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194 records · Page 11

Modest increased sensitivity to radiation oncogenesis in ATM heterozygous versus wild-type mammalian cells

Subpopulations that are genetically predisposed to radiation-induced cancer could have significant public health consequences. Individuals homozygous for null mutations at the ataxia telangiectasia gene are indeed highly radiosensitive, but their numbers are very small. Ataxia Telangiectasia heterozygotes (1-2% of the population) have been associated with somewhat increased radiosensitivity for some end points, but none directly related to carcinogenesis. Here, intralitter comparisons between wild-type mouse embryo fibroblasts and mouse embryo fibroblasts carrying ataxia telangiectasia mutated (ATM) null mutation indicate that the heterozygous cells are more sensitive to radiation oncogenesis than their normal, litter-matched, counterparts. From these data we suggest that Ataxia Telangiectasia heterozygotes could indeed represent a societally-significant radiosensitive human subpopulation.

Non-NASA Center↗

EPIC Study of Two Enigmatic Sources: The Mouse and SNR 359.1-0.5

The objective of the original proposal was to observe the Mouse pulsar wind nebula (associated with PSR J1744-2958) and the nearby supernova remnant G359.1-0.5, where the pulsar was probably born, with the XMM-Newton observatory to study the properties of these objects. SNR G359.1-0.5 was accepted as a Category C target and has not been observed. The Mouse was observed on April 27,2003 for 52 ks. The image analysis has shown that the Mouse is extended in the East-West direction, possibly along the direction of the pulsar's proper motion. The spectrum of this pulsar wind nebula can be described as an absorbed power law with the photon index GAMMA = 1.9 plus or minus 0.1, effective hydrogen column density n(sub H) = (2.6 plus or minus 0.1) x 10(exp 22) per square centimeter, and flux F = 1.8 x 10(exp -11) erg per square centimeter per second in the 1-10 keV energy range. Based on the n(sub H) value, the distance to the source is about 5 kpc, which results in the luminosity 3.7 x 10(exp 34) erg per second. We conclude that PSR J1744-2958 and the Mouse are not physically associated with G359.1-0.5, which lies at a larger distance. In addition to the Mouse, we also detected two Low-Mass X-ray Binaries, SLX 1744-299 and 1744-300, in the EPIC MOS and PN fields of view. The latter of these objects showed a Type I X-ray burst during our observation, with a rise time of 5 s and decay time of 60 s. A very strong pileup during the burst made the analysis of the burst properties unreliable. The spectral analysis of the persistent radiation from SLX 1744-299 and 1744-300 yields the hydrogen column densities of 3.2 plus or minus 0.1 and (3.6 plus or minus 0.2) x 10(exp 22) per square centimeter, respectively, which suggests that the sources are close to the Galactic center (d = 8-9 kpc). The spectra can be reasonably well fitted with a blackbody plus thin disk model, with the blackbody temperatures of 1.7 plus or minus 0.2 and 1.8 plus or minus 0.2 keV, respectively.

Pavlov, George↗

Fisher's Peak Ecological Forecasting: Mapping Biomass to Inform Conservation Planning of a Future State Park in Southern Colorado

Fisher’s Peak is a 77.5 km2 property southeast of Trinidad, Colorado that is planned to become Colorado’s newest state park. The area has experienced limited anthropogenic disturbance and is home to an abundance of unique habitats and species. A rapid, approximately 900 m change in elevation over the extent of the area nurtures a variety of plants and animals, including the endangered New Mexico meadow jumping mouse. In 2019, the State of Colorado obtained Fisher’s Peak with plans to make it Colorado’s second largest state park. A diverse group of collaborators, including the Colorado State Forest Service and The Nature Conservancy, worked closely to design the state park to maximize recreation opportunity while conserving the property’s rich habitats and biodiversity. The Fisher’s Peak Ecological Forecasting Team utilized Light Detection and Ranging (LiDAR) surveys, in situ forest inventory data, and Earth observations from Landsat8 Operational Land Imager (OLI), Sentinel-1 C-band Synthetic Aperture Radar (C-SAR), Sentinel-2 Multispectral Instrument (MSI), Advanced Land Observing Satellite 2 (ALOS-2) Phased Array type L-band Synthetic Aperture Radar (PALSAR-2) and the Shuttle Radar Topography Mission (SRTM) to quantify and map biomass over the extent of the study area. The results from modeling biomass had an out-of-bag root mean square error of 55 Mg/ha and an R2 of 12. The resulting map indicates areas where carbon storage on the property is high, informing decision-making processes for future park development. While more in situ training data may improve modeling capacity for biomass in the Fisher’s Peak area, this work represents a feasible attempt to better understand biomass distribution using earth observation.

DEVELOP Tech Paper↗

Software Displays Data on Active Regions of the Sun

The Solar Active Region Display System is a computer program that generates, in near real time, a graphical display of parameters indicative of the spatial and temporal variations of activity on the Sun. These parameters include histories and distributions of solar flares, active region growth, coronal mass ejections, size, and magnetic configuration. By presenting solar-activity data in graphical form, this program accelerates, facilitates, and partly automates what had previously been a time-consuming mental process of interpretation of solar-activity data presented in tabular and textual formats. Intended for original use in predicting space weather in order to minimize the exposure of astronauts to ionizing radiation, the program might also be useful on Earth for predicting solar-wind-induced ionospheric effects, electric currents, and potentials that could affect radio-communication systems, navigation systems, pipelines, and long electric-power lines. Raw data for the display are obtained automatically from the Space Environment Center (SEC) of the National Oceanic and Atmospheric Administration (NOAA). Other data must be obtained from the NOAA SEC by verbal communication and entered manually. The Solar Active Region Display System automatically accounts for the latitude dependence of the rate of rotation of the Sun, by use of a mathematical model that is corrected with NOAA SEC active-region position data once every 24 hours. The display includes the date, time, and an image of the Sun in H light overlaid with latitude and longitude coordinate lines, dots that mark locations of active regions identified by NOAA, identifying numbers assigned by NOAA to such regions, and solar-region visual summary (SRVS) indicators associated with some of the active regions. Each SRVS indicator is a small pie chart containing five equal sectors, each of which is color-coded to provide a semiquantitative indication of the degree of hazard posed by one aspect of the activity at the indicated location. The five aspects in question are the history of solar flares, the history of coronal mass ejections, the growth or decay of activity, the overall size, and the magnetic configuration. Mouse-clicking on an active-region-marking dot, SRVS indicator, or NOAA region number causes the program to generate a solar-region summary table (SRT) for the active region in question. The SRT contains additional quantitative and qualitative data, beyond those contained in the SRVS: These data include the solar coordinates of the region, the area of the region and its change in area during the past 24 hours, the change in the number of sunspots in the region during the past 24 hours, the magnetic configuration, and the types, dates, and times of the most recent flare and coronal mass ejection.

Golightly, Mike↗

Fisher's Peak Ecological Forecasting - Mapping Biomass to Inform Conservation Planning of a Future State Park in Southern Colorado

Fisher’s Peak is a 77.5 km2 property southeast of Trinidad, Colorado that is planned to become Colorado’s newest state park. The area has experienced limited anthropogenic disturbance and is home to an abundance of unique habitats and species. A rapid, approximately 900 m change in elevation over the extent of the area nurtures a variety of plants and animals, including the endangered New Mexico meadow jumping mouse. In 2019, the State of Colorado obtained Fisher’s Peak with plans to make it Colorado’s second largest state park. A diverse group of collaborators, including the Colorado State Forest Service and The Nature Conservancy, worked closely to design the state park to maximize recreation opportunity while conserving the property’s rich habitats and biodiversity. The Fisher’s Peak Ecological Forecasting Team utilized Light Detection and Ranging (LiDAR) surveys, in situ forest inventory data, and Earth observations from Landsat 8 Operational Land Imager (OLI), Sentinel-1 C-band Synthetic Aperture Radar (C-SAR), Sentinel-2 Multispectral Instrument (MSI), Advanced Land Observing Satellite 2 (ALOS-2) Phased Array type L-band Synthetic Aperture Radar (PALSAR-2) and the Shuttle Radar Topography Mission (SRTM) to quantify and map biomass over the extent of the study area. The results from modeling biomass had an out-of-bag root mean square error of 55 Mg/ha and an R2 of 12. The resulting map indicates areas where carbon storage on the property is high, informing decision-making processes for future park development. While more in situ training data may improve modeling capacity for biomass in the Fisher’s Peak area, this work represents a feasible attempt to better understand biomass distribution using earth observation

Lauren Lad↗

Developing Open-Source Training Materials for AI/ML and Space Biological Sciences Using NASA Cloud-Based Data

Artificial Intelligence (AI) and Machine Learning (ML) has gained significant traction in the biological and biomedical research fields in the last two decades, in part thanks to an increasing culture of open data sharing and reuse. Due to its capability for identifying complex relationships and patterns, AI/ML methodology is particularly well suited to recognize and predict biological patterns from high-dimensional next-generation sequencing data (e.g. whole genome sequencing, transcriptomic sequencing), as well as from biological or medical imaging data (e.g. microscopy, computed tomography, ultrasound, magnetic resonance imaging, radiography). These methodologies hold particular promise for space biosciences research and automated space health monitoring systems. However, there are many key considerations for properly training, validating, and testing a machine learning model in biological research or clinical application. Even with the positive culture of Open Science and data sharing, inexperienced researchers working quickly without proper checks can produce models that perform poorly outside of the immediate training dataset. Lessons learned from biological AI/ML research indicate that Open Science principles such as data sharing and open-source code must go hand-in-hand with publicly available, high-quality training curricula in best practices, with modules centered on real-life scientific use cases and data so future AI/ML practitioners gain experience on real problems. Here we present the development of open-source training materials for AI/ML and space biosciences, as part of the NASA Transform to Open Science Training (TOPST) initiative. We develop 4 independent training programs, focused on the following topics: 1) Fundamentals of Machine Learning and Space Biosciences Domain, 2) Open Science, Artificial Intelligence, and Ethical Best Practices for Data Sharing and Analysis, 3) Using AI/ML Classification to Identify Gene Networks Affected By Space Exposure in Mouse Liver, and 4) Using Neural Networks to Find DNA Damage Patterns in Immune Cells after Radiation. All programs leverage cloud-based NASA biological datasets. The curriculum we present will enable worldwide access to training in AI/ML and scientific analysis.

James Andrew Casaletto↗

TAE Plus: A conceptual view of TAE in the space station era

The use of the Transportable Applications Executive (TAE) for prototyping user interfaces has been the prime force behind the new TAE research and development work. The Data Systems Technology Division at GSFC is developing prototypes of user interfaces for different functions involved in the operation, analysis and data communication of space station payloads. TAE is a valuable prototyping tool because it enables a developer to build an entire application user interface model and run it without writing a single line of application code. One force driving new development is the need to update TAE's user interface to support the latest interactive graphic device technology. The current TAE, TAE Classic, uses interface techniques designed for an 80x24 character monochrome alphanumeric terminal, but does not effectively utilize features such as windowing, graphics, color, and selection devices available on newer workstations. To meet our needs, development of a TAE Plus began in FY-86 and involves augmenting TAE with three different sets of tools: a user interface toolkit; an application toolkit; and run-time service subroutines. A phased approach is being used to develop TAE Plus. In the first phase, we have met the needs of the user community and provided some support for rapid prototyping by developing a TAE Facelift, which adds an enhanced TAE interface (with windowing, mouse interaction, pull-down menus, etc.) to a select set of graphic workstations. The TAE Facelift allows many new concepts to be tested quickly for feedback and performance. In the second phase, a fully-integrated user interface management system, TAE Plus, will be built that supports the separation of interface from application, with the concomitant ability to prototype and rapidly change interfaces. This robust functionality will support, in an integrated manner, an application's development cycle from the prototype step through to the fully operational system.

Szczur, Martha↗

STRIPE: Remote Driving Using Limited Image Data

Driving a vehicle, either directly or remotely, is an inherently visual task. When heavy fog limits visibility, we reduce our car's speed to a slow crawl, even along very familiar roads. In teleoperation systems, an operator's view is limited to images provided by one or more cameras mounted on the remote vehicle. Traditional methods of vehicle teleoperation require that a real time stream of images is transmitted from the vehicle camera to the operator control station, and the operator steers the vehicle accordingly. For this type of teleoperation, the transmission link between the vehicle and operator workstation must be very high bandwidth (because of the high volume of images required) and very low latency (because delayed images can cause operators to steer incorrectly). In many situations, such a high-bandwidth, low-latency communication link is unavailable or even technically impossible to provide. Supervised TeleRobotics using Incremental Polyhedral Earth geometry, or STRIPE, is a teleoperation system for a robot vehicle that allows a human operator to accurately control the remote vehicle across very low bandwidth communication links, and communication links with large delays. In STRIPE, a single image from a camera mounted on the vehicle is transmitted to the operator workstation. The operator uses a mouse to pick a series of 'waypoints' in the image that define a path that the vehicle should follow. These 2D waypoints are then transmitted back to the vehicle, where they are used to compute the appropriate steering commands while the next image is being transmitted. STRIPE requires no advance knowledge of the terrain to be traversed, and can be used by novice operators with only minimal training. STRIPE is a unique combination of computer and human control. The computer must determine the 3D world path designated by the 2D waypoints and then accurately control the vehicle over rugged terrain. The human issues involve accurate path selection, and the prevention of disorientation, a common problem across all types of teleoperation systems. STRIPE is the only semi-autonomous teleoperation system that can accurately follow paths designated in monocular images on varying terrain. The thesis describes the STRIPE algorithm for tracking points using the incremental geometry model, insight into the design and redesign of the interface, an analysis of the effects of potential errors, details of the user studies, and hints on how to improve both the algorithm and interface for future designs.

REMOTE CONTROL↗

Formation of compact myelin is required for maturation of the axonal cytoskeleton

Although traditional roles ascribed to myelinating glial cells are structural and supportive, the importance of compact myelin for proper functioning of the nervous system can be inferred from mutations in myelin proteins and neuropathologies associated with loss of myelin. Myelinating Schwann cells are known to affect local properties of peripheral axons (de Waegh et al., 1992), but little is known about effects of oligodendrocytes on CNS axons. The shiverer mutant mouse has a deletion in the myelin basic protein gene that eliminates compact myelin in the CNS. In shiverer mice, both local axonal features like phosphorylation of cytoskeletal proteins and neuronal perikaryon functions like cytoskeletal gene expression are altered. This leads to changes in the organization and composition of the axonal cytoskeleton in shiverer unmyelinated axons relative to age-matched wild-type myelinated fibers, although connectivity and patterns of neuronal activity are comparable. Remarkably, transgenic shiverer mice with thin myelin sheaths display an intermediate phenotype indicating that CNS neurons are sensitive to myelin sheath thickness. These results indicate that formation of a normal compact myelin sheath is required for normal maturation of the neuronal cytoskeleton in large CNS neurons.

NASA Discipline Neuroscience↗

Behavioral consequences of radiation exposure to simulated space radiation in the C57BL/6 mouse: open field, rotorod, and acoustic startle

Two experiments were carried out to investigate the consequences of exposure to proton radiation, such as might occur for astronauts during space flight. C57BL/6 mice were exposed, either with or without 15-g/cm2 aluminum shielding, to 0-, 3-, or 4-Gy proton irradiation mimicking features of a solar particle event. Irradiation produced transient direct deficits in open-field exploratory behavior and acoustic startle habituation. Rotorod performance at 18 rpm was impaired by exposure to proton radiation and was impaired at 26 rpm, but only for mice irradiated with shielding and at the 4-Gy dose. Long-term (>2 weeks) indirect deficits in open-field activity appeared as a result of impaired experiential encoding immediately following exposure. A 2-week recovery prior to testing decreased most of the direct effects of exposure, with only rotorod performance at 26 rpm being impaired. These results suggest that the performance deficits may have been mediated by radiation damage to hippocampal, cerebellar, and possibly, forebrain dopaminergic function.

Non-NASA Center↗

A gradient in the duration of the G1 phase in the murine neocortical proliferative epithelium

Neuronogenesis in the neocortical pseudostratified ventricular epithelium (PVE) is initiated rostrolaterally and progresses caudo-medially as development progresses. Here we have measured the cytokinetic parameters and the fractional neuronal output parameter, Q, of laterally located early-maturing regions over the principal embryonic days (E12-E15) of neocortical neuronogenesis in the mouse. These measures are compared with ones previously made of a medial, late-maturing portion of the PVE. Laterally, as medially, the duration of the neuronogenetic interval is 6 days and comprises 11 integer cell cycles. Also, in both lateral and medial areas the length of G1 phase (TG1) increases nearly 4-fold and is the only cell cycle parameter to change. Q progresses essentially identically laterally and medially with respect to the succession of integer cell cycles. Most importantly, from E12 to E13 there is a steeply declining lateral to medial gradient in TG1. The gradient is due both to the lateral to medial graded stage of neuronogenesis and to the stepwise increase in TG1 with each integer cycle during the neuronogenetic interval. To our knowledge this gradient in TG1 of the cerebral PVE is the first cell biological gradient to be demonstrated experimentally in such an extensive proliferative epithelial sheet. We suggest that this gradient in TG1 is the cellular mechanism for positionally encoding a protomap of the neocortex within the PVE.

Non-NASA Center↗

Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as upstream targets for the effects of weightlessness. In the past year we have determined that the expression of E Proteins is restricted to specific fiber types by post-transcriptional mechanisms. By far, the most prevalent mechanism of cellular control for achieving post-transcriptional regulation of gene expression is selective proteolysis -through the ubiquitin -proteasome pathway. Steady-state levels of HEB message are similar in all fast and slow skeletal muscle fiber types, yet the protein is restricted to Type IIX fibers. HEB appears to be a nodal point for regulating fiber-specific transcription, as expression of the transcription factor is regulated at the post-transcriptional level. It is not clear at present whether the regulation is at the level of protein synthesis or degradation. We are now poised to evaluate the biological role of ubiquitination in fiber specific-gene expression by controlling the post-transcriptional expression of E Proteins. The use of metabolic labelling and pharmacological inhibitors of the ubiquitin pathway will be used to identify the mode of regulation of the Type IIX expression pattern. The potential role of specific kinases in effecting the restriction of HEB expression will be examined by using both inhibitors and activators. The results of these studies will provide the necessary information to evaluate the biological role of E proteins in controlling fiber type transitions, and in potentially attenuating the atrophic effects of microgravity conditions. We have also recently shown that ectopic expression of the HEB protein transactivates the Type IIX-specific skeletal a-actin reporter. The 218 bp skeletal a-actin promoter drives transgene expression solely in mature Type IIX fibers. A mouse also carrying the transgene MLCI/HEB (which ectopically expresses the E Protein HEB in Type IIB fibers) forces expression of the skeletal a-actin reporter gene in Type IIB fibers. We can now dissect the composition of this fiber-specific cis-element. The skeletal a-actin promoter is quite compact and has been extensively characterized in vitro for activity and binding factors. The single E box may act as a binding target of myogenic factor/HEB heterodimer to allow for IIX expression. The HEB transcription factor may recognize either the precise flanking sequences of the E Box, or perhaps interacting with other proteins bound nearby, and activating expression in Type IIX fibers. This E box will be both ablated, and alternatively, as ablation may well destroy any muscle-specific transcriptional activity, flanking sequences substituted with those surrounding the E box (El) of the myogenin promoter. Modification of fiber-specific transgene expression will be tested in transgenic mice. The results of these studies will provide basic information on the regulatory circuitry underlying fiber specificity, and will form the basis for building appropriate transgenic regulatory cassettes to effect fiber transitions in subsequent experimental manipulations on unweighted muscles.

Rosenthal, Nadia A.↗

Murine Spine Composition and Mechanics are Maintained After 30-Days of Spaceflight

As NASA prepares to send astronauts on deep space missions, understanding the detrimental effects of spaceflight on the body is imperative. Spaceflight is known to negatively affect the spine, with astronauts experiencing systemic bone loss and increased post-flight risk of intervertebral disc herniation. Space investigations with rodent models have characterized some of the effects of spaceflight on the mammalian body, but variable experimental conditions have made it difficult to cohesively interpret results. These conditions include housing, flight duration, and for the spine, anatomical location. Thus, the objective of this study was to comprehensively characterize the effects of spaceflight on the bulk properties of the murine lumbar spine. To do this, we examined the lumbar spine of mice flown on the NASA Rodent Research 10 mission and analyzed disc biochemical content, disc joint material properties, lumbar vertebral body microarchitecture, and proximal tibia microarchitecture. Finally, we qualitatively examined bone growth in the vertebral bodies using confocal microscopy and on-orbit injections of calcein. Contrary to prior results, we found little to no effect of spaceflight on lumbar spine properties. Spaceflight, however, did negatively affect both cortical and trabecular bone properties of the proximal tibia load-bearing site. We hypothesize that this may be due to loading associated with increased physical activity in the second half of the mission, observed on in-flight videos, that reload the lumbar spine as mice utilize quadruped ambulation. This increased activity occurs after an initial period of relative inactivity in microgravity. In support of this hypothesis, we observed new L5 bone formation in the last seven days of spaceflight, suggesting that current 30-day experimental flight conditions may not be as effective at lumbar spine unloading as previous shorter flights.

mouse↗

Population dynamics during cell proliferation and neuronogenesis in the developing murine neocortex

During the development of the neocortex, cell proliferation occurs in two specialized zones adjacent to the lateral ventricle. One of these zones, the ventricular zone, produces most of the neurons of the neocortex. The proliferating population that resides in the ventricular zone is a pseudostratified ventricular epithelium (PVE) that looks uniform in routine histological preparations, but is, in fact, an active and dynamically changing population. In the mouse, over the course of a 6-day period, the PVE produces approximately 95% of the neurons of the adult neocortex. During this time, the cell cycle of the PVE population lengthens from about 8 h to over 18 h and the progenitor population passes through a total of 11 cell cycles. This 6-day, 11-cell cycle period comprises the "neuronogenetic interval" (NI). At each passage through the cell cycle, the proportion of daughter cells that exit the cell cycle (Q cells) increases from 0 at the onset of the NI to 1 at the end of the NI. The proportion of daughter cells that re-enter the cell cycle (P cells) changes in a complementary fashion from 1 at the onset of the NI to 0 at the end of the NI. This set of systematic changes in the cell cycle and the output from the proliferative population of the PVE allows a quantitative and mathematical treatment of the expansion of the PVE and the growth of the cortical plate that nicely accounts for the observed expansion and growth of the developing neocortex. In addition, we show that the cells produced during a 2-h window of development during specific cell cycles reside in a specific set of laminae in the adult cortex, but that the distributions of the output from consecutive cell cycles overlap. These dynamic events occur in all areas of the PVE underlying the neocortex, but there is a gradient of maturation that begins in the rostrolateral neocortex near the striatotelencephalic junction and which spreads across the surface of the neocortex over a period of 24-36 h. The presence of the gradient across the hemisphere is a possible source of positional information that could be exploited during development to establish the areal borders that characterize the adult neocortex.

Non-NASA Center↗