Biology subjects

Cekanaviciute, E.

Publications and source records attributed to Cekanaviciute, E..

4 recordsLinked to original sources

bioRxiv2026

Electrophysiological and neuroimmune responses of a cortical tissue model to chronic gamma radiation exposure

Exposure to chronic space radiation is a major health concern for long-duration missions beyond low Earth orbit. While most experimental studies simulate mission-relevant doses using acute irradiation, astronauts will experience persistent low-dose-rate exposure over months. Here, we used engineered three-dimensional (3D) mouse cortical tissue models and two-dimensional (2D) primary cortical cultures to investigate the effects of radiation dose rate on neuroglial function, inflammatory responses, and neuronal network activity. Cultures were exposed to a cumulative 0.5 Gy dose of {gamma}-radiation delivered either acutely (1 h) or chronically (166 h), with or without pretreatment using the radioprotective agent amifostine. In 3D cortical tissue models, we quantified DNA damage, astrocyte and microglia reactivity, neuronal survival, neurite morphology, and secretion of pro-inflammatory cytokines. In parallel, microelectrode array recordings were used to assess electrophysiological function in 2D neuronal networks following {gamma}-radiation or treatment with the radiomimetic drug bleomycin. Acute gamma radiation induced modest astrocyte activation, whereas chronic exposure caused limited neuroimmune alterations. Neither exposure paradigm impaired neuronal network activity, despite measurable DNA damage responses. Together, these findings indicate that neuronal function is preserved following low-dose-rate gamma irradiation while glial populations display selective sensitivity to radiation exposure.

bioengineering↗

bioRxiv2022

Mouse Genomic Associations with Ex Vivo Sensitivity to Simulated Space Radiation

Exposure to ionizing radiation is considered by NASA to be a major health hazard for deep space exploration missions. Ionizing radiation sensitivity is modulated by both genomic and environmental factors. Understanding their contributions is crucial for designing experiments in model organisms, evaluating the risk of deep space (i.e. high-linear energy transfer, or LET, particle) radiation exposure in astronauts, and also selecting therapeutic irradiation regimes for cancer patients. We identified single nucleotide polymorphisms in 15 strains of mice, including 10 collaborative cross model strains and 5 founder strains, associated with spontaneous and ionizing radiation-induced ex vivo DNA damage quantified based on immunofluorescent 53BP1+ nuclear foci. Statistical analysis suggested an association with pathways primarily related to cellular signaling, metabolism, tumorigenesis and nervous system damage. We observed different genomic associations in early (4 and 8 hour) responses to different LET radiation, while later (24 hour) DNA damage responses showed a stronger overlap across all LETs. Furthermore, a subset of pathways was associated with spontaneous DNA damage, suggesting 53BP1+ foci as a potential biomarker for DNA integrity in mouse models. Based on our results, we suggest several mouse strains as new models to further study the impact of ionizing radiation and validate the identified genetic loci. We also highlight the importance of future human ex vivo studies to refine the association of genes and pathways with the DNA damage response to ionizing radiation and identify targets for space travel countermeasures.

genomics↗

bioRxiv2020

NASA GeneLab RNA-Seq Consensus Pipeline: Standardized Processing of Short-Read RNA-Seq Data

With the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed to spaceflight. Members of NASA GeneLab and GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data from spaceflight-associated experiments. The pipeline includes quality control, read trimming, mapping, and gene quantification steps, culminating in the detection of differentially expressed genes. This data analysis pipeline and the results of its execution using data submitted to GeneLab are now all publicly available through the GeneLab database. We present here the full details and rationale for the construction of this pipeline in order to promote transparency, reproducibility and reusability of pipeline data, to provide a template for data processing of future spaceflight-relevant datasets, and to encourage cross-analysis of data from other databases with the data available in GeneLab.

bioinformatics↗

bioRxiv2018

Multiple sclerosis-associated changes in the composition and immune functions of spore-forming bacteria

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by adaptive and innate immune system dysregulation. Recent work has revealed moderate alteration of gut microbial communities in subjects with MS and in experimental, induced models. However, a mechanistic understanding linking the observed changes in the microbiota and the presence of the disease is still missing. Chloroform-resistant, spore-forming bacteria have been shown to exhibit immunomodulatory properties in vitro and in vivo, but they have not yet been characterized in the context of human disease. This study addresses the community composition and immune function of this bacterial fraction in MS. We identify MS-associated spore-forming taxa and show that their presence correlates with impaired differentiation of IL-10 secreting, regulatory T lymphocytes in-vitro. Colonization of antibiotic-treated mice with spore-forming bacteria allowed us to identify some bacterial taxa favoring IL-10+ lymphocyte differentiation and others inducing differentiation of pro-inflammatory, IFN{gamma}+ T lymphocytes. However, when fed into antibiotic-treated mice, both MS and control derived spore-forming bacteria were able to induce immunoregulatory responses.\n\nOur analysis also identified Akkermansia muciniphila as a key organism that may interact either directly or indirectly with spore-forming bacteria to exacerbate the inflammatory effects of MS-associated gut microbiota. Thus, changes in the spore-forming fraction may influence T lymphocyte-mediated inflammation in MS. This experimental approach of isolating a subset of microbiota based on its functional characteristics may be useful to investigate other microbial fractions at greater depth.\n\nImportanceDespite the rapid emergence of microbiome related studies in human diseases, few go beyond a simple description of relative taxa levels in a select group of patients. Our study integrates computational analysis with in vitro and in vivo exploration of inflammatory properties of both complete microbial communities and individual taxa, revealing novel functional associations. We specifically show that while small differences exist between the microbiomes of MS patients and healthy subjects, these differences are exacerbated in the chloroform resistant fraction. We further demonstrate that, when purified from MS patients, this fraction is associated with impaired immunomodulatory responses in vitro.

immunology↗