7 results on '"J. Mateus"'
Search Results
2. Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight.
- Author
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Houerbi N, Kim J, Overbey EG, Batra R, Schweickart A, Patras L, Lucotti S, Ryon KA, Najjar D, Meydan C, Damle N, Chin C, Narayanan SA, Guarnieri JW, Widjaja G, Beheshti A, Tobias G, Vatter F, Hirschberg JW, Kleinman A, Afshin EE, MacKay M, Chen Q, Miller D, Gajadhar AS, Williamson L, Tandel P, Yang Q, Chu J, Benz R, Siddiqui A, Hornburg D, Gross S, Shirah B, Krumsiek J, Mateus J, Mao X, Matei I, and Mason CE
- Subjects
- Animals, Humans, Mice, Male, Secretome metabolism, Mice, Inbred C57BL, Extracellular Vesicles metabolism, Proteomics methods, Biomarkers metabolism, Biomarkers blood, Female, Adult, Blood Proteins metabolism, Middle Aged, Leukocytes, Mononuclear metabolism, Proteome metabolism, Space Flight, Oxidative Stress, Brain metabolism, Blood-Brain Barrier metabolism, Blood Coagulation physiology, Homeostasis
- Abstract
As spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated "spaceflight secretome profiles," which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight. Moreover, these proteomic alterations correlated better with peripheral blood mononuclear cells than whole blood, suggesting that immune cells contribute more DAPs than erythrocytes. Finally, to discern possible mechanisms leading to brain-enriched protein detection and blood-brain barrier (BBB) disruption, we examined protein changes in dissected brains of spaceflight mice, which showed increases in PECAM-1, a marker of BBB integrity. These data highlight how even short-duration spaceflight can disrupt human and murine physiology and identify spaceflight biomarkers that can guide countermeasure development., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
3. Collection of biospecimens from the inspiration4 mission establishes the standards for the space omics and medical atlas (SOMA).
- Author
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Overbey EG, Ryon K, Kim J, Tierney BT, Klotz R, Ortiz V, Mullane S, Schmidt JC, MacKay M, Damle N, Najjar D, Matei I, Patras L, Garcia Medina JS, Kleinman AS, Wain Hirschberg J, Proszynski J, Narayanan SA, Schmidt CM, Afshin EE, Innes L, Saldarriaga MM, Schmidt MA, Granstein RD, Shirah B, Yu M, Lyden D, Mateus J, and Mason CE
- Subjects
- Humans, Exobiology, Metagenomics standards, Specimen Handling standards, Space Flight, Biological Specimen Banks standards, Preservation, Biological standards
- Abstract
The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from four crew members longitudinally before (Launch: L-92, L-44, L-3 days), during (Flight Day: FD1, FD2, FD3), and after (Return: R + 1, R + 45, R + 82, R + 194 days) spaceflight, spanning a total of 289 days across 2021-2022. The collection process included venous whole blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies. Venous whole blood was further processed to obtain aliquots of serum, plasma, extracellular vesicles and particles, and peripheral blood mononuclear cells. In total, 2,911 sample aliquots were shipped to our central lab at Weill Cornell Medicine for downstream assays and biobanking. This paper provides an overview of the extensive biospecimen collection and highlights their processing procedures and long-term biobanking techniques, facilitating future molecular tests and evaluations.As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can aid future human spaceflight and space biology experiments., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
4. Spatial multi-omics of human skin reveals KRAS and inflammatory responses to spaceflight.
- Author
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Park J, Overbey EG, Narayanan SA, Kim J, Tierney BT, Damle N, Najjar D, Ryon KA, Proszynski J, Kleinman A, Hirschberg JW, MacKay M, Afshin EE, Granstein R, Gurvitch J, Hudson BM, Rininger A, Mullane S, Church SE, Meydan C, Church G, Beheshti A, Mateus J, and Mason CE
- Subjects
- Humans, Male, Single-Cell Analysis, Adult, Middle Aged, Female, Metagenomics methods, Gene Expression Profiling, Multiomics, Space Flight, Skin immunology, Skin metabolism, Skin pathology, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Inflammation immunology, Inflammation genetics, Inflammation metabolism
- Abstract
Spaceflight can change metabolic, immunological, and biological homeostasis and cause skin rashes and irritation, yet the molecular basis remains unclear. To investigate the impact of short-duration spaceflight on the skin, we conducted skin biopsies on the Inspiration4 crew members before (L-44) and after (R + 1) flight. Leveraging multi-omics assays including GeoMx™ Digital Spatial Profiler, single-cell RNA/ATAC-seq, and metagenomics/metatranscriptomics, we assessed spatial gene expressions and associated microbial and immune changes across 95 skin regions in four compartments: outer epidermis, inner epidermis, outer dermis, and vasculature. Post-flight samples showed significant up-regulation of genes related to inflammation and KRAS signaling across all skin regions. These spaceflight-associated changes mapped to specific cellular responses, including altered interferon responses, DNA damage, epithelial barrier disruptions, T-cell migration, and hindered regeneration were located primarily in outer tissue compartments. We also linked epithelial disruption to microbial shifts in skin swab and immune cell activity to PBMC single-cell data from the same crew and timepoints. Our findings present the inaugural collection and examination of astronaut skin, offering insights for future space missions and response countermeasures., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
5. Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight.
- Author
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Kim J, Tierney BT, Overbey EG, Dantas E, Fuentealba M, Park J, Narayanan SA, Wu F, Najjar D, Chin CR, Meydan C, Loy C, Mathyk B, Klotz R, Ortiz V, Nguyen K, Ryon KA, Damle N, Houerbi N, Patras LI, Schanzer N, Hutchinson GA, Foox J, Bhattacharya C, Mackay M, Afshin EE, Hirschberg JW, Kleinman AS, Schmidt JC, Schmidt CM, Schmidt MA, Beheshti A, Matei I, Lyden D, Mullane S, Asadi A, Lenz JS, Mzava O, Yu M, Ganesan S, De Vlaminck I, Melnick AM, Barisic D, Winer DA, Zwart SR, Crucian BE, Smith SM, Mateus J, Furman D, and Mason CE
- Subjects
- Animals, Female, Male, Humans, Mice, Astronauts, Cytokines metabolism, T-Lymphocytes immunology, Sex Factors, Gene Expression Profiling, Oxidative Phosphorylation, Space Flight, Single-Cell Analysis, Transcriptome
- Abstract
Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
6. Direct RNA sequencing of astronaut blood reveals spaceflight-associated m6A increases and hematopoietic transcriptional responses.
- Author
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Grigorev K, Nelson TM, Overbey EG, Houerbi N, Kim J, Najjar D, Damle N, Afshin EE, Ryon KA, Thierry-Mieg J, Thierry-Mieg D, Melnick AM, Mateus J, and Mason CE
- Subjects
- Humans, Transcriptome genetics, Weightlessness, Male, Hematopoiesis genetics, Nanopore Sequencing methods, Adult, RNA genetics, RNA blood, Methylation, Middle Aged, Space Flight, Astronauts, Sequence Analysis, RNA methods
- Abstract
The advent of civilian spaceflight challenges scientists to precisely describe the effects of spaceflight on human physiology, particularly at the molecular and cellular level. Newer, nanopore-based sequencing technologies can quantitatively map changes in chemical structure and expression at single molecule resolution across entire isoforms. We perform long-read, direct RNA nanopore sequencing, as well as Ultima high-coverage RNA-sequencing, of whole blood sampled longitudinally from four SpaceX Inspiration4 astronauts at seven timepoints, spanning pre-flight, day of return, and post-flight recovery. We report key genetic pathways, including changes in erythrocyte regulation, stress induction, and immune changes affected by spaceflight. We also present the first m
6 A methylation profiles for a human space mission, suggesting a significant spike in m6 A levels immediately post-flight. These data and results represent the first longitudinal long-read RNA profiles and RNA modification maps for each gene for astronauts, improving our understanding of the human transcriptome's dynamic response to spaceflight., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
7. Tumour antigen spreading mediated by vaccine-boosted CAR T cells.
- Author
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Mateus-Tique J and Brown B
- Subjects
- Humans, T-Lymphocytes, Receptors, Antigen, T-Cell, Antigens, Neoplasm, Vaccines
- Published
- 2023
- Full Text
- View/download PDF
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