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At least 379 records · Page 21
All sourcesNASA NTRSDOE OSTI
NASA NTRS2007

Effects of Artificial Gravity and Bed Rest on Spatial Orientation and Balance Control

While the vestibular system should be well-adapted to bed rest (a condition it experiences approximately 8/24 hrs each day), questions remain regarding the degree to which repeated exposures to the unusual gravito-inertial force environment of a short-radius centrifuge might affect central processing of vestibular information used in spatial orientation and balance control. Should these functions be impaired by intermittent AG, its feasibility as a counter-measure would be diminished. We, therefore, examined the effects of AG on spatial orientation and balance control in 15 male volunteers before and after 21 days of 6 HDT bed rest (BR). Eight of the subjects were treated with daily 1hr AG exposures (2.5g at the feet; 1.0g at the heart) aboard a short radius (3m) centrifuge, while the other seven served as controls (C). Spatial orientation was assessed by measures of ocular counter-rolling (OCR; rotation of the eye about the line of sight, an otolith-mediated reflex) and subjective visual vertical (SVV; perception of the spatial upright). Both OCR and SVV measurements were made with the subject upright, lying on their left sides, and lying on their right sides. OCR was measured from binocular eye orientation recordings made while the subjects fixated for 10s on a point target directly in front of the face at a distance of 1 m. SVV was assessed by asking subjects (in the dark) to adjust to upright (using a handheld controller) the orientation of a luminous bar randomly perturbed (15) to either side of the vertical meridian. Balance control performance was assessed using a computerized dynamic posturography (CDP) protocol similar to that currently required for all returning crew members. During each session, the subjects completed a combination of trials of sensory organization test (SOT) 2 (eyes closed, fixed platform) and SOT 5 (eyes closed, sway-referenced platform) with and without static and dynamic pitch plane head movements (plus or minus 20 deg., dynamic paced by an audible tone at 0.33Hz). OCR and CDP performance were unaffected by BR and BR+AG; post-BR measures were unchanged from baseline for both AG and C groups. Similarly, BR did not affect SVV in the C group. However, BR+AG disrupted one measure of spatial orientation: SVV error was significantly increased on R+0 and R+1 following BR in the AG group. These results suggest a transient untoward effect on central vestibular processing may accompany repeated exposure to intermittent AG, a potential side-effect that should be studied more closely in future studies.

Paloski, William H.↗
NASA NTRS2020

Circulating miRNA Signature Predicts Health Risks Associated with Cancer and Spaceflight

Biological risks associated with space radiation and microgravity are major concerns for long-term space travel. Through a Systems Biology approach, our previous NASA work has shown both TGF signaling pathways and miRNAs have a critical impact on defining health risks with and without space irradiation. We hypothesize that circulating microRNA (miRNA) signatures are driving microvascular disease and muscle degeneration associated with accelerating aging and will be enhanced by exposure to the space environment (radiation and microgravity). We are investigating this hypothesis with both in vivo and in vitro models to test novel antagonist therapies to these miRNA signatures as countermeasures to reduce space radiation-induced health risks. A comprehensive Systems Biology approach is utilized to examine the influence by high atomic number by high (H) atomic number (Z) and energy (E) (HZE) irradiation. To simulate low-dose exposure due to galactic cosmic rays (GCR), we used ions, energy, and doses determined by a NASA consensus formula of 7 different ions to represent GCR (referred to as GCR sim model). To similate high-dose radiation exposure due to solar particle events (SPE), we used a solar particle event (SPE) sim model which gave a total dose of 1Gy protons with energy ranges from 50MeV to 150MeV. C57BL/6 wild-type female mice were utilized for the irradiations with our established simulated microgravity model (hindlimb suspension model) and an in vitro 3D microvasculature tissue model under simulated microgravity (clinostat) conditions was also irradiated. To expand on the circulating miRNA signature determined from our preliminary data, we determined a group of conserved miRNAs which are commonly being regulated in the majority of the organs and tissues throughout the host using our established techniques. MiRNA-sequencing was done on serum (at time of sacrifice), liver, heart, and muscle (soleus muscle) tissue for all radiation groups. Additional validation of the key miRNAs was performed by droplet digital PCR (ddPCR). This revealed a key circulating miRNA signature (consisting of multiple miRNAs) impacting cardiovascular and muscular disease risk. Further in vitro experiments with CRISPR/Cas9 system to knockout the key miRNA signatures, novel self-delivering antagomirs, overexpression of the miRNAs test the functional impact of the miRNA signatures on both microvascular disease and muscle degeneration due to space irradiation. The current work has started to allow the possible development of a novel minimally invasive miRNA based radioprotector to be used as a countermeasure for space radiation. Collectively, understanding of how whole body space radiation impacts microvascular and tissue degeneration through circulating miRNAs will greatly enhance health risk prognostication and provide possible new mechanisms for protection against space radiation. This work is supported by the Translational Research Institute through NASA Cooperative Agreement NNX16AO69A (T-0404) awarded to AB.

Beheshti, Afshin↗
NASA NTRS2009

Validation of Cardiovascular Parameters during NASA's Functional Task Test

Microgravity exposure causes physiological deconditioning and impairs crewmember task performance. The Functional Task Test (FTT) is designed to correlate these physiological changes to performance in a series of operationally-relevant tasks. One of these, the Recovery from Fall/Stand Test (RFST), tests both the ability to recover from a prone position and cardiovascular responses to orthostasis. PURPOSE: Three minutes were chosen for the duration of this test, yet it is unknown if this is long enough to induce cardiovascular responses similar to the operational 5 min stand test. The purpose of this study was to determine the validity and reliability of heart rate variability (HRV) analysis of a 3 min stand and to examine the effect of spaceflight on these measures. METHODS: To determine the validity of using 3 vs. 5 min of standing to assess HRV, ECG was collected from 7 healthy subjects who participated in a 6 min RFST. Mean R-R interval (RR) and spectral HRV were measured in minutes 0-3 and 0-5 following the heart rate transient due to standing. Significant differences between the segments were determined by a paired t-test. To determine the reliability of the 3-min stand test, 13 healthy subjects completed 3 trials of the FTT on separate days, including the RFST with a 3 min stand. Analysis of variance (ANOVA) was performed on the HRV measures. One crewmember completed the FTT before a 14-day mission, on landing day (R+0) and one (R+1) day after returning to Earth. RESULTS VALIDITY: HRV measures reflecting autonomic activity were not significantly different during the 0-3 and 0-5 min segments. RELIABILITY: The average coefficient of variation for RR, systolic (SBP) and diastolic blood pressures during the RFST were less than 8% for the 3 sessions. ANOVA results yielded a greater inter-subject variability (p<0.006) than inter-session variability (p>0.05) for HRV in the RFST. SPACEFLIGHT: Lower RR and higher SBP were observed on R+0 in rest and stand. On R+1, both RR and SBP trended towards preflight rest and stand values. Postflight HRV showed higher LF/HF for rest and stand and lower HFnu during rest. CONCLUSION: These studies show that a 3 min stand delivers repeatable HRV data in the context of this larger series of FTT tests. Spaceflight-induced changes in blood pressure, RR and autonomic function (HRV) are evident from the RFST.

Arzeno, N. M.↗
NASA NTRS2003

Improvement in diastolic intraventricular pressure gradients in patients with HOCM after ethanol septal reduction

We sought to validate measurement of intraventricular pressure gradients (IVPG) and analyze their change in patients with hypertrophic obstructive cardiomyopathy (HOCM) after ethanol septal reduction (ESR). Quantitative analysis of color M-mode Doppler (CMM) images may be used to estimate diastolic IVPG noninvasively. Noninvasive IVPG measurement was validated in 10 patients undergoing surgical myectomy. Echocardiograms were then analyzed in 19 patients at baseline and after ESR. Pulsed Doppler data through the mitral valve and pulmonary venous flow were obtained. CMM was used to obtain the flow propagation velocity (Vp) and to calculate IVPG off-line. Left atrial pressure was estimated with the use of previously validated Doppler equations. Data were compared before and after ESR. CMM-derived IVPG correlated well with invasive measurements obtained before and after surgical myectomy [r = 0.8, P < 0.01, Delta(CMM - invasive IVPG) = 0.09 +/- 0.45 mmHg]. ESR resulted in a decrease of resting LVOT systolic gradient from 62 +/- 10 to 29 +/- 5 mmHg (P < 0.001). There was a significant increase in the Vp and IVPG (from 48 +/- 5to 74 +/- 7 cm/s and from 1.5 +/- 0.2 to 2.6 +/- 0.3 mmHg, respectively, P < 0.001 for both). Estimated left atrial pressure decreased from 16.2 +/- 1.1 to 11.5 +/- 0.9 mmHg (P < 0.001). The increase in IVPG correlated with the reduction in the LVOT gradient (r = 0.6, P < 0.01). Reduction of LVOT obstruction after ESR is associated with an improvement in diastolic suction force. Noninvasive measurements of IVPG may be used as an indicator of diastolic function improvement in HOCM.

NASA Program Biomedical Research and Countermeasur↗
NASA NTRS1991

Echocardiography in the flight program

Observations on American and Soviet astronauts have documented the association of changes in cardiovascular function during orthostasis with space flight. A basic understanding of the cardiovascular changes occurring in astronauts requires the determination of cardiac output and total peripheral vascular resistance as a minimum. In 1982, we selected ultrasound echocardiography as our means of acquiring this information. Ultrasound offers a quick, non-invasive and accurate means of determining stroke volume which, when combined with the blood pressure and heart rate measurements of the stand test, allows calculation of changes in peripheral vascular resistance, the body's major response to orthostatic stress. The history of echocardiography in the Space Shuttle Program is discussed and the results are briefly presented.

Charles, John B.↗
NASA NTRS2001

Effects of exercise pressor reflex activation on carotid baroreflex function during exercise in humans

1. This investigation was designed to determine the contribution of the exercise pressor reflex to the resetting of the carotid baroreflex during exercise. 2. Ten subjects performed 3.5 min of static one-legged exercise (20 % maximal voluntary contraction) and 7 min dynamic cycling (20 % maximal oxygen uptake) under two conditions: control (no intervention) and with the application of medical anti-shock (MAS) trousers inflated to 100 mmHg (to activate the exercise pressor reflex). Carotid baroreflex function was determined at rest and during exercise using a rapid neck pressure/neck suction technique. 3. During exercise, the application of MAS trousers (MAS condition) increased mean arterial pressure (MAP), plasma noradrenaline concentration (dynamic exercise only) and perceived exertion (dynamic exercise only) when compared to control (P < 0.05). No effect of the MAS condition was evident at rest. The MAS condition had no effect on heart rate (HR), plasma lactate and adrenaline concentrations or oxygen uptake at rest and during exercise. The carotid baroreflex stimulus-response curve was reset upward on the response arm and rightward to a higher operating pressure by control exercise without alterations in gain. Activation of the exercise pressor reflex by MAS trousers further reset carotid baroreflex control of MAP, as indicated by the upward and rightward relocation of the curve. However, carotid baroreflex control of HR was only shifted rightward to higher operating pressures by MAS trousers. The sensitivity of the carotid baroreflex was unaltered by exercise pressor reflex activation. 4. These findings suggest that during dynamic and static exercise the exercise pressor reflex is capable of actively resetting carotid baroreflex control of mean arterial pressure; however, it would appear only to modulate carotid baroreflex control of heart rate.

Non-NASA Center↗
NASA NTRS1976

Pre- and postflight systolic time intervals during LBNP - The second manned Skylab mission

Before and after the 59 day Skylab 3 flight, the astronauts were stressed with lower body negative pressure (LBNP), and their vectorcardiograms, pneumograms, phonocardiograms, and carotid pulse tracings were monitored together with the intervals of systole. In the immediate postflight period elevations in heart rate and blood pressure were observed in response to -50 mm Hg of LBNP. Postflight abnormalities in the systolic time intervals (STI) at rest and during stress were due to an increase in afterload and a decrease in preload. As blood volume was restored and blood pressure reduced, STI abnormalities persisted as long as one month, suggesting a possible reduction in ventricular contractility and/or a functional impairment to venous return.

Bergman, S. A., Jr.↗
NASA NTRS1977

Left ventricular function during lower body negative pressure

The response of the human left ventricle to lower body negative pressure (LBNP) and the relation between left ventricular function and hemodynamic response were investigated. Ventricular function curves relating stroke volume to end-diastolic volume were obtained in 12 normal men. Volume data were derived from echocardiographic measurements of left ventricular end-systolic and end-diastolic diameters at rest and during lower body negative pressure (LBNP) at minus 40 mm Hg. End-diastolic volume decreased by 19% and stroke volume by 22%. There were no significant changes in heart rate, arterial blood pressure, or end-systolic volume. Thus, moderate levels of LBNP significantly reduce preload and stroke volume without affecting contractile state. The absence of significant changes in heart rate and arterial blood pressure in the presence of a significant reduction in stroke volume is consistent with an increase in systemic peripheral resistance mediated by low-pressure baroreceptors.

Ahmad, M.↗
NASA NTRS2007

Cardiac and Vascular Function in Bedrested Volunteers: Effects of Artificial Gravity Training

Cardiovascular effects of an artificial gravity (AG) countermeasure on deconditioned male volunteers were studied. In two groups of men we measured cardiovascular parameters at rest and in response to 30 minutes of 80 deg. head up tilt (HUT) before, at the end of, and four days following 21 days of 6 deg. head down bed rest (HDBR). One group (N=7) underwent no countermeasure while the other (N=8) received a daily, one hour, dose (2.5 gz at the foot, decreasing to 1.0 gz at the heart) of AG training on the Johnson Space Center short radius centrifuge. Cardiovascular parameters measured included heart rate, blood pressure, stroke volume, cardiac output, peripheral vascular resistance, plasma volume shifts, and vasoactive hormones. Untrained subjects exhibited shorter tilt survival (on average 8 minutes shorter) compared to trained subjects. By the end of bed rest, mean heart rate (MHR) was elevated in both groups (both supine and during tilt). In addition, treated subjects demonstrated lower, tilt-induced, increases in MHR four days following HDBR, indicating a more rapid return to pre bed rest conditions. Results from an index of autonomic balance (percentage of MHR spectral power in the respiratory frequency range) in control of heart rate are consistent with the interpretation that parasympathetic nervous system withdrawal was responsible for both tilt- and bed rest-induced increases in MHR. Our data support our pre-study hypothesis that AG treatment would lessen cardiovascular effects of deconditioning in bed rested men and suggest that AG should be further pursued as a space flight countermeasure.

Meng, M.↗
NASA NTRS2002

Aging attenuates the vestibulosympathetic reflex in humans

BACKGROUND: The vestibular system contributes to sympathetic activation by engagement of the otolith organs. However, there is a significant loss of vestibular function with aging. Therefore, the purpose of the present study was to determine if young and older individuals differ in their cardiovascular and sympathetic responses to otolithic stimulation (ie, head-down rotation, HDR). We hypothesized that responses to otolithic stimulation would be attenuated in older adults because of morphological and physiological alterations that occur in the vestibular system with aging. METHODS AND RESULTS: Arterial blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), and head rotation were measured during HDR in 11 young (26 +/- 1 years) and 11 older (64 +/- 1 years) subjects in the prone posture. Five older subjects performed head rotation (chin to chest) in the lateral decubitus position, which simulates HDR but does not alter afferent inputs from the vestibular system. MSNA responses to HDR were significantly attenuated in older as compared with young subjects (P<0.01). MSNA increased in the older subjects by only 12 +/- 5% as compared with 85 +/- 16% in the young. Furthermore, HDR elicited significant reductions in mean arterial blood pressure in older (Delta-6 +/- 1 mm Hg; P<0.01) but not young subjects (Delta1 +/- 1 mm Hg). In contrast to HDR, head rotation performed in the lateral decubitus position did not elicit hypotension. MSNA responses to baroreceptor unloading and the cold pressor test were not different between the age groups. CONCLUSIONS: These data indicate that aging attenuates the vestibulosympathetic reflex in humans and may contribute to the increased prevalence of orthostatic hypotension with age.

NASA Discipline Neuroscience↗
NASA NTRS1999

Physiologic and Functional Responses of MS Patients to Body Cooling Using Commercially Available Cooling Garments

Personal cooling systems are widely used in industrial and aerospace environments to alleviate thermal stress. Increasingly they are also used by heat sensitive multiple sclerosis (HSMS) patients to relieve symptoms and improve quality of life. There are a variety of cooling systems commercially available to the MS community. However, little information is available regarding the comparative physiological changes produced by routine operation of these various systems. The objective of this study was to document and compare the patient response to two passive cooling vests and one active cooling garment. The Life Enhancement Technology, Inc. (LET) lightweight active cooling vest with cap, the MicroClimate Systems (MCS) Change of Phase garment, and the Steele Vest were each used to cool 13 male and 13 female MS subjects (31 to 67 yr.) in this study. The subjects, seated in an upright position at normal room temperature (approximately 22 C), were tested with one of the cooling garments. Oral, fight and left ear temperatures were logged manually every 5 min. An-n, leg, chest and rectal temperatures; heart rate; and respiration were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. Each subject was given a series of subjective and objective evaluation tests before and after cooling. The LET and Steele vests test groups had similar, significant (P less than 0.01) cooling effects on oral and ear canal temperature, which decreased approximately 0.4 C, and 0.3 C, respectively. Core temperature increased (N.S.) with all three vests during cooling. The LET vest produced the coldest (P less than 0.01) skin temperature. Overall, the LET vest provided the most improvement on subjective and objective performance measures. These results show that the garment configurations tested do not elicit a similar thermal response in all MS patients. Cooling with the LET active garment configuration resulted in the lowest body temperatures for the MS subjects; cooling with the MCS vest was least effective. For functional responses, the LET test group performed better than the other two vests.

Ku, Yu-Tsuan E.↗
NASA NTRS2007

Effect of Head-Down Bed Rest and Artificial Gravity Countermeasure on Cardiac Autonomic and Advanced Electrocardiographic Function

To study the effects of 21 days of head-down bed rest (HDBR), with versus without an artificial gravity (AG) countermeasure, on cardiac autonomic and advanced electrocardiographic function. Fourteen healthy men participated in the study: seven experienced 21 days of HDBR alone ("HDBR controls") and seven the same degree and duration of HDBR but with approximately 1hr daily short-arm centrifugation as an AG countermeasure ("AG-treated"). Five minute supine high-fidelity 12-lead ECGs were obtained in all subjects: 1) 4 days before HDBR; 2) on the last day of HDBR; and 3) 7 days after HDBR. Besides conventional 12-lead ECG intervals and voltages, all of the following advanced ECG parameters were studied: 1) both stochastic (time and frequency domain) and deterministic heart rate variability (HRV); 2) beat-to-beat QT interval variability (QTV); 3) T-wave morphology, including signal-averaged T-wave residua (TWR) and principal component analysis ratios; 4) other SAECG-related parameters including high frequency QRS ECG and late potentials; and 5) several advanced ECG estimates of left ventricular (LV) mass. The most important results by repeated measures ANOVA were that: 1) Heart rates, Bazett-corrected QTc intervals, TWR, LF/HF power and the alpha 1 of HRV were significantly increased in both groups (i.e., by HDBR), but with no relevant HDBR*group differences; 2) All purely "vagally-mediated" parameters of HRV (e.g., RMSSD, HF power, Poincare SD1, etc.), PR intervals, and also several parameters of LV mass (Cornell and Sokolow-Lyon voltages, spatial ventricular activation times, ventricular gradients) were all significantly decreased in both groups (i.e., by HDBR), but again with no relevant HDBR*group differences); 3) All "generalized" or "vagal plus sympathetic" parameters of stochastic HRV (i.e., SDNN, total power, LF power) were significantly more decreased in the AG-treated group than in the HDBR-only group (i.e., here there was a relevant HDBR*group difference); and 4) QTV index was also significantly more changed (increased) in the AG-treated group than in the HDBR-only group, although this was clearly due to a greater decrease in generalized HRV and not to a greater increase in QTV proper because there was no relevant HDBR*group effect for either the SDNN or the RMSSD of QTV. Brief daily AG treatment by short-arm centrifuge during each of 21 days of HDBR does not appear to protect against HDBR-related losses of cardiac autonomic function or of LV mass as estimated by ECG.

Schlegel, T. T.↗
NASA NTRS1992

NASA's extended duration orbiter medical program

The physiological issues involved in safely extending Shuttle flights from 10 to 16 days have been viewed by some as academic. After all, they reasoned, humans already have lived and worked in space for periods exceeding even 28 days in the United States Skylab Program and onboard the Russian space stations. The difference in the Shuttle program is in the physical position of the astronauts as they reenter the Earth's atmosphere. Crewmembers in the earlier Apollo, Skylab, and Russian programs were returned to Earth in the supine position. Space Shuttle crewmembers, in contrast, are seated upright during reentry and landing; reexperiencing the Earth's g forces in this position has far more pronounced effects on the crewmember's physiological functions. The goal of the Extended Duration Orbiter (EDO) Medical Project (EDOMP) has been to ensure that crewmembers maintain physiological reserves sufficient to perform entry, landing, and egress safely. Early in the Shuttle Program, it became clear that physiological deconditioning during space flight could produce significant symptoms upon return to Earth. The signs and symptoms observed during the entry, landing, and egress after Shuttle missions have included very high heart rates and low blood pressures upon standing. Dizziness, 'graying out,' and fainting have occurred on ambulation or shortly thereafter. Other symptoms at landing have included headache, light-headedness, nausea and vomitting, leg cramping, inability to stand for several minutes after wheel-stop, and unsteadiness of gait.

Pool, Sam Lee↗
NASA NTRS2004

Advanced Infant Car Seat Would Increase Highway Safety

An advanced infant car seat has been proposed to increase highway safety by reducing the incidence of crying, fussy behavior, and other child-related distractions that divert an adult driver s attention from driving. In addition to a conventional infant car seat with safety restraints, the proposed advanced infant car seat would include a number of components and subsystems that would function together as a comprehensive infant-care system that would keep its occupant safe, comfortable, and entertained, and would enable the driver to monitor the baby without having to either stop the car or turn around to face the infant during driving. The system would include a vibrator with bulb switch to operate; the switch would double as a squeeze toy that would make its own specific sound. A music subsystem would include loudspeakers built into the seat plus digital and analog circuitry that would utilize plug-in memory modules to synthesize music or a variety of other sounds. The music subsystem would include a built-in sound generator that could synthesize white noise or a human heartbeat to calm the baby to sleep. A second bulb switch could be used to control the music subsystem and would double as a squeeze toy that would make a distinct sound. An anti-noise sound-suppression system would isolate the baby from potentially disturbing ambient external noises. This subsystem would include small microphones, placed near the baby s ears, to detect ambient noise. The outputs of the microphone would be amplified and fed to the loudspeakers at appropriate amplitude and in a phase opposite that of the detected ambient noise, such that the net ambient sound arriving at the baby s ears would be almost completely cancelled. A video-camera subsystem would enable the driver to monitor the baby visually while continuing to face forward. One or more portable miniature video cameras could be embedded in the side of the infant car seat (see figure) or in a flip-down handle. The outputs of the video cameras would be transmitted by radio or infrared to a portable, miniature receiver/video monitor unit that would be attached to the dashboard of the car. The video-camera subsystem can also be used within transmission/reception range when the seat was removed from the car. The system would include a biotelemetric and tracking subsystem, which would include a Global Positioning System receiver for measuring its location. This subsystem would transmit the location of the infant car seat (even if the seat were not in a car) along with such biometric data as the baby s heart rate, perspiration rate, urinary status, temperature, and rate of breathing. Upon detecting any anomalies in the biometric data, this subsystem would send a warning to a paging device installed in the car or carried by the driver, so that the driver could pull the car off the road to attend to the baby. A motion detector in this subsystem would send a warning if the infant car seat were to be moved or otherwise disturbed unexpectedly while the infant was seated in it: this warning function, in combination with the position- tracking function, could help in finding a baby who had been kidnapped with the seat. Removable rechargeable batteries would enable uninterrupted functioning of all parts of the system while transporting the baby to and from the car. The batteries could be recharged via the cigarette-lighter outlet in the car or by use of an external AC-powered charger.

Dabney, Richard↗
NASA NTRS2003

Impact Mediated Loading Cytoplasmic Loading of Macromolecules into Adherent Cells

The advent of modern molecular biology, including the development of gene array technologies, has resulted in an explosion of information concerning the specific genes activated during normal cellular development, as well as those associated with a variety of pathological conditions. These techniques have served as a highly efficient, broacI.-based screening approach for those specific genes involved. in regulating normal cellular physiology and identifying candidate genes directly associated with the etiology of specific disease states. However, this approach provides information at the transcriptional' level only and does not necessarily indicate . that the gene in question is in fact translated i~to a protein, or whether or not post-translational modification of the protein occurs. The critical importance of post-translational modification (i.e. phosphorylation, glycosylation, sialyation, etc.) to protein function has been recognized with regard to a number of proteins involved in a variety of important disease states. For example, altered glycosylation of beta-amyloid precursor protein results in an increase in the amount of beta-amyloid peptide generated and hence secreted as insoluble extracellular amyloid deposits (Georgopoulou, McLaughlin et al. 2001; Walter, Fluhrer et al. 2001), a pathological hal1~nark of Alzheimer's disease. Abnormal phosphoryla~ion of synapsin I has been linked to alterations in synaptic vesicle trafficking leading to defective neurotransmission in Huntington's disease (Lievens, Woodman et al. 2002). Altered phosphorylation of the TAU protein involved in microtubule function has been linked to a number of neurodegenative diseases such as Alzheimer's disease (Billingsley and Kincaid 1997; Sanchez, Alvarez-T~llada et a1. 2001). Aberrant siaIyation of cell/I surface antigens has been detected in a number of different tumor cell types and has been linked to the acquisition of a neoplastic phenotype (Sell 1990), while improper' sia1yation of sodium channels in cardiac tissue has been linked to heart failure (Ufret-Vincenty, Baro et al. 2001; Fozzard and Kyle 2002).

Clarke, Mark S. F.↗
DOE OSTI2026

Function, Structure, and Regulation of Nitrogen Fixation-like Metalloproteins for Nitrogen, Energy, Carbon, and Sulfur Metabolism

Nitrogenases (N 2 ases) and nitrogen fixation-like (NFL) systems play distinct roles in nitrogen, carbon, sulfur, and energy metabolism based on their fundamental differences in structure and metallocofactor identity. As new NFL systems have recently been identified and characterized, striking parallels and differences compared to N 2 ase structure, catalysis, and regulation have emerged. NFL systems use metallocofactors that span from simple [4Fe-4S] clusters to complex clusters akin to FeMo-co, previously only thought to occur in N 2 ase. This review describes the present state of knowledge on the function, structure, catalytic mechanisms, and regulation of NFL systems that perform distinct biological roles across all three domains of life. Recent advancements in N 2 ase spectroscopic techniques for probing metallocofactor structure and electronic states guide current and future work on how each NFL system catalyzes its specific biological reaction(s). Key knowledge gaps and needed areas of research for uncovering the specific metallocofactors and structural motifs that are at the heart of NFL system reaction specificity, along with how these systems are regulated, are discussed.

Bacteria↗
NASA NTRS1999

Neurolab Biotelemetry System (NBS)

This system was developed by the Sensors 2000! Program (S2K!) at Ames Research Center for the E132 STS-90 Neurolab Shuttle mission experiment to monitor 12 untethered adult male rats housed in the Research Animal Habitat Facility (RAHF). The system monitored the animals for body temperature, heart rate, and activity, and stored the data on board for up to 21 days for downloading after landing. The principal investigator's monitoring requirements were accomplished integrating a combination of both commercial and in-house developed hardware and software, including an off-the-shelf implantable telemetry transmitter and receiver system. In addition, a custom-developed antenna system was incorporated into the RAHF cages to perform the unique function of near-field radio-frequency (rf) measurement in the metal cages. This system proved the ability to perform wireless physiological measurements in very non-ideal circumstances using existing habitats and cabling without interfering with other experiment or shuttle systems. S2K! is continuing development on a custom telemetry transmitter and receiver system which will expand measurement capabilities.

Schonfeld, J.↗
NASA NTRS2001

Function of human eccrine sweat glands during dynamic exercise and passive heat stress

The purpose of this study was to identify the pattern of change in the density of activated sweat glands (ASG) and sweat output per gland (SGO) during dynamic constant-workload exercise and passive heat stress. Eight male subjects (22.8 +/- 0.9 yr) exercised at a constant workload (117.5 +/- 4.8 W) and were also passively heated by lower-leg immersion into hot water of 42 degrees C under an ambient temperature of 25 degrees C and relative humidity of 50%. Esophageal temperature, mean skin temperature, sweating rate (SR), and heart rate were measured continuously during both trials. The number of ASG was determined every 4 min after the onset of sweating, whereas SGO was calculated by dividing SR by ASG. During both exercise and passive heating, SR increased abruptly during the first 8 min after onset of sweating, followed by a slower increase. Similarly for both protocols, the number of ASG increased rapidly during the first 8 min after the onset of sweating and then ceased to increase further (P > 0.05). Conversely, SGO increased linearly throughout both perturbations. Our results suggest that changes in forearm sweating rate rely on both ASG and SGO during the initial period of exercise and passive heating, whereas further increases in SR are dependent on increases in SGO.

NASA Discipline Cardiopulmonary↗