Space radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to ...estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether individual radiosensitivity, as determined by the ex vivo dose-response of the pre-flight chromosome aberration rate (CAR), contributes to the prediction of the post-flight CAR incurred from the radiation exposure during missions. Random-effects Poisson regression was used to estimate subject-specific radiosensitivities from the preflight dose-response data, which were in turn used to predict post-flight CAR and subject-specific relative biological effectiveness (RBEs) between space radiation and gamma radiation. Covariates age, gender were also considered. Results indicate that there is predictive value in background CAR as well as radiosensitivity determined preflight for explaining individual differences in post-flight CAR over and above that which could be explained by BFO dose alone. The in vivo RBE for space radiation was estimated to be approximately 3 relative to the ex vivo dose response to gamma irradiation. In addition, pre-flight radiosensitivity tended to be higher for individuals having a higher background CAR, suggesting that individuals with greater radiosensitivity can be more sensitive to other environmental stressors encountered in daily life. We also noted that both background CAR and radiosensitivity tend to increase with age, although both are highly variable. Finally, we observed no significant difference between the observed CAR shortly after mission and at > 6 months post-mission.
In space, multiple unique environmental factors, particularly microgravity and space radiation, pose constant threat to the DNA integrity of living organisms. Specifically, space radiation can cause ...damage to DNA directly, through the interaction of charged particles with the DNA molecules themselves, or indirectly through the production of free radicals. Although organisms have evolved strategies on Earth to confront such damage, space environmental conditions, especially microgravity, can impact DNA repair resulting in accumulation of severe DNA lesions. Ultimately these lesions, namely double strand breaks, chromosome aberrations, micronucleus formation, or mutations, can increase the risk for adverse health effects, such as cancer. How spaceflight factors affect DNA damage and the DNA damage response has been investigated since the early days of the human space program. Over the years, these experiments have been conducted either in space or using ground-based analogs. This review summarizes the evidence for DNA damage induction by space radiation and/or microgravity as well as spaceflight-related impacts on the DNA damage response. The review also discusses the conflicting results from studies aimed at addressing the question of potential synergies between microgravity and radiation with regard to DNA damage and cellular repair processes. We conclude that further experiments need to be performed in the true space environment in order to address this critical question.
Living organisms in space are constantly exposed to radiation, toxic chemicals or reactive oxygen species generated due to increased levels of environmental and psychological stresses. Understanding ...the impact of spaceflight factors, microgravity in particular, on cellular responses to DNA damage is essential for assessing the radiation risk for astronauts and the mutation rate in microorganisms. In a study conducted on the International Space Station, confluent human fibroblasts in culture were treated with bleomycin for three hours in the true microgravity environment. The degree of DNA damage was quantified by immunofluorescence staining for γ-H2AX, which is manifested in three types of staining patterns. Although similar percentages of these types of patterns were found between flight and ground cells, there was a slight shift in the distribution of foci counts in the flown cells with countable numbers of γ-H2AX foci. Comparison of the cells in confluent and in exponential growth conditions indicated that the proliferation rate between flight and the ground may be responsible for such a shift. We also performed a microarray analysis of gene expressions in response to bleomycin treatment. A qualitative comparison of the responsive pathways between the flown and ground cells showed similar responses with the p53 network being the top upstream regulator. The microarray data was confirmed with a PCR array analysis containing a set of genes involved in DNA damage signaling; with BBC3, CDKN1A, PCNA and PPM1D being significantly upregulated in both flight and ground cells after bleomycin treatment. Our results suggest that whether microgravity affects DNA damage response in space can be dependent on the cell type and cell growth condition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long-duration spaceflight is known to cause immune dysregulation in astronauts. Biomarkers of immune system function are needed to determine both the need for and effectiveness of potential immune ...countermeasures for astronauts. Whereas plasma cytokine concentrations are a well-established biomarker of immune status, salivary cytokine concentrations are emerging as a sensitive indicator of stress and inflammation. For this study, to aid in characterizing immune dysregulation during spaceflight, plasma and saliva cytokines were monitored in astronauts before, during and after long-duration spaceflight onboard the International Space Station. Blood was collected from 13 astronauts at 3 timepoints before, 5 timepoints during and 3 timepoints after spaceflight. Saliva was collected from 6 astronauts at 2 timepoints before spaceflight, 2 timepoints during and 3 timepoints following spaceflight. Samples were analyzed using multiplex array technology. Significant increases in the plasma concentration of IL-3, IL-15, IL-12p40, IFN-α2, and IL-7 were observed during spaceflight compared to before flight baseline. Significant decreases in saliva GM-CSF, IL-12p70, IL-10 and IL-13 were also observed during spaceflight as compared to compared to before flight baseline concentrations. Additionally, plasma TGFβ1 and TGFβ2 concentrations tended to be consistently higher during spaceflight, although these did not reach statistical significance. Overall, the findings confirm an
hormonal dysregulation of immunity, appearing pro-inflammatory and Th1 in nature, persists during long-duration orbital spaceflight. These biomarkers may therefore have utility for monitoring the effectiveness of biomedical countermeasures for astronauts, with potential application in terrestrial research and medicine.
ABSTRACT
Microgravity, or an altered gravity environment different from the 1 g of the Earth, has been shown to influence global gene expression patterns and protein levels in cultured cells. ...However, most of the reported studies that have been conducted in space or by using simulated microgravity on the ground have focused on the growth or differentiation of these cells. It has not been specifically addressed whether nonproliferating cultured cells will sense the presence of microgravity in space. In an experiment conducted onboard the International Space Station, confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 d, respectively, to investigate changes in gene and microRNA (miRNA) expression profiles in these cells. Results of the experiment showed that on d 3, both the flown and ground cells were still proliferating slowly, as measured by the percentage of Ki‐67+ cells. Gene and miRNA expression data indicated activation of NF‐kB and other growth‐related pathways that involve hepatocyte growth factor and VEGF as well as the down‐regulation of the Let‐7 miRNA family. On d 14, when the cells were mostly nonproliferating, the gene and miRNA expression profile of the flight sample was indistinguishable from that of the ground sample. Comparison of gene and miRNA expressions in the d 3 samples, with respect to d 14, revealed that most of the changes observed on d 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeletal changes via immunohistochemistry staining of the cells with antibodies for α‐tubulin and fibronectin showed no difference between the flown and ground samples. Taken together, our study suggests that in true nondividing human fibroblast cells in culture, microgravity experienced in space has little effect on gene and miRNA expression profiles.—Zhang, Y., Lu, T., Wong, M., Wang, X., Stodieck, L., Karouia, F., Story, M., Wu, H. Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight. FASEB J. 30, 2211–2224 (2016). www.fasebj.org
In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health ...impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions. RNA and protein levels in cellular and animal models have been targeted in order to identify pathways affected by spaceflight. Of the many pathways responsive to the space environment, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) network appears to commonly be affected across many different cell types under the true or simulated spaceflight conditions. NF-κB is of particular interest, as it is associated with many of the spaceflight-related health consequences. This review intends to summarize the transcriptomics studies that identified NF-κB as a responsive pathway to ground-based simulated microgravity or the true spaceflight condition. These studies were carried out using either human cell or animal models. In addition, the review summarizes the studies that focused specifically on NF-κB pathway in specific cell types or organ tissues as related to the known spaceflight-related health risks including immune dysfunction, bone loss, muscle atrophy, central nerve system (CNS) dysfunction, and risks associated with space radiation. Whether the NF-κB pathway is activated or inhibited in space is dependent on the cell type, but the potential health impact appeared to be always negative. It is argued that more studies on NF-κB should be conducted to fully understand this particular pathway for the benefit of crew health in space.
Strong metal-support interaction (SMSI) has been widely used to improve catalytic performance and to identify reaction mechanisms. We report that single Pt atoms anchored onto hollow nanocarbon ...(h-NC) edges possess strong metal-carbon interaction, which significantly modifies the catalytic behavior of the anchored Pt atoms for selective hydrogenation reactions. The strong Pt-C bonding not only stabilizes single Pt atoms but also modifies their electronic structure, tunes their adsorption properties, and enhances activation of reactants. The fabricated Pt1/h-NC single-atom catalysts (SACs) demonstrated excellent activity for hydrogenation of 3-nitrostyrene to 3-vinylaniline with a turnover number >31,000/h, 20 times higher than that of the best catalyst for such selective hydrogenation reactions reported in the literature. The strategy to strongly anchor Pt atoms by edge carbon atoms of h-NCs is general and can be extended to construct strongly anchored metal atoms, via SMSI, onto surfaces of various types of support materials to develop robust SACs.
Display omitted
•A strategy is proposed to anchor metal atoms to edge carbon atoms of graphene sheets•Formation of Pt1-C bond tunes performance of Pt1/h-NC single-atom catalyst (SAC)•Pt1/h-NC SAC is 20 times more active than the best catalyst for 3-nitrostyrene hydrogenation•Electronic SMSI can be effectively used to tune catalytic properties of SACs
Chemical Reaction Engineering; Catalysis; Nanostructure
Co@C core-shell particles with a uniform size of approximately 100 nm anchored on rGO nano sheets is synthesized by a one-pot hydrothermal process. The Co@C particle formation is realized with a ...self-assembly procedure of metal-organic framework (MOF), and with GO as the precursor of rGO, Co@C/rGO is achieved. After calcination, the synthesized Co@C/rGO with high crystallization is obtained. Fabricated as an electrode by electrophoretic deposition, the calcined Co@C/rGO is evaluated with a high specific capacity of 810 C g−1 at a current density of 1 A g−1. With the calcined Co@C/rGO served as positive electrode and with as-prepared 3D rGO aerogel as negative electrode, an assembled asymmetric supercapattery possesses a wide operating potential window of 1.2 V. The specific capacitance of the supercapattery can be as high as 120 F g−1 at 0.6 A g−1, while the energy density reaches 29.5 W h kg−1 at a power density of 720 W kg−1, and 11.2 W h kg−1 at 12,000 W kg−1. After 10,000 cycles of charge-discharge process at 5 A g−1, the asymmetric supercapattery device shows considerable cyclic stability with capacitance retention of 93.7%.
Display omitted
•Co@C/rGO hybrid composite is synthesized with specific capacity of 810 C g−1.•The fabricated supercapattery possesses energy density of 11.2 W h kg−1 at 12,000 W kg−1.•The supercapattery has more activated property with a capacity retention of 93.7% after 10,000 cycles at 5 A g−1.
•Fe3O4@N-PCNR/rGO hybrid composite with a core shell structure is synthesized.•Specific capacity of 495 Cg-1 of calcined Fe3O4@N-PCNR/rGO is achieved.•The asymmetric supercapacitor possesses energy ...density of 30 W h kg-1 at 500 W kg-1.•The supercapacitor has capacitance retention of 80% after 10,000 cycles at 10 Ag-1.
Display omitted
Fe3O4 particles are designed to originate reversible faradaic process and carbon material with a rice-like shape and meso-pore dominated structure is designed to encapsulate the Fe3O4 particles. Synthesized carbon nano rice wrapped Fe3O4 are uniformly anchored on the surface of reduced graphene oxide (rGO) nano sheets in a one-pot facile hydrothermal procedure. A significant amount (13.28 at%) of N is also doped into the carbon nano rice in the hydrothermal process, simultaneously. The synthesized Fe3O4@N-Carbon nano rice/rGO (Fe3O4@N-PCNR/rGO) delivers a high capacity of 495 Cg-1at a current density of 1 Ag-1 and high long-term stability of 70% after 1000 charge-discharge cycles at 10 Ag-1. The Fe3O4@N-Carbon/rGO is utilized as a positive electrode, and synthesized 3D rGO aerogel is employed as a negative electrode to fabricate a supercapattery, which exhibits a wide operating potential window of 1.5 V, a high energy density of 46 W h kg-1 at 750 W kg-1, and even 10 W h kg-1 at an elevated power density of 7500 W kg-1. The supercapattery also performs well in terms of long-life stability with 80% of capacitance retention after 10,000 charge-discharge cycles at 10 Ag-1.
Detrimental health consequences from exposure to space radiation are a major concern for long-duration human exploration missions to the Moon or Mars. Cellular responses to radiation are expected to ...be heterogeneous for space radiation exposure, where only high-energy protons and other particles traverse a fraction of the cells. Therefore, assessing DNA damage and DNA damage response in individual cells is crucial in understanding the mechanisms by which cells respond to different particle types and energies in space. In this project, we identified a cell-specific signature for radiation response by using single-cell transcriptomics of human lymphocyte subpopulations. We investigated gene expression in individual human T lymphocytes 3 h after ex vivo exposure to 2-Gy gamma rays while using the single-cell sequencing technique (10X Genomics). In the process, RNA was isolated from ~700 irradiated and ~700 non-irradiated control cells, and then sequenced with ~50 k reads/cell. RNA in each of the cells was distinctively barcoded prior to extraction to allow for quantification for individual cells. Principal component and clustering analysis of the unique molecular identifier (UMI) counts classified the cells into three groups or sub-types, which correspond to CD4+, naïve, and CD8+/NK cells. Gene expression changes after radiation exposure were evaluated using negative binomial regression. On average,
,
and other
related genes that are known to respond to radiation in human T cells showed increased activation. While most of the
responsive genes were upregulated in all groups of cells, the expressions of
,
and
were only upregulated in the CD4+ and naïve groups, but were unchanged in the CD8+/NK group, which suggests that the interferon-gamma pathway does not respond to radiation in CD8+/NK cells. Thus, single-cell RNA sequencing technique was useful for simultaneously identifying the expression of a set of genes in individual cells and T lymphocyte subpopulation after gamma radiation exposure. The degree of dependence of UMI counts between pairs of upregulated genes was also evaluated to construct a similarity matrix for cluster analysis. The cluster analysis identified a group of
-responsive genes and a group of genes that are involved in the interferon gamma pathway, which demonstrate the potential of this method for identifying previously unknown groups of genes with similar expression patterns.
PDF
