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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.

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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Comparison of distribution and toxicity following repeated oral dosing of different vanadium oxide nanoparticles in mice

Vanadium is an important ultra-trace element derived from fuel product combustion. With the development of nanotechnology, vanadium oxide nanoparticles (VO NPs) have been considered for application in various fields, thus the possibility of release into the environment and human exposure is also increasing. Considering that verification of bioaccumulation and relevant biological responses are essential for safe application of products, in this study, we aimed to identify the physicochemical properties that determine their health effects by comparing the biological effects and tissue distribution of different types of VO NPs in mice. For this, we prepared five types of VO NPs, commercial (C)-VO{sub 2} and -V{sub 2}O{sub 5} NPs and synthetic (S)-VO{sub 2}, -V{sub 2}O{sub 3,} and -V{sub 2}O{sub 5} NPs. While the hydrodynamic diameter of the two types of C-VO NPs was irregular and impossible to measure, those of the three types of S-VO NPs was in the range of 125–170 nm. The S- and C-V{sub 2}O{sub 5} NPs showed higher dissolution rates compared to other VO NPs. We orally dosed the five types of VO NPs (70 and 210 μg/mouse, approximately 2 and 6 mg/kg) to mice for 28 days and compared their biodistribution and toxic effects. We found that S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs more accumulated in tissues compared to other three types of VO NPs, and the accumulated level was in order of heart>liver>kidney>spleen. Additionally, tissue levels of redox reaction-related elements and electrolytes (Na{sup +}, K{sup +}, and Ca{sup 2+}) were most clearly altered in the heart of treated mice. Notably, all S- and C-VO NPs decreased the number of WBCs at the higher dose, while total protein and albumin levels were reduced at the higher dose of S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs. Taken together, we conclude that the biodistribution and toxic effects of VO NPs depend on their dissolution rates and size (surface area). Additionally, we suggest that further studies are needed to clarify effects of VO NPs on functions of the heart and the immune system. - Highlights: • We used commercial (C)-VO{sub 2} and -V{sub 2}O{sub 5} and synthetic (S)-VO{sub 2}, -V{sub 2}O{sub 3,} and -V{sub 2}O{sub 5} NPs. • The S- and C-V{sub 2}O{sub 5} NPs showed higher dissolution rates compared to other VO NPs. • S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs more accumulated in tissues compared to other types of VO NPs. • Redox reaction-related elements and electrolytes were clearly altered in the heart. • With decreased body weight, immune and blood-related factors influence by all VO NPs. • Biodistribution and toxicity of VO NPs depend on their dissolution rates and size.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2001

Comparison of aortic and carotid baroreflex stimulus-response characteristics in humans

In order to characterize the stimulus-response relationships of the arterial, aortic, and carotid baroreflexes in mediating cardiac chronotropic function, we measured heart rate (HR) responses elicited by acute changes in mean arterial pressure (MAP) and carotid sinus pressure (CSP) in 11 healthy individuals. Arterial (aortic + carotid) baroreflex control of HR was quantified using ramped changes in MAP induced by bolus injection of phenylephrine (PE) and sodium nitroprusside (SN). To assess aortic-cardiac responses, neck pressure (NP) and suction (NS) were applied during PE and SN administration, respectively, to counter alterations in CSP thereby isolating the aortic baroreflex. Graded levels of NP and NS were delivered to the carotid sinus using a customized neck collar device to assess the carotid-cardiac baroreflex, independent of drug infusion. The operating characteristics of each reflex were determined from the logistic function of the elicited HR response to the induced change in MAP. The arterial pressures at which the threshold was located on the stimulus-response curves determined for the arterial, aortic and carotid baroreflexes were not significantly different (72+/-4, 67+/-3, and 72+/-4 mm Hg, respectively, P > 0.05). Similarly, the MAP at which the saturation of the reflex responses were elicited did not differ among the baroreflex arcs examined (98+/-3, 99+/-2, and 102+/-3 mm Hg, respectively). These data suggest that the baroreceptor populations studied operate over the same range of arterial pressures. This finding indicates each baroreflex functions as both an important anti-hypotensive and anti-hypertensive mechanism. In addition, this investigation describes a model of aortic baroreflex function in normal healthy humans, which may prove useful in identifying the origin of baroreflex dysfunction in disease- and training-induced conditions.

Non-NASA Center↗
NASA NTRS2001

Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery

OBJECTIVES: This study was conducted to evaluate follow-up results in patients with hypertrophic obstructive cardiomyopathy (HOCM) who underwent either percutaneous transluminal septal myocardial ablation (PTSMA) or septal myectomy. BACKGROUND: Controversy exists with regard to these two forms of treatment for patients with HOCM. METHODS: Of 51 patients with HOCM treated, 25 were treated by PTSMA and 26 patients via myectomy. Two-dimensional echocardiograms were performed before both procedures, immediately afterwards and at a three-month follow-up. The New York Heart Association (NYHA) functional class was obtained before the procedures and at follow-up. RESULTS: Interventricular septal thickness was significantly reduced at follow-up in both groups (2.3 +/- 0.4 cm vs. 1.9 +/- 0.4 cm for septal ablation and 2.4 +/- 0.6 cm vs. 1.7 +/- 0.2 cm for myectomy, both p < 0.001). Estimated by continuous-wave Doppler, the resting pressure gradient (PG) across the left ventricular outflow tract (LVOT) significantly decreased immediately after the procedures in both groups (64 +/- 39 mm Hg vs. 28 +/- 29 mm Hg for PTSMA, 62 +/- 43 mm Hg vs. 7 +/- 7 mm Hg for myectomy, both p < 0.0001). At three-month follow-up, the resting PG remained lower in the PTSMA and myectomy groups (24 +/- 19 mm Hg and 11 +/- 6 mm Hg, respectively, vs. those before procedures, both p < 0.0001). The NYHA functional class was also significantly improved in both groups (3.5 +/- 0.5 vs. 1.9 +/- 0.7 for PTSMA, 3.3 +/- 0.5 vs. 1.5 +/- 0.7 for myectomy, both p < 0.0001). CONCLUSIONS: Both myectomy and PTSMA reduce LVOT obstruction and significantly improve NYHA functional class in patients with HOCM. However, there are benefits and drawbacks for each therapeutic method that must be counterbalanced when deciding on treatment for LVOT obstruction.

Non-NASA Center↗
DOE OSTI2023

Chitosan-Based Scaffolds for the Treatment of Myocardial Infarction: A Systematic Review

Cardiovascular diseases (CVD), such as myocardial infarction (MI), constitute one of the world’s leading causes of annual deaths. This cardiomyopathy generates a tissue scar with poor anatomical properties and cell necrosis that can lead to heart failure. Necrotic tissue repair is required through pharmaceutical or surgical treatments to avoid such loss, which has associated adverse collateral effects. However, to recover the infarcted myocardial tissue, biopolymer-based scaffolds are used as safer alternative treatments with fewer side effects due to their biocompatibility, chemical adaptability and biodegradability. For this reason, a systematic review of the literature from the last five years on the production and application of chitosan scaffolds for the reconstructive engineering of myocardial tissue was carried out. Seventy-five records were included for review using the “preferred reporting items for systematic reviews and meta-analyses” data collection strategy. It was observed that the chitosan scaffolds have a remarkable capacity for restoring the essential functions of the heart through the mimicry of its physiological environment and with a controlled porosity that allows for the exchange of nutrients, the improvement of the electrical conductivity and the stimulation of cell differentiation of the stem cells. In addition, the chitosan scaffolds can significantly improve angiogenesis in the infarcted tissue by stimulating the production of the glycoprotein receptors of the vascular endothelial growth factor (VEGF) family. Therefore, the possible mechanisms of action of the chitosan scaffolds on cardiomyocytes and stem cells were analyzed. For all the advantages observed, it is considered that the treatment of MI with the chitosan scaffolds is promising, showing multiple advantages within the regenerative therapies of CVD.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1983

Human sinus arrhythmia as an index of vagal cardiac outflow

The human central vagal mechanisms were investigated by measuring the intervals between heartbeats during controlled breathing (at breathing intervals of 2.5-10 s and nominal tidal volumes of 1000 and 1500 ml) in six young men and women. It was found that as the breathing interval increased, the longest heart periods became longer, the shortest heart periods became shorter, and the peak-valley P-P intervals increased asymptotically. Peak-valley intervals also increased in proportion to tidal volume, although this influence was small. The phase angles between heart period changes and respiration were found to vary as linear functions of breathing interval. Heart period shortening began in inspiration at short breathing intervals and in expiration at long breathing intervals, while heart period lengthening began in early expiration at all breathing intervals studied. It is concluded that a close relationship exists between variations of respiratory depth and interval and the quantity, periodicity, and timing of vagal cardiac outflow in conscious humans. The results indicate that at usual breathing rates, phasic respiration-related changes of vagal motoneuron activity begin in expiration, progress slowly, and are incompletely expressed at fast breathing ratges.

Eckberg, D. L.↗
NASA NTRS1990

Morphological and biochemical examination of Cosmos 1887 rat heart tissue. Part 1: Ultrastructure

Morphological changes were observed in the left ventricle of rat heart tissue from animals flown on the Cosmos 1887 biosatellite for 12.5 days. These tissues were compared to the synchronous and vivarium control hearts. While many normal myofibrils were observed, others exhibited ultrastructural alterations, i.e., damaged and irregular-shaped mitochondria and generalized myofibrillar edema. Analysis of variance (ANOVA) of the volume density data revealed a statistically significant increase in glycogen and a significant decrease in mitochondria compared to the synchronous and vivarium controls. Point counting indicated an increase in lipid and myeloid bodies and a decrease in microtubules, but these changes were not statistically significant. In addition, the flight animals exhibited some patchy loss of protofibrils (actin and myosin filaments) and some abnormal supercontracted myofibrils that were not seen in the controls. This study was undertaken to gain insight into the mechanistic aspects of cardiac changes in both animals and human beings as a consequence of space travel. Cardiac hypotrophy and fluid shifts have been observed after actual or simulated weightlessness and raise concerns about the functioning of the heart and circulatory system during and after travel in space.

Philpott, D. E.↗
DOE OSTI2015

Multiple immunophenotypes of cardiac telocytes

Aims: Telocytes (TCs) form a 3-dimensional network in the myocardial interstitium, which most probably play important role(s) in heart development. However, the dynamics of their prolongations, continuous cell shape changes and adherence properties have not been well documented till recently. The aim of this study was to investigate dynamics of extension of prolongations (Telopods) and multiple phenotypes of cardiac TCs cultured in vitro. Methods: Cardiac TCs were isolated from neonatal rats by a combined enzyme digestion process and identified by light microscopy, immunofluorescence analysis and scanning using electron microscopy (SEM). Their continuous changes in shape were analyzed by a Live Cell Imaging System and multiple phenotypes were identified by immunofluorescence analysis using various markers, like vimentin, c-kit, CD34, nanog and sca-1. Results: Cardiac TCs displayed piriform/spindle/triangular shapes with long and slender telopodes showing extremely long prolongations. The morphology of cell body was continuously changing while their prolongations were extending gradually. After adhering to the surface, TCs’ movement and extension of their prolongations lasted for approximately 1.5 h. Cardiac TCs expressed mesenchymal cell marker vimentin, hematopoietic stem cell marker CD34, embryonic stem cell-associated gene of Nanog, and myocardial stem cell markers sca-1 and c-kit. Conclusion: These findings indicate that cultured TCs in vitro have multiple phenotypes, which are most likely important for evaluating their functional roles in heart development. - Highlights: • TCs’ movement and extension of their prolongations lasted for approximately 1.5 h. • The unique structural characteristics of TCs were observed by SEM for the first time. • Cardiac TCs cultured in vitro expressed vimentin, CD34, nanog, sca-1 and c-kit.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Plasma proteomic biomarkers of physical frailty in heart failure: a propensity score matched discovery-based pilot study

Background: Physical frailty is highly prevalent in heart failure (HF), but we lack an understanding of the underlying pathophysiology. Proteomics evaluation of plasma samples may elucidate potential mechanisms and biomarkers of physical frailty in HF. We aimed to identify plasma proteomic biomarkers that are differentially expressed between physically frail and non physically frail adults with HF. Methods: This was a secondary analysis of a subset of data and plasma samples from a study of frailty among patients with New York Heart Association (NYHA) Functional Classification I-IV HF. Physical frailty was measured using the Frailty Phenotype Criteria. Propensity score matching was used to match pairs of physically frail (n = 20) vs. non-physically frail (n = 20) patients on clinical characteristics. Plasma samples were processed using a sensitive liquid chromatography mass spectrometry platform, utilizing a multiplexed tandem mass tag-labeled quantitative proteomics approach. Differentially expressed proteins were quantified individually using paired t tests with associated log fold change of 0.3 and Fisher’s combined p values. Results: The sample (n = 40) was 62.8±16.9 years old, 58% female, and 55% NYHA Class III/IV. Proteomics analysis revealed 7 proteins differentially expressed using full differential criteria: matrix metalloproteinase-14 was downregulated in frailty, and copine-1, low affinity immunoglobulin gamma Fc region receptor III-A and III-B, probable non-functional immunoglobulin kappa variable 2D-24, glutathione S-transferase Mu 1, and argininosuccinate lyase were upregulated in frailty. Conclusions: Proteomic biomarkers related to the immune system, stress response, and detoxification were differentially expressed between physically frail and non-physically frail adults with HF.

Biomarkers↗
NASA NTRS2017

Fluid Shifts

Introduction. NASA's Human Research Program is focused on addressing health risks associated with long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but now more than 50 percent of ISS astronauts have experienced more profound, chronic changes with objective structural findings such as optic disc edema, globe flattening and choroidal folds. These structural and functional changes are referred to as the visual impairment and intracranial pressure (VIIP) syndrome. Development of VIIP symptoms may be related to elevated intracranial pressure (ICP) secondary to spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to determine if a relation exists with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as any VIIP-related effects of those shifts, are predicted by the crewmember's pre-flight status and responses to acute hemodynamic manipulations, specifically posture changes and lower body negative pressure. Methods. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, and calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography; intraocular pressure; 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness; Doppler ultrasound of ophthalmic and retinal arteries and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, otoacoustic emissions). Pre- and post-flight, acute head-down tilt will induce cephalad fluid shifts, whereas lower body negative pressure will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome. Discussion. Ten subjects have consented to participate in this experiment, including the recent One-Year Mission crewmembers, who have recently completed R plus180 testing; all other subjects have completed pre-flight testing. Preliminary results from the One-Year Mission crewmembers will be presented, including measures of ocular structure and function, vascular dimensions, fluid distribution, and non-invasive estimates of intracranial pressure.

Stenger, M. B.↗
NASA NTRS2016

Fluid Shifts

NASA is focusing on long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low-Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but more than 50% of ISS astronauts experienced more profound, chronic changes with objective structural and functional findings such as papilledema and choroidal folds. Globe flattening, optic nerve sheath dilation, and optic nerve tortuosity also are apparent. This pattern is referred to as the visual impairment and intracranial pressure (VIIP) syndrome. VIIP signs and symptoms, as well as postflight lumbar puncture data, suggest that elevated intracranial pressure (ICP) may be associated with the spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight, and to correlate these findings with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as the VIIP-related effects of those shifts, is predicted by the crewmember's preflight conditions and responses to acute hemodynamic manipulations (such as head-down tilt). Lastly, we will evaluate the patterns of fluid distribution in ISS astronauts during acute reversal of fluid shifts through application of lower body negative pressure (LBNP) interventions to characterize and explain general and individual responses. METHODS: We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the Figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography, intraocular pressure, 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness, Doppler ultrasound of ophthalmic and retinal arteries, and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, distortion-product otoacoustic emissions, and ICP calculated by MRI). On the ground, acute head-down tilt will induce cephalad fluid shifts, whereas LBNP will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome.

Stenger, M.↗
NASA NTRS2014

Fluid Shifts

NASA is focusing on long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but more than 30% of ISS astronauts experience more profound, chronic changes with objective structural and functional findings such as papilledema and choroidal folds. Globe flattening, optic nerve sheath dilation, and optic nerve tortuosity also are apparent. This pattern is referred to as the visual impairment and intracranial pressure (VIIP) syndrome. VIIP signs and symptoms, as well as postflight lumbar puncture data, suggest that elevated intracranial pressure (ICP) may be associated with the space flight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration space flight, and to correlate these findings with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during space flight, as well as the VIIP-related effects of those shifts, is predicted by the crewmember's pre-flight condition and responses to acute hemodynamic manipulations (such as head-down tilt). Lastly, we will evaluate the patterns of fluid distribution in ISS astronauts during acute reversal of fluid shifts through application of lower body negative pressure (LBNP) interventions to characterize and explain general and individual responses. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the Figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography, intraocular pressure, 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness, Doppler ultrasound of ophthalmic and retinal arteries, and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, distortion-product otoacoustic emissions, and ICP calculated by MRI). On the ground, acute head-down tilt will induce cephalad fluid shifts, whereas LBNP will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome. This study has been selected for flight implementation and is one of the candidate investigations being considered for the one year mission.

Stenger, Michael↗
DOE OSTI2017

Triiodothyronine promotes the proliferation of epicardial progenitor cells through the MAPK/ERK pathway

Thyroid hormone has important functions in the development and physiological function of the heart. The aim of this study was to determine whether 3,5,3′-Triiodothyronine (T3) can promote the proliferation of epicardial progenitor cells (EPCs) and to investigate the potential underlying mechanism. Our results showed that T3 significantly promoted the proliferation of EPCs in a concentration- and time-dependent manner. The thyroid hormone nuclear receptor inhibitor bisphenol A (100 μmol/L) did not affect T3's ability to induce proliferation. Further studies showed that the mRNA expression levels of mitogen-activated protein kinase 1 (MAPK1), MAPK3, and Ki67 in EPCs in the T3 group (10 nmol/L) increased 2.9-, 3-, and 4.1-fold, respectively, compared with those in the control group (P < 0.05). In addition, the mRNA expression of the cell cycle protein cyclin D1 in the T3 group increased approximately 2-fold compared with the control group (P < 0.05), and there were more EPCs in the S phase of the cell cycle (20.6% vs. 12.0%, P < 0.05). The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway inhibitor U0126 (10 μmol/L) significantly inhibited the ability of T3 to promote the proliferation of EPCs and to alter cell cycle progression. This study suggested that T3 significantly promotes the proliferation of EPCs, and this effect may be achieved through activation of the MAPK/ERK signaling pathway. - Highlights: • Epicardial progenitor cells were successfully cultured from E12.5 mice. • Thyroid hormone T3 significantly promoted the proliferation of EPCs. • This biological effect may be mediated via activation of the MAPK/ERK pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Structure and dynamics underlying elementary ligand binding events in human pacemaking channels

Although molecular recognition is crucial for cellular signaling, mechanistic studies have relied primarily on ensemble measures that average over and thereby obscure underlying steps. Single-molecule observations that resolve these steps are lacking due to diffraction-limited resolution of single fluorophores at relevant concentrations. Here, we combined zero-mode waveguides with fluorescence resonance energy transfer (FRET) to directly observe binding at individual cyclic nucleotide-binding domains (CNBDs) from human pacemaker ion channels critical for heart and brain function. Our observations resolve the dynamics of multiple distinct steps underlying cyclic nucleotide regulation: a slow initial binding step that must select a 'receptive' conformation followed by a ligand-induced isomerization of the CNBD. X-ray structure of the apo CNBD and atomistic simulations reveal that the isomerization involves both local and global transitions. Our approach reveals fundamental mechanisms underpinning ligand regulation of pacemaker channels, and is generally applicable to weak-binding interactions governing a broad spectrum of signaling processes.

Goldschen-Ohm, Marcel P.↗
NASA NTRS1982

Embryonic development during chronic acceleration

Experiments carried out on chicken eggs indicate that the embryo is affected during very early development, especially over the first four days, and during hatching. In the first four days, the brain develops as well as the anlage for all other organs. In addition, the heart commences to function and the extraembryonic membranes that compartmentalize the egg contents form. The latter require an appreciable extension and folding of tissue which may be disrupted by the mechanical load. Observations of embryonic abnormalities that occur during chronic acceleration suggest an inhibition of development of the axial skeleton, which is rarely seen otherwise, a general retardation of embryonic growth, and circulatory problems. The final stages of development (after 18 days) involve the uptake of fluids, the transition to aerial respiration, and the reorientation of the embryo into a normal hatching position. At 4 G mortality is very high during this period, with a majority of embryos failing to reorient into the normal hatching position.

Smith, A. H.↗
NASA NTRS2002

Cross-talk in abscisic acid signaling

"Cross-talk" in hormone signaling reflects an organism's ability to integrate different inputs and respond appropriately, a crucial function at the heart of signaling network operation. Abscisic acid (ABA) is a plant hormone involved in bud and seed dormancy, growth regulation, leaf senescence and abscission, stomatal opening, and a variety of plant stress responses. This review summarizes what is known about ABA signaling in the control of stomatal opening and seed dormancy and provides an overview of emerging knowledge about connections between ABA, ethylene, sugar, and auxin synthesis and signaling.

Review, Tutorial↗
NASA NTRS2009

The ICV Study: Integrated Cardiovascular

This viewgraph presentation describes the effects of long duration manned spaceflight on heart structure and function. Clinical consequences for orthostatic tolerance, cardiac arrhythmias, and countermeasures to prevent clinical problems are also discussed.

Levine, Benjamin D.↗
NASA NTRS2015

NASA's Functional Task Test: High Intensity Exercise Improves the Heart Rate Response to a Stand Test Following 70 Days of Bedrest

Cardiovascular adaptations due to spaceflight are modeled with 6deg head-down tilt bed rest (BR) and result in decreased orthostatic tolerance. We investigated if high-intensity resistive and aerobic exercise with and without testosterone supplementation would improve the heart rate (HR) response to a 3.5-min stand test and how quickly these changes recovered following BR. During 70 days of BR male subjects performed no exercise (Control, n=10), high intensity supine resistive and aerobic exercise (Exercise, n=9), or supine exercise plus supplemental testosterone (Exercise+T, n=8; 100 mg i.m., weekly in 2-week on/off cycles). We measured HR for 2 min while subjects were prone and for 3 min after standing twice before and 0, 1, 6, and 11 days after BR. Mixed-effects linear regression models were used to evaluate group, time, and interaction effects. Compared to pre-bed rest, prone HR was elevated on BR+0 and BR+1 in Control, but not Exercise or Exercise+T groups, and standing HR was greater in all 3 groups. The increase in prone and standing HR in Control subjects was greater than either Exercise or Exercise+T groups and all groups recovered by BR+6. The change in HR from prone to standing more than doubled on BR+0 in all groups, but was significantly less in the Exericse+T group compared to the Control, but not Exercise group. Exercise reduces, but does not prevent the increase in HR observed in response to standing. The significantly lower HR response in the Exercise+T group requires further investigation to determine physiologic significance.

Laurie, Steven S.↗