Astronaut omics and the impact of space on the human body at scale.

Future multi-year crewed planetary missions will motivate advances in aerospace nutrition and telehealth. On Earth, the Human Cell Atlas project aims to spatially map all cell types in the human body. Here, we propose that a parallel Human Cell Space Atlas could serve as an openly available, global resource for space life science research. As humanity becomes increasingly spacefaring, high-resolution omics on orbit could permit an advent of precision spaceflight healthcare. Alongside the scientific potential, we consider the complex ethical, cultural, and legal challenges intrinsic to the human space omics discipline, and how philosophical frameworks may benefit from international perspectives.

Aging and putative frailty biomarkers are altered by spaceflight.

Human space exploration poses inherent risks to astronauts' health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth. However, our understanding of the connection between these molecular shifts and disease development in space remains limited. Frailty syndrome, a clinical syndrome associated with biological aging, has not been comprehensively investigated during spaceflight. To bridge this knowledge gap, we leveraged murine data obtained from NASA's GeneLab, along with astronaut data gathered from the JAXA and Inspiration4 missions. Our objective was to assess the presence of biological markers and pathways related to frailty, aging, and sarcopenia within the spaceflight context. Through our analysis, we identified notable changes in gene expression patterns that may be indicative of the development of a frailty-like condition during space missions. These findings suggest that the parallels between spaceflight and the aging process may extend to encompass frailty as well. Consequently, further investigations exploring the utility of a frailty index in monitoring astronaut health appear to be warranted.

Leveraging natural capital accounting to support businesses with nature-related risk assessments and disclosures.

Nature loss threatens businesses, the global economy and financial stability. Understanding and addressing these risks for business will require credible measurement approaches and data. This paper explores how natural capital accounting (NCA) can support business data and information needs related to nature, including disclosures aligned with the Taskforce on Nature-related Financial Disclosures recommendations. As businesses seek to measure, manage and disclose their nature-related risks and opportunities, they will need well-organized, consistent and high-quality information regarding their dependencies and impacts on nature, which few businesses currently collect or track in-house. NCA may be useful for these purposes but has not been widely used or applied by businesses. National NCA guided by the U.N. System of Environmental-Economic Accounting may provide: (i) a useful framework for businesses in conceptualizing, organizing and managing nature-related data and statistics; and (ii) data and information that can directly support business disclosures, corporate NCA and other business applications. This paper explores these opportunities as well as synergies between national and corporate natural capital accounts. In addition, the paper discusses key barriers to advancing the wider use and benefits of NCA for business, including: awareness of NCA, data access, business capabilities related to NCA, spatial and temporal scales of data, audit and assurance considerations, potential risks, and costs and incentives. This article is part of the theme issue 'Bringing nature into decision-making'.

Meta-analysis of the space flight and microgravity response of the Arabidopsis plant transcriptome.

Spaceflight presents a multifaceted environment for plants, combining the effects on growth of many stressors and factors including altered gravity, the influence of experiment hardware, and increased radiation exposure. To help understand the plant response to this complex suite of factors this study compared transcriptomic analysis of 15 Arabidopsis thaliana spaceflight experiments deposited in the National Aeronautics and Space Administration's GeneLab data repository. These data were reanalyzed for genes showing significant differential expression in spaceflight versus ground controls using a single common computational pipeline for either the microarray or the RNA-seq datasets. Such a standardized approach to analysis should greatly increase the robustness of comparisons made between datasets. This analysis was coupled with extensive cross-referencing to a curated matrix of metadata associated with these experiments. Our study reveals that factors such as analysis type (i.e., microarray versus RNA-seq) or environmental and hardware conditions have important confounding effects on comparisons seeking to define plant reactions to spaceflight. The metadata matrix allows selection of studies with high similarity scores, i.e., that share multiple elements of experimental design, such as plant age or flight hardware. Comparisons between these studies then helps reduce the complexity in drawing conclusions arising from comparisons made between experiments with very different designs.

Estimating population size: The importance of model and estimator choice.

We consider estimator and model choice when estimating abundance from capture-recapture data. Our work is motivated by a mark-recapture distance sampling example, where model and estimator choice led to unexpectedly large disparities in the estimates. To understand these differences, we look at three estimation strategies (maximum likelihood estimation, conditional maximum likelihood estimation, and Bayesian estimation) for both binomial and Poisson models. We show that assuming the data have a binomial or multinomial distribution introduces implicit and unnoticed assumptions that are not addressed when fitting with maximum likelihood estimation. This can have an important effect in finite samples, particularly if our data arise from multiple populations. We relate these results to those of restricted maximum likelihood in linear mixed effects models.

The vacuolar H+/Ca transporter CAX1 participates in submergence and anoxia stress responses.

A plant's oxygen supply can vary from normal (normoxia) to total depletion (anoxia). Tolerance to anoxia is relevant to wetland species, rice (Oryza sativa) cultivation, and submergence tolerance of crops. Decoding and transmitting calcium (Ca) signals may be an important component to anoxia tolerance; however, the contribution of intracellular Ca transporters to this process is poorly understood. Four functional cation/proton exchangers (CAX1-4) in Arabidopsis (Arabidopsis thaliana) help regulate Ca homeostasis around the vacuole. Our results demonstrate that cax1 mutants are more tolerant to both anoxic conditions and submergence. Using phenotypic measurements, RNA-sequencing, and proteomic approaches, we identified cax1-mediated anoxia changes that phenocopy changes present in anoxia-tolerant crops: altered metabolic processes, diminished reactive oxygen species production post anoxia, and altered hormone signaling. Comparing wild-type and cax1 expressing genetically encoded Ca indicators demonstrated altered cytosolic Ca signals in cax1 during reoxygenation. Anoxia-induced Ca signals around the plant vacuole are involved in the control of numerous signaling events related to adaptation to low oxygen stress. This work suggests that cax1 anoxia response pathway could be engineered to circumvent the adverse effects of flooding that impair production agriculture.

Analysis of Plant Root Gravitropism.

Gravity is a powerful element in shaping plant development, with gravitropism, the oriented growth response of plant organs to the direction of gravity, leading to each plant's characteristic form both above and below ground. Despite being conceptually simple to follow, monitoring a plant's directional growth responses can become complex as variation arises from both internal developmental cues as well as effects of the environment. In this protocol, we discuss approaches to gravitropism assays, focusing on automated analyses of root responses. For Arabidopsis, we recommend a simple 90° rotation using seedlings that are 5-8 days old. If images are taken at regular intervals and the environmental metadata is recorded during both seedling development and gravitropic assay, these data can be used to reveal quantitative kinetic patterns at distinct stages of the assay. The use of software that analyzes root system parameters and stores this data in the RSML format opens up the possibility for a host of root parameters to be extracted to characterize growth of the primary root and a range of lateral root phenotypes.

Inpatient COVID-19 mortality has reduced over time: Results from an observational cohort.

BACKGROUND: The Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes for those admitted with severe Covid were different in the first and second waves. METHODS: The study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and March 2021, who tested positive for Covid-19 by PCR within 3-days of admissions. Primary outcome was death within 28-days of admission. Socio-demographics (age, sex, ethnicity), hypertension, diabetes, obesity, baseline physiological observations, CRP, neutrophil, chest x-ray abnormality, remdesivir and dexamethasone were incorporated as co-variates. Proportional subhazards models compared mortality risk between wave 1 and wave 2. Cox-proportional hazard model with propensity score adjustment were used to compare mortality in patients prescribed remdesivir and dexamethasone. RESULTS: There were 3,949 COVID-19 admissions, 3,195 hospital discharges and 733 deaths. There were notable differences in age, ethnicity, comorbidities, and admission disease severity between wave 1 and wave 2. Twenty-eight-day mortality was higher during wave 1 (26.1% versus 13.1%). Mortality risk adjusted for co-variates was significantly lower in wave 2 compared to wave 1 [adjSHR 0.49 (0.37, 0.65) p<0.001]. Analysis of treatment impact did not show statistically different effects of remdesivir [HR 0.84 (95%CI 0.65, 1.08), p = 0.17] or dexamethasone [HR 0.97 (95%CI 0.70, 1.35) p = 0.87]. CONCLUSION: There has been substantial improvements in COVID-19 mortality in the second wave, even accounting for demographics, comorbidity, and disease severity. Neither dexamethasone nor remdesivir appeared to be key explanatory factors, although there may be unmeasured confounding present.

Genomic Characterization of Potential Plant Growth-Promoting Features of Sphingomonas Strains Isolated from the International Space Station.

In an ongoing microbial tracking investigation of the International Space Station (ISS), several Sphingomonas strains were isolated. Based on the 16S rRNA gene sequence, phylogenetic analysis identified the ISS strains as Sphingomonas sanguinis (n = 2) and one strain isolated from the Kennedy Space Center cleanroom (used to assemble various Mars mission spacecraft components) as Sphingomonas paucimobilis. Metagenomic sequence analyses of different ISS locations identified 23 Sphingomonas species. An abundance of shotgun metagenomic reads were detected for S. sanguinis in the location from where the ISS strains were isolated. A complete metagenome-assembled genome was generated from the shotgun reads metagenome, and its comparison with the whole-genome sequences (WGS) of the ISS S. sanguinis isolates revealed that they were highly similar. In addition to the phylogeny, the WGS of these Sphingomonas strains were compared with the WGS of the type strains to elucidate genes that can potentially aid in plant growth promotion. Furthermore, the WGS comparison of these strains with the well-characterized Sphingomonas sp. LK11, an arid desert strain, identified several genes responsible for the production of phytohormones and for stress tolerance. Production of one of the phytohormones, indole-3-acetic acid, was further confirmed in the ISS strains using liquid chromatography-mass spectrometry. Pathways associated with phosphate uptake, metabolism, and solubilization in soil were conserved across all the S. sanguinis and S. paucimobilis strains tested. Furthermore, genes thought to promote plant resistance to abiotic stress, including heat/cold shock response, heavy metal resistance, and oxidative and osmotic stress resistance, appear to be present in these space-related S. sanguinis and S. paucimobilis strains. Characterizing these biotechnologically important microorganisms found on the ISS and harnessing their key features will aid in the development of self-sustainable long-term space missions in the future. IMPORTANCESphingomonas is ubiquitous in nature, including the anthropogenically contaminated extreme environments. Members of the Sphingomonas genus have been identified as potential candidates for space biomining beyond earth. This study describes the isolation and identification of Sphingomonas members from the ISS, which are capable of producing the phytohormone indole-3-acetic acid. Microbial production of phytohormones will help future in situ studies, grow plants beyond low earth orbit, and establish self-sustainable life support systems. Beyond phytohormone production, stable genomic elements of abiotic stress resistance, heavy metal resistance, and oxidative and osmotic stress resistance were identified, rendering the ISS Sphingomonas isolate a strong candidate for biotechnology-related applications.

Using the Automated Botanical Contact Device (ABCD) to Deliver Reproducible, Intermittent Touch Stimulation to Plants.

Despite mechanical stimulation having profound effects on plant growth and development and modulating responses to many other stimuli, including to gravity, much of the molecular machinery triggering plant mechanical responses remains unknown. This gap in our knowledge arises in part from difficulties in applying reproducible, long-term touch stimulation to plants. We describe the design and implementation of the Automated Botanical Contact Device (ABCD) that applies intermittent, controlled, and highly reproducible mechanical stimulation by drawing a plastic sheet across experimental plants. The device uses a computer numerical control platform and continuously monitors plant growth and development using automated computer vision and image analysis. The system is designed around an open-source architecture to help promote the generation of comparable datasets between laboratories. The ABCD also offers a scalable system that could be deployed in the controlled environment setting, such as a greenhouse, to manipulate plant growth and development through controlled, repetitive mechanostimulation.

What Aspects of Illness Influence Public Preferences for Healthcare Priority Setting? A Discrete Choice Experiment in the UK.

BACKGROUND: Decisions on funding new healthcare technologies assume that all health improvements are valued equally. However, public reaction to health technology assessment (HTA) decisions suggests there are health attributes that matter deeply to them but are not currently accounted for in the assessment process. We aimed to determine the relative importance of attributes of illness that influence the value placed on alleviating that illness. METHOD: We conducted a discrete choice experiment survey that presented general public respondents with 15 funding decisions between hypothetical health conditions. The conditions were defined by five attributes that characterise serious illnesses, plus the health gain from treatment. Respondent preferences were modelled using conditional logistic regression and latent class analysis. RESULTS: 905 members of the UK public completed the survey in November 2017. Respondents generally preferred to provide treatments for conditions with 'better' characteristics. The exception was treatment availability, where respondents preferred to provide treatments for conditions where there is no current treatment, and were prepared to accept lower overall health gain to do so. A subgroup of respondents preferred to prioritise 'worse' health states. CONCLUSION: This study suggests a preference among the UK public for treating an unmet need; however, it does not suggest a preference for prioritising other distressing aspects of health conditions, such as limited life expectancy, or where patients are reliant on care. Our results are not consistent with the features currently prioritised in UK HTA processes, and the preference heterogeneity we identify presents a major challenge for developing broadly acceptable policy.

NASA GeneLab RNA-seq consensus pipeline: standardized processing of short-read RNA-seq data.

With the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed to spaceflight. Members of NASA GeneLab and GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data from spaceflight-associated experiments. The pipeline includes quality control, read trimming, mapping, and gene quantification steps, culminating in the detection of differentially expressed genes. This data analysis pipeline and the results of its execution using data submitted to GeneLab are now all publicly available through the GeneLab database. We present here the full details and rationale for the construction of this pipeline in order to promote transparency, reproducibility, and reusability of pipeline data; to provide a template for data processing of future spaceflight-relevant datasets; and to encourage cross-analysis of data from other databases with the data available in GeneLab.

Evaluating the impact of acid-reducing agents on drug absorption using biorelevant in vitro tools and PBPK modeling - case example dipyridamole.

BACKGROUND: In vitro and in silico methods have become an essential tool in assessing metabolic drug-drug interactions (DDI) and avoiding reduced efficacy and increased side-effects. Another important type of DDI is the impact of acid-reducing agent (ARA) co-therapy on drug pharmacokinetics due to changes in gastric pH, especially for poorly soluble weakly basic drugs. METHODS: One-stage, two-stage and transfer dissolution experiments with dipyridamole tablets using novel biorelevant media representing the ARA effect were conducted and the results were coupled with a PBPK model. Clinical pharmacokinetic data were compared with the simulations from the PBPK model and with output from TIM-1 experiments, an evolved in vitro system which aims to simulate the physiology in the upper GI tract. RESULTS: Two-stage and transfer experiments confirmed that these in vitro set-ups tend to overestimate the extent of dipyridamole precipitation occurring in the intestines in vivo. Consequently, data from one-stage dissolution testing under elevated gastric pH conditions were used as an input for PBPK modeling of the ARA/dipyridamole interaction. Using media representing the ARA effect in conjunction with the PBPK model, the ARA effect observed in vivo was successfully bracketed. As an alternative, the TIM-1 system with gastric pH values adjusted to simulate ARA pre-treatment can be used to forecast the ARA effect on dipyridamole pharmacokinetics. CONCLUSION: Drug-drug interactions of dipyridamole with ARA were simulated well with a combination of dissolution experiments using biorelevant media representing the gastric environment after an ARA treatment together with the PBPK model. Adjustment of the TIM-1 model to reflect ARA-related changes in gastric pH was also successful in forecasting the interaction. Further testing of both approaches for predicting ARA-related DDIs using a wider range of drugs should be conducted to verify their utility for this purpose.

Real-time clinician text feeds from electronic health records.

Analyses of search engine and social media feeds have been attempted for infectious disease outbreaks, but have been found to be susceptible to artefactual distortions from health scares or keyword spamming in social media or the public internet. We describe an approach using real-time aggregation of keywords and phrases of freetext from real-time clinician-generated documentation in electronic health records to produce a customisable real-time viral pneumonia signal providing up to 4 days warning for secondary care capacity planning. This low-cost approach is open-source, is locally customisable, is not dependent on any specific electronic health record system and can provide an ensemble of signals if deployed at multiple organisational scales.

Mechanistic Insights of Dissolution and Mechanical Breakdown of FeCO3 Corrosion Films.

Carbon steel is a universally used material in various transportation and construction industries. Research related to CO2 corrosion environments agrees on the occurrence of siderite (FeCO3) as a main product conforming corrosion films, suggested to impart protection to carbon steel. Identifying and understanding the presence of all corrosion products under certain conditions is of greatest importance to elucidate the behavior of corrosion films under operation conditions (e.g., flow, pH, temperature), but information regarding the nature and formation of other Fe corrosion products apart from FeCO3 is lacking. Corrosion products in CO2 environments typically consist of common Fe minerals that in nature have been demonstrated to undergo transformations, forming other Fe phases. This fact of nature has not been yet explored in the corrosion science field, which can help us to describe mechanisms associated with industrial processes. In this work, we present a multiscale and multidisciplinary approach to understand the mechanisms occurring on corrosion films under the key factors of flow and pH through the combination of molecular techniques with imaging. We report that certainly siderite (FeCO3, cylindrical with trigonal-pyramidal caps) is the main product identified under the conditions used (representative of brine transport at 80 °C), but wustite (FeO) and magnetite (Fe3O4) minerals also form, likely from the de-carbonation of FeCO3 → FeO → Fe3O4, depending on pH under the action of flow. These minerals exist across the corrosion films evidencing a more complex nature of the three-dimensional layer not currently accounted for in the mechanistic models. A relatively low flow velocity (1 m/s), as recognized for industrial operations, is enough to produce chemo-mechanical damage to the FeCO3 crystals, causing breakage at low pH where dissolution of FeCO3 occurs with a rapid crystal size reduction of the cylindrical FeCO3 geometry of ∼80% in just 8 h, changing also the local chemical structure of Fe3C under the film. Similarly, a flow velocity of 1 m/s is capable of inducing crystal removal at neutral pH, promoting further degradation of the steel, compromising the protectiveness assumption of FeCO3 corrosion films. The chemo-mechanical damage and Fe phase transformations will affect the critical localized corrosion, and therefore, they need to be accounted for in mechanistic models aiming to find new avenues for control and mitigation of carbon steel corrosion.

Mapping sites of gibberellin biosynthesis in the Arabidopsis root tip.

Root elongation depends on the action of the gibberellin (GA) growth hormones, which promote cell production in the root meristem and cell expansion in the elongation zone. Sites of GA biosynthesis in the roots of 7-d-old Arabidopsis thaliana seedlings were investigated using tissue-specific GA inactivation in wild-type (Col-0) or rescue of GA-deficient dwarf mutants. Tissue-specific GA depletion was achieved by ectopic expression of the GA-inactivating enzyme AtGA2ox2, which is specific for C19 -GAs, and AtGA2ox7, which acts on C20 -GA precursors. In addition, tissue-specific rescue of ga20ox triple and ga3ox double mutants was shown. Furthermore, GUS reporter lines for major GA20ox, GA3ox and GA2ox genes were used to observe their expression domains in the root. The effects of expressing these constructs on the lengths of the root apical meristem and cortical cells in the elongation zone confirmed that roots are autonomous for GA biosynthesis, which occurs in multiple tissues, with the endodermis a major site of synthesis. The results are consistent with the early stages of GA biosynthesis within the root occurring in the meristematic region and indicate that the penultimate step of GA biosynthesis, GA 20-oxidation, is required in both the meristem and elongation zone.

A New Era for Space Life Science: International Standards for Space Omics Processing.

Space agencies have announced plans for human missions to the Moon to prepare for Mars. However, the space environment presents stressors that include radiation, microgravity, and isolation. Understanding how these factors affect biology is crucial for safe and effective crewed space exploration. There is a need to develop countermeasures, to adapt plants and microbes for nutrient sources and bioregenerative life support, and to limit pathogen infection. Scientists across the world are conducting space omics experiments on model organisms and, more recently, on humans. Optimal extraction of actionable scientific discoveries from these precious datasets will only occur at the collective level with improved standardization. To address this shortcoming, we established ISSOP (International Standards for Space Omics Processing), an international consortium of scientists who aim to enhance standard guidelines between space biologists at a global level. Here we introduce our consortium and share past lessons learned and future challenges related to spaceflight omics.

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration.

Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.