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Leveraging bioinformatics approaches for drug repositioning in space radiation protection.

The health effects of space radiation, primarily Galactic Cosmic Rays (GCRs), on humans remain largely unknown, with potential cardiovascular consequences posing a significant threat to astronauts on long-duration spaceflight missions. Currently, there are no established pharmacological countermeasures for GCR exposure. Drug repositioning offers a promising strategy to accelerate pharmaceutical research in space medicine. This study leverages existing bioinformatics techniques to identify and prioritize potential drug candidates associated with proteomic perturbations following simulated GCR exposure using previously published murine cardiac proteomic data. A protein-protein interaction (PPI) network was constructed using the top differentially expressed proteins (DEPs) from murine heart tissue following exposure to 5-ion GCRs as seed nodes, focusing on experimentally supported interactions. Network topology, Markov clustering, and functional enrichment analyses were used to characterize biologically relevant proteins and pathways. Drug-protein interactions were predicted using Drugst.One and mapped to PPI clusters of interest to identify candidate drugs. Selected drug-macromolecule interactions were further explored using CB-Dock2 molecular docking and short-duration molecular dynamics simulations as hypothesis-generating structural assessments. Analysis of a key PPI network cluster consisting of several ATP synthase proteins identified 23 unique drug candidates. These analyses demonstrate a systematic approach for leveraging bioinformatics techniques to identify candidate molecular targets and generate pharmacological hypotheses in the context of space radiation countermeasures. Ultimately, this strategy introduces a hypothesis-generating framework for the prioritization of potential drug candidates for future computational characterization and experimental investigation against spaceflight stressors.

Animals

Cohort Studies and Multi-omics Approaches to Low-Dose Ionizing Radiation-Induced Cardiovascular Disease: A Comprehensive Review.

The effect of low-dose ionizing radiation exposure on the risk of cardiovascular disease (CVD) represents a significant concern in the field of radiation protection. The prevailing approach to mitigating the adverse effects of low-dose or low-dose-rate radiation does not currently incorporate the potential risk of CVD, despite the possibility that such risk may be a substantial contributor to overall health hazards. Current evidence suggests a potential association between radiation exposure and CVD; however, the overall findings remain inconclusive. This is particularly due to the uncertainty surrounding the influence of significant non-radiation risk factors on the associations reported in epidemiological studies. It is difficult to discern the underlying connection in observational epidemiology when there is substantial variation in baseline risk factors. The paucity of epidemiological research in this domain is being partially offset by the advancement of multi-omics approaches. These methods assist in identifying radiosensitive targets, comprehending underlying biological processes, and pinpointing biomarkers. This, in turn, fortifies the evidence gleaned from epidemiological studies. In this review, we delve into the body of epidemiological research pertaining to CVD induced by low-dose ionizing radiation and the application of multi-omics techniques. The integration of these two methodologies holds the promise of identifying specific molecules or biological pathways that can be employed to validate endpoints related to radiation risk assessment.

Humans

Shielding performance and clinical applicability of lead-free materials in computed tomography.

Owing to the high radiation exposure associated with computed tomography (CT) examinations and the image quality degradation caused by conventional radiation shielding materials, this study evaluated the dose reduction performance and image quality maintenance potential of a newly developed lead-free composite shielding material. This material was composed of bismuth, tungsten, tungsten carbide, aluminium, and polyurethane. Phantom-based dose measurements demonstrated that the shielding material achieved dose reduction rates ranging from 17.6% to 37.6%, depending on tube voltage. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and changes in tube current-time product (mAs) under a scout-based automatic exposure control (AEC) protocol were analysed according to the presence or absence of the shielding material across regions. For the clinical evaluation, CT scans were performed on four patients. Furthermore, the images were reviewed to evaluate whether this material affected image quality. The shielding material exhibited radiation reduction levels comparable to those reported in previous studies. SNR and CNR analyses showed minor statistical variations in certain regions; however, most differences were not statistically significant, and even significant differences remained within a range that did not compromise diagnostic image quality. Under the scout-based AEC protocol, the use of the shielding material resulted in less than 1% variation in mAs values. No visually perceptible artefacts or clinically significant image quality degradation were observed. The proposed composite shielding material demonstrated the potential to mitigate some limitations of conventional shielding materials and showed preliminary clinical feasibility as an adjunctive strategy for radiation dose reduction in CT examinations.

Radiation Protection

Microbial decaprenoxanthin: From understanding an extremophile-derived C50 carotenoid to its bioprocessing for large-scale applications.

Decaprenoxanthin (DPXT) is an unusual bacterial C50 carotenoid that has historically received limited attention despite its well-defined structure. For decades, carotenoid research and industrial development have been dominated by C40 carotenoids, leaving longer-chain carotenoids largely overlooked. Recent discoveries, particularly from microorganisms inhabiting Antarctic and other extreme environments, have repositioned DPXT as an adaptive pigment shaped by intense environmental pressures. Its extended polyene chain and membrane-associated behavior suggest roles in membrane stabilization and protection against ultraviolet radiation and oxidative stress, features that may hold relevance for food and biotechnological applications. This review integrates historical and recent knowledge on DPXT, covering its structural characteristics, biosynthetic pathways, ecological function, and emerging technological relevance. Special attention is given to microbial sources, particularly Actinomycetota from extreme environments, and to recent advances in microbial genomics, metabolic engineering, and sustainable bioprocess development that enable the production and exploration of C50 carotenoids beyond their native extremophilic context. The analysis highlights DPXT as a representative example of stress-resilient carotenoids, with physicochemical and membrane-interacting properties that may offer advantages for future food and biotechnological systems. Although significant challenges remain in cultivation strategies, yield optimization, and downstream recovery, advances in microbial cell factories and green extraction technologies open new opportunities for valorizing C50 carotenoids. This review bridges extremophile microbiology, carotenoid biochemistry, and sustainable food innovation, positioning DPXT as an emerging molecule that may expand the functional and structural landscape of carotenoids relevant to food science.

Carotenoids

Biochemical and Structural Analyses of the Tardigrade DNA-Damage Suppressor Protein, Dsup.

Tardigrades are extremophiles that withstand harsh environments through unique molecular strategies. One such strategy involves Damage Suppressor (Dsup), a protein shown to protect cells from radiation-induced DNA damage. Little is known about the biochemical and structural characteristics of Dsup that lead to DNA protection. To gain insight into the mechanism of DNA protection by Dsup, we examined its fundamental biochemical and structural properties using mass photometry, biolayer interferometry, small-angle X-ray scattering, and microfluidic modulation spectroscopy. We found that Dsup is largely intrinsically disordered and binds DNA with high affinity via a multi-valent interface. This interaction induced conformational changes in both Dsup and the DNA, suggesting a potential structural mechanism of its DNA protection ability. We propose that Dsup alters DNA structure, possibly by partially unwinding it, to reduce its susceptibility to damage. These findings offer new insights into how a disordered protein such as Dsup functions as radioprotectants in extreme environments.

Tardigrada

Prevalence and determinants of profound vitamin D deficiency (25-hydroxyvitamin D <10 nmol/L) in the UK Biobank and potential implications for disease association studies.

BACKGROUND: 25-hydroxyvitamin D (25OHD) is the principal biomarker of vitamin D status. Values below the assay detection limit (<10 nmol/L) are often reported as missing. Thus the most severely deficient participants are excluded from research which can lead to inaccurate findings such as underestimated prevalence of deficiency, overlooked risk factors, and biased evaluation of disease associations. METHODS: In total 369,626 individuals from the UK Biobank cohort were included in this study. Data on 25OHD concentration and relevant demographic and lifestyle factors such as age, supplement intake, diet, and time spent outdoors were used in the analyses. Ambient UVB radiation was approximated for each participant. 25OHD was evaluated as a categorical outcome and we reintroduced participants with 25OHD values <&#x202f;10 nmol/L (conventionally reported as missing values) back to the dataset. Adjusted regression models were used to investigate the determinants of profound (25OHD <10 nmol/L) and severe (10-25 nmol/L) vitamin D deficiency and to assess disease associations (with 25-50 nmol/L as the reference category). RESULTS: 1,784 (0.48&#x202f;%) individuals were profoundly deficient and a further 47,226 (12.78 %) individuals were severely vitamin D deficient. The proportions of profoundly and severely deficient were highest among Asians, 9&#x202f;% and 47&#x202f;%, respectively. Ambient UVB radiation was the second strongest predictor: comparing the lowest vs. highest quartile, the risk of profound deficiency was 17-fold increased and that of severe deficiency 7.5-fold increased. Use of vitamin D supplements substantially reduced risk of profound (4.4-fold) and severe (2.5-fold) deficiency, as did fish intake (5- and 1.9-fold, respectively). Profound deficiency was more strongly associated with chronic illness, diabetes, and emphysema compared to severe deficiency. CONCLUSION: The prevalence of profound and severe vitamin D deficiency among Asian and Black ethnicities in the UK is high and requires targeted action. Solar radiation is potent in protecting against profound and severe vitamin D deficiency. Studies evaluating the relationship between vitamin D status and other health outcomes may be biased if profoundly deficient participants are excluded.

Humans

Low-Dose Radiation-Induced Expression of Exosomal miRNAs in the Serum of Medical Radiation Workers.

Objective: Long-term low-dose ionizing radiation may alter genomes and cause diseases. This study examined serum exosomal miRNA differences among radiation-exposed medical workers by work types. Methods: High-throughput sequencing screened serum exosomal miRNAs in diagnostic radiologists, interventional radiologists, and nuclear medicine doctors. qRT-PCR validated differentially expressed miRNAs. Results: 410 differentially expressed miRNAs, including 102 downregulated and 308 upregulated miRNAs, enriched in 15 KEGG pathways. Four miRNAs were validated. miR-30e-5p, miR-155-5p and miR-486-5p differed significantly among groups(P<0.01).The expression levels of these three miRNAs were lower in the nuclear medicine group than in the diagnostic group (0.25&#xb1;0.05vs3.89&#xb1;8.62,0.10&#xb1;0.15vs7.03&#xb1;15.75,0.37&#xb1;0.39vs4.46&#xb1;9.64;Z=3.542,3.335,9.859;P<0.01), whereas miR-155-5p was lower in the interventional group than in the diagnostic group(1.32&#xb1;2.43vs 7.03&#xb1;15.75;H=11.889,P=0.003), miR-486-5p was higher(9.54&#xb1;19.39vs4.46&#xb1;9.64; H=9.859,P=0.007). All four miRNAs showed higher expression in the 14-31-year work-experience group, and all four also showed age-dependent differences, with miR-30d-5p and miR-486-5p showing the age-related differences (P<0.01). Combined detection of the four miRNAs improved discrimination among occupational categories (AUC=0.784). Multiple linear regression analysis showed that sex was associated with all four miRNAs, whereas work type was associated with miR-30d-5p and miR-155-5p (P<0.05). Conclusion: Serum exosomal miR-30e-5p, miR-155-5p, and miR-486-5p are promising biomarkers for monitoring radiation-induced damage, supporting occupational protection and health management.

exosomes

Insights into Tardigrade Damage-Suppression Protein, Dsup.

Tardigrades are microscopic invertebrates capable of surviving extreme environmental conditions through unique molecular adaptations. Among the proteins implicated in their remarkable resilience is a novel protein known as damage suppressor (Dsup), a key factor in protecting cellular DNA from elevated levels of radiation. Since its discovery, numerous studies have explored the biochemical, structural, and functional properties of Dsup. In this review, we summarize the current knowledge surrounding these properties and describe several proposed mechanisms by which Dsup may confer protection. For each proposed mechanism, we outline the foundational model, present supporting evidence, and highlight critical gaps in our understanding. Taken together, we believe that Dsup likely employs multiple complementary mechanisms to protect DNA. Finally, we discuss emerging applications of Dsup and Dsup-inspired technologies for human health. Overall, this review synthesizes our current understanding and provides a framework to guide future investigations into this remarkable protein.

Animals

UVB photoprotection by thiourea and (thio)semicarbazone derivatives: cellular and molecular evidence.

BACKGROUND: Ultraviolet B (UVB) radiation is a major environmental stressor that contributes to oxidative stress, inflammation, DNA damage, and ultimately an increased risk of skin carcinogenesis. The development of safer, multifaceted UV filters with improved photostability and bioprotective properties remains an important research priority. Here, alkyl chain-conjugated thiourea (I-XIX) and aryl-linked (thio)semicarbazone (XX-XXV) derivatives have been systematically assessed for their photoprotective potential against UVB-induced cellular damage. METHODS: The UV absorption properties, molar absorptivity, and photostability of the test compounds were assessed through spectroscopic studies. Cytotoxicity, effective concentrations, and bioprotective effects of the compounds were evaluated using in vitro cellular methods. RESULTS: Several compounds exhibited robust UVB absorption with high molar absorptivity, particularly semicarbazone derivatives, while displaying minimal cytotoxicity to normal human dermal fibroblasts. Among the evaluated compounds, ten compounds were found to be more photostable than benzophenone (reference compound). Selected compounds significantly reduced UVB-induced intracellular reactive oxygen species and nitric oxide production, signifying effective attenuation of oxidative and nitrosative stress. In addition, compounds IV, XXI, and XXIII alleviated UVB-induced inflammatory cascades by diminishing Interleukin-1 beta (IL-1&#x3b2;) and Tumor Necrosis Factor alpha (TNF-&#x3b1;) levels. Therefore, these compounds also protected fibroblast morphology. Moreover, the same compounds protected from DNA damage by preventing UVB-induced genomic DNA fragmentation and formation of cyclobutane pyrimidine dimers. In particular, compound XXIII displayed selective UVB absorption, better photostability, low cytotoxicity, and moderate biological photoprotection (SPF 16). CONCLUSION: Together, the results suggest that thiourea and (thio)semicarbazone derivatives, notably compound XXIII, represent promising photoprotective scaffolds requiring further formulation, in vivo, permeability, phototoxicity, and safety studies to validate their potential as UV-filtering agents.

Humans

The KEAP1-NFE2L2/NRF2 Axis in Non-Small Cell Lung Cancer Radioresistance: Redox Homeostasis and Emerging DNA Damage Response Mechanisms.

Radioresistance and local recurrence remain major barriers to effective radiotherapy in non-small cell lung cancer (NSCLC). Loss-of-function KEAP1 alterations or activating NFE2L2 alterations can stabilize NRF2, but do not alone establish sustained transcriptional activity or functional dependency. This focused narrative review evaluates clinical radiotherapy studies and mechanistically informative preclinical studies linking the KEAP1-NFE2L2/NRF2 axis to NSCLC radioresistance. We prioritized clinical studies reporting radiotherapy-specific outcomes and preclinical studies coupling NRF2-related molecular status or perturbation with radiation-response endpoints; contextual studies informed metabolic, DNA damage response (DDR), immune and normal-lung effects. Evidence most consistently supports NRF2-mediated redox protection through glutathione-dependent defense, cellular reducing capacity and antioxidant enzymes, limiting radiation-induced reactive oxygen species (ROS) accumulation and oxidative injury. Limited studies further suggest that NRF2 may affect DNA-damage signaling, checkpoint control and repair. The detailed RPA32-TOPBP1-ATR-CHK1 model is therefore considered proposed rather than established in NRF2-active NSCLC. Retrospective clinical studies associate pathogenic KEAP1/NFE2L2 alterations with impaired local control in some radiotherapy-treated cohorts, but do not justify treating genomic status, protein abundance, transcriptional activity and functional dependency as equivalent measures or demonstrate treatment-predictive value. NRF2-mediated normal-lung protection also constrains systemic inhibition. Prospective studies integrating molecular classification, radiation-response endpoints, local control and normal-tissue toxicity are required before biomarker-guided radiosensitization can be considered.

DNA damage response

Dosimetric Parameters of the Heart and Its Substructures in Predicting Cardiac Events or Survival in Patients With Lung Cancer After Radiation Therapy: A Systematic Review and Meta-analysis.

The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in patients with lung cancer remains uncertain. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between these associations. A systematic meta-analysis was performed following PRISMA guidelines. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. Outcomes were classified into major adverse cardiac events (MACE), arrhythmias, pericardial effusion, and survival. Depending on heterogeneity, random- or fixed-effects models were applied to calculate pooled hazard ratios (HRs) for univariable and multivariable analyses. A total of 80 studies, including 21,645 patients, were analyzed. Of these, 25 studies reported CEs, and 69 reported survival outcomes. Among 91 WH and 215 CS parameters evaluated, several showed significant associations. Key findings from our meta-analysis include: (1) left anterior descending (LAD) V15 was significantly associated with MACE. The mean heart dose (MHD), as well as ventricle and LAD doses, were significantly associated with ischemic events. (2) Multiple CS parameters were associated with different arrhythmia subtypes. (3) MHD, heart V5/V35/V55 and pericardial doses were significantly associated with pericardial effusion. (4) MHD was significantly associated with survival; CS parameters also showed predictive value, and especially, heart base dose being the most significant. (5) We also identified several thresholds with potential predictive values, such as LAD V15 <10% for MACE, left pulmonary vein (LPV) V55 <2%, and right pulmonary vein (RPV) V10 <54% for atrial fibrillation (AF), right atrium (RA) V60 <0.03 cc for non-AF supraventricular tachyarrhythmia, and left main artery (LMA) V10 &#x2265;1 cc for bradyarrhythmia. This study identified 130 WH and CS dosimetric parameters associated with CEs and 131 with survival outcomes. These findings enhance our understanding of radiation-induced heart injury mechanisms and provide guidance for potential protective and intervention strategies.

Humans

Evolutionary Reorganization of Transcriptomic Architecture Across a UVB Tolerance Gradient in Fish.

Environmental stressors such as ultraviolet radiation impose strong selective pressures on organisms, yet how adaptation to such stressors shapes transcriptomic responses at the network level remains poorly understood. Although stratospheric ozone is recovering globally, substantial regional variation in UV exposure persists, particularly in high-altitude environments where extreme UV levels can occur. Here, we compared three fish models representing distinct biological responses to UVB exposure: wild-type zebrafish (Danio rerio), a melanin-deficient zebrafish mutant (nacre) lacking a major protective mechanism against UVB damage, and the high-altitude Andean killifish Orestias ascotanensis, a species naturally exposed to extreme UVB radiation. Together, these models define a gradient spanning physiological protection, impaired protection, and evolutionary adaptation to UVB stress. Using RNA-seq and protein-protein interaction networks, we show that transcriptomic responses differ markedly across this gradient. Wild-type and nacre zebrafish exhibited relatively limited transcriptomic changes (&#x223c;2%-2.4% of genes changing), whereas O. ascotanensis displayed a large-scale and highly coordinated response (&#x223c;21.6% of genes changing) characterized by functionally specialized networks enriched in DNA repair pathways. These differences involved not only transcriptomic magnitude but also marked reorganization of transcriptomic architecture. Integration with positive selection analyses revealed that positively selected genes were concentrated within highly interconnected regions of transcriptomic networks, consistent with adaptation involving network reorganization. Furthermore, ortholog-based analyses suggest that adaptive responses involve differential reorganization of a conserved functional background. Together, our results support a model in which adaptation to environmental stress is associated with the reorganization of conserved transcriptomic networks across physiological and evolutionary contexts, providing a systems-level perspective on the molecular basis of adaptation.

UVB radiation

A UG5 reverse transcriptase-nitrilase antiviral module confers phage immunity in the plant symbiont Sinorhizobium meliloti.

Bacteriophages exert strong selective pressure on soil- and rhizosphere-associated bacteria, including plant-associated symbionts. Reverse transcriptase-associated defense systems of the UG family are widespread across bacterial lineages, yet their ecological roles remain largely undefined. Within this family, UG5 systems are distinguished by reverse transcriptases fused to or associated with a nitrilase domain. Here, we combine phylogenetic, metagenomic, and functional analyses to investigate the evolutionary context and antiviral activity of UG5-associated systems. Phylogenetic analysis of 728 nitrilase domains places UG5-associated nitrilases within a well-supported UG-related radiation encompassing the UG1, UG5, and UG6 families, with UG1 nested within a broader UG5 lineage. Metagenomic analysis further revealed UG5-associated reverse transcriptases in soil- and rhizosphere-derived metagenomes. Based on this observation, we characterized a UG5-large reverse transcriptase (RT)-associated system, here designated DRT11, encoded on the pSymA megaplasmid of Sinorhizobium meliloti RMO17, a nitrogen-fixing symbiont of Medicago sativa. Despite lacking the transmembrane protein typical of canonical UG5-large architectures, DRT11 confers protection against naturally occurring M. sativa rhizosphere phages with podovirus-like morphology. Phage infection assays reveal protection at low multiplicities of infection, consistent with an abortive-infection-like mechanism. Moreover, mutational analyses demonstrate that antiviral activity requires only the RT and its fused C-terminal nitrilase domain, establishing DRT11 as a minimal UG5-associated antiviral system.IMPORTANCEIn this study, we report the functional characterization of a UG5-large reverse transcriptase-associated defense system (DRT11) encoded on the pSymA megaplasmid of the nitrogen-fixing plant symbiont Sinorhizobium meliloti. Using a combination of phylogenetic, metagenomic, genomic, and experimental approaches, we demonstrate that DRT11 functions as a bona fide antiviral defense module, providing protection against naturally occurring rhizosphere phages through a minimal reverse transcriptase-nitrilase architecture. This work establishes direct functional evidence for antiviral activity within the UG5 family and clarifies the evolutionary placement of UG5-associated systems within the broader UG radiation.

Phylogeny

Stepwise allelic trajectory of ETP2 underlies trade-off between UVB tolerance and submergence adaptation in Arabidopsis thaliana.

Strong UVB radiation critically restricts plant growth, yield, and distribution, while mechanisms enabling adaptation to intense UVB remain unclear. Here, we uncover that the F-box ubiquitin E3 ligase UVBT1 (also known as ETP2) is indispensable for UVB tolerance in A. thaliana. In the high-altitude Tibet accession, a distinctive 166-bp deletion in ETP2 promoter leads to the complete absence of the W-box element, thereby eliminating WRKY36-mediated transcriptional repression. This results in elevated ETP2 levels, which degrade EIN2 and activate the protective anthocyanin/flavonoid pathway. Conversely, in low-altitude accessions, which are often exposed to lower UVB and higher precipitation conditions, WRKY36-mediated repression of ETP2 stabilizes EIN2 and WRKY22, endowing the plants with submergence tolerance. Notably, aside from the Tibet-accession-specific 166-bp deletion, the geographical distribution of the promoter allelic shift from C to G near the ETP2 W-box within the 166-bp region is tightly associated with UVB radiation with increasing altitudes for the other global accessions. This allelic change also enhances WRKY36-mediated repression of ETP2, suggesting an additional stepwise adaptation process. This work thus defines the WRKY36-ETP2-EIN2/WRKY22 module as a key regulator of UVB tolerance and submergence adaptation, potentially enabling A. thaliana to adapt to environments with varying UVB and precipitation conditions.

Arabidopsis

Using Organoids to Unlock the Potential of Human Torpor for Spaceflight.

PURPOSE OF REVIEW: This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. RECENT FINDINGS: On future deep space missions such as NASA's planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement - all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. SUMMARY: This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.

Astronaut Health

Dating the origin of a viral domestication event in parasitoid wasps attacking Diptera.

Over the course of evolution, hymenopteran parasitoids have developed a close relationship with heritable viruses, sometimes integrating viral genes into their chromosomes. For example, in Drosophila parasitoids belonging to the Leptopilina genus, 13 viral genes from the Filamentoviridae family have been domesticated to deliver immunosuppressive factors to host immune cells, thereby protecting parasitoid offspring from the host immune response. The present study aims to comprehensively characterize this domestication event in terms of the viral genes involved, the wasp diversity affected by this event and its chronology. Our genomic analysis of 41 Cynipoidea wasps from six subfamilies revealed 18 viral genes that were endogenized during the early radiation of the Eucoilini/Trichoplastini clade around 75 million years ago. Wasps from this highly diverse clade develop not only from Drosophila but also from a variety of Schizophora. This event coincides with the radiation of Schizophora, a highly speciose Diptera clade, suggesting that viral domestication facilitated wasp diversification in response to host diversification. Additionally, in one of the species, at least one viral gene was replaced by another gene derived from a related filamentovirus. This study highlights the impact of viral domestication on the diversification of parasitoid wasps.

Animals