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Exercise and pharmacological countermeasures for bone loss during long-duration space flight

Bone loss in the lower extremities and lumbar spine is an established consequence of long-duration human space flight. Astronauts typically lose as much bone mass in the proximal femur in 1 month as postmenopausal women on Earth lose in 1 year. Pharmacological interventions have not been routinely used in space, and countermeasure programs have depended solely upon exercise. However, it is clear that the osteogenic stimulus from exercise has been inadequate to maintain bone mass, due to insufficient load or duration. Attention has therefore been focused on several pharmacological interventions that have been successful in preventing or attenuating osteoporosis on Earth. Anti-resorptives are the class of drugs most commonly used to treat osteoporosis in postmenopausal women, notably alendronate sodium, risedronate sodium, zoledronic acid, and selective estrogen receptor modulators, such as raloxifene. There has also been considerable recent interest in anabolic agents such as parathyroid hormone (PTH) and teriparatide (rhPTH [1-34]). Vitamin D and calcium supplementation have also been used. Recent studies of kindreds with abnormally high bone mineral density have provided insight into the genetic regulation of bone mass. This has led to potential therapeutic interventions based on the LRP5, Wnt and BMP2 pathways. Another target is the RANK-L/osteoprotegerin signaling pathway, which influences bone turnover by regulating osteoclast formation and maturation. Trials using such therapies in space are being planned. Among the factors to be considered are dose-response relationships, bone quality, post-use recovery, and combination therapies--all of which may have unique characteristics when the drugs are used in space.

NASA Discipline Musculoskeletal↗

Surveillance for Jugular Venous Thrombosis in Long-Duration Space Flight: Findings From Twenty-Eight U.S. Astronauts

BACKGROUND: Given the high incidence of internal jugular vein (IJV) flow anomalies aboard the International Space Station and a case of thrombosis, the National Aeronautics and Space Administration (NASA) instituted an occupational surveillance program to evaluate astronauts for venous thromboembolism (VTE). Current findings of the program are presented. METHODS: NASA astronauts undergo pre- and in-flight VTE surveillance examinations using a standardized vascular ultrasound protocol, which includes evaluation for bilateral IJV compressibility, filling, flow, and spontaneous echo contrast (SEC). RESULTS: Twenty-eight NASA astronauts had terrestrial baseline examinations and at least one in-flight imaging session. The reduction of in-flight peak IJV flow speeds was significant and more pronounced on the left. Comparing the first in-flight measurement to the terrestrial baseline, peak flow speeds were reduced from 90.1±41.9 cm/s (average ±SD) to 62.1±31.6 cm/s on the right and from 76.9±41.8 cm/s to 26.8±18.2 cm/s on the left. Seven astronauts showed stagnant or retrograde flow in the left IJV. Fourteen developed appreciable SEC in the left IJV (7 greater than mild); none developed significant right-sided SEC. All IJVs were fully compressible and free from thrombi. DISCUSSION: Bilateral IJV flow speed reduction is observed in microgravity, possibly due to the multitude of available flow redistribution paths for cranial drainage. In a subset of astronauts, significant flow anomalies develop that may facilitate thrombus formation through changes in blood viscosity and speed, especially if combined with other thrombogenic factors. These findings warrant attention to the interplay between individual vascular configurations and the dynamic properties of blood as a non-Newtonian fluid in the reduced-shear flow environment of microgravity.

Ashot Sargsyan↗

Bosch Carbon Catalyst Regeneration in Water II: Analysis of Bosch Catalyst Beads Throughout the Initial Regeneration Process

Catalyst integrity is an important factor in reactor longevity since it changes the effectiveness of a reaction. A Carbon Formation Reactor (CFR), used within Series Bosch (S-Bosch), utilizes an iron alloy catalyst to convert carbon monoxide and hydrogen into water and solid carbon. The catalyst promotes the formation of carbon to such an extent that pressure-causing clogs form within the reactor and reaction sites on the catalyst become limited. To remove carbon from both the reactor and the surface of the iron alloy catalyst, a technique was developed that utilizes water, an In-Situ Resource Utilization (ISRU) Resource, and agitation to regenerate the reactor. To ascertain catalyst integrity throughout this regenerative process, sample catalyst beads were taken before and after the carbon formation reaction, and then after the regeneration process. Additionally, wastewater from the regeneration process was sampled. The sampled beads and wastewater were observed under a Scanning Electron Microscopy (SEM) microscope and the beads were chemically etched to determine if the catalyst had degraded at any point during this process, and if catalyst was lost. Minimal catalyst degradation was observed after carbon formation in the CFR.

regeneration↗

Bosch Carbon Catalyst Regeneration in Water II: Analysis of Bosch Catalyst Beads Throughout the Initial Regeneration Process

Catalyst integrity is an important factor in reactor longevity since it changes the effectiveness of a reaction. A Carbon Formation Reactor (CFR), used within Series Bosch (S-Bosch), utilizes an iron alloy catalyst to convert carbon monoxide and hydrogen into water and solid carbon. The catalyst promotes the formation of carbon to such an extent that pressure-causing clogs form within the reactor and reaction sites on the catalyst become limited. To remove carbon from both the reactor and the surface of the iron alloy catalyst, a technique was developed that utilizes water, an In-Situ Resource Utilization (ISRU) Resource, and agitation to regenerate the reactor. To ascertain catalyst integrity throughout this regenerative process, sample catalyst beads were taken before and after the carbon formation reaction, and then after the regeneration process. Additionally, wastewater from the regeneration process was sampled. The sampled beads and wastewater were observed under a Scanning Electron Microscopy (SEM) microscope and the beads were chemically etched to determine if the catalyst had degraded at any point during this process, and if catalyst was lost. Minimal catalyst degradation was observed after carbon formation in the CFR.

Series Bosch↗

Novel Multiplexing Technique for Detector and Mixer Arrays

Future submillimeter and far-infrared space telescopes will require large-format (many 1000's of elements) imaging detector arrays to perform state-of-the-art astronomical observations. A crucial issue related to a focal plane array is a readout scheme which is compatible with large numbers of cryogenically-cooled (typically < 1 K) detectors elements. When the number of elements becomes of the order of thousands, the physical layout for individual readout amplifiers becomes nearly impossible to realize for practical systems. Another important concern is the large number of wires leading to a 0.1-0.3 K platform. In the case of superconducting transition edge sensors (TES), a scheme for time-division multiplexing of SQUID read-out amplifiers has been recently demonstrated. In this scheme the number of SQUIDs is equal to the number (N) of the detectors, but only one SQUID is turned on at a time. The SQUIDs are connected in series in each column of the array, so the number of wires leading to the amplifiers can be reduced, but it is still of the order of N. Another approach uses a frequency domain multiplexing scheme of the bolometer array. The bolometers are biased with ac currents whose frequencies are individual for each element and are much higher than the bolometer bandwidth. The output signals are connected in series in a summing loop which is coupled to a single SQUID amplifier. The total number of channels depends on the ratio between the SQUID bandwidth and the bolometer bandwidth and can be at least 100 according to the authors. An important concern about this technique is a contribution of the out-of-band Johnson noise which multiplies by factor N(exp 1/2) for each frequency channel. We propose a novel solution for large format arrays based on the Hadamard transform coding technique which requires only one amplifier to read out the entire array of potentially many 1000's of elements and uses approximately 10 wires between the cold stage and room temperature electronics. This can significantly reduce the complexity of the readout circuits.

Karasik, Boris S.↗

Short Range-Ordered Minerals: Insight into Aqueous Alteration Processes on Mars

Short range-ordered (SRO) aluminosilicates (e.g., allophane) and nanophase ferric oxides (npOx) are common SRO minerals derived during aqueous alteration of basaltic materials. NpOx refers to poorly crystalline or amorphous alteration products that can be any combination of superparamagnetic hematite and/or goethite, akaganeite, schwertmannite, ferrihydrite, iddingsite, and nanometer-sized ferric oxide particles that pigment palagonitic tephra. Nearly 30 years ago, SRO phases were suggested as alteration phases on Mars based on similar spectral properties for altered basaltic tephra on the slopes of Mauna Kea in Hawaii and Martian bright regions measured by Earth-based telescopes. Detailed characterization of altered basaltic tephra on Mauna Kea have identified a variety of alteration phases including allophane, npOx, hisingerite, jarosite, alunite, hematite, goethite, ferrihydrite, halloysite, kaolinite, smectite, and zeolites. The presence of npOx and other Fe-bearing minerals (jarosite, hematite, goethite) was confirmed by the M ssbauer Spectrometer onboard the Mars Exploration Rovers. Although the presence of allophane has not been definitely identified on Mars robotic missions, chemical analysis by the Spirit and Opportunity rovers and thermal infrared spectral orbital measurements suggest the presence of allophane or allophane-like phases on Mars. SRO phases form under a variety of environmental conditions on Earth ranging from cold and arid to warm and humid, including hydrothermal conditions. The formation of SRO aluminosilicates such as allophane (and crystalline halloysite) from basaltic material is controlled by several key factors including activity of water, extent of leaching, Si activity in solution, and available Al. Generally, a low leaching index (e.g., wet-dry cycles) and slightly acidic to alkaline conditions are necessary. NpOx generally form under aqueous oxidative weathering conditions, although thermal oxidative alteration may occasional be involved. The style of aqueous alteration (hydrolytic vs. acid sulfate) impacts which phases will form (e.g., oxides, oxysulfates, and oxyhydroxides). Knowledge on the formation processes of SRO phases in basaltic materials on Earth has allowed significant enhancement in our understanding of the aqueous processes at work on Mars. The 2011 Mars Science Laboratory (MSL) will provide an instrument suite that should improve our understanding of the mineralogical and chemical compositions of SRO phases. CheMin is an X-ray diffraction instrument that may provide broad X-ray diffraction peaks for SRO phases; e.g., broad peaks around 0.33 and 0.23 nm for allophane. Sample Analysis at Mars (SAM) heats samples and detects evolved gases of volatile-bearing phases including SRO phases (i.e., carbonates, sulfates, hydrated minerals). The Alpha Particle X-ray Spectrometer (APXS) and ChemCam element analyzers will provide chemical characterization of samples. The identification of SRO phases in surface materials on MSL will be challenging due to their nanocrystalline properties; their detection and identification will require utilizing the MSL instrument suite in concert. Ultimately, sample return missions will be required to definitively identify and fully characterize SRO minerals with state-of-the-art laboratory instrumentation back on Earth.

Ming, Douglas W.↗

Formation Of the Giant Planets By Concurrent Accretion Of Solids And Gas

New numerical simulations of the formation of the giant planets are presented, in which for the first time both the gas and planetesimal accretion rates are calculated in a self-consistent, interactive fashion. The simulations combine three elements: 1) three-body accretion cross-sections of solids onto an isolated planetary embryo, 2) a stellar evolution code for the planet's gaseous envelope, and 3) a planetesimal dissolution code within the envelope, used to evaluate the planet's effective capture radius and the energy deposition profile of accreted material. Major assumptions include: The planet is embedded in a disk of gas and small planetesimals with locally uniform initial surface mass density, and planetesimals are not allowed to migrate into or out of the planet's feeding zone. All simulations are characterized by three major phases. During the first phase, the planet's mass consists primarily of solid material. The planetesimal accretion rate, which dominates that of gas, rapidly increases owing to runaway accretion, then decreases as the planet's feeding zone is depleted. During the second phase, both solid and gas accretion rates are small and nearly independent of time. The third phase, marked by runaway gas accretion, starts when the solid and gas masses are about equal. It is engendered by a strong positive feedback on the gas accretion rates, driven by the rapid contraction of the gaseous envelope and the rapid expansion of the outer boundary, which depends on the planet's total mass. The overall evolutionary time scale is generally determined by the length of the second phase. The actual rates at which the giant planets accreted small planetesimals is probably intermediate between the constant rates assumed in most previous studies and the highly variable rates that we have used. Within the context, of the adopted model of planetesimal accretion, the joint constraints of the time scale for dissipation of the solar nebula and the current high-Z masses of the giant planets lead to estimates of the initial surface density (sigma(sub init)) of planetesimals in the outer region of the solar nebula. The results show sigma(sub init) approx. = 10 g/sq cm near Jupiter's orbit and that sigma(sub init) proportional to alpha(sup -2), where alpha is the distance from the Sun. These values are a factor of 3 - 4 times as high as that of the "minimum mass" solar nebula at Jupiter's distance and a factor of 2 - 3 times as high it Saturn's distance. Our estimates for the formation time of Jupiter and Saturn are 1 - 10 million years while those for Uranus fall in the range of 2 - 16 million years. These estimates follow from the properties of our Solar System and do not necessarily apply to giant planets in other planetary systems.

Pollack, James B.↗

Conditions of formation of pyroxene excentroradial chondrules

Understanding the exact mechanism of origin of chondrules and the attendant physical conditions remains a key factor in understanding the early evolution of the solar system. The present investigation is concerned with an interpretation of the range of cooling histories needed to make chondrules. Chondrule-like spherules were formed in dynamic crystallization experiments, using gas-mixing facilities. It is found that textures in pyroxene-rich chondrules are well reproduced in the laboratory by cooling melts of chondrule composition from just above the liquidus. The range of pyroxene dendrite widths is slightly greater for natural chondrules than for droplets cooled from 50 C/hr to greater than 3000 C/hr. A blanketing medium of variable thickness explains the cooling rates lower than expected for radiative cooling. Experimental results, textures indicating incomplete melting, and isotopic disequilibrium are compatible with reheating of primitive material in the early solar nebula.

Hewins, R. H.↗

Computing Needs for Astrobiology: Models of Planetary Formation

Theories of planet formation indicate that a diverse range of physical and chemical processes determine the characteristics of a planetary system. Extensive numerical modeling is required to understand how planetary systems form, and to make quantitative assessments of the factors which determine the masses, spacings and volatile compound inventories of planets and small bodies within a planetary system. Fluid flow problems associated with the formation and evolution of protoplanetary disks include specific local calculations to provide physical insight, which are best performed on workstations, and large multifaceted simulations which require supercomputers with large memories. Formation and early growth of planetesimals display a similar range of computational requirements. Modeling the late stages of planetary accumulation is very CPU intensive, as it requires following a simple system of approx. hundreds of bodies for millions of dynamical (orbital) times. These varied computational needs could be met in the most cost-effective manner by a diverse set of computers, including workstations for individual PI's and dedicated time on various types of supercomputers which are specialized for differing tasks.

Lissauer, Jack J.↗

Improving Our Understanding of Antarctic Sea Ice with NASA's Operation IceBridge and the Upcoming ICESat-2 Mission

Antarctic sea ice is a crucial component of the global climate system. Rapid sea ice production regimes around Antarctica feed the lower branch of the Southern Ocean overturning circulation through intense brine rejection and the formation of Antarctic Bottom Water (e.g., Orsi et al. 1999; Jacobs 2004), while the northward transport and subsequent melt of Antarctic sea ice drives the upper branch of the overturning circulation through freshwater input (Abernathy et al. 2016). Wind-driven trends in Antarctic sea ice (Holland Kwok 2012) have likely increased the transport of freshwater away from the Antarctic coastline, significantly altering the salinity distribution of the Southern Ocean (Haumann et al. 2016). Conversely, weaker sea ice production and the lack of shelf water formation over the Amundsen and Bellingshausen shelf seas promote intrusion of warm Circumpolar Deep Water onto the continental shelf and the ocean-driven melting of several ice shelves fringing the West Antarctic Ice Sheet (e.g., Jacobs et al. 2011; Pritchard et al. 2012; Dutrieux et al. 2014). Sea ice conditions around Antarctica are also increasingly considered an important factor impacting local atmospheric conditions and the surface melting of Antarctic ice shelves (e.g., Scambos et al. 2017). Sea ice formation around Antarctica is responsive to the strong regional variability in atmospheric forcing present around Antarctica, driving this bimodal variability in the behavior and properties of the underlying shelf seas (e.g., Petty et al. 2012; Petty et al. 2014).

Arctic↗

Future Direction of Research in Wear and Wear Resistant Materials. Status of Understanding

The adhesion of materials is one of the most popular interactions occuring between mating solid surfaces in contact, and was regarded as a key factor in wear process. However, because the adhesion is not a separation factor but a joining factor for mating materials, it is not easy to show a general plot of the formation process of wear particle through adhesion. A new idea on the mechanism of formation of wear particles in adhesive wear is shown. The wear particles are not separated from their mother surfaces directly as their final form, but minute adhered fragments are assembled and piled up to form a big particle which should be called as a wear particle after it is removed out of the rubbing system. From this proposed mechanism many other phenomena related to wear are interpreted.

Sasada, T.↗

Human factors of flight-deck checklists: The normal checklist

Although the aircraft checklist has long been regarded as the foundation of pilot standardization and cockpit safety, it has escaped the scrutiny of the human factors profession. The improper use, or the non-use, of the normal checklist by flight crews is often cited as the probable cause or at least a contributing factor to aircraft accidents. An attempt is made to analyze the normal checklist, its functions, format, design, length, usage, and the limitations of the humans who must interact with it. The development of the checklist from the certification of a new model to its delivery and use by the customer are discussed. The influence of the government, particularly the FAA Principle Operations Inspector, the manufacturer's philosophy, the airline's culture, and the end user, the pilot, influence the ultimate design and usage of this device. The effects of airline mergers and acquisitions on checklist usage and design are noted. In addition, the interaction between production pressures and checklist usage and checklist management are addressed. Finally, a list of design guidelines for normal checklists is provided.

Degani, Asaf↗

The Bosch Process-Performance of a Developmental Reactor and Experimental Evaluation of Alternative Catalysts

Bosch-based reactors have been in development at NASA since the 1960's. Traditional operation involves the reduction of carbon dioxide with hydrogen over a steel wool catalyst to produce water and solid carbon. While the system is capable of completely closing the loop on oxygen and hydrogen for Atmosphere Revitalization, steel wool requires a reaction temperature of 650C or higher for optimum performance. The single pass efficiency of the reaction over steel wool has been shown to be less than 10% resulting in a high recycle stream. Finally, the formation of solid carbon on steel wool ultimately fouls the catalyst necessitating catalyst resupply. These factors result in high mass, volume and power demands for a Bosch system. Interplanetary transportation and surface exploration missions of the moon, Mars, and near-earth objects will require higher levels of loop closure than current technology cannot provide. A Bosch system can provide the level of loop closure necessary for these long-term missions if mass, volume, and power can be kept low. The keys to improving the Bosch system lie in reactor and catalyst development. In 2009, the National Aeronautics and Space Administration refurbished a circa 1980's developmental Bosch reactor and built a sub-scale Bosch Catalyst Test Stand for the purpose of reactor and catalyst development. This paper describes the baseline performance of two commercially available steel wool catalysts as compared to performance reported in the 1960's and 80's. Additionally, the results of sub-scale testing of alternative Bosch catalysts, including nickel- and cobalt-based catalysts, are discussed.

Abney, Morgan B.↗

A Self-Perpetuating Catalyst for the Production of Complex Organic Molecules in Protostellar Nebulae

The formation of abundant carbonaceous material in meteorites is a long standing problem and an important factor in the debate on the potential for the origin of life in other stellar systems. Many mechanisms may contribute to the total organic content in protostellar nebulae, ranging from organics formed via ion-molecule and atom-molecule reactions in the cold dark clouds from which such nebulae collapse, to similar ion-molecule and atom-molecule reactions in the dark regions of the nebula far from the proto star, to gas phase reactions in sub-nebulae around growing giant planets and in the nebulae themselves. The Fischer-Tropsch-type (FTT) catalytic reduction of CO by hydrogen was once the preferred model for production of organic materials in the primitive solar nebula. The Haber-Bosch catalytic reduction of N2 by hydrogen was thought to produce the reduced nitrogen found in meteorites. However, the clean iron metal surfaces that catalyze these reactions are easily poisoned via reaction with any number of molecules, including the very same complex organics that they produce and both reactions work more efficiently in the hot regions of the nebula. We have demonstrated that many grain surfaces can catalyze both FTT and HB-type reactions, including amorphous iron and magnesium silicates, pure silica smokes as well as several minerals. Although none work as well as pure iron grains, and all produce a wide range of organic products rather than just pure methane, these materials are not truly catalysts.

Nuth, Joseph A.↗

Evaluation of Contrail Reduction Strategies Based on Environmental and Operational Costs

This paper evaluates a set of contrail reduction strategies based on environmental and operational costs. A linear climate model was first used to convert climate effects of carbon dioxide emissions and aircraft contrails to changes in Absolute Global Temperature Potential, a metric that measures the mean surface temperature change due to aircraft emissions and persistent contrail formations. The concept of social cost of carbon and the carbon auction price from recent California's cap-and-trade system were then used to relate the carbon dioxide emissions and contrail formations to an environmental cost index. The strategy for contrail reduction is based on minimizing contrail formations by altering the aircraft's cruising altitude. The strategy uses a user-defined factor to trade off between contrail reduction and additional fuel burn and carbon dioxide emissions. A higher value of tradeoff factor results in more contrail reduction but also more fuel burn and carbon emissions. The strategy is considered favorable when the net environmental cost benefit exceeds the operational cost. The results show how the net environmental benefit varies with different decision-making time-horizon and different carbon cost. The cost models provide a guidance to select the trade-off factor that will result in the most net environmental benefit.

social cost of carbon↗

Three-Dimensional Analysis and Modeling of a Wankel Engine

A new computer code, AGNI-3D, has been developed for the modeling of combustion, spray, and flow properties in a stratified-charge rotary engine (SCRE). The mathematical and numerical details of the new code are described by the first author in a separate NASA publication. The solution procedure is based on an Eulerian-Lagrangian approach where the unsteady, three-dimensional Navier-Stokes equations for a perfect gas-mixture with variable properties are solved in generalized, Eulerian coordinates on a moving grid by making use of an implicit finite-volume, Steger-Warming flux vector splitting scheme. The liquid-phase equations are solved in Lagrangian coordinates. The engine configuration studied was similar to existing rotary engine flow-visualization and hot-firing test rigs. The results of limited test cases indicate a good degree of qualitative agreement between the predicted and measured pressures. It is conjectured that the impulsive nature of the torque generated by the observed pressure nonuniformity may be one of the mechanisms responsible for the excessive wear of the timing gears observed during the early stages of the rotary combustion engine (RCE) development. It was identified that the turbulence intensities near top-dead-center were dominated by the compression process and only slightly influenced by the intake and exhaust processes. Slow mixing resulting from small turbulence intensities within the rotor pocket and also from a lack of formation of any significant recirculation regions within the rotor pocket were identified as the major factors leading to incomplete combustion. Detailed flowfield results during exhaust and intake, fuel injection, fuel vaporization, combustion, mixing and expansion processes are also presented. The numerical procedure is very efficient as it takes 7 to 10 CPU hours on a CRAY Y-MP for one entire engine cycle when the computations are performed over a 31 x16 x 20 grid.

Raju, M. S.↗

Multi-model Comparison of the Volcanic Sulfate Deposition from the 1815 Eruption of Mt. Tambora

The eruption of Mt. Tambora in 1815 was the largest volcanic eruption of the past 500 years. The eruption had significant climatic impacts, leading to the 1816 "year without a summer", and remains a valuable event from which to understand the climatic effects of large stratospheric volcanic sulfur dioxide injections. The eruption also resulted in one of the strongest and most easily identifiable volcanic sulfate signals in polar ice cores, which are widely used to reconstruct the timing and atmospheric sulfate loading of past eruptions. As part of the Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP), five state-of-the-art global aerosol models simulated this eruption. We analyze both simulated background (no Tambora) and volcanic (with Tambora) sulfate deposition to polar regions and compare to ice core records. The models simulate overall similar patterns of background sulfate deposition, although there are differences in regional details and magnitude. However, the volcanic sulfate deposition varies considerably between the models with differences in timing, spatial pattern and magnitude. Mean simulated deposited sulfate on Antarctica ranges from 19 to 264 kgkm-2 and on Greenland from 31 to 194 kgkm-2, as compared to the mean ice-core derived estimates of roughly 50 kgkm-2 for both Greenland and Antarctica. The ratio of the hemispheric atmospheric sulfate aerosol burden after the eruption to the average ice sheet deposited sulfate varies between models by up to a factor of 15. Sources of this inter-model variability include differences in both the formation and the transport of sulfate aerosol. Our results suggest that deriving relationships between sulfate deposited on ice sheets and atmospheric sulfate burdens from model simulations may be associated with greater uncertainties than previously thought.

Marshall, Lauren↗

A Novel Bone Marrow Single Cell Atlas of Mechanotransduction in Microgravity, Normal Gravity, Exercise, and Hindlimb Unloading for WT and CDKN1A-Null Regenerative Mice

Mechanical loading of adult stem cell progenitors is a key factor in modulating their proliferation, differentiation, and tissue regenerative potential, with loading generally promoting tissue formation and unloading mediating tissue loss. To address the role of mechanotransduction in maintaining stem cell-based tissue regenerative health, we generated a single cell transcriptomic atlas mapping responses of femur bone marrow mesenchymal and hematopoietic lineages to a range of altered mechanical loading conditions, both in WT B1629SF2/J mice as well as the p21/CDKN1A-null regenerative mice. We selected the femur marrow compartment as a model because of the diversity and high numbers of stem cell progenitor stages present, and because it undergoes static and cyclic hydrostatic pressure loading associated with weight-bearing and ambulation. Our study included normally loaded mice at 1g, unloading in microgravity during spaceflight as well as tail suspension hindlimb unloading, and voluntary running wheel exercise. Basal, one-year natural aging, and habitat controls were also conducted. Overall, the atlas encompasses 18 different experimental conditions with N=3 mice per condition and includes more than 500,000 single cell expressomes. Key specific findings include: increased mature reticulocyte populations in aging and unloading mice compared to active mice; greater hematopoietic and mesenchymal differentiating progenitors cluster identification in CDKN1A-null samples, especially the exercise model; distinct pseudotime cell trajectory shifts in the hematopoietic lineage for spaceflight and unloaded mice; and shifts in monocytic cell populations toward osteoclastic bone degenerative lineages in unloading and spaceflight samples. Overall mechanical loading shows increased marrow progenitor population differentiation while unloading is associated with increased CDKN1A expression and maintenance of marrow population stemness. Deletion of CDKN1A appears to remove a negative check on progenitor lineages commitment to differentiation. Finally, the Bone Marrow Mechanotransduction Single Cell Atlas will serve as a reference tool for studying marrow regenerative responses across a range of mechanical environments as they relate to CDKN1A status.

single-cell↗