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1. Electrophysiological recording of human neuronal networks during suborbital spaceflight

   Andie E. Padilla, Candice Hovell (October 2022, bioRxiv)

   The use of microfluidic tissue-on-a-chip devices in conjunction with electrophysiology (EPHYS) techniques has become prominent in recent years to study cell-cell interactions critical to the understanding of cellular function in extreme environments, including spaceflight and microgravity. Current techniques are confined to invasive whole-cell recording at intermittent time points during spaceflight, limiting data acquisition and overall reduced insight on cell behaviour. Currently, there exists no validated technology that offers continuous EPHYS recording and monitoring in physiological systems exposed to microgravity. In collaboration with imec and SpaceTango, we have developed an enclosed, automated research platform that enables continuous monitoring of electrically active human cell cultures during spaceflight. The Neuropixels probe system (imec) will be integrated for the first time within an engineered in-vitro neuronal tissue-on-a-chip model that facilitates the EPHYS recording of cells in response to extracellular electrical activity in the assembled neuronal tissue platform. Our goal is to study the EPHYS recordings and understand how exposure to microgravity affects cellular interaction within human tissue-on-a-chip systems in comparison to systems maintained under Earth’s gravity. Results may be useful for dissecting the complexity of signals obtained from other tissue systems, such as cardiac or gastrointestinal, when exposed to microgravity. This study will yield valuable knowledge regarding physiological changes in human tissue-on-a-chip models due to spaceflight, as well as validate the use of this type of platform for more advanced research critical in potential human endeavours to space. 

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2. Astrovirology: how viruses enhance our understanding of life in the Universe

   https://doi.org/10.1017/S1473550423000058  

   Trubl, Gareth; Stedman, Kenneth M.; Bywaters, Kathryn F.; Matula, Emily E.; Sommers, Pacifica; Roux, Simon; Merino, Nancy; Yin, John; Kaelber, Jason T.; Avila-Herrera, Aram; et al (August 2023, International Journal of Astrobiology)

   Abstract Viruses are the most numerically abundant biological entities on Earth. As ubiquitous replicators of molecular information and agents of community change, viruses have potent effects on the life on Earth, and may play a critical role in human spaceflight, for life-detection missions to other planetary bodies and planetary protection. However, major knowledge gaps constrain our understanding of the Earth's virosphere: (1) the role viruses play in biogeochemical cycles, (2) the origin(s) of viruses and (3) the involvement of viruses in the evolution, distribution and persistence of life. As viruses are the only replicators that span all known types of nucleic acids, an expanded experimental and theoretical toolbox built for Earth's viruses will be pivotal for detecting and understanding life on Earth and beyond. Only by filling in these knowledge and technical gaps we will obtain an inclusive assessment of how to distinguish and detect life on other planetary surfaces. Meanwhile, space exploration requires life-support systems for the needs of humans, plants and their microbial inhabitants. Viral effects on microbes and plants are essential for Earth's biosphere and human health, but virus–host interactions in spaceflight are poorly understood. Viral relationships with their hosts respond to environmental changes in complex ways which are difficult to predict by extrapolating from Earth-based proxies. These relationships should be studied in space to fully understand how spaceflight will modulate viral impacts on human health and life-support systems, including microbiomes. In this review, we address key questions that must be examined to incorporate viruses into Earth system models, life-support systems and life detection. Tackling these questions will benefit our efforts to develop planetary protection protocols and further our understanding of viruses in astrobiology. 

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3. Complexity of human death: its physiological, transcriptomic, and microbiological implications

   https://doi.org/10.3389/fmicb.2023.1345633  

   Javan, Gulnaz T.; Singh, Kanhaiya; Finley, Sheree J.; Green, Robert L.; Sen, Chandan K. (January 2024, Frontiers in Microbiology)

   Human death is a complex, time-governed phenomenon that leads to the irreversible cessation of all bodily functions. Recent molecular and genetic studies have revealed remarkable experimental evidence of genetically programmed cellular death characterized by several physiological processes; however, the basic physiological function that occurs during the immediate postmortem period remains inadequately described. There is a paucity of knowledge connecting necrotic pathologies occurring in human organ tissues to complete functional loss of the human organism. Cells, tissues, organs, and organ systems show a range of differential resilience and endurance responses that occur during organismal death. Intriguingly, a persistent ambiguity in the study of postmortem physiological systems is the determination of the trajectory of a complex multicellular human body, far from life-sustaining homeostasis, following the gradual or sudden expiry of its regulatory systems. Recent groundbreaking investigations have resulted in a paradigm shift in understanding the cell biology and physiology of death. Two significant findings are that (i) most cells in the human body are microbial, and (ii) microbial cell abundance significantly increases after death. By addressing the physiological as well as the microbiological aspects of death, future investigations are poised to reveal innovative insights into the enigmatic biological activities associated with death and human decomposition. Understanding the elaborate crosstalk of abiotic and biotic factors in the context of death has implications for scientific discoveries important to informing translational knowledge regarding the transition from living to the non-living. There are important and practical needs for a transformative reestablishment of accepted models of biological death (i.e., artificial intelligence, AI) for more precise determinations of when the regulatory mechanisms for homeostasis of a living individual have ceased. In this review, we summarize mechanisms of physiological, genetic, and microbiological processes that define the biological changes and pathways associated with human organismal death and decomposition. 

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4. A magnetic levitation based low-gravity simulator with an unprecedented large functional volume

   https://doi.org/10.1038/s41526-021-00174-4  

   Sanavandi, Hamid; Guo, Wei (October 2021, npj Microgravity)

   Abstract Low-gravity environment can have a profound impact on the behaviors of biological systems, the dynamics of fluids, and the growth of materials. Systematic research on the effects of gravity is crucial for advancing our knowledge and for the success of space missions. Due to the high cost and the limitations in the payload size and mass in typical spaceflight missions, ground-based low-gravity simulators have become indispensable for preparing spaceflight experiments and for serving as stand-alone research platforms. Among various simulator systems, the magnetic levitation-based simulator (MLS) has received long-lasting interest due to its easily adjustable gravity and practically unlimited operation time. However, a recognized issue with MLSs is their highly non-uniform force field. For a solenoid MLS, the functional volumeV_1%, where the net force results in an acceleration <1% of the Earth’s gravityg, is typically a few microliters (μL) or less. In this work, we report an innovative MLS design that integrates a superconducting magnet with a gradient-field Maxwell coil. Through an optimization analysis, we show that an unprecedentedV_1%of over 4000 μL can be achieved in a compact coil with a diameter of 8 cm. We also discuss how such an MLS can be made using existing high-T_c-superconducting materials. When the current in this MLS is reduced to emulate the gravity on Mars (g_M = 0.38g), a functional volume where the gravity varies within a few percent ofg_Mcan exceed 20,000 μL. Our design may break new ground for future low-gravity research. 

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5. The ongoing need for rates: can physiology and omics come together to co-design the measurements needed to understand complex ocean biogeochemistry?

   https://doi.org/10.1093/plankt/fbac026  

   Strzepek, Robert F; Nunn, Brook L; Bach, Lennart T; Berges, John A; Young, Erica B; Boyd, Philip W (June 2022, Journal of Plankton Research)

   Dolan, John (Ed.)

   Abstract The necessity to understand the influence of global ocean change on biota has exposed wide-ranging gaps in our knowledge of the fundamental principles that underpin marine life. Concurrently, physiological research has stagnated, in part driven by the advent and rapid evolution of molecular biological techniques, such that they now influence all lines of enquiry in biological oceanography. This dominance has led to an implicit assumption that physiology is outmoded, and advocacy that ecological and biogeochemical models can be directly informed by omics. However, the main modeling currencies are biological rates and biogeochemical fluxes. Here, we ask: how do we translate the wealth of information on physiological potential from omics-based studies to quantifiable physiological rates and, ultimately, to biogeochemical fluxes? Based on the trajectory of the state-of-the-art in biomedical sciences, along with case-studies from ocean sciences, we conclude that it is unlikely that omics can provide such rates in the coming decade. Thus, while physiological rates will continue to be central to providing projections of global change biology, we must revisit the metrics we rely upon. We advocate for the co-design of a new generation of rate measurements that better link the benefits of omics and physiology. 

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