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At least 145 records · Page 8

Modifications to the steady-state 41-node thermoregulatory model including validation of the respiratory and diffusional water loss equations

After the simplified version of the 41-Node Stolwijk Metabolic Man Model was implemented on the Sigma 3 and UNIVAC 1110 computers in batch mode, it became desirable to make certain revisions. First, the availability of time-sharing terminals makes it possible to provide the capability and flexibility of conversational interaction between user and model. Secondly, recent physiological studies show the need to revise certain parameter values contained in the model. Thirdly, it was desired to make quantitative and accurate predictions of evaporative water loss for humans in an orbiting space station. The result of the first phase of this effort are reported.

Source record↗

Medical experiment M-171 - Results from the second manned Skylab mission

Preflight, inflight, and postflight exercise response tests were conducted on the astronauts of the second Skylab mission as part of an evaluation of physiological adaptation to long-term weightlessness. The flight phase of this mission was 59 days in duration. An exercise protocol was designed around a bicycle ergometer which was used to apply work loads approximating 25, 50, and 75% of each crewman's measured maximum aerobic capacity. Respiratory gas exchange, heart rate, and blood pressure were measured during all tests; cardiac output was measured at selected times during preflight and postflight tests. Data obtained both at rest and during exercise in flight showed no consistent changes which would indicate a degraded physical work capacity. In fact, heart rate during exercise actually decreased for all crewmen in flight. This response indicated improved physical fitness in flight relative to preflight. The postflight period of readaptation to 1 G was characterized by a marked tachycardia, during which time stroke volume was decreased. This response returned to normal within 5-day postflight.

Rummel, J. A.↗

USSR space life sciences digest, issue 27

This is the twenty-fifth issue of NASA's Space Life Sciences Digest. It contains abstracts of 30 journal papers or book chapters published in Russian and of 2 Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. The abstracts in this issue have been identified as relevant to 18 areas of space biology and medicine. These areas include: adaptation, aviation medicine, biological rhythms, biospherics, botany, cardiovascular and respiratory systems, endocrinology, enzymology, exobiology, habitability and environmental effects, hematology, immunology, metabolism, musculoskeletal system, neurophysiology, radiobiology, and space medicine. A Soviet book review of a British handbook of aviation medicine and a description of the work of the division on aviation and space medicine of the Moscow Physiological Society are also included.

Stone, Lydia Razran↗

Host cell and viral protease targets of human SERPINs identified by in silico docking

Serine protease inhibitors (SERPINs) are involved in various physiological processes and diseases, such as inflammation, cancer metastasis, and neurodegeneration. Their role in viral infections is poorly understood, as their expression patterns during infection and the range of proteases they target have yet to be fully characterized. Here, we show widespread expression of human SERPINs in response to respiratory virus infections, both in bronchioalveolar lavages from COVID-19 patients and in polarized human airway epithelial cultures. Using in silico docking of 10 SERPINs to 48 host proteases, we confirm known targets and predict new interactions. Protease activity assays validated selected interactions, confirming the newly predicted host targets for PAI-1 (SERPINE1) and PAI-2 (SERPINB2). PAI-1 inhibits cathepsin L, essential for SARS-CoV-2 maturation, and suppresses multi-cycle replication of both ancestral SARS-CoV-2 WA-1 and its variant Omicron BA.1. In addition, we identify PAI-2 as an antiviral SERPIN that reduces infectivity of human adenovirus 5 by directly inhibiting the adenoviral protease. Our study leverages in silico docking using full-length 3D protein structures to uncover new SERPIN targets, offering a range of candidate targets for therapeutic interventions.

59 BASIC BIOLOGICAL SCIENCES↗

Metabolic and cardiovascular adaptation, monkey. NASA SMD 3, project 76, experiment 44 conducted at NASA/JSC, 14-25 May 1977

The biomedical results from an experiment on a monkey subjected to space flight conditions are reported. A background history of the development and testing of an experiment system designed to permit measurement of physiological parameters in subhuman primates during continuous, comfortable, couch restraint for periods of up to 30 days is reviewed. Of major importance in the experimental design of the system was the use of a fiberglass pod, which could be sealed and subdivided into upper and lower parts, to monitor and control the physiological responses for various parts of the animal's body. The experiment was conducted within the Spacelab Simulator for a period of 11 days. Data recorded includes: Spacelab Simulator cabin temperature; ventilation rate; pod internal temperature; fraction percent oxygen; fraction percent carbon dioxide; oxygen consumption rate; carbon dioxide production rate; respiratory quotient; intrathoracic temperature; heart rate; mean aortic pressure; mean ventricular pressure; diurnal variation of parameters measured; comparison of mean preflight, flight, and postflight values of the parameters measured; and correlation matrix for the parameters measured.

Pace, N.↗

In Vivo Model to Test Implanted Biosensors for Blood pH

Biosensors for monitoring physiologic data continuously through telemetry are available for heart rate, respiration, and temperature but not for blood pH or ions affected by hydrogen ion concentration. A telemetric biosensor for monitoring blood pH on-line could be used to identify and manage problems in fluid and electrolyte metabolism, cardiac and respiratory function during space flight and the acid-base status of patients without the need for venipuncture in patients on Earth. Critical to the development of biosensors is a method for evaluating their performance after implantation. Mature rats, prepared with jugular, cannulas for repeated blood samples, were exposed to a gas mixture containing high levels of carbon dioxide (7%) in a closed environment to induce mild respiratory acidosis. Serial blood gas and pH measurements in venous blood were compared with electrical responses from sensors implanted in the subcutaneous tissue. Animals became slightly tachypneic after exposure to excess CO2, but remained alert and active. After 5 minutes, basal blood pH decreased from 7.404 +/- 0.013 to 7.289 +/- 0.010 (p less than 0.001)and PC02 increased from 45 +/- 6 to 65 +/- 4 mm. Hg (p les than 0.001). Thereafter pH and blood gas parameters remained stable. Implanted sensors showed a decrease in millivolts (mV) which paralleled the change in pH and averaged 5-6 mV per 0.1 unit pH. Implanted sensors remained sensitive to modest changes in tissue pH for one week. A system for inducing acidosis in rats was developed to test the in vivo performance of pH biosensors. The system provides a method which is sensitive, rapid and reproducible in the same and different animals with full recovery, for testing the performance of sensors implanted in subcutaneous tissues.

Arnaud, Sara B.↗

Exploring Heart and Lung Function in Space: ARMS Experiments

The Advanced Respiratory Monitoring System (ARMS) is a suite of monitoring instruments and supplies used to study the heart, lungs, and metabolism. Many experiments sponsored by the European Space Agency (ESA) will be conducted using ARMS during STS-107. The near-weightless environment of space causes the body to undergo many physiological adaptations, and the regulation of blood pressure is no exception. Astronauts also experience a decrease in blood volume as an adaptation to microgravity. Reduced blood volume may not provide enough blood pressure to the head during entry or landing. As a result, astronauts often experience light-headedness, and sometimes even fainting, when they stand shortly after returning to Earth. To help regulate blood pressure and heart rate, baroreceptors, sensors located in artery walls in the neck and near the heart, control blood pressure by sending information to the brain and ensuring blood flow to organs. These mechanisms work properly in Earth's gravity but must adapt in the microgravity environment of space. However, upon return to Earth during entry and landing, the cardiovascular system must readjust itself to gravity, which can cause fluctuation in the control of blood pressure and heart rate. Although the system recovers in hours or days, these occurrences are not easily predicted or understood - a puzzle investigators will study with the ARMS equipment. In space, researchers can focus on aspects of the cardiovascular system normally masked by gravity. The STS-107 experiments using ARMS will provide data on how the heart and lungs function in space, as well as how the nervous system controls them. Exercise will also be combined with breath holding and straining (the Valsalva maneuver) to test how heart rate and blood pressure react to different stresses. This understanding will improve astronauts' cardiopulmonary function after return to Earth, and may well help Earthbound patients who experience similar effects after long-term bed rest.

Andre Kuipers↗

Effects of Three-Day Bed Rest on Physiological Responses to Graded Exercise in Endurance Athletes, Body Builders and Sedentary Men

To test the hypotheses that short-term bed rest (BR) deconditioning influences metabolic, cardiorespiratory and neurohormonal responses to exercise and that these effects depend on the subjects' training status 12 sedentary men, and 10 endurance- and 10 strength-trained athletes were submitted to three-day BR. Before and after BR they performed incremental exercise test until volitional exhaustion. Respiratory gas exchange and HR were recorded continuously and stroke volume (SV) was measured at submaximal loads. Blood was taken for lactate [LA], adrenaline [A], noradrenaline, [NA], renting activity (PRA), growth hormone [hGH], testosterone and cortisol determination. Reduction of peak oxygen uptake (VO2peak) after BR was greater in the endurance athletes (than in the remaining groups (17 % vs. 100%). Decrements in VO2peak correlated positively with the initial values (r = 0.73, p less than 0.001). Resting and exercise respiratory exchange ratios were increased in athletes. Cardiac output was unchanged by BR in all groups, but exercise HR was increased and SV diminished in the sedentary subjects. The submaximal [LA] and [LA] thresholds were decreased the in endurance athletes from 71 to 60 %VO2 peak (p less than 0.001); they also had an earlier increase in [NA], and an attenuated increase in [hGH), and accentuated PRA and cortisol elevations during exercise. These effects were insignificant in the remaining subjects. In conclusion: reduction of exercise performance and modifications in neurohormonal response to exercise after BR depend on the previous level and mode of physical training, being the most pronounced in the endurance athletes.

Smorawinski, J.↗

Effects of Three-Day Bed Rest on Physiological Responses to Graded Exercise in Endurance Athletes, Body Builders and Sedentary Men

To test the hypotheses that short-term bed rest (BR) deconditioning influences metabolic, cardiorespiratory and neurohormonal responses to exercise and that these effects depend on the subjects' training status, 12 sedentary men, and 10 endurance- and 10 strength-trained athletes were submitted to three-day BR. Before and after BR they performed incremental exercise tests until volitional exhaustion. Respiratory gas exchange and HR were recorded continuously and stroke volume (SV) was measured at submaximal loads. Blood was taken for lactate [LA], adrenaline [A], noradrenaline [NA], renin activity (PRA), growth hormone [hGH], testosterone and cortisol determination. Reduction of peak oxygen uptake (V02peak) after BR was greater in the endurance athletes than in the remaining groups (17 % vs. 10%). Decrements in VO2peak correlated positively with the initial values (r = 0.73, p is less than 0.001). Resting and exercise respiratory exchange ratios were increased in athletes. Cardiac output was unchanged by BR in all groups, but exercise HR was increased and SV diminished in the sedentary subjects. The submaximal [LA] and [LA] thresholds were decreased the in endurance athletes from 71 to 60% V02 peak (p is less than0.001), they also had an earlier increase in [NA], an attenuated increase in [hGH], and accentuated PRA and cortisol elevations during exercise. These effects were insignificant in the remaining subjects. In conclusion: reduction of exercise performance and modifications in neurohormonal response to exercise after BR depend on the previous level and mode of physical training, being the most pronounced in the endurance athletes.

Smorawinski, J.↗

Allowable exposure limits for carbon dioxide during extravehicular activity

The intent was to review the research pertaining to human exposure to carbon dioxide (CO2) and to recommend allowable exposure limits for extravehicular activity (EVA). Respiratory, renal, and gastrointestinal systems may be adversely affected by chronic low dose CO2 exposure. Ventilation was increased 15 percent with 1 percent CO2 and 50 percent with 2 percent CO2. Chronic exposure to less than 2 percent CO2 led to 20 day cycles of uncompensated and compensated respiratory acidosis. Acid-base changes were small. Histopathologic changes in guinea pig lungs have been noted with long term exposure to 1 percent CO2. No changes were seen with exposure to 0.5 percent CO2. Cycling of bone calcium stores with associated changes in blood and urinary calcium levels occurs with long term CO2 exposure. Histologic changes in bone have been noted in guinea pigs exposed to 1 percent CO2. Renal calcification has been noted in guinea pigs with exposure to as low as 0.5 percent CO2. An increase in gastric acidity was noted in subjects with long term exposure to 1 percent CO2. Cardiovascular and neurologic function were largely unaffected. A decrease in the incidence of respiratory, renal, and gastrointestinal disease was noted in submariners coincident with a decrease in ambient CO2 from 1.2 percent to 0.8-0.9 percent. Oxygen (O2) and CO2 stimulate respiration independently and cumulatively. The addition of CO2 to high dose O2 led to the faster onset of seizure activity in mice. Experiments evaluating the physiologic responses to intermittent, repetitive exposures to low dose CO2 and 100 percent O2 mixtures should be performed. A reduction in the current NASA standard for CO2 exposure during EVA of 1 percent (7.6 mmHg) for nominal and 2 percent (15.2 mmHg) for heavy exertion to 0.5 percent (3.8 mmHg) for nominal and 1 percent (7.6 mmHg) for heavy exertion may be prudent. At a minimum, the current NASA standard should not be liberalized.

Seter, Andrew J.↗

Electron Transfer Beyond the Outer Membrane: Putting Electrons to Rest

Extracellular electron transfer (EET) is the physiological process that enables the reduction or oxidation of molecules and minerals beyond the surface of a microbial cell. The first bacteria characterized with this capability were Shewanella and Geobacter, both reported to couple their growth to the reduction of iron or manganese oxide minerals located extracellularly. A key difference between EET and nearly every other respiratory activity on Earth is the need to transfer electrons beyond the cell membrane. The past decade has resolved how well-conserved strategies conduct electrons from the inner membrane to the outer surface. However, recent data suggest a much wider and less well understood collection of mechanisms enabling electron transfer to distant acceptors. This review reflects the current state of knowledge from Shewanella and Geobacter, specifically focusing on transfer across the outer membrane and beyond—an activity that enables reduction of highly variable minerals, electrodes, and even other organisms.

59 BASIC BIOLOGICAL SCIENCES↗

Olivine Dissolution in Simulated Lung and Gastric Fluid as an Analog to the Behavior of Lunar Particulate Matter Inside the Human Respiratory and Gastrointestinal Systems

With the Artemis III mission scheduled to land humans on the Moon in 2025, work must be done to understand the hazards lunar dust inhalation would pose to humans. In this study, San Carlos olivine was used as an analog of lunar olivine, a common component of lunar dust. Olivine was dissolved in a flow-through apparatus in both simulated lung fluid and 0.1 M HCl (simulated gastric fluid) over a period of approximately 2 weeks at physiological temperature, 37°C. Effluent samples were collected periodically and analyzed for pH, iron, silicon, and magnesium ion concentrations. The dissolution rate data derived from our measurements allow us to estimate that an inhaled 1.0 μm diameter olivine particle would take approximately 24 years to dissolve in the human lungs and approximately 3 weeks to dissolve in gastric fluid. Results revealed that inhaled olivine particles may generate the toxic chemical, hydroxyl radical, for up to 5–6 days in lung fluid. Olivine dissolved in 0.1 M HCl for 2 weeks transformed to an amorphous silica-rich solid plus the ferric iron oxy-hydroxide ferrihydrite. Olivine dissolved in simulated lung fluid shows no detectable change in composition or crystallinity. Equilibrium thermodynamic models indicate that olivine in the human lungs can precipitate secondary minerals with fibrous crystal structures that have the potential to induce detrimental health effects similar to asbestos exposure. Our work indicates that inhaled lunar dust containing olivine can settle in the human lungs for years and could induce long-term potential health effects like that of silicosis.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Controlled breathing protocols probe human autonomic cardiovascular rhythms

The purpose of this study was to determine how breathing protocols requiring varying degrees of control affect cardiovascular dynamics. We measured inspiratory volume, end-tidal CO2, R-R interval, and arterial pressure spectral power in 10 volunteers who followed the following 5 breathing protocols: 1) uncontrolled breathing for 5 min; 2) stepwise frequency breathing (at 0.3, 0.25, 0.2, 0.15, 0.1, and 0.05 Hz for 2 min each); 3) stepwise frequency breathing as above, but with prescribed tidal volumes; 4) random-frequency breathing (approximately 0.5-0.05 Hz) for 6 min; and 5) fixed-frequency breathing (0.25 Hz) for 5 min. During stepwise breathing, R-R interval and arterial pressure spectral power increased as breathing frequency decreased. Control of inspired volume reduced R-R interval spectral power during 0.1 Hz breathing (P < 0.05). Stepwise and random-breathing protocols yielded comparable coherence and transfer functions between respiration and R-R intervals and systolic pressure and R-R intervals. Random- and fixed-frequency breathing reduced end-tidal CO2 modestly (P < 0.05). Our data suggest that stringent tidal volume control attenuates low-frequency R-R interval oscillations and that fixed- and random-rate breathing may decrease CO2 chemoreceptor stimulation. We conclude that autonomic rhythms measured during different breathing protocols have much in common but that a stepwise protocol without stringent control of inspired volume may allow for the most efficient assessment of short-term respiratory-mediated autonomic oscillations.

Non-NASA Center↗

Noninvasive Breath Analysis Using NASA E-Nose Technology for Health Assessment

Clinical breath analysis is based on the fact that many important metabolites and biomarker molecules are present at detectable levels in exhaled breath, and many of these molecules correlate with human disease or correlate with physiological states that could lead to a decline in health. Presented is a technology that utilizes an array of chemical sensors combined with humidity, temperature and pressure for real time breath analysis to correlate the chemical information in the breath with the state and functioning of different human organs. For example, a marker for pulmonary inflammation processes of the lower respiratory tract, e.g. asthma, is the increase of the nitrogen oxide (NO) concentration in breath. Other volatile biomarkers may correlate with infectious process, metabolic conditions and inflammatory diseases, such as traumatic brain injury (TBI). This technology is also called "electronic nose" (E-Nose) in the sense that the device can mimic human nose to smell odors using a pattern recognition technique to analyze the sensor array data. Breath sampling is non-invasive and can be analyzed in real-time.

Li, Jing↗

The physiological effects of simultaneous exposures to heat and vibration

Determination of the effects of exposure to vibration on the body's ability to handle heat stress, and, if so, identification of the specific vibration parameters (frequency and intensity) for both whole-body (wbv) and segmental-body vibration (sbv) that would have the most detrimental effect on the body's ability to maintain thermal homeostasis were studied. Rectal and skin temperatures, heart rates, localized sweat rates, arm-segment blood perfusion rates, respiration rates, oxygen uptakes, and respiratory exchange ratios were measured in six men (22 to 33 yr) during simultaneous exposures to heat and vibration - either wbv or sbv, and during a heated 50 min recovery period. The heat conditions were T (sub db) = 43.5 + or - 0.5 C (mean + or S.E.M.), and RH = 20 + or - 4%. All vibration exposures were divided into two exposure conditions - identical frequencies but at a high intensity (HI) and a low intensity (LI) level. The HI wbv exposure was for 25 min/day at 5 Hz, 0.37 g-rms; 10 Hz, 0.46 g-rms; 16 Hz, 0.72 g-rms; 30 Hz, 1.40 g-rms; 80 Hz, 3.70 g-rms. The LI wbv exposure was for 2.5 hr/day at the same frequencies but at the following accelerations: 0.14 g-rms; 0.18 g-rms; 0.28 g-rms; 0.55 g-rms; 1.44 g-rms. During the sbv the subject stood and grasped a vibrating, in the Z-axis, hand grip with both hands.

Spaul, W. A.↗

Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing

The COVID-19 pandemic has resulted in 198 million reported infections and more than 4 million deaths as of July 2021 (covid19.who.int). Research to identify effective therapies for COVID-19 includes: (1) designing a vaccine as future protection; (2) de novo drug discovery; and (3) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determine two apo structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease at ambient temperature by serial femtosecond X-ray crystallography. We employ detailed molecular simulations of selected known main protease inhibitors with the structures and compare binding modes and energies. The combined structural and molecular modeling studies not only reveal the dynamics of small molecules targeting the main protease but also provide invaluable opportunities for drug repurposing and structure-based drug design strategies against SARS-CoV-2.

59 BASIC BIOLOGICAL SCIENCES↗

Heterotrophic Thaumarchaea with Small Genomes Are Widespread in the Dark Ocean

The Thaumarchaeota is a diverse archaeal phylum comprising numerous lineages that play key roles in global biogeochemical cycling, particularly in the ocean. To date, all genomically characterized marine thaumarchaea are reported to be chemolithoautotrophic ammonia oxidizers. In this study, we report a group of putatively heterotrophic marine thaumarchaea (HMT) with small genome sizes that is globally abundant in the mesopelagic, apparently lacking the ability to oxidize ammonia. We assembled five HMT genomes from metagenomic data and show that they form a deeply branching sister lineage to the ammonia-oxidizing archaea (AOA). We identify this group in metagenomes from mesopelagic waters in all major ocean basins, with abundances reaching up to 6% of that of AOA. Surprisingly, we predict the HMT have small genomes of ~1 Mbp, and our ancestral state reconstruction indicates this lineage has undergone substantial genome reduction compared to other related archaea. The genomic repertoire of HMT indicates a versatile metabolism for aerobic chemoorganoheterotrophy that includes a divergent form III-a RuBisCO, a 2M respiratory complex I that has been hypothesized to increase energetic efficiency, and a three-subunit heme-copper oxidase complex IV that is absent from AOA. We also identify 21 pyrroloquinoline quinone (PQQ)-dependent dehydrogenases that are predicted to supply reducing equivalents to the electron transport chain and are among the most highly expressed HMT genes, suggesting these enzymes play an important role in the physiology of this group. Our results suggest that heterotrophic members of the Thaumarchaeota are widespread in the ocean and potentially play key roles in global chemical transformations.

59 BASIC BIOLOGICAL SCIENCES↗

Alterations in mitochondria and sarcoplasmic reticulum from heart and skeletal muscle of horizontally casted primates

Horizontally body-casted rhesus monkeys are used as an animal model in order to study the physiological changes known as cardiovascular deconditioning which occur during weightless conditions. No difference was found between the experimental and control animals in heart mitochondrial oxidative phosphorylation which indicates that no apparent changes occurred in the primary energy-producing system of the heart. A marked increase in cytochrome oxidase activity was observed in the casted primate heart mitochondria compared to controls, while a 25% decrease in respiratory substrate-supported calcium uptake was found in casted primate heart mitochondria compared to controls. Sacroplasmic reticulum isolated from the primate hearts revealed marked changes in calcium transport activities. It is concluded that the marked depression in cardiac sarcoplasmic reticulum functions indicates altered calcium homeostasis in the casted-primate heart which could be a factor in cardiovascular deconditioning.

Sordahl, L. A.↗