loss of sensory hair cells. In mammals, new hair cells are not produced postnatally and do not regenerate after damage, leading to permanent hearing impairment. By contrast, fish produce hair cells throughout life and robustly regenerate these cells after toxic insult. Despite these regenerative abilities, zebrafish show features of ARHL. Here, we show that aged zebrafish of both sexes exhibited significant hair cell loss and decreased cell proliferation in all inner ear epithelia (saccule, lagena, utricle). Ears from aged zebrafish had increased expression of pro-inflammatory genes and significantly more macrophages than ears from young adult animals. Aged zebrafish also had fewer lateral line hair cells and less cell proliferation than young animals, although lateral line hair cells still robustly regenerated following damage. Unlike zebrafish, African turquoise killifish (an emerging aging model) only showed hair cell loss in the saccule of aged males, but both sexes exhibit age-related changes in the lateral line. Our work demonstrates that zebrafish exhibit key features of auditory aging, including hair cell loss and increased inflammation. Further, our finding that aged zebrafish have fewer lateral line hair cells yet retain regenerative capacity, suggests a decoupling of homeostatic hair cell addition from regeneration following acute trauma. Finally, zebrafish and killifish show species-specific strategies for lateral line homeostasis that may inform further comparative research on aging in mechanosensory systems.
View details for DOI 10.1038/s41598-024-57182-z
View details for PubMedID 38509148
View details for PubMedCentralID 7589617
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Dense, Continuous Membrane Labeling and Expansion Microscopy Visualization of Ultrastructure in Tissues.
bioRxiv : the preprint server for biology
2024
Abstract
Lipid membranes are key to the nanoscale compartmentalization of biological systems, but fluorescent visualization of them in intact tissues, with nanoscale precision, is challenging to do with high labeling density. Here, we report ultrastructural membrane expansion microscopy (umExM), which combines a novel membrane label and optimized expansion microscopy protocol, to support dense labeling of membranes in tissues for nanoscale visualization. We validated the high signal-to-background ratio, and uniformity and continuity, of umExM membrane labeling in brain slices, which supported the imaging of membranes and proteins at a resolution of ~60 nm on a confocal microscope. We demonstrated the utility of umExM for the segmentation and tracing of neuronal processes, such as axons, in mouse brain tissue. Combining umExM with optical fluctuation imaging, or iterating the expansion process, yielded ~35 nm resolution imaging, pointing towards the potential for electron microscopy resolution visualization of brain membranes on ordinary light microscopes.
View details for DOI 10.1101/2024.03.07.583776
View details for PubMedID 38496681
View details for PubMedCentralID PMC10942445
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An automated feeding system for the African killifish reveals effects of dietary restriction on lifespan and allows scalable assessment of associative learning.
eLife
2022; 11
Abstract
The African turquoise killifish is an exciting new vertebrate model for aging studies. A significant challenge for any model organism is the control over its diet in space and time. To address this challenge, we created an automated and networked fish feeding system. Our automated feeder is designed to be open-source, easily transferable, and built from widely available components. Compared to manual feeding, our automated system is highly precise and flexible. As a proof-of-concept for the feeding flexibility of these automated feeders, we define a favorable regimen for growth and fertility for the African killifish and a dietary restriction regimen where both feeding time and quantity are reduced. We show that this dietary restriction regimen extends lifespan in males (but not in females) and impacts the transcriptomes of killifish livers in a sex-specific manner. Moreover, combining our automated feeding system with a video camera, we establish a quantitative associative learning assay to provide an integrative measure of cognitive performance for the killifish. The ability to precisely control food delivery in the killifish opens new areas to assess lifespan and cognitive behavior dynamics and to screen for dietary interventions and drugs in a scalable manner previously impossible with traditional vertebrate model organisms.
View details for DOI 10.7554/eLife.69008
View details for PubMedID 36354233
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Population imaging of neural activity in awake behaving mice
NATURE
2019; 574 (7778): 413-+
Abstract
A longstanding goal in neuroscience has been to image membrane voltage across a population of individual neurons in an awake, behaving mammal. Here we describe a genetically encoded fluorescent voltage indicator, SomArchon, which exhibits millisecond response times and is compatible with optogenetic control, and which increases the sensitivity, signal-to-noise ratio, and number of neurons observable several-fold over previously published fully genetically encoded reagents1-8. Under conventional one-photon microscopy, SomArchon enables the routine population analysis of around 13 neurons at once, in multiple brain regions (cortex, hippocampus, and striatum) of head-fixed, awake, behaving mice. Using SomArchon, we detected both positive and negative responses of striatal neurons during movement, as previously reported by electrophysiology but not easily detected using modern calcium imaging techniques9-11, highlighting the power of voltage imaging to reveal bidirectional modulation. We also examined how spikes relate to the subthreshold theta oscillations of individual hippocampal neurons, with SomArchon showing that the spikes of individual neurons are more phase-locked to their own subthreshold theta oscillations than to local field potential theta oscillations. Thus, SomArchon reports both spikes and subthreshold voltage dynamics in awake, behaving mice.
View details for DOI 10.1038/s41586-019-1641-1
View details for Web of Science ID 000490988300067
View details for PubMedID 31597963
View details for PubMedCentralID PMC6858559
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Expansion microscopy of zebrafish for neuroscience and developmental biology studies
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2017; 114 (50): E10799-E10808
Abstract
Expansion microscopy (ExM) allows scalable imaging of preserved 3D biological specimens with nanoscale resolution on fast diffraction-limited microscopes. Here, we explore the utility of ExM in the larval and embryonic zebrafish, an important model organism for the study of neuroscience and development. Regarding neuroscience, we found that ExM enabled the tracing of fine processes of radial glia, which are not resolvable with diffraction-limited microscopy. ExM further resolved putative synaptic connections, as well as molecular differences between densely packed synapses. Finally, ExM could resolve subsynaptic protein organization, such as ring-like structures composed of glycine receptors. Regarding development, we used ExM to characterize the shapes of nuclear invaginations and channels, and to visualize cytoskeletal proteins nearby. We detected nuclear invagination channels at late prophase and telophase, potentially suggesting roles for such channels in cell division. Thus, ExM of the larval and embryonic zebrafish may enable systematic studies of how molecular components are configured in multiple contexts of interest to neuroscience and developmental biology.
View details for DOI 10.1073/pnas.1706281114
View details for Web of Science ID 000417806200025
View details for PubMedID 29162696
View details for PubMedCentralID PMC5740639