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PROVIDER: PRJEB36081 | ENA |
REPOSITORIES: ENA
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Project description:Interplanetary human spaceflight represents a formidable medical challenge, but also provides a unique platform for investigating human adaptation to extreme environmental changes. Understanding the long-term effects of isolation has relevance in a range of scenarios and it is well recognized that a better understanding of the relationship between environmental exposure and the epigenome can lead to more effective preventive measures. Here we conduct a longitudinal epigenetic, mood state and biochemical profiling of 6 crew members in an experiment simulating a 520-day mission to Mars. Illumina HumanMethylation450 BeadChip was used to obtain DNA methylation profiles. Firstly, we found that long-term isolation can induce global DNA methylation remodeling, and this change seems to be an active adaptation (rather than a random process or a by-product of the isolation). This study is the first to demonstrate the dynamic relationship between global epigenetic remodeling and isolation-induced mood state and biochemical changes. Secondly, by considering the location of methylation sites within the genome and using gene-pathway annotation, we were able to identify pathways that were significantly enriched in methylation events and consider their association with specific function and the timeline of the mission. Thirdly, via our definition of epi-entropy, a measure of entropy adapted to methylation events, we observed that the methylation remodeling produced a marked reduction in epi-entropy. Results suggest that DNA methylation change is an indicator of change rather than its by-product, i.e., there is a psychology-epigenome-metabolism model of long-term depression; DNA methylation programs the environment signal into the epigenome, which is subsequently transformed into the biochemical output and health outcome. Thus, longitudinal epigenetic profiling could code the effect of isolation and act as early indicators of latent health outcome. A longitudinal epigenetic, mood state and biochemical profiling of 6 crew members in an experiment simulating a 520-day mission to Mars. 36 samples of blood cell DNA methylation profiling were obtained by Illumina HumanMethylation450 BeadChip, across 6 sampling points during the 520 days mission for all of the 6 crew members.
2015-01-14 | E-GEOD-64950 | biostudies-arrayexpress
Project description:Claret2009 - Predicting phase III overall survival in colorectal cancer
This model is described in the article:
Model-based prediction of
phase III overall survival in colorectal cancer on the basis of
phase II tumor dynamics.
Claret L, Girard P, Hoff PM, Van
Cutsem E, Zuideveld KP, Jorga K, Fagerberg J, Bruno R.
J. Clin. Oncol. 2009 Sep; 27(25):
4103-4108
Abstract:
PURPOSE: We developed a drug-disease simulation model to
predict antitumor response and overall survival in phase III
studies from longitudinal tumor size data in phase II trials.
METHODS: We developed a longitudinal exposure-response
tumor-growth inhibition (TGI) model of drug effect (and
resistance) using phase II data of capecitabine (n = 34) and
historical phase III data of fluorouracil (FU; n = 252) in
colorectal cancer (CRC); and we developed a parametric survival
model that related change in tumor size and patient
characteristics to survival time using historical phase III
data (n = 245). The models were validated in simulation of
antitumor response and survival in an independent phase III
study (n = 1,000 replicates) of capecitabine versus FU in CRC.
RESULTS: The TGI model provided a good fit of longitudinal
tumor size data. A lognormal distribution best described the
survival time, and baseline tumor size and change in tumor size
from baseline at week 7 were predictors (P < .00001).
Predicted change of tumor size and survival time distributions
in the phase III study for both capecitabine and FU were
consistent with observed values, for example, 431 days (90%
prediction interval, 362 to 514 days) versus 401 days observed
for survival in the capecitabine arm. A modest survival
improvement of 39 days (90% prediction interval, -21 to 110
days) versus 35 days observed was predicted for capecitabine.
CONCLUSION: The modeling framework successfully predicted
survival in a phase III trial on the basis of capecitabine
phase II data in CRC. It is a useful tool to support
end-of-phase II decisions and design of phase III studies.
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MODEL1708310001.
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2017-08-31 | MODEL1708310001 | BioModels
Project description:Dynamic nature of epigenetic patterns observed during the Mars 520-d mission simulation
| PRJNA272552 | ENA
Project description:Individuals in a population respond differently to stressful situations. While resilient individuals recover efficiently, others are susceptible to the same stressors. Most existing information regarding the factors regulating stress resilience in vertebrates is from specific areas of the brain from adult rodents or humans. In order to study resilience during development, we established a new paradigm to identify resilience in zebrafish larvae. Using this assay, we identified resilient and susceptible subsets of zebrafish larvae at 6 days post fertilization and performed gene expression analysis on whole larvae.
2023-01-05 | GSE193433 | GEO
Project description:Purpose: Sequencing analysis of plasma cell-free RNA was performed to study the effects of space flight and microgravity environment in mice. Methods: Plasma samples were collected during the JAXA MHU-1 mission as reported previously (Shiba et al., 2017, Scientific Reports). Total RNA was purified from plasma samples and processed for sequencing analysis, to compare RNA expression profiles in ground control, space flight and artificial 1-G control groups.
2022-11-16 | GSE213808 | GEO
Project description:Space radiations and microgravity both could cause DNA damage in cells, but the effects of microgravity on DNA damage response to space radiations are still controversial.A mRNA microarray and microRNA microarray in dauer larvae of Caenorhabditis elegans (C. elegans) that endured spaceflight environment and space radiations environment during 16.5-day Shenzhou-8 space mission was performed. The analyzation this study are further described in Gao, Y., Xu, D., Zhao, L., Zhang, M. and Sun, Y. (2015) Effects of microgravity on DNA damage response in Caenorhabditis elegans during Shenzhou-8 spaceflight. International journal of radiation biology, 91, 531-539.
2017-03-01 | GSE90872 | GEO
Project description:Space radiations and microgravity both could cause DNA damage in cells, but the effects of microgravity on DNA damage response to space radiations are still controversial. A mRNA microarray and microRNA microarray in dauer larvae of Caenorhabditis elegans (C. elegans) that endured spaceflight environment and space radiations environment during 16.5-day Shenzhou-8 space mission were performed. The analyzation this study are further described in Gao, Y., Xu, D., Zhao, L., Zhang, M. and Sun, Y. (2015) Effects of microgravity on DNA damage response in Caenorhabditis elegans during Shenzhou-8 spaceflight. International journal of radiation biology, 91, 531-539.
2017-03-01 | GSE90823 | GEO
Project description:Space radiations and microgravity both could cause DNA damage in cells, but the effects of microgravity on DNA damage response to space radiations are still controversial. A mRNA microarray and microRNA microarray in dauer larvae of Caenorhabditis elegans (C. elegans) that endured spaceflight environment and space radiations environment during 16.5-day Shenzhou-8 space mission were performed. The analyzation this study are further described in Gao, Y., Xu, D., Zhao, L., Zhang, M. and Sun, Y. (2015) Effects of microgravity on DNA damage response in Caenorhabditis elegans during Shenzhou-8 spaceflight. International journal of radiation biology, 91, 531-539.
2017-03-01 | GSE90786 | GEO
Project description:Understanding individual capability to adjust to protracted confinement and isolation may inform adaptive plasticity and disease vulnerability/resilience, and may have long-term implications for operations requiring prolonged presence in distant and restricted environments. Individual coping depends on many different factors encompassing psychological dispositional traits, endocrine reactivity and their underlying molecular mechanisms (e.g. gene expression). A positive view of self and others (secure attachment style) has been proposed to promote individual resilience under extreme environmental conditions. Here, we tested this hypothesis and investigated the underlying molecular mechanisms in 13 healthy volunteers confined and isolated for 12 months in a research station located 1670 km away from the south geographic pole on the Antarctic Plateau at 3233 m above sea level. Study participants, stratified for attachment style, were characterised longitudinally (before, during and after confinement) for their psychological appraisal of the stressful nature of the expedition, diurnal fluctuations in endocrine stress reactivity, and gene expression profiling (Agilent microarray transcriptomics). Predictably, a secure attachment style was associated with reduced psychological distress and endocrine vulnerability to stress. In addition, while prolonged confinement and isolation remarkably altered overall patterns of gene expression, such alteration was largely reduced in individuals characterized by a secure attachment style. Furthermore, increased resilience was associated with a reduced expression of genes involved in energy metabolism (mitochondrial function and oxidative phosphorylation). Ultimately, our data indicate that a secure attachment style may favour individual resilience in extreme environments and that such resilience can be mapped onto identifiable molecular substrates.
2020-04-26 | GSE149321 | GEO