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At least 937 records · Page 52

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.

Non-NASA Center↗

Carotid baroreflex response following 30 days exposure to simulated microgravity

The mechanism of the carotid-baroreflex response to weightlessness was investigated in human subjects exposed to simulated microgravity (30 days of 6-day head-down bed rest followed by 5 days of recovery). Baroreceptor-cardiac reflex responses were elicited by a complex sequence of pressure changes delivered to a neck chamber device. The shape of the sigmoid baroreceptor-cardiac response curve was examined for alterations and the occurrence of resetting, as well as for a possible association of the impaired baroreflex function with hypotension during the postexposure orthostatic stress. It was found that the exposure to head-down bed rest caused a significant shift on the R-R interval axis, which paralleled reductions and elevations in baseline HR such that the baseline R-R (operational point) remained in the same position on the response curve. This shift in the location of the reflex relation indicates a significant resetting of the carotid baroreceptors, which may represent an appropriate adaptation which contributes to the maintenance of a constant resting arterial blood pressure before, during, and after bed rest, observed in these study.

Convertino, V. A.↗

Human Thermal Model Evaluation Using the JSC Human Thermal Database

Human thermal modeling has considerable long term utility to human space flight. Such models provide a tool to predict crew survivability in support of vehicle design and to evaluate crew response in untested space environments. It is to the benefit of any such model not only to collect relevant experimental data to correlate it against, but also to maintain an experimental standard or benchmark for future development in a readily and rapidly searchable and software accessible format. The Human thermal database project is intended to do just so; to collect relevant data from literature and experimentation and to store the data in a database structure for immediate and future use as a benchmark to judge human thermal models against, in identifying model strengths and weakness, to support model development and improve correlation, and to statistically quantify a model s predictive quality. The human thermal database developed at the Johnson Space Center (JSC) is intended to evaluate a set of widely used human thermal models. This set includes the Wissler human thermal model, a model that has been widely used to predict the human thermoregulatory response to a variety of cold and hot environments. These models are statistically compared to the current database, which contains experiments of human subjects primarily in air from a literature survey ranging between 1953 and 2004 and from a suited experiment recently performed by the authors, for a quantitative study of relative strength and predictive quality of the models.

Bue, Grant↗

Plasticity of the human otolith-ocular reflex

The eye movement response to earth vertical axis rotation in the dark, a semicircular canal stimulus, can be altered by prior exposure to combined visual-vestibular stimuli. Such plasticity of the vestibulo-ocular reflex has not been described for earth horizontal axis rotation, a dynamic otolith stimulus. Twenty normal human subjects underwent one of two types of adaptation paradigms designed either to attenuate or enhance the gain of the semicircular canal-ocular reflex prior to undergoing otolith-ocular reflex testing with horizontal axis rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about a vertical axis with a 0.2 Hz optokinetic stripe pattern that was deliberately mismatched in peak velocity. Pre- and post-adaptation horizontal axis rotations were at 60 degrees/s in the dark and produced a modulation in the slow component velocity of nystagmus having a frequency of 0.17 Hz due to putative stimulation of the otolith organs. Results showed that the magnitude of this modulation component response was altered in a manner similar to the alteration in semicircular canal-ocular responses. These results suggest that physiologic alteration of the vestibulo-ocular reflex using deliberately mismatched visual and semicircular canal stimuli induces changes in both canal-ocular and otolith-ocular responses. We postulate, therefore, that central nervous system pathways responsible for controlling the gains of canal-ocular and otolith-ocular reflexes are shared.

Non-NASA Center↗

Telerobotics Workstation (TRWS) for Deep Space Habitats

On medium- to long-duration human spaceflight missions, latency in communications from Earth could reduce efficiency or hinder local operations, control, and monitoring of the various mission vehicles and other elements. Regardless of the degree of autonomy of any one particular element, a means of monitoring and controlling the elements in real time based on mission needs would increase efficiency and response times for their operation. Since human crews would be present locally, a local means for monitoring and controlling all the various mission elements is needed, particularly for robotic elements where response to interesting scientific features in the environment might need near- instantaneous manipulation and control. One of the elements proposed for medium- and long-duration human spaceflight missions, the Deep Space Habitat (DSH), is intended to be used as a remote residence and working volume for human crews. The proposed solution for local monitoring and control would be to provide a workstation within the DSH where local crews can operate local vehicles and robotic elements with little to no latency. The Telerobotics Workstation (TRWS) is a multi-display computer workstation mounted in a dedicated location within the DSH that can be adjusted for a variety of configurations as required. From an Intra-Vehicular Activity (IVA) location, the TRWS uses the Robot Application Programming Interface Delegate (RAPID) control environment through the local network to remotely monitor and control vehicles and robotic assets located outside the pressurized volume in the immediate vicinity or at low-latency distances from the habitat. The multiple display area of the TRWS allows the crew to have numerous windows open with live video feeds, control windows, and data browsers, as well as local monitoring and control of the DSH and associated systems.

Mittman, David S.↗

Cardiovascular responses to microgravity - Adaptation, maladjustment, and countermeasures

Humans have worked in space for up to 237 days without significant inflight limitations, although major cardiovascular disability is seen following space flight of even a few days duration. Most of the cardiovascular research on microgravity deconditioning has been observational in character. Detailed studies of mechanisms and causes of postflight exercise intolerance, low blood pressure and fainting in astronauts and cosmonauts have not been done, despite almost 30 years of manned space flight. A review of possible mechanisms of postflight cardiovascular deconditioning and directions for study is provided.

Gaffney, F. Andrew↗

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies.

Chappell, Lori J.↗

NASA's Earth Science Flight Program Meets the Challenges of Today and Tomorrow

NASA's Earth science flight program is a dynamic undertaking that consists of a large fleet of operating satellites, an array of satellite and instrument projects in various stages of development, a robust airborne science program, and a massive data archiving and distribution system. Each element of the flight program is complex and present unique challenges. NASA builds upon its successes and learns from its setbacks to manage this evolving portfolio to meet NASA's Earth science objectives. NASA fleet of 16 operating missions provide a wide range of scientific measurements made from dedicated Earth science satellites and from instruments mounted to the International Space Station. For operational missions, the program must address issues such as an aging satellites operating well beyond their prime mission, constellation flying, and collision avoidance with other spacecraft and orbital debris. Projects in development are divided into two broad categories: systematic missions and pathfinders. The Earth Systematic Missions (ESM) include a broad range of multi-disciplinary Earth-observing research satellite missions aimed at understanding the Earth system and its response to natural and human-induced forces and changes. Understanding these forces will help determine how to predict future changes, and how to mitigate or adapt to these changes. The Earth System Science Pathfinder (ESSP) program provides frequent, regular, competitively selected Earth science research opportunities that accommodate new and emerging scientific priorities and measurement capabilities. This results in a series of relatively low-cost, small-sized investigations and missions. Principal investigators whose scientific objectives support a variety of studies lead these missions, including studies of the atmosphere, oceans, land surface, polar ice regions, or solid Earth. This portfolio of missions and investigations provides opportunity for investment in innovative Earth science that enhances NASA's capability for better understanding the current state of the Earth system. ESM and ESSP projects often involve partnerships with other US agencies and/or international organizations. This adds to the complexity of mission development, but allows for a greater scientific return on NASA's investments. The Earth Science Airborne Science Program provides manned and unmanned aircraft systems that further science and advance the use of satellite data. NASA uses these assets worldwide in campaigns to investigate extreme weather events, observe Earth system processes, obtain data for Earth science modeling activities, and calibrate instruments flying aboard Earth science spacecraft. The Airborne Science Program has six dedicated aircraft and access to many other platforms. The Earth Science Multi-Mission Operations program acquires, preserves, and distributes observational data from operating spacecraft to support Earth Science research focus areas. The Earth Observing System Data and Information System (EOSDIS), which has been in operations since 1994, primarily accomplishes this. EOSDIS acquires, processes, archives, and distributes Earth Science data and information products. The archiving of NASA Earth Science information happens at eight Distributed Active Archive Centers (DAACs) and four disciplinary data centers located across the United States. The DAACs specialize by topic area, and make their data available to researchers around the world. The DAACs currently house over 9 petabytes of data, growing at a rate of 6.4 terabytes per day. NASA's current Earth Science portfolio is responsive to the National Research Council (NRC) 2007 Earth Science Decadal Survey and well as the 2010 NASA Response to President Obama's Climate Plan. As the program evolves into the future it will leverage the lessons learned from the current missions in operations and development, and plan for adjustments to future objectives in response to the anticipated 2017 NRC Decadal Survey.

Flight Program↗

Developing High-Throughput Organ-On-A-Chip Models to Investigate the Effects of Ionizing Radiation on the Central Nervous System

One of the main health risks in human space exploration is central nervous system (CNS) damage by ionizing radiation. Irradiation with simulated GCRs or their components, or high doses of low-LET radiation such as gamma rays, in animal models has been shown to cause neuronal damage together with glial cell activation and neuroinflammation and has been associated with prolonged cognitive and behavioral dysfunction. The extent of CNS damage in response to any insult, including ionizing radiation, is partially regulated by the blood-brain barrier (BBB), which enables immune cells to enter the CNS. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, immune responses and oxidative stress, and thus could serve as a robust CNS-specific target for countermeasure development. However, studies on BBB permeability and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we have established a high throughput 3D organ-on-a-chip system to study human CNS functions in response to ionizing radiation, with the eventual goal of adapting it to spaceflight missions. We utilized commercially available OrganoPlate system (Mimetas, Inc.) seeded with primary or induced pluripotent stem cell-derived human cells for developing 3D neuronal-astrocytic and BBB models. We investigated both immediate and delayed CNS dose responses to 0.5-1 Gy X-rays by measuring BBB permeability and morphology, and astrocyte activation. We have also quantified secreted markers of oxidative stress and cell viability. In the future, we are planning to monitor dendritic, axonal and synaptic changes in neurons, evaluate the combined exposures to simulated microgravity and ionizing radiation, and compare the responses to low and high-LET ionizing radiation. We anticipate these studies could indicate novel cellular and mechanistic targets for countermeasure developments to improve CNS functions in astronauts.

Malkani, Sherina↗

The hazard components of representative key risks. The physical climate perspective

The framework of Representative Key Risks (RKRs) has been adopted by the Intergovernmental Panel on Climate Change Working Group II in order to categorize, assess and communicate a wide range of regional and sectoral key risks, expected to become severe as a consequence of the potentially detrimental convergence of changing climate conditions, exposure and vulnerability of human and natural systems, and responses through (mal)adaptation measures. Other papers in this special issue treat each of eight RKRs by holistically assessing their current status and future evolution as a result of this convergence. However, their treatment cannot always organize such assessment according to a systematic gradation of climatic changes, often times having to extrapolate the big-picture evolution of risk from either qualitative effects of “low” medium” and “high” warming, or limited/focused analysis of the consequences of particular mitigation choices (e.g., benefits of limiting warming to 1.5 or 2C). In this study we offer as systematic a representation as possible – given current literature and assessments – of the future evolution of the hazard components of RKRs. We draw on the assessment of changes in climatic impact-drivers relevant to RKRs described in the 6th Assessment Report by Working Group 1 (WGI) supplemented when needed by more recent literature. We identify the relevant hazards for each RKR, based upon the WGII authors’ assessment, and we report on their current state and expected future changes in magnitude, intensity and/or frequency, linking these changes to Global Warming Levels to the extent possible. For some of these quantities - like regional trends in oceanic and atmospheric temperature and precipitation, some heat and precipitation extremes, permafrost thaw and Northern Hemisphere snow cover - a strong and quantitative relationship with global average temperature change has been assessed. For others - like frequency and intensity of tropical cyclones and extra-tropical storms, and fire weather - the link to increasing global temperatures can only be described qualitatively. For some processes - like the behavior of ice-sheets, or changes in circulation dynamics - large uncertainties about the effects of different levels of warming remain, and for a few others - like ocean pH and air pollution - the composition of the scenario of anthropogenic emissions is most relevant, rather than the warming reached. In almost all cases, however, the basic message remains that every small increment in CO2 concentration in the atmosphere and associated warming will bring changes in climate phenomena that will contribute to increasing risk of impacts on human and natural systems when these changes happen in conjunction with these systems’ conditions of exposure and vulnerability, and in lack of effective adaptation. Our picture of the evolution of RKR-relevant climatic impact-drivers complements and enriches the treatment of RKRs in the other papers in at least two ways: by filling in an often only cursory or limited representation of the physical climate aspects driving impacts, and by providing a fuller representation of their future possible evolution which represents an important component – if never the only one – of the potential future evolution of risk severity.

54 ENVIRONMENTAL SCIENCES↗

Age-related changes in human vestibulo-ocular reflexes: Sinusoidal rotation and caloric tests

The dynamic response properties of horizontal vestibulo-ocular reflex (VOR) were characterized in 216 human subjects ranging in age from 7 to 81 years. The object of this cross-sectional study was to determine the effects of aging on VOR dynamics, and to identify the distributions of parameters which describe VOR responses to caloric and to sinusoidal rotational stimuli in a putatively normal population. Caloric test parameters showed no consistent trend with age. Rotation test parameters showed declining response amplitude and slightly less compensatory response phase with increasing age. The magnitudes of these changes were not large relative to the variability within the population. The age-related trends in VOR were not consistent with the anatomic changes in the periphery reported by others which showed an increasing rate of peripheral hair cell and nerve fiber loss in subjects over 55 years. The poor correlation between physiological and anatomical data suggest that adaptive mechanisms in the central nervous system are important in maintaining the VOR.

Peterka, R. J.↗

Erythropoietin withdrawal alters interactions between young red blood cells, splenic endothelial cells, and macrophages: an in vitro model of neocytolysis

BACKGROUND: We have described the rapid destruction of young red blood cells (neocytolysis) in astronauts adapting to microgravity, in polycythemic high altitude dwellers who descend to sea level, and in patients with kidney disorders. This destruction results from a decrease in erythropoietin (EPO) production. We hypothesized that such EPO withdrawal could trigger physiological changes in cells other than red cell precursors and possibly lead to the uptake and destruction of young red cells by altering endothelial cell-macrophage interactions, most likely occurring in the spleen. METHODS: We identified EPO receptors on human splenic endothelial cells (HSEC) and investigated the responses of these cells to EPO withdrawal. RESULTS: A monolayer of HSEC, unlike human endothelial cells from aorta, glomerulus, or umbilical vein, demonstrated an increase in permeability upon EPO withdrawal that was accompanied by unique morphological changes. When HSEC were cultured with monocyte-derived macrophages (but not when either cell type was cultured alone), EPO withdrawal induced an increased ingestion of young red cells by macrophages when compared with the constant presence or absence of EPO. CONCLUSIONS: HSEC may represent a unique cell type that is able to respond to EPO withdrawal by increasing permeability and interacting with phagocytic macrophages, which leads to neocytolysis.

NASA Discipline Cardiopulmonary↗

International Space Station Benefits for Humanity

The ISS partnership has seen a substantial increase in research accomplished, crew efforts devoted to research, and results of ongoing research and technology development. The ISS laboratory is providing a unique environment for research and international collaboration that benefits humankind. Benefits come from the engineering development, the international partnership, and from the research results. Benefits can be of three different types: scientific discovery, applications to life on Earth, and applications to future exploration. Working across all ISS partners, we identified key themes where the activities on the ISS improve the lives of people on Earth--not only within the partner nations, but also in other nations of the world. Three major themes of benefits to life on earth emerged from our review: benefits to human health, education, and Earth observation and disaster response. Other themes are growing as use of the ISS continues. Benefits to human health range from advancements in surgical technology, improved telemedicine, and new treatments for disease. Earth observations from the ISS provide a wide range of observations that include: marine vessel tracking, disaster monitoring and climate change. The ISS participates in a number of educational activities aimed to inspire students of all ages to learn about science, technology, engineering and mathematics. To date over 63 countries have directly participated in some aspect of ISS research or education. In summarizing these benefits and accomplishments, ISS partners are also identifying ways to further extend the benefits to people in developing countries for the benefits of humankind.

Thumm, Tracy L.↗

International Space Station Research Benefits for Humanity

The ISS partnership has seen a substantial increase in research accomplished, crew efforts devoted to research, and results of ongoing research and technology development. The ISS laboratory is providing a unique environment for research and international collaboration that benefits humankind. Benefits come from the engineering development, the international partnership, and from the research results. Benefits can be of three different types: scientific discovery, applications to life on Earth, and applications to future exploration. Working across all ISS partners, we identified key themes where the activities on the ISS improve the lives of people on Earth -- not only within the partner nations, but also in other nations of the world. Three major themes of benefits to life on earth emerged from our review: benefits to human health, education, and Earth observation and disaster response. Other themes are growing as use of the ISS continues. Benefits to human health range from advancements in surgical technology, improved telemedicine, and new treatments for disease. Earth observations from the ISS provide a wide range of observations that include: marine vessel tracking, disaster monitoring and climate change. The ISS participates in a number of educational activities aimed to inspire students of all ages to learn about science, technology, engineering and mathematics. To date over 63 countries have directly participated in some aspect of ISS research or education. In summarizing these benefits and accomplishments, ISS partners are also identifying ways to further extend the benefits to people in developing countries for the benefits of humankind.

Thumm, Tracy↗

A new rat model for studies of hypokinesia and antiorthostasis

A new rat model (suspension and immobilization) is described for induction of hypokinesia and orthostatic manipulations. Hypokinetic responses were comparable to those in prolonged bed rest and weightlessness in humans, body or limb casted and small cage restrained animals. Responses to antiorthostasis (15 to 20 deg head down tilt) in rats were similar to those in neutral bouyancy tests in humans and animals and to those in prolonged bed rest in humans. During seven days of hypokinesia there was an atrophy of the gastrocnemius and increased excretion of urinary nitrogeneous end products. The antiorthostatic (AOH) 15 to 20 deg head down tilt resulted in diuresis, natriuresis and kaliuresis. No comparable responses were observed in orthostatic hypokinetic (OH) rats. Readaptation from AOH and OH occurred during one week recovery in metabolic cage conditions.

Musacchia, X. J.↗

Establishment of FXS-A9 panel with a single human X chromosome from fragile X syndrome-associated individual

Highlights: • We established mouse A9 cells with human X chromosome from FXS carrier and patient. • FXS-associated CGG repeats were stably maintained in established rodent cells. • Epigenetic status of CGG repeat region were maintained in established rodent cells. • Human FMR1 expression in these cells was according to each CGG repeat length. Fragile X syndrome (FXS) is the most common inheritable form of intellectual disability. FMR1, the gene responsible for FXS, is located on human chromosome Xq27.3 and contains a stretch of CGG trinucleotide repeats in its 5′ untranslated region. FXS is caused by CGG repeats that expand beyond 200, resulting in FMR1 silencing via promoter hypermethylation. The molecular mechanism underlying CGG repeat expansion, a fundamental cause of FXS, remains poorly understood, partly due to a lack of experimental systems. Accumulated evidence indicates that the large chromosomal region flanking a CGG repeat is critical for repeat dynamics. In the present study, we isolated and introduced whole human X chromosomes from healthy, FXS premutation carriers, or FXS patients who carried disease condition-associated CGG repeat lengths, into mouse A9 cells via microcell-mediated chromosome transfer. The CGG repeat length-associated methylation status and human FMR1 expression in these monochromosomal hybrid cells mimicked those in humans. Thus, this set of A9 cells containing CGG repeats from three different origins (FXS-A9 panel) may provide a valuable resource for investigating a series of genetic and epigenetic CGG repeat dynamics during FXS pathogenesis.

60 APPLIED LIFE SCIENCES↗

Skeletal responses to spaceflight

The role of gravity in the determination of bone structure is elucidated by observations in adult humans and juvenile animals during spaceflight. The primary response of bone tissue to microgravity is at the interface of the mineral and matrix in the process of biomineralization. This response is manifested by demineralization or retarded growth in some regions of the skeleton and hypermineralization in others. The most pronounced effects are seen in the heelbone and skull, the most distally located bones relative to the heart. Ground based flight simulation models that focus on changes in bone structure at the molecular, organ, and whole body levels are described and compared to flight results. On Earth, the morphologic and compositional changes in the unloaded bones are very similar to changes during flight; however, the ground based changes appear to be more transient. In addition, a redistribution of bone mineral in gravity-dependent bones occurs both in space and during head down positioning on Earth. Longitudinal data provided considerable information on the influence of endocrine and muscular changes on bone structure after unloading.

Morey-Holton, Emily↗

Solution structure for an Encephalitozoon cuniculi adrenodoxin-like protein in the oxidized state

Encephalitozoon cuniculi is a unicellular, obligate intracellular eukaryotic parasite in the Microsporidia family and one of the agents responsible for microsporidosis infections in humans. Like most Microsporidia, the genome of E. cuniculi is markedly reduced and the organism contains mitochondria-like organelles called mitosomes instead of mitochondria. Here we report the solution NMR structure for a protein physically associated with mitosome-like organelles in E. cuniculi, the 128-residue, adrenodoxin-like protein Ec-Adx (UniProt ID Q8SV19) in the [2Fe-2S] ferredoxin superfamily. Oxidized Ec-Adx contains a mixed four-strand β-sheet, β2-β1-β4-β3 (↓↑↑↓), loosely encircled by three α-helices and two 310-helices. This fold is similar to the structure observed in other adrenodoxin and adrenodoxin-like proteins except for the absence of a fifth anti-parallel β-strand next to β3 and the position of α3. Cross peaks are missing or cannot be unambiguously assigned for 20 amide resonances in the 1 H- 15 N HSQC spectrum of Ec-Adx. These missing residues are clustered primarily in two regions, G48-V61 and L94-L98, containing the four cysteine residues predicted to ligate the paramagnetic [2Fe-2S] cluster. Missing amide resonances in 1 H- 15 N HSQC spectra are detrimental to NMR-based solution structure calculations because 1 H- 1 H NOE restraints are absent (glass half-empty) and this may account for the absent β-strand (β5) and the position of α3 in oxidized Ec-Adx. On the other hand, the missing amide resonances unambiguously identify the presence, and immediate environment, of the paramagnetic [2Fe-2S] cluster in oxidized Ec-Adx (glass half-full).

59 BASIC BIOLOGICAL SCIENCES↗