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At least 253 records · Page 14

Atg12 Maintains Skeletal Integrity by Modulating Pro-Osteoclastogenic Signals and Chondrocyte Differentiation

Weightlessness and radiation, two unique elements of space, profoundly decreases bone mass. We aimed to elucidate the role of autophagy in maintaining structural integrity of the skeleton. We hypothesize that loss of autophagy in bone leads to an imbalance in pro-osteoclastogenic and pro-osteogenic signals, resulting in net bone loss. To test our hypothesis, we performed global postnatal deletion of Atg12 using tamoxifen-inducible Cre. Compared to Vehicle (Control) groups, Tamoxifen (Atg12 iKO) groups showed decreased LC3B-I to II conversion and increased p62 protein levels, consistent with loss of autophagy. qPCR revealed increased expression of pro-osteoclastogenic cytokines in bone and marrow respectively in male iKOs compared to controls. Microcomputed tomography revealed decreased cortical bone volume, cortical thickness and periosteal perimeter consistent with bone loss; and a longer primary spongiosa in male Atg12 iKOs display compared to male controls. Histology showed that compared to male controls, male iKOs had a profound increase in chondrocyte column length of the growth plate with hyper-expansion of both proliferating and hypertrophic zones. Taken together, these findings indicate that autophagy plays an important role in the maintenance of bone structural integrity by mediating the production of pro-osteoclastogenic signals and regulating chondrocyte proliferation and differentiation.

Atg12↗

Mitochondrial Oxidative Stress: Importance for Skeletal Structure and Responses to Simulated Spaceflight

Spaceflight environment poses challenges to the human body. Both microgravity and radiation may lead to excess production of reactive oxygen species (ROS) and resulting oxidative stress and tissue damage. Specifically in bone, elevated ROS can contribute to excess bone resorption by osteoclasts over bone formation by osteoblasts, reduced viability of osteocytes, and ultimately, osteoporosis. Thus, we hypothesized that suppression of mitochondrial ROS in bone cells improves overall bone structure in the adult skeleton and skeletal defenses from spaceflight. To begin to test our hypothesis, we (1) modified ROS levels in bone cells using mCAT (Malonyl CoA-acyl carrier protein transacylase) mice, which overexpress the human anti-oxidant catalase gene targeted to the mitochondria. We also increased ROS and stimulated skeletal remodeling by exposing mice to simulated spaceflight (hindlimb-unloading and total body-irradiation) or sham treatment. When challenged with treatment, bones from wildtype mice showed elevated levels of oxidative damage whereas mCAT mice did not. Treatment caused expected bone loss in wildtype mice. Treatment caused deficits in microarchitecture of mCAT mice, although lower in magnitude than wildtype. In conclusion, our results indicate mitochondrial ROS generation in osteoblast and osteoclast lineage cells of skeletal tissue contributes to skeletal remodeling and quenching oxidative damage may improve the skeletal responses to spaceflight.

Radiation↗

To the Bone: Spaceflight and the Skeletal System

During spaceflight, astronauts experience weightlessness and are exposed to novel types of radiation. These environmental conditions may contribute to bone loss and reduction of structural integrity of the skeleton, which have negative implications for long-duration missions. The aim of this talk is to provide an overview of skeletal changes observed both in astronauts and in ground-based models of spaceflight, focusing on the fundamental biology and the prevention of deleterious skeletal changes.

Alwood, Joshua↗

Does Simulated Weightlessness Alter the Methylation Status of Gene Promoters During Bone Remodeling?

The skeleton interacts with its environment in a way that resembles a mechanostat - through a controlled process of bone remodeling, namely local formation and resorption, to maintain a healthy structure. During weightlessness, astronauts lose structure in weight-bearing bones due to decreased formation by osteoblasts and increased resorption by osteoclasts. In contrast, increased mechanical loading through exercise targets bone remodeling to remove and repair microdamage, improving structural integrity. In fact, recent advances in astronaut exercise regimens have prevented the deleterious changes in skeletal structure during spaceflight. However, knowledge of the molecular underpinnings of the skeletal response to spaceflight and to mechanical stimulation is limited. We propose that epigenetic modification, specifically DNA methylation, may influence osteoblast differentiation and activity during spaceflight and exercise. We hypothesize that simulated weightlessness hypermethylates pro-osteoblastogenic gene promoters and decreases expression of osteoblastogenic genes. Oppositely, we hypothesize that mechanical loading hypomethylates pro-osteoblastogenic gene promoters and increases expression of osteoblastogenic genes.

Stevick, Rebecca J.↗

L’Ralph Integration and Testing

This paper describes the plans, flows, key facilities, components and equipment necessary to fully integrate, functionally test, qualify and calibrate the L’Ralph instrument on the Lucy observatory. Lucy is currently in the final design and fabrication phase (phase C) of mission development. It is scheduled to launch out of Cape Canaveral, Florida, in October 2021. Lucy will be the first space mission to study the Trojan asteroids associated with Jupiter, that are thought to be remnants of the primordial material that formed the outer planets. Lucy will fly by and carry out remote sensing on six different Trojan asteroids. The mission takes its name from the fossilized human ancestor (called “Lucy” by her discoverers) whose skeleton provided unique insight into humanity's evolution. Likewise, the Lucy mission will revolutionize our knowledge of planetary origins and the formation of the solar system. L’Ralph is one of the instruments on Lucy and it is provided by the NASA Goddard Space Flight Center (GSFC). L’Ralph is a combined multi-band visible imager (the Multi-spectral Visible Imaging Camera, MVIC, 0.4-0.85 microns) and wedge-filter infrared spectrometer (Linear Etalon Imaging Spectral Array, LEISA, 1-3.6 microns). LEISA will allow the team to look for the absorption lines that serve as the fingerprints for different silicates, ices and organics that likely will be on the surface of the Trojan asteroids. MVIC will take color images of the Trojan asteroid targets, and help determine how active they are. This paper will focus on the Integration and Test (I&T) activities for L’Ralph while it is at the NASA GSFC. L’Ralph has two assemblies, the telescope detector assembly (TDA) and main electronics box (MEB). The TDA is a single telescope feeding two focal planes, MVIC and LEISA. L’Ralph integration consists of assembly and alignment of the telescope, electronics box integration, thermal systems integration and the final assembly and testing. This I&T phase will be followed by the L’Ralph calibration and characterization, environmental tests which include electromagnetic interference (EMI)/electromagnetic compatibility (EMC), vibration with sine sweep, acoustics, shock, thermal balance, thermal vacuum, mass properties and center of gravity determination. This paper will briefly discuss L’Ralph shipment and delivery to the spacecraft vendor for observatory level I&T as well as some launch preparation activities.

Spaceflight Instruments↗

Cavity Ring Down Spectroscopy of Cold Neutral Phenanthrene and Phenanthridine in Supersonic Jets

Here we study the effect of nitrogen insertion on the electronic spectra of polycyclic aromatic hydrocarbon (PAH) molecules measured under laboratory conditions that are relevant for comparison with astronomical data. We examine the case of the substitution of carbon atoms by nitrogen atoms in the benzenoid skeleton of phenanthrene (C 14 H 10 ), a prototype non-compact PAH. The vibronic transitions of the 2 1 A 1 (S 1 )←X 1 A 1 (S 0 ) electronic absorption band system of neutral phenanthrene (C 14 H 10 ) and phenanthridine (C 13 H 9 N) molecules seeded in a supersonic free jet expansion of argon gas are measured in the 315-345 nm region using the cavity ring down spectroscopy (CRDS) technique. Additional measurements of the absorption spectra of the phenanthrene, phenanthridine, and 1,10-phenanthroline (C 12 H 8 N 2 ) molecules isolated in 10-K solid argon matrices are also presented. The results obtained confirm that laboratory spectra of cold, isolated molecules obtained under astrophysically relevant conditions are required for a direct, unambiguous comparison with astronomical observations as well as for the understanding of the physical evolution of the interstellar medium.

Absorption band↗

Simulation of Solar-Induced Chlorophyll Fluorescence from 3D Canopies with the Dart Model

The potential of solar-induced chlorophyll fluorescence (SIF) to monitor photosynthesis and plant stress has attracted considerable interest in SIF remote sensing (RS). However, canopy SIF and RS observations are impacted by topography, vegetation three dimension (3D) structure, leaf orientation, non foliar elements (e.g., tree woody skeleton), ... Physically based downscaling of canopy SIF RS data to leaf-level (i.e., to leaf photosynthesis) requires 3D radiative transfer (RT) models simulating canopy SIF and its observation. These models are necessary to better exploit the potential of SIF, by linking leaf SIF and SIF in RS observations as a function of canopy 3D architecture and experimental configurations (sun and viewing directions, etc.). The Discrete Anisotropic Radiative Transfer (DART) model is a comprehensive 3D radiative transfer (RT) model for urban and natural landscapes. This paper presents its SIF modeling for vegetation simulated with facets, its validation with the SCOPE/mSCOPE 1D models, and its recent extension to SIF modelling for landscapes simulated with 3D turbid medium.

radiative transfer↗

Simulation of Solar-Induced Chlorophyll Fluorescence from 3D Canopies with the Dart Model

The potential of solar-induced chlorophyll fluorescence (SIF) to monitor photosynthesis and plant stress has attracted considerable interest in SIF remote sensing (RS). However, canopy SIF and RS observations are impacted by topography, vegetation three dimension (3D) structure, leaf orientation, non foliar elements (e.g., tree woody skeleton), ... Physically based downscaling of canopy SIF RS data to leaf-level (i.e., to leaf photosynthesis) requires 3D radiative transfer (RT) models simulating canopy SIF and its observation. These models are necessary to better exploit the potential of SIF, by linking leaf SIF and SIF in RS observations as a function of canopy 3D architecture and experimental configurations (sun and viewing directions, etc.). The Discrete Anisotropic Radiative Transfer (DART) model is a comprehensive 3D radiative transfer (RT) model for urban and natural landscapes. This paper presents its SIF modeling for vegetation simulated with facets, its validation with the SCOPE/mSCOPE 1D models, and its recent extension to SIF modelling for landscapes simulated with 3D turbid medium.

Radiative transfer↗

Data-constrained Solar Modeling with GX Simulator

To facilitate the study of solarflares and active regions, we have created a modeling framework, the freelydistributed GX Simulator IDL package, that combines 3D magnetic and plasma structures with thermal andnonthermal models of the chromosphere, transition region, and corona. Its object-based modular architecture,which runs on Windows, Mac, and Unix/Linux platforms, offers the ability to either import 3D density andtemperature distribution models, or to assign numerically defined coronal or chromospheric temperatures anddensities, or their distributions, to each individual voxel. GX Simulator can apply parametric heating modelsinvolving average properties of the magneticfield lines crossing a given voxel, as well as compute and investigatethe spatial and spectral properties of radio,(sub)millimeter, EUV, and X-ray emissions calculated from the model,and quantitatively compare them with observations. The package includes a fully automatic model productionpipeline that, based on minimal users input, downloads the required SDO/HMI vector magneticfield data,performs potential or nonlinear force-freefield extrapolations, populates the magneticfield skeleton withparameterized heated plasma coronal models that assume either steady-state or impulsive plasma heating, andgenerates non-LTE density and temperature distribution models of the chromosphere that are constrained byphotospheric measurements. The standardized models produced by this pipeline may be further customizedthrough specialized IDL scripts, or a set of interactive tools provided by the graphical user interface. Here, wedescribe the GX Simulator framework and its applications.

Solar active regions↗

Assessing the Added Value of Miniature X-Ray in the Setting of Portable Ultrasound in Spaceflight

INTRODUCTION: Point-of-care ultrasound (POCUS) has become the standard of care for imaging diagnosis and management in low-Earth Orbit (LEO) spaceflight and it has long been hypothesized that POCUS will also be the standard of care for exploration spaceflight. However, like the trajectory for which ultrasound became more portable and user-friendly, the mass, volume, and power requirements of radiography devices for both diagnostic and therapeutic applications have also been dramatically reduced. This study seeks to determine the clinical utility and added value of miniature x-ray (XR) for the diagnosis and management of each of the 119 conditions within NASA Exploration Medical Capability’s IMPACT Condition List (ICL) given that the medical system is presumed to already be carrying a handheld portable POCUS device. METHODS: For each condition, a team of reviewers performed a rapid systematic literature review seeking sensitivity and specificity data for both handheld portable ultrasound and miniature XR. When there was a paucity of data, subject matter expertise and clinical experience was added to semi-quantitatively score the added value of miniature XR, given an US was already available for both diagnosis and management. Diagnostic utility of a modality for a condition was evaluated in the setting of both the best- and worst-case scenario definitions included and defined by the ICL. Evidence tracing and quality of evidence scores were also recorded. RESULTS/DISCUSSION: Conditions for which it was determined that miniature XR added diagnostic or therapeutic value are provided in this presentation. Previously presented work by our team has demonstrated that XR provides diagnostic and management capabilities that are hypothesized to complement or surpass ultrasound for over one-third of medical conditions that may arise during exploration spaceflight (i.e., diagnosis of injuries to the axial skeleton, teeth, and lungs as well as management of orthopedic reductions, endotracheal tube placement, and drain placement confirmation). In the setting of known inclusion of a handheld portable POCUS device, there remains significant added value of portable miniature XR. Whether or not this added clinical benefit is worth the mass, volume, and power requirements of the radiography system remains yet unknown and is the focus of future work. LEARNING OBJECTIVES: 1) Understand the value of ultrasound and radiography in the diagnosis and management of medical comorbidities that may arise in exploration spaceflight; 2) Understand the medical conditions of highest concern on exploration class missions for which miniature x-ray may provide added value to portable ultrasound.

J G Steller↗

Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

BACKGROUND . Calculated loss rates in trabecular (Trb) volumetric bone mineral density (vBMD), in astronauts after return from 6-month long-duration (LD) spaceflight, are rapid relative to menopause-induced loss rates and could contribute to the observed lack of recovery. Perforations in the Trb bony struts, skeletal fragility and fractures [5] have been associated with the rapid rate of bone loss in women due to menopause. The more rapid loss rate observed in astronauts could be inducing similar, irreversible losses of trabecular connectivity as seen in cadaver studies of female skeletons. These changes are not detectable by DXA technology and would not be discovered in astronauts during scheduled, triennial DXA testing for primary osteoporosis. High-resolution-peripheral quantitative computed tomography (HR-pQCT) of the lower leg have detected losses in Trb vBMD (vBMD) and changes in Trb microarchitecture (µArch) in astronauts immediately following routine 6-month spaceflights and continuing in some individuals for 1 or more years postflight with no signs of recovery. Resolution of these microarchitectural changes by whole body QCT, especially in the deeply embedded hip bone, is prohibitive due to excessive and unsafe radiation exposures. While HR-pQCT has sufficient resolution to study Trb µArch at safe and lower radiation exposure testing is restricted only to the lower leg and wrist. Hence, a technology to detect detrimental changes to Trb µArch in astronauts, especially of the hip, is needed to inform type and timing of countermeasures to irreversible deficits (preflight, inflight and postflight). METHODS . This HRP-funded study (2023-2027) will verify the sensitivity of a protocol for MRI scanning (on a 3T Siemens Vida) to detect changes to hip Trb µArch in persons following spinal cord injury (SCI); skeletal immobilization below the spinal lesion will serve as an analog for non-weight-bearing during spaceflight. The study period has been extended by 1 yr due to delayed Richmond IRB approval in Y1. A 3T MRI protocol will characterize serial changes in hip Trb µArch in SCI patients from time of admission at the Richmond VA Medical Center to their scheduled annual exam 12-months later. SCI patients with age, sex, and physical characteristics like ISS astronauts will be consented. The ability of 3T MRI hip scan to discriminate loss of trabecular connectivity subjects with SCI will be compared to age- and sex-matched ambulatory controls. A comparison between HR-pQCT and MRI measurements at the ankle (distal tibia) of study subjects will also be performed. A modified DXA scan analysis (3D-Shaper) will also be verified as a potential method for monitoring concurrent changes in hip Trb bone over 12-month. SIGNIFICANCE . Deliverables: a surveillance method for assessing for irreversible losses of connectivity and how skeletal changes after LD spaceflight(s) would modify the terrestrial risk of primary osteoporosis.

Spinal Cord Injury↗

Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

BACKGROUND . Calculated loss rates in trabecular (Trb) volumetric bone mineral density (vBMD), in astronauts after return from 6-month long-duration (LD) spaceflight, are rapid relative to menopause-induced loss rates and could contribute to the observed lack of recovery. Perforations in the Trb bony struts, skeletal fragility and fractures [5] have been associated with the rapid rate of bone loss in women due to menopause. The more rapid loss rate observed in astronauts could be inducing similar, irreversible losses of trabecular connectivity as seen in cadaver studies of female skeletons. These changes are not detectable by DXA technology and would not be discovered in astronauts during scheduled, triennial DXA testing for primary osteoporosis. High-resolution-peripheral quantitative computed tomography (HR-pQCT) of the lower leg have detected losses in Trb vBMD (vBMD) and changes in Trb microarchitecture (µArch) in astronauts immediately following routine 6-month spaceflights and continuing in some individuals for 1 or more years postflight with no signs of recovery. Resolution of these microarchitectural changes by whole body QCT, especially in the deeply embedded hip bone, is prohibitive due to excessive and unsafe radiation exposures. While HR-pQCT has sufficient resolution to study Trb µArch at safe and lower radiation exposure testing is restricted only to the lower leg and wrist. Hence, a technology to detect detrimental changes to Trb µArch in astronauts, especially of the hip, is needed to inform type and timing of countermeasures to irreversible deficits (preflight, inflight and postflight). METHODS . This HRP-funded study (2023-2027) will verify the sensitivity of a protocol for MRI scanning (on a 3T Siemens Vida) to detect changes to hip Trb µArch in persons following spinal cord injury (SCI); skeletal immobilization below the spinal lesion will serve as an analog for non-weight-bearing during spaceflight. The study period has been extended by 1 yr due to delayed Richmond IRB approval in Y1. A 3T MRI protocol will characterize serial changes in hip Trb µArch in SCI patients from time of admission at the Richmond VA Medical Center to their scheduled annual exam 12-months later. SCI patients with age, sex, and physical characteristics like ISS astronauts will be consented. The ability of 3T MRI hip scan to discriminate loss of trabecular connectivity subjects with SCI will be compared to age- and sex-matched ambulatory controls. A comparison between HR-pQCT and MRI measurements at the ankle (distal tibia) of study subjects will also be performed. A modified DXA scan analysis (3D-Shaper) will also be verified as a potential method for monitoring concurrent changes in hip Trb bone over 12-month. SIGNIFICANCE . Deliverables: a surveillance method for assessing for irreversible losses of connectivity and how skeletal changes after LD spaceflight(s) would modify the terrestrial risk of primary osteoporosis.

Risk Surveillance↗

Assessing the Added Value of Miniature X-Ray in the Setting of US in Spaceflight

INTRODUCTION: Point-of-care ultrasound (POCUS) has become the standard of care for imaging diagnosis and management in lowEarth Orbit (LEO) spaceflight and it has long been hypothesized that POCUS will also be the standard of care for exploration spaceflight. However, like the trajectory for which ultrasound became more portable and user-friendly, the mass, volume, and power requirements of radiography devices for both diagnostic and therapeutic applications have also been dramatically reduced. This study seeks to determine the clinical utility and added value of miniature x-ray (XR) for the diagnosis and management of each of the 119 conditions within NASA Exploration Medical Capability’s IMPACT Condition List (ICL) given that the medical system is presumed to already be carrying a handheld portable POCUS device. METHODS: For each condition, a team of reviewers performed a rapid systematic literature review seeking sensitivity and specificity data for both handheld portable ultrasound and miniature XR. When there was a paucity of data, subject matter expertise and clinical experience was added to semi-quantitatively score the added value of miniature XR, given an US was already available for both diagnosis and management. Diagnostic utility of a modality for a condition was evaluated in the setting of both the best- and worst-case scenario definitions included and defined by the ICL. Evidence tracing and quality of evidence scores were also recorded. RESULTS/DISCUSSION: Conditions for which it was determined that miniature XR added diagnostic or therapeutic value are provided in this presentation. Previously presented work by our team has demonstrated that XR provides diagnostic and management capabilities that are hypothesized to complement or surpass ultrasound for over one-third of medical conditions that may arise during exploration spaceflight (i.e., diagnosis of injuries to the axial skeleton, teeth, and lungs as well as management of orthopedic reductions, endotracheal tube placement, and drain placement confirmation). In the setting of known inclusion of a handheld portable POCUS device, there remains significant added value of portable miniature XR. Whether or not this added clinical benefit is worth the mass, volume, and power requirements of the radiography system remains yet unknown and is the focus of future work. LEARNING OBJECTIVES: 1) Understand the value of ultrasound and radiography in the diagnosis and management of medical comorbidities that may arise in exploration spaceflight; 2) Understand the medical conditions of highest concern on exploration class missions for which miniature x-ray may provide added value to portable ultrasound.

Jon Steller↗

Raven: An On-Orbit Relative Navigation Demonstration Using International Space Station Visiting Vehicles

Since the last Hubble Servicing Mission five years ago, the Satellite Servicing Capabilities Office (SSCO) at the NASA Goddard Space Flight Center (GSFC) has been focusing on maturing the technologies necessary to robotically service orbiting legacy assets-spacecraft not necessarily designed for in-flight service. Raven, SSCO's next orbital experiment to the International Space Station (ISS), is a real-time autonomous non-cooperative relative navigation system that will mature the estimation algorithms required for rendezvous and proximity operations for a satellite-servicing mission. Raven will fly as a hosted payload as part of the Space Test Program's STP-H5 mission, which will be mounted on an external ExPRESS Logistics Carrier (ELC) and will image the many visiting vehicles arriving and departing from the ISS as targets for observation. Raven will host multiple sensors: a visible camera with a variable field of view lens, a long-wave infrared camera, and a short-wave flash lidar. This sensor suite can be pointed via a two-axis gimbal to provide a wide field of regard to track the visiting vehicles as they make their approach. Various real-time vision processing algorithms will produce range, bearing, and six degree of freedom pose measurements that will be processed in a relative navigation filter to produce an optimal relative state estimate. In this overview paper, we will cover top-level requirements, experimental concept of operations, system design, and the status of Raven integration and test activities.

Rendezvous↗

Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

Entry into low earth orbit and beyond causes profound shifts in environmental conditions that have the potential to influence human productivity, long term health, and even survival. We now have evidence that microgravity, radiation and/or confinement in space can lead to demonstrably detrimental changes in the cardiovascular (e.g. vessel function, orthostatic intolerance), musculoskeletal (muscle atrophy, bone loss) and nervous (eye, neurovestibular) systems of astronauts. Because of both the limited number of astronauts who have flown (especially females) and the high degree of individual variability in the human population, important unanswered questions about responses to the space environment remain: What are the sex differences with respect to specific physiological systems? Are the responses age-dependent and/or reversible after return to Earth? Do observed detrimental changes that resemble accelerated aging progress continuously over time or plateau? What are the mechanisms of the biological responses? Answering these important questions certainly demands a multi-pronged approach, and the study of multicellular model organisms (such as rodents and flies) already has provided opportunities for exploring those questions in some detail. Recent long duration spaceflight experiments with rodents show that mice in space provide a mammalian model that uniquely combines the influence of reduced gravitational loading with increased physical activity. In addition, multiple investigators have shown that ground-based models that simulate aspects of spaceflight (including rodent hind limb unloading to mimic weightlessness and exposure to ionizing radiation), cause various transient and persistent detrimental consequences in multiple physiological systems. In general, we have found that adverse skeletal effects of simulated weightlessness and space radiation when combined, can be quantitatively, if not qualitatively, different from the influence of each environmental factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

skeleton↗