npj Microgravity
○ Springer Science and Business Media LLC
Preprints posted in the last 90 days, ranked by how well they match npj Microgravity's content profile, based on 11 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.
Zuccoli, E.; Vega Gutierrez, D. M.; Castro, A. C.; Amaya Mejia, L. M.; Delgado-Centeno, J. I.; Olivares Mendez, M. A.; Martinez Luna, C.; Schwamborn, J. C.
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As human spaceflight becomes increasingly relevant, understanding how microgravity affects the human brain is an important but largely unexplored question, particularly in the context of neuronal function and vulnerability to neurodegeneration. Direct investigation of these processes in humans is not feasible, necessitating the use of physiologically relevant in vitro model systems. Three-dimensional human brain organoids recapitulate key aspects of brain development and organization and provide an experimentally accessible platform to study neuronal responses under controlled conditions. Here, within the framework of the student competition "Uberflieger 2", we investigated the effects of long-term microgravity on human midbrain organoids cultured for 40 days aboard the International Space Station (ISS). Midbrain organoids reproduce essential features of dopaminergic neuron development and are widely used to model Parkinsons disease and related neurodegenerative processes. To enable spaceflight experiments, we developed and implemented an autonomous culture system adapted to the constraints of the ISS environment. During the mission, a hardware malfunction impaired scheduled medium exchange, introducing an additional metabolic stress condition. Despite these limitations, ISS-cultured organoids remained viable and showed robust neurite outgrowth. Molecular and imaging analyses revealed that exposure to microgravity in combination with nutrient limitation induced a coordinated response involving cytoskeletal remodeling, neuronal plasticity, and selective vulnerability of dopaminergic neurons. These findings demonstrate that human midbrain organoids can maintain key structural and functional properties under prolonged spaceflight-associated stress while activating adaptive response programs. This work highlights the potential of organoid-based systems to investigate neurobiological effects of microgravity and provides a foundation for future studies addressing mechanisms relevant to neurodegenerative disease.
Kiffer, F. C.; Scott, R. T.; Martens, M. T.; Mayo, A.; Li, Y.; Mendoza, M.; Gautam, S.; Huang, J.; Bathwal, M.; Jaikumar, S.; Mahajan, A.; Sanders, L. M.; Eisch, A. J.; Pereira, T. D.
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The NASA Rodent Habitat aboard the International Space Station enabled long-duration studies of behavioral responses to spaceflight, but video-based behavioral analysis has relied on laborious manual annotation. No study has tested whether deep learning tools can automate this analysis under the demanding imaging conditions of orbital vivaria. We applied pose estimation (SLEAP) and behavioral segmentation (DeepEthogram) to archival footage from the Rodent Research-1 mission. Nine labelers annotated 3,249 pose labels across 2,063 frames, and three behaviorists labeled 411,194 frames across 66 videos. Pose tracking accuracy approximated human inter-annotator variability despite progressive lens soiling, grid occlusions, and spherical aberration. Behavioral classification across eight categories achieved accuracy of 0.86-0.90 and suggests progressive behavioral adaptations to microgravity. Kinematic reconstruction of circling estimated centripetal accelerations periodically approaching 1g. This is the first application of deep learning-based pose estimation and behavioral segmentation to rodents in spaceflight, establishing benchmarks for future monitoring systems.
Jones, S. W.; Hasoon, M.; Adair, K.; Shigdar, S.; Hemmings, K.; Henstock, J.; Brownridge, P.; McArdle, C.; Neri, G.; Blackler, W.; Olentsenko, G.; Jones, A. R.; Eyers, C.; Hoettges, K.; Jackson, M. J.; McArdle, A.
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Age-related loss of skeletal muscle mass and function, or sarcopenia, presents a growing clinical challenge, mirroring the accelerated muscle atrophy seen in microgravity. This study, part of the UK Space Agencys MicroAge Mission, aimed to investigate microgravity-induced proteomic changes in 3D human skeletal muscle constructs and assess whether mitochondrial Heat Shock Protein 10 (HSP10) overexpression could modulate these responses. Constructs derived from control human AB1167 myoblasts and AB1167 myoblasts that were transduced to overexpress HSP10, were flown to the International Space Station (ISS), with a ground reference experiment (GRE) conducted post-flight. Proteomic analysis using mass spectrometry and bioinformatics revealed significant alterations in metabolic, structural, and mitochondrial protein profiles after microgravity exposure. Microgravity caused downregulation of key proteins involved in energy metabolism, stress responses and structural integrity, while upregulating catabolic and apoptotic enzymes. Many of these modifications parallel previously reported changes in protein composition of muscle with ageing on earth. Overexpression of HSP10 attenuated the effects of microgravity, with fewer proteins showing significant changes and reduced disruption to mitochondrial and cytoskeletal components. Pathway analysis indicated that HSP10 overexpression preserved mitochondrial protein expression, particularly in the matrix, and promoted mitochondrial gene expression and translation under microgravity conditions. Notably, 284 proteins altered by microgravity in unmodified muscle constructs remained stable in HSP10-overexpressing constructs, suggesting a protective effect. MitoCarta 3.0 analysis confirmed that HSP10 expression modulated protein responses at the mitochondrial level, mitigating declines in bioenergetic proteins that are typically associated with microgravity. Collectively, the findings demonstrate that microgravity induces extensive proteomic remodelling in human muscle, which is partially offset by HSP10 overexpression. These results offer insights into muscle atrophy in spaceflight and suggest that targeting mitochondrial stress pathways via chaperone modulation may be a viable strategy to combat sarcopenia and disuse-induced muscle loss on Earth and in space.
Latham, A. P.; Skountzos, E. N.; Lantin, S.; Quarton, T.; Ravichandran, A.; Lee, J. A.; Lawson, J. W.
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As the duration of space flights increases, so does the need to optimize off-planet microbial growth. Microbes can both be unintentionally brought into space and cause human disease or be intentionally harnessed for on-site bioengineering functions. However, optimizing microbial growth is challenging due to an insufficient understanding of how microbial communities are affected by the extraterrestrial environment. To address this gap, we have modified a previously developed model for cell growth in microgravity. By improving the functional form used for cell growth as well as the code usability, we enable further research into how microbial communities are influenced by gravity. Applying this model to isolate individual effects of gravity on cell growth indicates that a lack of gravity-driven flow decreases cell growth in microgravity, while the absence of sedimentation increases cell growth in microgravity. These opposite effects likely contribute to the system-dependent effects of microgravity observed experimentally.
Burchett Darantiere, A.; Zarodniuk, M.; Giza, S.; Rexroat, J.; Kuehl, P.; Clements, T.; Balraj, K.; Najera, J.; Bhargava, R.; Datta, M.
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Glioblastoma (GBM) is an incurable brain cancer characterized by its highly immunosuppressive tumor microenvironment and aggressive malignant features that resist treatment. To overcome limitations of Earth-based models (sedimentation and disaggregation) and leverage the unique biological effects of space (accelerated disease progression and immune dysregulation), we developed a panel of GBM-myeloid organoids for extended culture on the International Space Station. After 40 days, the spaceflight-grown organoids had more uniform and reproducible morphology compared to identical ground controls. Organoids containing GBM cells + monocytes had increased expression of chronic innate inflammation, adaptive immune activation, and tissue and vascular remodeling-associated genes. There was an increase in organization of gene expression patterns, with mesenchymal-related genes enriched in the core and inflammation-related genes enriched at the periphery, mimicking GBM tumor architecture. Secretomics confirmed the generation of more immunosuppressive organoids, with enrichment of proteins associated with more aggressive disease, including CXCL12 and LOX-1. GBM co-culture organoids thus had enhanced transcriptomic, proteomic, and architectural features when grown in microgravity that are associated with worse patient outcomes from retrospective data. Infrared laser scanning microscopy confirmed spatial chemical gradients for DNA, protein, and lipid species in both space- and terrestrially-grown organoids. In summary, we present not only a novel and superior model of glioblastoma for more relevant basic, mechanistic, and translational research, but also demonstrate methods to acquire high-quality and diverse data from organoids compatible with the unique experimental constraints of biological research in space to help establish a working model for orbital oncology.
Andreev-Andrievskiy, A. A.; Mashkin, M. A.; Drugova, S. V.; Shurshakov, V. A.; Popov, D. V.; Tarasova, O. S.; Buravkova, L. B.; Vinogradova, O. L.; Sychev, V. N.; Orlov, O. I.; Bion-M 2 Team,
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The combined effects of microgravity and deep-space radiation on whole-body physiology remain poorly quantified for future crewed missions. Bion-M 2, a 30-day high-latitude biosatellite carrying group-housed mice, achieved an ISS-comparable total dose with an enriched galactic cosmic ray fraction, approximating conditions beyond low-Earth orbit. A quantitative atlas of 73 physiological endpoints revealed pronounced antigravity muscle atrophy, immune and gastrointestinal remodeling, and delayed recovery of hematologic and visceral indices through 30 days post-landing. A dry-food-hydrogel diet transformed this response into a stress-dominated, densely interconnected physiological state. Pharmacological Nrf2 activation with omaveloxolone preserved hindlimb muscle mass at ground-control levels and protected visceral organs. These findings establish a systems-level baseline for mammalian adaptation to a deep-space-analog orbit and identify diet and Nrf2 activation as tractable countermeasure levers.
Burke, M.; Kara, G.; Holcomb, M.; Mason, C.; Villapol, S.
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Simulated spaceflight perturbs multiple organ systems, yet the integrated impact of spaceflight-relevant stressors on the immune-gut-brain axis remains poorly defined. We used a ground-based model combining hindlimb unloading (HU) with low-dose ionizing radiation (IR; 50 or 100cGy) to quantify neuropathology, peripheral immune phenotypes, intestinal barrier integrity, and behavioral performance in male and female C57BL/6 mice. HU and/or IR induced region-selective neurodegenerative changes consistent with axonal injury across the cortex and major white-matter tracts. In the somatosensory cortex, MAP-2+ neurons were reduced and SMI-312-labeled axonal injury increased, lowering the intact-to-dystrophic axonal area ratio. Long-range fiber pathways (corpus callosum, cingulate gyrus, external capsule) showed robust axonal damage accompanied by gliosis, with elevated Iba-1+ microglia and GFAP+ astrocytes most prominent after HU+IR (100cGy). Peripheral immunophenotyping revealed a sustained, sex-dependent innate inflammatory bias, with expanded CD11b+ myeloid cells and increased TNF-+ myeloid activation after IR and IR+HU, alongside maladaptive T-cell polarization despite largely unchanged total CD8+ and CD4+ frequencies. In parallel, the gut exhibited architectural remodeling and barrier failure, including altered mucin profiles, reduced ZO-1 tight-junction labeling, and increased CD45+ leukocyte infiltration across the jejunum, ileum, and colon. Behavioral assays demonstrated sex-dependent deficits spanning affective, motor, and cognitive domains, including increased anxiety- and depressive-like behaviors, impaired rotarod performance, reduced recognition memory, and less efficient spatial strategies. Overall, these findings identify a sex-dependent immune-gut-brain vulnerability in which combined HU and low-dose IR drive gut barrier breakdown and immune imbalance that coincide with neuroinflammatory axonopathy and measurable neurobehavioral dysfunction.
Bonnard, T.; Doat, E.; Cazalets, J.-R.; Morgat, C.; Guehl, D.; GUILLAUD, E.
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ABSTRACTMotion sickness (MS) is commonly hypothesized to arise from sensory conflicts between incongruent sources of sensory information. Different types of sensory conflicts can induce MS, yet it remains unclear whether distinct contexts produce different physiological responses. Moreover, there is a lack of reliable objective predictors of MS, particularly for space motion sickness (SMS), which appears unrelated to motion sickness susceptibility on Earth. This study examined multiple physiological measures as potential objective markers of MS, including heart rate, blood pressure, salivary cortisol, skin conductance, skin surface temperature, and facial skin colorimetry. Subjective motion sickness severity and symptomatology were assessed using standardized questionnaires (SSQ, MSAQ, MSSQ). All measures were collected before and immediately after exposure to two sensory conflict paradigms: virtual reality (visuo-vestibular conflict) and parabolic flight (otolitho-canal conflict). Post-exposure, both paradigms were associated with increased cortisol, skin conductance, and skin greeness. Notably, increased skin greenness was associated with greater MS severity in parabolic flight and strongly correlated with subjective nausea ratings in both paradigms. Skin temperature and systolic blood were affected differently by VR and parabolic flight. No robust new physiological predictors of MS were identified. Overall, our findings suggest that facial skin color -particularly skin greenness- may serve as a simple, non-invasive, and reliable objective indicator of MS severity.
Gloersen, O.; Lundervold, A.; Werkhausen, A.
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Conventional diagonal stride skiing traditionally includes a glide phase, characterised by a period of relatively passive gliding on one ski. While the glide phase may take advantage of low ski-snow friction, it does not exhibit the same whole-cycle mechanical energy fluctuations seen in running or walking on foot. A new sub-technique, known as running style, substantially reduces the glide phase and may alter the role of elastic tissues, making the movement pattern more similar to uphill running on foot in its temporal organisation. We examined knee extensor and plantar flexor muscle-tendon behaviour in eight competitive skiers performing conventional diagonal and running techniques on a treadmill inclined at 10{degrees}. Using synchronised ultrasonography, 3D kinematics, ski forces and EMG, we quantified gastrocnemius medialis and vastus lateralis fascicle and muscle-tendon unit (MTU) dynamics in both the running (RUN) and conventional (CON) styles. Shorter glide and total cycle durations during RUN shifted MTU peak length and velocity earlier during the kick phase. Fascicles in both muscles operated at similar velocities across techniques, showing MTU-fascicle decoupling. Vastus lateralis fascicles shortened at higher absolute peak velocities than gastrocnemius in both conditions, while normalised velocities were similar. RUN increased preactivation and advanced EMG timing, while integrated EMG during the kick was lower compared to CON. These findings suggest that, despite large shifts in external mechanics between glide-based and more running-like skiing, elastic tissues may help stabilise fascicle behaviour and preserve a similar contractile strategy across muscles and techniques.
Burr, D. J.; Nitsche, R.; Ravaro, E.; Wipf, S.; Ganga, P. L.; Balsamo, M.; Pellari, S. S.; Caltavituro, F.; Gisi, M.; de Almeida, R. C.; Manieri, P.; Sgambati, A.; Moratto, C.; Nürnberg, D. J.; Kish, A.; Elsaesser, A.
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Space-based platforms currently represent the most accurate means to experimentally assess the influence of the space environment on biological systems. However, performing such experiments remains technically challenging and requires highly specialized instrumentation. This study describes the current development and hardware qualification of ExocubeBio, a miniaturized experimental platform for in-situ biological space exposure. This experiment is scheduled for installation on the exterior of the International Space Station in 2027, as part of Exobio, the European Space Agencys new generation exobiology exposure facility. ExocubeBio will expose live microbial samples to the low Earth orbit environment, and combine autonomous in-situ optical density and fluorescence measurements, with the capacity to return preserved samples to Earth. Achieving these experimental goals requires a specialized, robust and reliable hardware system. The ExocubeBio hardware testing described here includes assessment of material biocompatibility and durability, functional validation of the miniaturized fluidic system, and optimization of the integrated optical subsystem for optical density and fluorescence measurements. These results demonstrate that the ExocubeBio experimental hardware components can each execute their core functional and operational requirements; subsystems allow for sample exposure, in-situ measurements of microbial cultures, and the chemical preservation of samples for post-flight analysis. As ExocubeBio transitions from hardware development to mission readiness, the results presented here validate the overall design and engineering approaches utilized. By combining the strengths of in-situ monitoring and sample return, ExocubeBio represents a significant advancement in space-based experimentation, and will provide new insights into microbial responses to the space environment.
Greene, H.; Nattermann, U.; Stork, D. A.; Martin, F. R.; Schubert, M. G.; Pedersen, T.; Sukarto, E.; Spens, A.; Mancuso, J. E.; Isaev, K.; Hicks, N. D.; Liu, J.; Harris, R.; Cockell, C. S.; Kounaves, S. P.; DeBenedictis, E. A.
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Mars relatively moderate surface conditions, availability of solar energy, and in situ resources like water ice, carbon dioxide, and mineral-rich regolith make it a compelling target for supporting life beyond Earth. However, existing experiments testing habitability in Mars conditions generally rely on leachates of physical regolith simulants, which vary in composition across simulant types, leaching conditions, and production batches. We introduce a defined Mars media (DMM) that accurately simulates the biologically relevant nutrients (nitrogen, phosphorus, and sulfur) and stressors (perchlorates, heavy metals) in Martian regolith when it is leached in water at neutral pH. We formulated DMM by combining direct rover and lander measurements from Mars with laboratory measurements of regolith simulant leachates. We validate DMM from a lx to 20x concentrate, equivalent to 40 g/L to 800 g/L of leached regolith. Using DMM with acetate as a Mars atmosphere-derived carbon source, we grew eight heterotrophic bacteria, confirming that organisms can source all essential nutrients from Martian resources. We also show that microbial growth in DMM is robust to uncertainties in Martian regolith composition: sensitivity experiments can identify limiting trace element nutrients and toxins in DMM, and demonstrate that bacterial growth is maintained across at least an order of magnitude variation in their concentrations. This is the first defined Mars regolith media recipe containing both macro- and micro- nutrients, and designed specifically for biological experimentation. By shifting from variable leachate-based approaches to a defined aqueous analog, we enable controlled hypothesis testing of microbial survival, growth, and function. DMM will enable further research on astrobiology, biological in situ resource utilization, large-scale soil remediation, and terraforming. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/719001v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1314b20org.highwire.dtl.DTLVardef@13b57d4org.highwire.dtl.DTLVardef@103315eorg.highwire.dtl.DTLVardef@9e18fe_HPS_FORMAT_FIGEXP M_FIG C_FIG
O'Connor, S. A.; Narain, P.; Mahajan, A.; Bancroft, G. L.; Haas, H. A.; Wallen-Friedman, E.; Vasisht, S.; Takano, H.; Kiffer, F. C.; Eisch, A. J.; Yun, S.
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Environmental stressors rarely affect just one brain circuit. Most studies assess single cognitive endpoints, obscuring whether vulnerabilities are global or circuit-selective and how effects distribute across interconnected systems. To address this, we used galactic cosmic radiation (GCR), a Mars mission-relevant stressor that disrupts the hippocampal-nucleus accumbens-prefrontal circuit. C57BL/6J mice received 33-ion GCR simulation (33-GCR, 0.75 Gy) or sham radiation with the Nrf2-activating compound CDDO-EA or vehicle, followed by multi-domain behavioral testing in both sexes. Under very high memory load, male Veh/33-GCR mice showed enhanced pattern separation compared to Veh/Sham males, an effect normalized by CDDO-EA. Female mice showed no radiation-induced changes in pattern separation but weighed 9-18% more than Veh/Sham females and had reduced locomotor activity. Reward-based learning differed by sex: males showed no changes, while female Veh/33-GCR mice displayed enhanced reward anticipation that was further increased by CDDO-EA alone, with both treatments contributing to elevated goal-tracking. For behavioral flexibility, CDDO-EA impaired reversal learning in males regardless of radiation, while 33-GCR impaired reversal learning in females regardless of CDDO-EA. Principal component analysis revealed that treatments disrupted specific circuit relationships while leaving others intact, consistent with selective rather than global cognitive effects. Fiber photometry showed enhanced dentate gyrus encoding activity in irradiated males under high memory load. Combined CDDO-EA/33-GCR selectively reduced dentate gyrus progenitors in females. Males and females showed distinct, circuit-selective vulnerability patterns, demonstrating that multi-domain, both-sex assessment is necessary to capture how stressors and interventions affect integrated brain function. CDDO-EA proved to be a double-edged sword: protecting one cognitive domain while impairing another, a trade-off invisible to single-endpoint assessment. This framework has immediate relevance for astronaut risk assessment and extends to any context where neuroprotective interventions are evaluated against environmental stressors.
Dolgin, J.; Vaid, A.; Hendrixson, D.; Cai, Y.; Cheung, L. K. Y.; Xu, L.; Kaplan, D. L.; Nair, N. U.
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Reducing the cost and environmental impact of cell culture media is an important goal for cultivated meat, the process of generating meat in vitro using proliferating animal cells. While prior approaches have demonstrated the use of microbial lysates to replace expensive animal-based fetal bovine serum (FBS) in media, these formulations still rely on large quantities of growth factors such as fibroblast-like growth factor 2 (FGF2). Here, we demonstrate the use of FGF2-expressing Vibrio natriegens to create whole-cell lysates that replace both FBS and FGF2 in cell culture media for cultivated meat applications. This medium, named "VN40FGF", supports rapid proliferation of immortalized bovine muscle satellite cells (iBSCs) in the absence of supplemented FGF2. Cells grown in VN40FGF maintain phenotype and differentiation capacity. We also demonstrate that engineered V. natriegens can grow in spent cell culture media, further improving sustainability and economics, and reducing potential eutrophication concerns associated with waste disposal. Our approach combines multiple strategies for reducing the total number of media inputs, demonstrating opportunities for more economical and sustainable cell culture, especially for cultivated meats.
Lantin, S.; Bansal, M.; Alper, H.; Lee, J. A.
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As human space exploration expands to the Moon, Mars, and beyond, there is a growing need to study the effects of altered gravity on the microbial systems that we will bring with us for life support. Because spaceflight experiment opportunities are rare and resource-intensive, most space biology experiments are conducted using ground-based simulators. The most common microgravity simulator for microbial experiments, the rotating wall vessel, can approximate the low-shear and low-turbulence conditions that characterize microgravity. However, current designs do not allow for real-time measurement of growth or metabolic activity during rotation: experiments require destructive sampling or disruption of the microgravity simulation conditions. Here, we describe the development of an in situ spectroscopy system compatible with the Cell Spinpod rotating wall vessel, which enables measurement of both optical absorbance and fluorescence with high temporal resolution, producing growth curves similar to those from an off-the-shelf plate reader. These results are validated using two common microbial hosts: Escherichia coli and Saccharomyces cerevisiae. The Spinpod Optical System has the potential to diversify the types of microbiology experiments possible in simulated microgravity, allowing the measurement of not only growth curve parameters but also metabolic activity, gene expression, or community dynamics. It thus has the potential to improve the quality of experiments seeking to characterize microbial responses to spaceflight conditions.
Wiest, T. A.; Bais, H.
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Advances in NASAs astrobiology program have demonstrated the feasibility of cultivating plants in space and in analog extraterrestrial habitats. In addition to abiotic stressors, plants grown in terrestrial and space-like environments are challenged by both phytopathogens and opportunistic human pathogens, with implications for plant productivity and human health. The persistence of human-associated pathogens in spacecraft and space stations raises significant concerns regarding food safety. The molecular, biochemical, and signaling mechanisms governing stomatal development and function under microgravity remain poorly understood. We employed an experimental system incorporating human pathogen Salmonella enterica and lettuce microgreens exposed to simulated microgravity through two-dimensional clinorotation to investigate plant innate immunity and stomatal development and function. We further evaluated four lettuce cultivars to determine whether genetic variation impacts these factors under simulated microgravity conditions. Our findings indicate that simulated microgravity significantly influences stomatal development and function, as evidenced by an increase in stomatal density and variable changes to stomatal aperture. Notably, cultivar-dependent variation in stomatal traits and responses to Salmonella enterica was observed under microgravity conditions. Although increased stomatal density was hypothesized to enhance pathogen ingression, internalization was more strongly predicted by cultivar selection and simulated microgravity; simulated microgravity increased ingression, with red pigmented cultivars having less pathogen than green cultivars. These results suggest that targeted selection of cultivars with favorable physiological traits may improve food safety and the viability of crop production systems in space environments. They also suggest that development and function of stomata may change in spaceflight conditions.
Choi, J.; Umalkar, V.; Wang, X.; Zheng, S.
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Understanding how airborne particulates disrupt the human alveolar barrier requires in vitro systems that accurately replicate its composition and function. We present a biodegradable lung alveoli-on-a-chip that reproduces the architecture and physiology of the human air-blood interface using a porous poly(lactic-co-glycolic acid) (PLGA) membrane positioned between epithelium and endothelium under air-liquid interface (ALI) culture. The membrane, fabricated by porogen-assisted nonsolvent-induced phase separation, exhibited >50 % porosity, [~]2 {micro}m thickness, and mechanical compliance over 100-fold higher than conventional Transwell inserts, closely resembling the native interstitium. During co-culture, gradual PLGA degradation was compensated by cell-secreted extracellular-matrix (ECM) proteins such as collagen IV and laminin, forming a self-remodeling barrier that maintained integrity for at least 11 days. The platform supported stable epithelial-endothelial co-culture, high transepithelial electrical resistance, and physiologically relevant permeability. To demonstrate its utility, the chip was used to assess pulmonary toxicity of four types of waste-combustion-derived particulates, including rubber, plastic bags, plastic bottles, and textile fibers, delivered apically under ALI conditions. All combustion products reduced cell viability, increased hydrogen-peroxide release, and elevated {gamma}-H2AX expression, indicating oxidative and genotoxic stress, while disrupting barrier permeability. Rubber combustion particles elicited the most severe toxicity, causing the greatest loss of viability, accumulation of reactive oxygen species, and formation of DNA double-strand breaks. Together, these results establish a biodegradable, ECM-remodeling lung alveoli-on-a-chip as a physiologically relevant platform for investigating source-specific particulate toxicity and alveolar-barrier pathophysiology. By bridging environmental exposure models with human-relevant lung biology, this system provides a quantitative and translatable tool for evaluating respiratory risks and therapeutic interventions.
Nigro, M.; Montanino, A.; Soudah, E.
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Spaceflight-Associated Neuro-ocular Syndrome (SANS) involves complex interactions between intracranial pressure (ICP), intraocular pressure (IOP), and cerebrospinal fluid (CSF) dynamics within the optic nerve subarachnoid space (ONSAS). While existing computational models address specific aspects of these interactions, they lack a comprehensive, system-level representation. To bridge this gap, we present the HEAD (Hemodynamic Eye-brain Associated Dynamics) model. By consistently integrating several previously proposed physiological sub-models, HEAD provides a unified lumped-parameter framework that fully couples cerebrovascular autoregulation, multi-territory ocular hemodynamics, and compartmentalized craniospinal-ONSAS CSF circulation under gravitational loading. This formulation enables the simultaneous analysis of eye-brain-CSF dynamics within a single computational tool. Model predictions were validated against experimental data from supine (0{degrees}) to head-down tilt (HDT, -30{degrees}) postures, accurately reproducing posture-dependent IOP increases and achieving an excellent ICP match against clinical benchmarks at the -6{degrees} HDT standard bed-rest angle. The coupled system predicts bed-specific ocular hemodynamic responses, with retinal blood flow exhibiting the largest relative increase under HDT compared to the ciliary and choroidal circulations. Crucially, explicitly modeling the ONSAS as a distinct compartment reveals a posture-dependent pressure drop of 1.89-3.69 mmHg between the intracranial and perioptic spaces. This compartmentalization yields a translaminar pressure profile that remains positive (8.05-11.83 mmHg) across all simulated conditions but is chronically reduced under sustained HDT. Ultimately, the HEAD model elucidates the physiological mechanisms linking gravitational stress to translaminar mechanics, providing a robust computational foundation to investigate SANS and supply boundary conditions for structural models of the optic nerve head.
Kaimaki, D.-M.; Alves de Freitas, H.; Read, A. G. D.; Dickson, T. D. M.; White, T.; Neilson, H. C. A. W.
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Head rotation is the leading cause of diffuse brain injuries from cycling accidents, with severe, long-term or even fatal consequences. Here, we present a novel helmet safety technology, the Release Layer System (RLS), designed to enhance conventional helmets and reduce the likelihood of such injuries. RLS is located on the outer side of the helmet and thus gets impacted first. The force of the impact activates a rolling mechanism triggering the release of an outer polycarbonate panel, thereby dispersing and transforming a substantial portion of the incident rotational energy. To evaluate the effectiveness of the technology, we conducted oblique impact tests on three popular helmet types, in conventional and RLS-equipped configurations, at three impact locations. RLS-equipped helmets reduced Peak Angular Velocity (PAV) by 57-66%, averaged across impact locations, compared to their conventional counterparts. This corresponds to a 68-86% reduction in the probability of an AIS2+ brain injury, as estimated by the Brain Injury Criterion. The most notable improvement was observed at the pYrot location (front impacts, mid-sagittal plane), with up to 85% PAV reduction. Testing across headforms further demonstrated the effectiveness of the technology in mitigating head rotation irrespective of variations in evaluation setups. This work introduces a novel mechanism for rotational impact mitigation and provides evidence of its potential benefits compared with conventional helmets. As an outer-layer approach, RLS may offer an alternative pathway for managing rotational kinematics in future helmet designs.
Korkmaz, D.; Bi, Q.; Moller, M.; Koenig, J.; Peters, J.
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Stress is a major risk factor for mental disorders, and urban living is a key environmental contributor. Nature exposure may promote stress recovery and mental health, but how physiological arousal and subjective stress change across green versus gray space during naturalistic urban mobility is poorly understood. This preregistered study (https://doi.org/10.17605/OSF.IO/HF4RW) employed geolocation-based ambulatory assessment to examine psychophysiological arousal and subjective stress during transitions between urban green and gray environments. Thirty-six healthy urban residents completed a counterbalanced circular walking route in Cologne, Germany, with continuous GPS, cardiovascular, and electrodermal recording alongside ecological momentary assessment of subjective stress, affect, and exertion. Green compared to gray spaces were associated with lower subjective stress and higher affective well-being, with cardiac indices reflecting reduced autonomic arousal during green space exposure. Autonomic changes surrounding environmental transitions persisted beyond the immediate transition window, suggesting that physiological benefits of green space exposure extend into subsequent gray environments. These findings underscore the public health potential of urban green infrastructure for preventing stress-related mental health conditions.
Collins, S. H.; De Groote, F.; Gregg, R. D.; Huang, H.; Lenzi, T.; Sartori, M.; Sawicki, G. S.; Si, J.; Slade, P.; Young, A. J.
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In "Experiment-free exoskeleton assistance via learning in simulation", Luo et al. [1] present an ambitious framework for developing exoskeleton controllers through reinforcement learning exclusively in computer simulation. The authors report that a control policy trained on a small dataset from one subject was directly transferred to physical hardware, reducing human metabolic cost during walking, running, and stair climbing by more than any prior device. If confirmed, this would represent a major breakthrough for the field of wearable robotics and their clinical applications. However, a close examination of the published materials casts doubt on these claims. The reported experimental results violate physiological limits on the relationship between mechanical power and muscle energy use during gait2,3,4. The algorithmic claims are surprising and cannot be verified; in contrast with established replicability standards in machine learning5,6, executable code has not been made available. We conclude that the goals of this study have not yet been verifiably achieved and make recommendations for avoiding publication errors of this type in the future.