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27 records · Page 2

All sources NASA NTRS DOE OSTI

NASA NTRSDate not supplied

Radiation Transport Models in Space: from Supernovae to Cells

Humans embarking on deep space exploration missions will encounter persistent exposure to galactic cosmic rays (GCR) - an energetic and highly complex radiation field that is unlike anything found on Earth. Exposure to such radiation fields is attributed to various adverse health effects, including cancer, cardiovascular disease, and cognitive impairment and is identified by NASA as one of the five main hazards of human spaceflight. It is therefore critical to be able to fully characterize the exposure received by humans behind shielding in space and project consequent health risks. A wide variety of computational models have been developed over the years to help meet this requirement. In this talk, an overview of the GCR environment in deep space is provided. Methods of propagating GCR fields through the shielding that protects humans in space are described along with simulation tools used to assess biological damage at the cellular scale. Finally, the NASA cancer risk model is briefly described, and risk projections are provided for various mission scenarios. Radiation transport models and solution methods pervade many aspects of this talk. For example, the GCR spectrum impinging on spacecraft is determined by solving the Fokker-Planck transport equation to propagate cosmic rays (believed to originate from supernovae) from the edge of the heliosphere to the vicinity of Earth. The Boltzmann transport equation is solved to transport this GCR spectrum through shielding and human tissue. Monte Carlo methods are used to simulate the transport of low energy electrons that dominate biological damage at the cellular scale. Progress and challenges in each of these areas will be highlighted.

Tony C. Slaba↗

DOE OSTI2023

Cdk5 mediates rotational force-induced brain injury

Abstract Millions of traumatic brain injuries (TBIs) occur annually. TBIs commonly result from falls, traffic accidents, and sports-related injuries, all of which involve rotational acceleration/deceleration of the brain. During these injuries, the brain endures a multitude of primary insults including compression of brain tissue, damaged vasculature, and diffuse axonal injury. All of these deleterious effects can contribute to secondary brain ischemia, cellular death, and neuroinflammation that progress for weeks, months, and lifetime after injury. While the linear effects of head trauma have been extensively modeled, less is known about how rotational injuries mediate neuronal damage following injury. Here, we developed a new model of repetitive rotational head trauma in rodents and demonstrated acute and prolonged pathological, behavioral, and electrophysiological effects of rotational TBI (rTBI). We identify aberrant Cyclin-dependent kinase 5 (Cdk5) activity as a principal mediator of rTBI. We utilized Cdk5-enriched phosphoproteomics to uncover potential downstream mediators of rTBI and show pharmacological inhibition of Cdk5 reduces the cognitive and pathological consequences of injury. These studies contribute meaningfully to our understanding of the mechanisms of rTBI and how they may be effectively treated.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2024

Non-DNA radiosensitive targets that initiate persistent behavioral deficits in rats exposed to space radiation

Predicting future CNS risks for astronauts during deep-space missions will rely substantially on ground-based rodent data with space-relevant ions and behaviors. For rats, the accumulated evidence indicates that less densely ionizing radiation, such as 4 He and 12 C ions, induce behavior deficits at lower doses than densely ionizing ions, such as 48 Ti and 56 Fe. However, this observation conflicts with standard somatic radiobiology, in which densely ionizing ions are generally more effective than less densely ionizing ions, and where the DNA/nucleus is the accepted target for radiation-induced tumorigenesis, cytogenetic aberrations, genetic mutations, and reproductive cell death. To gain deeper insight into the subcellular nature of the radiation targets for behavior risks, we compared the effects of dose, fluence, and linear energy transfer (LET) of 4 He and 56 Fe particles using existing datasets for four distinct behavioral outcomes in rats: elevated plus maze (EPM-anxiety), novel object recognition (NOR-memory), operant responding (OR-response to environmental stimuli), and attentional set-shifting (ATSET-cognitive flexibility). We confirmed that less densely ionizing particles (except protons) showed ~100-fold lower threshold doses than densely ionizing particles for behavioral deficits (0.1–1 cGy for 4 He vs. 15–100 cGy for 56 Fe). However, when analyzed by fluence the behavioral responses converged, indicating that 4 He and 56 Fe were equally effective on a per-track basis. When analyzed by LET, there were ~100-fold differences in the LET for maximum effectiveness for behavioral deficits and DNA endpoints (~1 vs ~100 keV/μm, respectively). These unique features of radiation-induced behavioral deficits (high sensitivity to particles in the 1-keV/μm range, insensitivity to protons in the 0.2 keV/μm range, and isofluence dependence for particles with LET>1 keV/μm) provide evidence in support of a new hypothesis of sub-micron sized radiosensitive targets for behavioral effects consistent with the thickness of plasma membranes and/or small subcellular structures, smaller than a whole synapse. Like our behavior findings, mouse immature oocyte killing which is known to have a plasma membrane target was also better explained by fluence, rather than dose. In contrast, fluence analyses for DNA/nuclear endpoints in somatic cells (e.g., tumor induction, chromosome aberrations) showed opposite results, suggesting that behavior targets are not DNA. Our findings raise questions regarding the identity of subcellular targets and the multi-cellular functional unit for behavior risks, low-dose susceptibility, and generalizability from rat to other species and astronauts.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

NASA NTRS2019

NASA’s Galactic Cosmic Ray Simulator at Brookhaven National Laboratory: Enabling Human Exploration Missions to the Moon and Mars

With exciting new Agency plans for a sustainable return to the moon, astronauts will once again leave earth’s protective magnetosphere only to endure higher levels of radiation from galactic cosmic rays (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, and surface habitats will be designed to protect crew against SPE’s with vehicle optimization, storm shelter concepts, and/or active dosimetry; however, the ever-penetrating GCR will continue to pose the most significant health risks especially as lunar missions increase in duration and as NASA sets its aspirations on Mars. The primary risks of concern include epithelial carcinogenesis and leukemia, central nervous system effects resulting in potential in-mission cognitive or behavioral impairment and/or late neurological disorders, degenerative tissue effects including cataracts, circulatory and heart disease, as well as, potential immune system decrements impacting multiple aspects of crew health. Characterization and mitigation of these risks requires a significant reduction in the large biological uncertainties of chronic (low-dose rate) heavy ion exposures and the validation of countermeasures in a relevant space environment. NASA has developed the “GCR Simulator” at Brookhaven National Laboratory to generate a spectrum of ion beams that approximates the primary and secondary GCR field experienced at human organ locations within a deep-space vehicle. The majority of the dose is delivered from protons (~65-75%) and alpha particles (~10-20%) with heavier ions (Z≤3) contributing the remainder. The “GCR Simulator” exposes state-of-the art cellular and animal model systems to 33 sequential beams including 4 proton energies plus degrader, 4 helium energies plus degrader, and the five heavy ions of C, O, Si, Ti, and Fe. A polyethylene degrader is used with the 100 MeV/n H and He beams to provide a nearly continuous distribution of low energy particles. A 500 mGy exposure, delivering doses from each of the 33 beams, requires 75-90 minutes. To more closely simulate the low dose rates found in space, sequential field exposures can be divided into daily fractions over 2-4 weeks, with individual fractions as low as 0.1-0.2 mGy. In the large beam configuration (60 x 60 cm(exp 2)), 54 special housing cages can accommodate 2-3 mice each for a 70-75 min duration or ~15 individually housed rats. Emerging research results from our 2018 runs utilizing mixed heavy ion fields and protracted space exposures are forthcoming and deepen our understanding of the numerous health risks faced by our astronauts. This paper discusses NASA’s innovative technology solution for a ground-based GCR simulator at the NASA Space Radiation Laboratory to enable future exploration missions.

Lisa C Simonsen↗

NASA NTRSDate not supplied

NASA Space Radiation Laboratory Galactic Cosmic Ray Simulator

With exciting new Agency plans for a sustainable return to the moon, astronauts will once again leave earth’s protective magnetosphere only to endure higher levels of radiation from galactic cosmic rays (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, and surface habitats will be designed to protect crew against SPEs with vehicle optimization, storm shelter concepts, and/or active dosimetry; however, the ever-penetrating GCR will continue to pose the most significant health risks especially as lunar missions increase in duration and as NASA sets its aspirations on Mars. The primary risks of concern include carcinogenesis, central nervous system effects resulting in potential in-mission cognitive or behavioral impairment and/or late neurological disorders, degenerative tissue effects including cataracts, circulatory and heart disease, as well as, potential immune system decrements impacting multiple aspects of crew health. Characterization and mitigation of these risks requires a significant reduction in the large biological uncertainties of chronic (low-dose rate) heavy ion exposures and the validation of countermeasures in a relevant space environment. NASA has developed the “GCR Simulator” at Brookhaven National Laboratory to generate a spectrum of ion beams that approximates the primary and secondary GCR field experienced at human organ locations within a deep-space vehicle. The majority of the dose is delivered from protons (~65-75%) and helium ions (~10-20%) with heavier ions (Z>3) contributing the remainder. The “GCR Simulator” exposes state-of-the art cellular and animal model systems to 33 sequential beams including 4 proton energies plus degrader, 4 helium energies plus degrader, and the five heavy ions of C, O, Si, Ti, and Fe. A polyethylene degrader is used with the 100 MeV/n H and He beams to provide a nearly continuous distribution of low energy particles. A 500 mGy exposure, delivering doses from each of the 33 beams, requires 75-90 minutes. To more closely simulate the low dose rates found in space, sequential field exposures can be divided into daily fractions over 2-6 weeks, with individual beam fractions as low as 0.1-0.2 mGy. In the large beam configuration (60 x 60 cm2), 54 special housing cages can accommodate 2-3 mice each for a 70-75 min duration or ~15 individually housed rats. Emerging research results from our 2018 runs utilizing mixed heavy ion fields and protracted space exposures are forthcoming and will deepen our understanding of the numerous health risks faced by astronauts. This talk discusses NASA’s innovative technology solution for a ground-based GCR simulator at the NASA Space Radiation Laboratory to enable future exploration missions.

galactic cosmic ray simulator↗

NASA NTRS1990

Toward applied behavior analysis of life aloft

This article deals with systems at multiple levels, at least from cell to organization. It also deals with learning, decision making, and other behavior at multiple levels. Technological development of a human behavioral ecosystem appropriate to space environments requires an analytic and synthetic orientation, explicitly experimental in nature, dictated by scientific and pragmatic considerations, and closely approximating procedures of established effectiveness in other areas of natural science. The conceptual basis of such an approach has its roots in environmentalism which has two main features: (1) knowledge comes from experience rather than from innate ideas, divine revelation, or other obscure sources; and (2) action is governed by consequences rather than by instinct, reason, will, beliefs, attitudes or even the currently fashionable cognitions. Without an experimentally derived data base founded upon such a functional analysis of human behavior, the overgenerality of "ecological systems" approaches render them incapable of ensuring the successful establishment of enduring space habitats. Without an experimentally derived function account of individual behavioral variability, a natural science of behavior cannot exist. And without a natural science of behavior, the social sciences will necessarily remain in their current status as disciplines of less than optimal precision or utility. Such a functional analysis of human performance should provide an operational account of behavior change in a manner similar to the way in which Darwin's approach to natural selection accounted for the evolution of phylogenetic lines (i.e., in descriptive, nonteleological terms). Similarly, as Darwin's account has subsequently been shown to be consonant with information obtained at the cellular level, so too should behavior principles ultimately prove to be in accord with an account of ontogenetic adaptation at a biochemical level. It would thus seem obvious that the most productive conceptual and methodological approaches to long-term research investments focused upon human behavior in space environments will require multidisciplinary inputs from such wide-ranging fields as molecular biology, environmental physiology, behavioral biology, architecture, sociology, and political science, among others.

Review↗

DOE OSTI2024

Cysteine Rich Intestinal Protein 2 is a copper-responsive regulator of skeletal muscle differentiation and metal homeostasis

Copper (Cu) is essential for respiration, neurotransmitter synthesis, oxidative stress response, and transcription regulation, with imbalances leading to neurological, cognitive, and muscular disorders. Here we show the role of a novel Cu-binding protein (Cu-BP) in mammalian transcriptional regulation, specifically on skeletal muscle differentiation using murine primary myoblasts. Utilizing synchrotron X-ray fluorescence-mass spectrometry, we identified murine cysteine-rich intestinal protein 2 (mCrip2) as a key Cu-BP abundant in both nuclear and cytosolic fractions. mCrip2 binds two to four Cu + ions with high affinity and presents limited redox potential. CRISPR/Cas9-mediated deletion of mCrip2 impaired myogenesis, likely due to Cu accumulation in cells. CUT&RUN and transcriptome analyses revealed its association with gene promoters, including MyoD1 and metallothioneins, suggesting a novel Cu-responsive regulatory role for mCrip2. Our work describes the significance of mCrip2 in skeletal muscle differentiation and metal homeostasis, expanding understanding of the Cu-network in myoblasts. Copper (Cu) is essential for various cellular processes, including respiration and stress response, but imbalances can cause serious health issues. This study reveals a new Cu-binding protein (Cu-BP) involved in muscle development in primary myoblasts. Using unbiased metalloproteomic techniques and high throughput sequencing, we identified mCrip2 as a key Cu-BP found in cell nuclei and cytoplasm. mCrip2 binds up to four Cu + ions and has a limited redox potential. Deleting mCrip2 using CRISPR/Cas9 disrupted muscle formation due to Cu accumulation. Further analyses showed that mCrip2 regulates the expression of genes like MyoD1, essential for muscle differentiation, and metallothioneins in response to copper supplementation. This research highlights the importance of mCrip2 in muscle development and metal homeostasis, providing new insights into the Cu-network in cells.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

NASA’s first ground-based Galactic Cosmic Ray Simulator: Enabling a new era in space radiobiology research

With exciting new NASA plans for a sustainable return to the moon, astronauts will once again leave Earth’s protective magnetosphere only to endure higher levels of radiation from galactic cosmic radiation (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, and surface habitats will be designed to protect crew against SPEs with vehicle optimization, storm shelter concepts, and/or active dosimetry; however, the ever penetrating GCR will continue to pose the most significant health risks especially as lunar missions increase in duration and as NASA sets its aspirations on Mars. The primary risks of concern include carcinogenesis, central nervous system (CNS) effects resulting in potential in-mission cognitive or behavioral impairment and/or late neurological disorders, degenerative tissue effects including circulatory and heart disease, as well as potential immune system decrements impacting multiple aspects of crew health. Characterization and mitigation of these risks requires a significant reduction in the large biological uncertainties of chronic (low-dose rate) heavy-ion exposures and the validation of countermeasures in a relevant space environment. Historically, most research on understanding space radiation-induced health risks has been performed using acute exposures of monoenergetic single-ion beams. However, the space radiation environment consists of a wide variety of ion species over a broad energy range. Using the fast beam switching and controls systems technology recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory, a new era in radiobiological research is possible. NASA has developed the “GCR Simulator” to generate a spectrum of ion beams that approximates the primary and secondary GCR field experienced at human organ locations within a deep-space vehicle. The majority of the dose is delivered from protons (approximately 65%–75%) and helium ions (approximately 10%–20%) with heavier ions (Z ≥ 3) contributing the remainder. The GCR simulator exposes state-of-the art cellular and animal model systems to 33 sequential beams including 4 proton energies plus degrader, 4 helium energies plus degrader, and the 5 heavy ions of C, O, Si, Ti, and Fe. A polyethylene degrader system is used with the 100 MeV/n H and He beams to provide a nearly continuous distribution of low-energy particles. A 500 mGy exposure, delivering doses from each of the 33 beams, requires approximately 75 minutes. To more closely simulate the low-dose rates found in space, sequential field exposures can be divided into daily fractions over 2 to 6 weeks, with individual beam fractions as low as 0.1 to 0.2 mGy. In the large beam configuration (60 × 60 cm 2 ), 54 special housing cages can accommodate 2 to 3 mice each for an approximately 75 min duration or 15 individually housed rats. On June 15, 2018, the NSRL made a significant achievement by completing the first operational run using the new GCR simulator. This paper discusses NASA’s innovative technology solution for a ground-based GCR simulator at the NSRL to accelerate our understanding and mitigation of health risks faced by astronauts. Ultimately, the GCR simulator will require validation across multiple radiogenic risks, endpoints, doses, and dose rates.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Outsourced hearing in an orb-weaving spider that uses its web as an auditory sensor

Hearing is a fundamental sense of many animals, including all mammals, birds, some reptiles, amphibians, fish, and arthropods. The auditory organs of these animals are extremely diverse in anatomy after hundreds of millions of years of evolution, yet all are made up of cellular tissue and are morphologically part of the bodies of animals. Here, we show that hearing in the orb-weaving spider Larinioides sclopetarius is not constrained by the organism’s body but is extended through outsourcing hearing to its extended phenotype, the proteinaceous, self-manufactured orb web. We find that the wispy, wheel-shaped orb web acts as a hyperacute acoustic antenna to capture the sound-induced air particle movements that approach the maximum physical efficiency better than the acoustic responsivity of all previously known eardrums. By sensing the motion of web threads, the spider remotely detects and localizes the source of an incoming airborne acoustic wave, such as those emitted by approaching prey or predators. By outsourcing its acoustic sensors to its web, the spider is released from body size constraints and permits the araneid spider to increase its sound-sensitive surface area enormously, up to 10,000 times greater than the spider itself. The spider also enables the flexibility to functionally adjust and regularly regenerate its external "eardrum" according to its needs. The outsourcing and supersizing of auditory function in spiders provides unique features for studying extended and regenerative sensing and designing novel acoustic flow detectors for precise fluid dynamic measurement and manipulation.

60 APPLIED LIFE SCIENCES↗