Effect of isolation in a constant environment on periodicity of physiological functions and performance levels.
Isolation effects in constant environment on cycles of physiological functions and performance levels of man
HUMAN REACTION↗
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An on-line digital integrator for physiological data.
On-line digital integrator for physiological data
PHYSIOLOGICAL FACTORS↗
Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology
Great advances have been made in the identification of the soluble angiogenic factors, insoluble extracellular matrix (ECM) molecules, and receptor signaling pathways that mediate control of angiogenesis--the growth of blood capillaries. This review focuses on work that explores how endothelial cells integrate these chemical signals with mechanical cues from their local tissue microenvironment so as to produce functional capillary networks that exhibit specialized form as well as function. These studies have revealed that ECM governs whether an endothelial cell will switch between growth, differentiation, motility, or apoptosis programs in response to a soluble stimulus based on its ability to mechanically resist cell tractional forces and thereby produce cell and cytoskeletal distortion. Transmembrane integrin receptors play a key role in this mechanochemical transduction process because they both organize a cytoskeletal signaling complex within the focal adhesion and preferentially focus mechanical forces on this site. Molecular filaments within the internal cytoskeleton--microfilaments, microtubules, and intermediate filaments--also contribute to the cell's structural and functional response to mechanical stress through their role as discrete support elements within a tensegrity-stabilized cytoskeletal array. Importantly, a similar form of mechanical control also has been shown to be involved in the regulation of contractility in vascular smooth muscle cells and cardiac myocytes. Thus, the mechanism by which cells perform mechanochemical transduction and the implications of these findings for morphogenetic control are discussed in the wider context of vascular development and cardiovascular physiology.
Non-NASA Center↗
Physiological changes, sleep, and morning mood in an isolated environment
BACKGROUND: Previous isolation studies have shown increased 24-h urine volumes and body weight gains in subjects. This project examined those and other physiological variables in relationship to sleep motor activity, subjective sleep quality, mood, and complaints during confinement. METHODS: Six male and two female subjects lived for 7 d in the National Space Development Agency of Japan's isolation chamber, which simulates the interior of the Japanese Experiment Module. Each 24-h period included 6 h of sleep, 3 meals, and 20 min of exercise. Each morning, subjects completed Sleep Sensation and Complaint Index questionnaires. Catecholamine and creatinine excretion, urine volume, and body weight were measured on the 2 d before and 2 d after confinement, and sleep motor activity was measured during confinement. RESULTS: Confinement produced no significant change in body weight, urine volume, or questionnaire results. In contrast, epinephrine, norepinephrine, and sleep motor activity exhibited significant differences during confinement (p < 0.05). Higher nocturnal norepinephrine excretion correlated with higher sleep motor activity. CONCLUSION: The 24-h epinephrine values were slightly higher than normal throughout the experiment, but lower than for subjects working under time-stress. High sympathetic activity (as indicated by norepinephrine) may have interfered with sleep.
NASA Discipline Space Human Factors↗
The exercise and environmental physiology of extravehicular activity
Extravehicular activity (EVA), i.e., exercise performed under unique environmental conditions, is indispensable for supporting daily living in weightlessness and for further space exploration. From 1965-1996 an average of 20 h x yr(-1) were spent performing EVA. International Space Station (ISS) assembly will require 135 h x yr(-1) of EVA, and 138 h x yr(-1) is planned for post-construction maintenance. The extravehicular mobility unit (EMU), used to protect astronauts during EVA, has a decreased pressure of 4.3 psi that could increase astronauts' risk of decompression sickness (DCS). Exercise in and repeated exposure to this hypobaria may increase the incidence of DCS, although weightlessness may attenuate this risk. Exercise thermoregulation within the EMU is poorly understood; the liquid cooling garment (LCG), worn next to the skin and designed to handle thermal stress, is manually controlled. Astronauts may become dehydrated (by up to 2.6% of body weight) during a 5-h EVA, further exacerbating the thermoregulatory challenge. The EVA is performed mainly with upper body muscles; but astronauts usually exercise at only 26-32% of their upper body maximal oxygen uptake (VO2max). For a given ground-based work task in air (as opposed to water), the submaximal VO2 is greater while VO2max and metabolic efficiency are lower during ground-based arm exercise as compared with leg exercise, and cardiovascular responses to exercise and training are also different for arms and legs. Preflight testing and training, whether conducted in air or water, must account for these differences if ground-based data are extrapolated for flight requirements. Astronauts experience deconditioning during microgravity resulting in a 10-20% loss in arm strength, a 20-30% loss in thigh strength, and decreased lower-body aerobic exercise capacity. Data from ground-based simulations of weightlessness such as bed rest induce a 6-8% decrease in upper-body strength, a 10-16% loss in thigh extensor strength, and a 15-20% decrease in lower-body aerobic exercise capacity. Changes in EVA support systems and training based on a greater understanding of the physiological aspects of exercise in the EVA environment will help to insure the health, safety, and efficiency of working astronauts.
Review↗
Physiological assessment of bacteria using fluorochromes
This minireview focuses on the application of fluorogenic compounds in the detection of bacteria with particular emphasis on the assessment of physiological activity using epifluorescence microscopy. Microbiological applications of several related methods will also be reviewed.
NASA Discipline Environmental Health↗
Polyamines in plant physiology
The diamine putrescine, the triamine spermidine, and the tetramine spermine are ubiquitous in plant cells, while other polyamines are of more limited occurrence. Their chemistry and pathways of biosynthesis and metabolism are well characterized. They occur in the free form as cations, but are often conjugated to small molecules like phenolic acids and also to various macromolecules. Their titer varies from approximately micromolar to more than millimolar, and depends greatly on environmental conditions, especially stress. In cereals, the activity of one of the major polyamine biosynthetic enzymes, arginine decarboxylase, is rapidly and dramatically increased by almost every studied external stress, leading to 50-fold or greater increases in putrescine titer within a few hours. The physiological significance of this increase is not yet clear, although most recent work suggests an adaptive, protective role. Polyamines produced through the action of ornithine decarboxylase, by contrast, seem essential for DNA replication and cell division. The application of exogenous polyamines produces effects on patterns of senescence and morphogenesis, suggesting but not proving a regulatory role for polyamines in these processes. The evidence for such a regulatory role is growing.
Review↗
The prevention of adverse physiological change in Space Station crewmembers
Various physiological countermeasures, consisting primarily of isotonic and isometric exercises but also including prescribed nutrient intake, have been used in all manned spaceflights exceeding about one month in duration. So consistent has been this practice that the effects of weightlessness on the human, unconfounded by the use of countermeasures, are difficult to discern. Equally elusive, in the absence of control studies conducted in weightlessness, is an accurate assessment of the efficacy of the countermeasures themselves. Changes in body composition occurring during and following flights from Gemini through Shuttle, when compared with changes during and following bedrest, demonstrate certain mitigating effects that may be attributable to countermeasures and which provide some rationale for the choice of countermeasures in the Space Station.
Skylab Project↗
Physiologic and thermal responses of male and female patients with multiple sclerosis to head and neck cooling
Personal cooling systems are used to alleviate symptoms of multiple sclerosis and to prevent increased core temperature during daily activities. The objective of this study was to determine the thermal and physiologic responses of patients with multiple sclerosis to short-term maximal head and neck cooling. A Life Support Systems, Inc. Mark VII portable cooling system and a liquid cooling helmet were used to cool the head and neck regions of 24 female and 26 male patients with multiple sclerosis in this study. The subjects, seated in an upright position at normal room temperature (approximately 22 degrees C), were cooled for 30 min by the liquid cooling garment, which was operated at its maximum cooling capacity. Oral, right, and left ear temperatures and cooling system parameters were logged manually every 5 min. Forearm, calf, chest, and rectal temperatures, heart rate, and respiration rate were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. This protocol was performed during the winter and summer to investigate the seasonal differences in the way patients with multiple sclerosis respond to head and neck cooling. No significant differences were found between the male and female subject group's mean rectal or oral temperature responses during any phase of the experiment. The mean oral temperature decreased significantly (P < 0.05) for both groups approximately 0.3 degrees C after 30 min of cooling and continued to decrease further (approximately 0.1-0.2 degrees C) for a period of approximately 15 min after removal of the cooling helmet. The mean rectal temperatures decreased significantly (P < 0.05) in both male and female subjects in the winter studies (approximately 0.2-0.3 degrees C) and for the male subjects during the summer test (approximately 0.2 degrees C). However, the rectal temperature of the female subjects did not change significantly during any phase of the summer test. These data indicate that head and neck cooling may, in general, be used to reduce the oral and body temperatures of both male and female patients with multiple sclerosis by the approximate amount needed for symptomatic relief as shown by other researchers. However, thermal response of patients with multiple sclerosis may be affected by gender and seasonal factors, which should be considered in the use of liquid cooling therapy.
NASA Discipline Environmental Health↗
Neocytolysis: physiological down-regulator of red-cell mass
It is usually considered that red-cell mass is controlled by erythropoietin-driven bone marrow red-cell production, and no physiological mechanisms can shorten survival of circulating red cells. In adapting to acute plethora in microgravity, astronauts' red-cell mass falls too rapidly to be explained by diminished red-cell production. Ferrokinetics show no early decline in erythropolesis, but red cells radiolabelled 12 days before launch survive normally. Selective destruction of the youngest circulating red cells-a process we call neocytolysis-is the only plausible explanation. A fall in erythropoietin below a threshold is likely to initiate neocytolysis, probably by influencing surface-adhesion molecules. Recognition of neocytolysis will require re-examination of the pathophysiology and treatment of several blood disorders, including the anaemia of renal disease.
Review, Tutorial↗
Exercise as a countermeasure for physiological adaptation to prolonged spaceflight
Exercise represents the primary countermeasure used during spaceflight to maintain or restore maximal aerobic capacity (VO2max), musculoskeletal structure, and orthostatic function. However, no single exercise or combination of prescriptions has proven entirely effective in restoring cardiovascular and musculoskeletal functions to preflight levels following prolonged spaceflight. As human spaceflight exposures increase in duration, assessment and development of various effective exercise-based protective procedures become paramount. This must involve improvement in specific countermeasure prescription as well as development of additional approaches that will allow space travelers greater flexibility and medical safety during long flights. Effective exercise prescription will be based on identification of basic physiological stimuli that maintain normal function in terrestrial gravity and understanding of how specific combinations of exercise characteristics e.g., duration, frequency, intensity, mode) can mimic these stimuli and affect the overall process of adaptation to microgravity. This can be accomplished only with greater emphasis of research on ground-based experiments. Future attention must be directed to improving exercise compliance while minimizing both crew time and the impact of the exercise on life-support resources.
Skylab Project↗
Physiological adaptations and countermeasures associated with long-duration spaceflights
Since 1961, there have been more than 165 flights involving several hundred individuals who have remained in a space environment from 15 min to more than a year. In addition, plans exist for humans to explore, colonize, and remain in microgravity for 1000 d or more. This symposium will address the current state of knowledge in select aspects associated with the cardiovascular, fluid and electrolytes, musculoskeletal, and the neuroendocrine and immune systems. The authors will focus on responses, mechanisms, and the appropriate countermeasures to minimize or prevent the physiological and biochemical consequences of a microgravity environment. Since exercise is frequently cited as a generic countermeasure, this topic will be covered in greater detail. Models for simulated microgravity conditions will be discussed in subsequent manuscripts, as will future directions for ground-based research.
NASA Center ARC↗
Nutrition and human physiological adaptations to space flight
Space flight provides a model for the study of healthy individuals undergoing unique stresses. This review focuses on how physiological adaptations to weightlessness may affect nutrient and food requirements in space. These adaptations include reductions in body water and plasma volume, which affect the renal and cardiovascular systems and thereby fluid and electrolyte requirements. Changes in muscle mass and function may affect requirements for energy, protein and amino acids. Changes in bone mass lead to increased urinary calcium concentrations, which may increase the risk of forming renal stones. Space motion sickness may influence putative changes in gastro-intestinal-hepatic function; neurosensory alterations may affect smell and taste. Some or all of these effects may be ameliorated through the use of specially designed dietary countermeasures.
Review↗
Nitrogen dynamics and physiological N use efficiency in high‐biomass sorghum
Improving nitrogen (N) efficiency is essential for sustainable high-biomass sorghum ( Sorghum bicolor L. Moench) production. This study evaluated leaf and stem N dynamics, canopy N remobilization, and physiological nitrogen use efficiency (pNUE) in two photoperiod-sensitive sorghum hybrids under two N rates (0 and 168 kg-N ha −1 ) across multiple environments in Texas and Illinois. Leaf N concentrations increased with plant height in the canopy with steeper gradients under low-N conditions, indicating enhanced N remobilization when N is limited. Stem tissue showed less variation in N concentration across canopy nodal positions, with within-plant differences ranging from 1.2 to 7.6 g kg −1 , compared to 3.1 to 16.3 g kg −1 in leaves. While pNUE was generally higher under unfertilized conditions, it varied largely by site; however, genotypic differences were minimal within the given year. These results highlight the importance of integrating environmental and management factors into breeding and fertilization strategies to enhance N efficiency in high-biomass sorghum.
60 APPLIED LIFE SCIENCES↗
Evaluating the combined effects of light and water availability on the early growth and physiology of Tamarindus indica : Implications for restoration
Abstract Premise The tamarind tree (Tamarindus indica) is a species of significant cultural, economic, and ecological value, with a pantropical distribution. However, the tamarind is experiencing a decline in wild populations in its native range, but the reasons for its decline remain unknown. Methods We examined the critical early life‐history stages for tamarind establishment to understand how varying levels of light and water availability and watering frequency affect its regeneration. Through three greenhouse experiments, we assessed the impact of these resources on the germination, survival, growth, and physiological responses of tamarind seedlings and saplings. Results Water availability was critical for seed germination, but not light levels or pre‐germination treatments. Light was the primary limiting factor for seedling growth. Tamarinds in high light availability grew taller, had more biomass and larger diameter, but the effect of light was modulated by water availability, indicating that there was an interaction between both resources. Water and light affected specific leaf area and leaf dry matter content but not biomass allocation, root‐to‐shoot ratio, or stomatal conductance. Water availability influenced sapling growth, but watering frequency did not, indicating a resilience of tamarind saplings to changes in rainfall periodicity but a sensitivity to total rainfall amounts. Conclusions Our study underscores the importance of considering both light and water availability in tamarind restoration efforts and contribute to understanding plant responses and trade‐offs under different levels of critical resources. Our findings will inform conservation strategies to support the regeneration and long‐term survival ofTamarindus indicain its native habitats.
Plant Sciences↗
A Novel Physiologically Based Model of Creatinine Renal Disposition to Integrate Current Knowledge of Systems Parameters and Clinical Observations
Creatinine is the most common clinical biomarker of renal function. As a substrate for renal transporters, its secretion is susceptible to inhibition by drugs, resulting in transient increase in serum creatinine and false impression of damage to kidney. Novel physiologically based models for creatinine were developed here and (dis)qualified in a stepwise manner until consistency with clinical data. Data from a matrix of studies were integrated, including systems data (common to all models), proteomics‐informed in vitro – in vivo extrapolation of all relevant transporter clearances, exogenous administration of creatinine (to estimate endogenous synthesis rate), and inhibition of different renal transporters (11 perpetrator drugs considered for qualification during creatinine model development and verification on independent data sets). The proteomics‐informed bottom‐up approach resulted in the underprediction of creatinine renal secretion. Subsequently, creatinine‐trimethoprim clinical data were used to inform key model parameters in a reverse translation manner, highlighting best practices and challenges for middle‐out optimization of mechanistic models.
Scotcher, Daniel↗
Regulatory utility of physiologically based pharmacokinetic modeling for assessing food impact in bioequivalence studies: A workshop summary report
This workshop report summarizes the presentations and panel discussion related to the use of physiologically based pharmacokinetic (PBPK) modeling approaches for food effect assessment, collected from Session 2 of Day 2 of the workshop titled “Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches.” The US Food and Drug Administration in collaboration with the Center for Research on Complex Generics organized this workshop where this particular session titled “Oral PBPK for Evaluating the Impact of Food on BE” presented successful cases of PBPK modeling approaches for food effect assessment. Recently, PBPK modeling has started to gain popularity among academia, industries, and regulatory agencies for its potential utility during bioavailability (BA) and/or bioequivalence (BE) studies of new and generic drug products to assess the impact of food on BA/BE. Considering the promises of PBPK modeling in generic drug development, the aim of this workshop session was to facilitate knowledge sharing among academia, industries, and regulatory agencies to understand the knowledge gap and guide the path forward. This report collects and summarizes the information presented and discussed during this session to disseminate the information into a broader audience for further advancement in this area.
60 APPLIED LIFE SCIENCES↗
Extracellular electron uptake by autotrophic microbes: physiological, ecological, and evolutionary implications
Abstract Microbes exchange electrons with their extracellular environment via direct or indirect means. This exchange is bidirectional and supports essential microbial oxidation–reduction processes, such as respiration and photosynthesis. The microbial capacity to use electrons from insoluble electron donors, such as redox-active minerals, poised electrodes, or even other microbial cells is called extracellular electron uptake (EEU). Autotrophs with this capability can thrive in nutrient and soluble electron donor-deficient environments. As primary producers, autotrophic microbes capable of EEU greatly impact microbial ecology and play important roles in matter and energy flow in the biosphere. In this review, we discuss EEU-driven autotrophic metabolisms, their mechanism and physiology, and highlight their ecological, evolutionary, and biotechnological implications.
59 BASIC BIOLOGICAL SCIENCES↗