Search NASA⌕ Search

SEARCH · Search NASA

Results for “dynamic metabolic regulation”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

14 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2000

Dynamics of Molecular Hydrogen in Hypersaline Microbial Mars

Early Earth microbial communities that centered around the anaerobic decomposition of organic molecular hydrogen as a carrier of electrons, regulator of energy metabolism, and facilitator of syntroph'c microbial interactions. The advent of oxygenic photosynthetic organisms added a highly dynamic and potentially dominant term to the hydrogen economy of these communities. We have examined the daily variations of hydrogen concentrations in cyanobacteria-dominated microbial mats from hypersaline ponds in Baja California Sur, Mexico. These mats bring together phototrophic and anaerobic bacteria (along with virtually all other trophic groups) in a spatially ordered and chemically dynamic matrix that provides a good analog for early Earth microbial ecosystems. Hydrogen concentrations in the photic zone of the mat can be three orders of magnitude or more higher than in the photic zone, which are, in turn, an order of magnitude higher than in the unconsolidated sediments underlying the mat community. Within the photic zone, hydrogen concentrations can fluctuate dramatically during the diel (24 hour day-night) cycle, ranging from less than 0.001% during the day to nearly 10% at night. The resultant nighttime flux of hydrogen from the mat to the environment was up to 17% of the daytime oxygen flux. The daily pattern observed is highly dependent on cyanobacterial species composition within the mat, with Lyngbya-dominated systems having a much greater dynamic range than those dominated by Microcoleus; this may relate largely to differing degrees of nitrogen-fixing and fermentative activity in the two mats. The greatest H2 concentrations and fluxes were observed in the absence of oxygen, suggesting an important potential feedback control in the context of the evolution of atmospheric composition. The impact of adding this highly dynamic photosynthetic term to the hydrogen economy of early microbial ecosystems must have been substantial. From an evolutionary standpoint, the H2 generated in mats could have represented a very important new source of electrons and energy - but one that could not be harnessed without substantial adaptation to the highly variable chemistry of the mat surface. In addition, the emergent chemistry of anaerobic communities is often highly dependent on ambient hydrogen concentrations, so that incorporation of these communities into photosynthetic mats could have significantly affected the composition and flux of reduced "biosignature' gases to the environment.

Hoehler, Tori M.↗
NASA NTRS1978

Water-salt exchange during bedrest of varying duration

Problems associated with the status of water-sodium metabolism under bedrest programs of varying lengths were studied. The dynamics of electrolyte concentration in blood serum, functional status of kidney osmosis regulating function, and other problems are discussed.

Natochin, Y. V.↗
NASA NTRS1999

Control of skeletal muscle perfusion at the onset of dynamic exercise

At the onset of exercise there is a rapid increase in skeletal muscle vascular conductance and blood flow. Several mechanisms involved in the regulation of muscle perfusion have been proposed to initiate this hyperemic response, including neural, metabolic, endothelial, myogenic, and muscle pump mechanisms. Investigators utilizing pharmacological blockade of cholinergic muscarinic receptors and sympathectomy have concluded that neither sympathetic cholinergic nor adrenergic neural mechanisms are involved in the initial hyperemia. Studies have also shown that the time course for vasoactive metabolite release, diffusion, accumulation, and action is too long to account for the rapid increase in vascular conductance at the initiation of exercise. Furthermore, there is little or no evidence to support an endothelium or myogenic mechanism as the initiating factor in the muscle hyperemia. Thus, the rise in muscle blood flow does not appear to be explained by known neural, metabolic, endothelial, or myogenic influences. However, the initial hyperemia is consistent with the mechanical effects of the muscle pump to increase the arteriovenous pressure gradient across muscle. Because skeletal muscle blood flow is regulated by multiple and redundant mechanisms, it is likely that neural, metabolic, and possibly endothelial factors become important modulators of mechanically induced exercise hyperemia following the first 5-10 s of exercise.

Review, Tutorial↗
NASA NTRSDate not supplied

Bioreactor Development for CO2-Based In Situ Resource Utilization Manufacturing

Sustainable long-duration manned missions on both the Moon and Mars will require in situ resource utilization (ISRU). Carbon dioxide (CO2) has great potential as a harvestable resource, making up 95% of the atmosphere on Mars and being produced as respiratory waste in spacecraft and future planetary habitats. Through ISRU, biomanufacturing has the capability to produce a near limitless array of products from local space resources, which include pharmaceuticals, bioplastics, chemical feedstocks, and industrial enzymes. Here, a CO2-based ISRU recombinant protein bioreactor and associated biomanufacturing organisms were designed to produce a highly stable carbonic anhydrase (CA). Initial work characterized candidate organisms for growth on acetate and formic acid, carbon substrates that can be synthesized via electrochemical conversion of CO2. To improve growth on the CO2 producing substrate formic acid and for direct integration of ISRU CO2, a synthetic Calvin-Benson-Bassam cycle was designed for use in Cyberlindnera jadinii and Escherichia coli. Genetic modifications in E. coli will be facilitated by a tailored CRISPR/Cas9 and λ red recombineering two-vector system. For expression of CA, a blue light regulated T7 promoter was employed for dynamic and small molecule free induction. Efficient bioproduction through a fed-batch exponential feeding strategy was determined via mass balance calculations from ISRU substrates to biomass and CA yield. Flux balance analysis was used to model ISRU substrate metabolism and metabolic pathway engineering in candidate organisms under cultivation strategy conditions for both metabolism reconstruction and pathway design optimization. Finally, a small-scale, disposable bag bioreactor concept for use in the NASA Bioculture System infrastructure was designed to enable CO2-based CA production in reduced-gravity environments.

Biomanufacturing, Pathway Engineering, Flux Balanc↗
NASA NTRSDate not supplied

Bioreactor Development for CO2-Based In Situ Resource Utilization Manufacturing

Sustainable long-duration manned missions on both the Moon and Mars will require in situ resource utilization (ISRU). Carbon dioxide (CO2) has great potential as a harvestable resource, making up 95% of the atmosphere on Mars and being produced as respiratory waste in spacecraft and future planetary habitats. Through ISRU, biomanufacturing has the capability to produce a near limitless array of products from local space resources. Here, a CO2-based ISRU recombinant protein producing bioreactor and associated biomanufacturing organisms were designed to produce a highly stable carbonic anhydrase (CA). Candidate organisms were selected by growth characterization on acetate and formic acid, carbon substrates that are synthesized via electrochemical conversion of CO2. To improve growth on the CO2 producing substrate formic acid and for direct integration of ISRU CO2, a synthetic Calvin-Benson-Bassam cycle was designed for use in Escherichia coli. Multiplex genetic modification in E. coli was facilitated by a tailored CRISPR/Cas9 and λ red recombineering two-vector system. For expression of CA, a blue light regulated T7 promoter was employed for dynamic and small molecule free induction. Efficient bioproduction through a fed-batch exponential feeding strategy was determined via mass balance analysis from ISRU substrates to biomass and CA yield. Flux balance analysis was used to model ISRU substrate metabolism and metabolic pathway engineering in candidate organisms under cultivation strategy conditions for both metabolism reconstruction and pathway design optimization. Finally, a small-scale, disposable bag bioreactor for use in the NASA Bioculture System infrastructure was designed to enable CO2-based CA biomanufacturing in reduced-gravity environments.

biomanufacturing↗
NASA NTRS1999

A Quantitative Study of Oxygen as a Metabolic Regulator

An acute reduction in oxygen (O2) delivery to a tissue is generally associated with a decrease in phosphocreatine, increases in ADP, NADH/NAD, and inorganic phosphate, increased rates of glycolysis and lactate production, and reduced rates of pyruvate and fatty acid oxidation. However, given the complexity of the human bioenergetic system and its components, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in tissue O2 availability affect the pathways of ATP synthesis and the metabolites that control these pathways. In this study, we extend a previously developed mathematical model of human bioenergetics to provide a physicochemical framework that permits quantitative understanding of O2 as a metabolic regulator. Specifically, the enhancement permits studying the effects of variations in tissue oxygenation and in parameters controlling the rate of cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The whole body is described as a bioenergetic system consisting of metabolically distinct tissue/organ subsystems that exchange materials with the blood. In order to study the dynamic response of each subsystem to stimuli, we solve the ordinary differential equations describing the temporal evolution of metabolite levels, given the initial concentrations. The solver used in the present study is the packaged code LSODE, as implemented in the NASA Lewis kinetics and sensitivity analysis code, LSENS. A major advantage of LSENS is the efficient procedures supporting systematic sensitivity analysis, which provides the basic methods for studying parameter sensitivities (i.e., changes in model behavior due to parameter variation). Sensitivity analysis establishes relationships between model predictions and problem parameters (i.e., initial concentrations, rate coefficients, etc). It helps determine the effects of uncertainties or changes in these input parameters on the predictions, which ultimately are compared with experimental observations in order to validate the model. Sensitivity analysis can identify parameters that must be determined accurately because of their large effect on the model predictions and parameters that need not be known with great precision because they have little or no effect on the solution. This capability may prove to be important in optimizing the design of experiments, thereby reducing the use of animals. This approach can be applied to study the metabolic effects of reduced oxygen delivery to cardiac muscle due to local myocardial ischemia and the effects of acute hypoxia on brain metabolism. Other important applications of sensitivity analysis include identification of quantitatively relevant pathways and biochemical species within an overall mechanism, when examining the effects of a genetic anomaly or pathological state on energetic system components and whole system behavior.

Radhakrishnan, Krishnan↗
NASA NTRS2010

Mapping and Quantification of Vascular Branching in Plants, Animals and Humans by VESGEN Software

Humans face daunting challenges in the successful exploration and colonization of space, including adverse alterations in gravity and radiation. The Earth-determined biology of plants, animals and humans is significantly modified in such extraterrestrial environments. One physiological requirement shared by larger plants and animals with humans is a complex, highly branching vascular system that is dynamically responsive to cellular metabolism, immunological protection and specialized cellular/tissue function. VESsel GENeration (VESGEN) Analysis has been developed as a mature beta version, pre-release research software for mapping and quantification of the fractal-based complexity of vascular branching. Alterations in vascular branching pattern can provide informative read-outs of altered vascular regulation. Originally developed for biomedical applications in angiogenesis, VESGEN 2D has provided novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and other microvascular remodeling phenomena. Vascular trees, networks and tree-network composites are mapped and quantified. Applications include disease progression from clinical ophthalmic images of the human retina; experimental regulation of vascular remodeling in the mouse retina; avian and mouse coronary vasculature, and other experimental models in vivo. We envision that altered branching in the leaves of plants studied on ISS such as Arabidopsis thaliana cans also be analyzed.

Parsons-Wingerter, P. A.↗
NASA NTRS2010

Mapping and Quantification of Vascular Branching in Plants, Animals and Humans by VESGEN Software

Humans face daunting challenges in the successful exploration and colonization of space, including adverse alterations in gravity and radiation. The Earth-determined biology of humans, animals and plants is significantly modified in such extraterrestrial environments. One physiological requirement shared by humans with larger plants and animals is a complex, highly branching vascular system that is dynamically responsive to cellular metabolism, immunological protection and specialized cellular/tissue function. The VESsel GENeration (VESGEN) Analysis has been developed as a mature beta version, pre-release research software for mapping and quantification of the fractal-based complexity of vascular branching. Alterations in vascular branching pattern can provide informative read-outs of altered vascular regulation. Originally developed for biomedical applications in angiogenesis, VESGEN 2D has provided novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and other microvascular remodeling phenomena. Vascular trees, networks and tree-network composites are mapped and quantified. Applications include disease progression from clinical ophthalmic images of the human retina; experimental regulation of vascular remodeling in the mouse retina; avian and mouse coronary vasculature, and other experimental models in vivo. We envision that altered branching in the leaves of plants studied on ISS such as Arabidopsis thaliana cans also be analyzed.

Parsons-Wingerter, Patricia A.↗
NASA NTRS1993

Growth factor involvement in tension-induced skeletal muscle growth

Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

Vandenburgh, Herman H.↗
NASA NTRS1999

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS)

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Review↗
NASA NTRS2000

[Role of membrane lipids in myocardial cytoprotection]

The cardiomyocyte capacity to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. This process is based on a balanced fatty acid (FA) metabolism, because FA is the main fuel of the heart, although the most expensive one in oxygen. The pathway is, however, weakly controlled by the cardiac myocyte which can well regulate FA mitochondrial entry but not cell FA uptake. For this reason, several pathological situations often result from either harmful accumulation of FA and derivatives or excess FA-oxidation. Control of the FA/glucose balance by decreased energy production from FA would thus offer an alternative strategy in the treatment of ischaemia, providing the cardiomyocytes weak ability in handling the non-metabolised FA is controlled. The initiation and the regulation of cardiac contraction both result from membrane activity; the other major role of lipids in the heart is their contribution to membrane homeostasis through phospholipid synthesis pathways and phospholipases. The anti-anginal activity of Trimetazidine, reported as a cytoprotective effect without a haemo-dynamic component; is associated with reduced use of FA for energy. However, accumulation of FA and derivatives has never been observed. Trimetazidine is reported to increase significantly the synthesis of phospholipids without influencing the other lipid classes, thus increasing the incorporation of FA in membrane structures. This cytoprotection appears to be based on the redirection of the use of FA to phospholipid synthesis, which would decrease their availability for energy production. This class of compounds, with the same properties as Trimetazidine, offers a metabolic approach to the treatment of ischaemia.

Cytoprotection/physiology↗
NASA NTRS1982

Computer simulation analysis of the behavior of renal-regulating hormones during hypogravic stress

A computer simulation of a mathematical circulation model is used to study the alterations of body fluids and their electrolyte composition that occur in weightlessness. The behavior of the renal-regulating hormones which control these alterations is compared in simulations of several one-g analogs of weightlessness and space flight. It is shown that the renal-regulating hormones represent a tightly coupled system that responds acutely to volume disturbances and chronically to electrolyte disturbances. During hypogravic conditions these responses lead to an initial suppression of hormone levels and a long-term effect which varies depending on metabolic factors that can alter the plasma electrolytes. In addition, it is found that if pressure effects normalize rapidly, a transition phase may exist which leads to a dynamic multiphasic endocrine response.

Leonard, J. I.↗
NASA NTRS1975

Study report on interfacing major physiological subsystem models: An approach for developing a whole-body algorithm

Using a whole body algorithm simulation model, a wide variety and large number of stresses as well as different stress levels were simulated including environmental disturbances, metabolic changes, and special experimental situations. Simulation of short term stresses resulted in simultaneous and integrated responses from the cardiovascular, respiratory, and thermoregulatory subsystems and the accuracy of a large number of responding variables was verified. The capability of simulating significantly longer responses was demonstrated by validating a four week bed rest study. In this case, the long term subsystem model was found to reproduce many experimentally observed changes in circulatory dynamics, body fluid-electrolyte regulation, and renal function. The value of systems analysis and the selected design approach for developing a whole body algorithm was demonstrated.

Fitzjerrell, D. G.↗
NASA NTRSDate not supplied

Human Thermal Assessment of Traverse and Geology Task Iterations During Simulated Lunar Extravehicular Activity

Spacewalks or extravehicular activities (EVA) in microgravity are mentally and physically demanding. Current microgravity EVAs are predominantly focused on upper body tasks on engineered surfaces; however, the introduction of gravity means that crew members during future lunar EVAs will be required to perform tasks that generate full body workloads such as navigating natural lunar terrain while conducting geological sampling. To date, only 12 people have walked on the surface of the Moon resulting in limited knowledge of suited thermal regulation under lunar-relevant physical workloads. To address this gap, a study is underway to focus on spacesuit operations with simulated lunar EVA workloads. This study presents methodology for collecting standard thermal measures during suit testing. In this pilot study, two suited subjects underwent simulated lunar EVAs using the NASA Active Response Gravity Offload System (ARGOS) to simulate the effects of partial gravity. Each lunar EVA, lasting three to five hours, included various metabolically demanding EVA tasks. Subjects donned the NASA Mark III (MK III) space suit and were offloaded to 1/6th G (lunar gravity). A subset task circuit from one of these simulations replicated an EVA traverse to a lunar crater, taking a geological sample, and returning to base. The suited subject walked one 1500 m (0% grade) and three 500 m traverses at three different grades (10, 20, 30%). Between each traverse, subjects performed geology sampling tasks (0 and 10% grade). Thermal measurements included core and skin temperature, liquid cooling garment (LCG) inlet and outlet temperature, and spacesuit gas inlet and outlet temperature and humidity. Compared to baseline core temperature (S1 = 37.07±0.32 °C, S2 = 37.27±0.01 °C) and mean skin temperature (S1 = 32.38±0.34 °C, S2 = 33.62±0.03 °C), after a 1500 m traverse, each suited subject showed an increased core temperature (S1 = 37.23±0.12 °C, S2 = 37.41±0.11°C) and decreased mean skin temperature (S1 = 32.16±0.17 °C, S2 = 31.53±1.15 °C) at a delta LCG temperature (S1 = 1.86±0.24 °C, S2 = 2.20±0.76 °C) and delta suit humidity (S1 = 9.66±1.49 %, S2 = 11.50±1.58 %). Core temperature continued to increase from compounding traverse and geology tasks (S1 = 38.04±0.03 °C, S2 = 38.1±0.02 °C) accompanied by an increase in delta LCG temperature (S1 = 2.24±0.13 °C, S2 = 2.67±0.12 °C) and delta suit humidity (S1 = 28±2.42 %, S2 = 31±2.13 %). Conversely, as the circuit progressed, mean skin temperature continued to decrease due to sustained LCG heat rejection (S1 = 30.08±0.15 °C, S2 = 30.28±0.07 °C). During the simulated EVA circuit core temperature increased to elevated values and remained elevated as heat was retained while mean skin temperature decreased due to peripheral heat offloaded to the LCG. The thermal measures collected during this study provided critical heat loading dynamics during lunar EVA tasks. Including core and skin temperatures along with suited thermal measures provides a standard data collection scheme for human thermal metrics during EVA task management. Data collected in this configuration can be used to build future lunar EVA task circuits and human thermal predictions.

Bradley Hoffmann↗