Changes in respiratory and cardiovascular functions after prolonged exposure to low barometric pressure
Changes in respiratory and cardiovascular functions after prolonged exposure to low barometric pressure
RESPIRATION↗
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Optimization of Spirulina for biomanufacturing and the delivery of protein therapeutics
Lumen Bioscience has developed a novel cyanobacterial platform that enormously decreases the cost of pharmaceuticals used to prevent and treat illnesses. Arthrospira platensis (spirulina), is a photosynthetic microorganism that has been consumed as a dietary supplement for centuries in part because of its high protein content. Commercial cultivation operations have matured over the last 50 years to allow large-scale cultivation in outdoor ponds. Lumen recently discovered methods that transform this commercially important cyanobacterium into a genetically tractable platform for bioengineering. The high protein accumulation in spirulina makes it an ideal chassis for heterologous protein expression, and centuries of safe human consumption suggest its utility as an administration vehicle for biologic drugs. Lumen can express a broad range of recombinant proteins in spirulina and has developed manufacturing processes and strains to mucosally deliver bioactive proteins to treat and/or prevent disease. For example, Lumen has produced an oral cocktail of dried whole-cell spirulina biomass, containing 3 toxin-neutralizing antibodies and 1 endolysin, that is efficacious in a preclinical in vivo models of C. difficile infection. Lumen has also demonstrated that intranasal administration of a spirulina-manufactured neutralizing antibody can prevent disease by a respiratory pathogen, SARS-CoV-2, in a hamster model. Lumen’s current pipeline includes therapeutics to treat or prevent C. difficile infection, COVID-19, inflammatory bowel disease, cardiometabolic disease, and traveler’s diarrhea. Lumen deploys strategies to maximize the expression of these therapeutics for optimal dose sizing, a key limiting factor with past food crop-based expression systems. Spirulina can express exogenous proteins at unusually high levels (>15% of dry weight) but reaching this maximum value requires optimization of multiple interacting factors. We describe our current statistics design of experiments approach that optimizes these factors with minimal replicates. This maximizes exogenous protein expression allowing Lumen to generate spirulina-based therapeutics for a rapidly expanding range of medical uses.
Heinnickel, Mark↗
Quantifying Airborne Allergen Levels Before and After Rain Events Using TRMM/GPM and Ground-Sampled Data
Allergies affect millions of Americans, increasing health risks and also increasing absenteeism and reducing productivity in the workplace. Outdoor allergens, such as airborne pollens and mold spores, commonly trigger respiratory distress symptoms, but rainfall reduces the quantity of allergens in the air (EPA, 2003). The current NASA Tropical Rainfall Measuring Mission provides accurate information related to rain events. These capabilities will be further enhanced with the future Global Precipitation Measurement mission. This report examines the effectiveness of combining these NASA resources with established ground-based allergen/spore sampling systems to better understand the benefits that rain provides in removing allergens and spores from the air.
Stewart, Randy M.↗
Efficacy of Antimicrobials on Bacteria Cultured in a Spaceflight Analogue
As humans travel in space, they will interact with microbial flora from themselves, other crewmembers, their food, and the environment. While evaluations of microbial ecology aboard the Mir and ISS suggest a predominance of common environmental flora, the presence of (and potential for) infectious agents has been well documented. Likewise, pathogens have been detected during preflight monitoring of spaceflight food, resulting in the disqualification of that production lot from flight. These environmental and food organisms range from the obligate pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium), which has been responsible for disqualification and removal of food destined for ISS and has previously been reported from Shuttle crew refuse, to the opportunistic pathogen Staphylococcus aureus, isolated numerous times from ISS habitable compartments and the crew. Infectious disease events have affected spaceflight missions, including an upper respiratory infection that delayed the launch of STS-36 and an incapacitating Pseudomonas aeruginosa urinary tract infection of a crewmember during Apollo 13. These observations indicate that the crew has the potential to be exposed to obligate and opportunistic pathogens. This risk of exposure is expected to increase with longer mission durations and increased use of regenerative life support systems. As antibiotics are the primary countermeasure after infection, determining if their efficacy during spaceflight missions is comparable to terrestrial application is of critical importance. The NASA Rotating Wall Vessel (RWV) culture system has been successfully used as a spaceflight culture analogue to identify potential alterations in several key microbial characteristics, such as virulence and gene regulation, in response to spaceflight culture. We hypothesized that bacteria cultured in the low fluid shear RWV environment would demonstrate changes in efficacy of antibiotics compared to higher fluid shear controls. This study investigated the response of three medically significant microorganisms grown in the RWV to antibiotics that could be used on spaceflight missions. Our findings suggest potential alterations in antibiotic efficacy during spaceflight and indicate that future studies on the antibiotic response require additional basic research using the RWV and/or true spaceflight. However, while this analogue has reinforced these potential alterations, the results suggest the best approach for applied forward work is evaluating an in vivo system during spaceflight, including human and rodent studies. The complex nature of the analysis for many antibiotics and organism suggests the best approach to determine in vivo responses during pharmaceutical treatment is evaluating an in vivo system during spaceflight.
Nickerson, CA↗
Environmental Public Health Surveillance for Exposure to Respiratory Health Hazards: A Joint NASA/CDC Project to Use Remote Sensing Data for Estimating Airborne Particulate Matter Over the Atlanta, Georgia Metropolitan Area
As part of the National Environmental Public Health Tracking Network (EPHTN) the National Center for Environmental Health (NCEH) at the Centers for Disease Control and Prevention (CDC) is leading a project called Health and Environment Linked for Information Exchange (HELiX-Atlanta). The goal of developing the National Environmental Public Health Tracking Network is to improve the health of communities. Currently, few systems exist at the state or national level to concurrently track many of the exposures and health effects that might be associated with environmental hazards. An additional challenge is estimating exposure to environmental hazards such as particulate matter whose aerodynamic diameter is less than or equal to 2.5 micrometers (PM2.5). HELIX-Atlanta's goal is to examine the feasibility of building an integrated electronic health and environmental data network in five counties of Metropolitan Atlanta, GA. NASA Marshall Space Flight Center (NASA/MSFC) is collaborating with CDC to combine NASA earth science satellite observations related to air quality and environmental monitoring data to model surface estimates of PM2.5 concentrations that can be linked with clinic visits for asthma. While use of the Air Quality System (AQS) PM2.5 data alone could meet HELIX-Atlanta specifications, there are only five AQS sites in the Atlanta area, thus the spatial coverage is not ideal. We are using NASA Moderate Resolution Imaging Spectroradiometer (MODIS) satellite Aerosol Optical Depth (AOD) data for estimating daily ground level PM2.5 at 10 km resolution over the metropolitan Atlanta area supplementing the AQS ground observations and filling their spatial and temporal gaps.
Quattrochi, Dale A.↗
Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using Ultrasound and Braslet-M Occlusion Cuffs
The objective of this joint U.S. - Russian project was the development and validation of an in-flight methodology to assess a number of cardiac and vascular parameters associated with circulating volume and its manipulation in long-duration space flight. Responses to modified Valsalva and Mueller maneuvers were measured by cardiac and vascular ultrasound (US) before, during, and after temporary volume reduction by means of Braslet-M thigh occlusion cuffs (Russia). Materials and Methods: The study protocol was conducted in 14 sessions on 9 ISS crewmembers, with an average exposure to microgravity of 122 days. Baseline cardiovascular measurements were taken by echocardiography in multiple modes (including tissue Doppler of both ventricles) and femoral and jugular vein imaging on the International Space Station (ISS). The Braslet devices were then applied and measurements were repeated after >10 minutes. The cuffs were then released and the hemodynamic recovery process was monitored. Modified Valsalva and Mueller maneuvers were used throughout the protocol. All US data were acquired by the HDI-5000 ultrasound system aboard the ISS (ATL/Philips, USA) during remotely guided sessions. The study protocol, including the use of Braslet-M for this purpose, was approved by the ISS Human Research Multilateral Review Board (HRMRB). Results: The effects of fluid sequestration on a number of echocardiographic and vascular parameters were readily detectable by in-flight US, as were responses to respiratory maneuvers. The overall volume status assessment methodology appears to be valid and practical, with a decrease in left heart lateral E (tissue Doppler) as one of the most reliable measures. Increase in the femoral vein cross-sectional areas was consistently observed with Braslet application. Other significant differences and trends within the extensive cardiovascular data were also observed. (Decreased - RV and LV preload indices, Cardiac Output, LV E all maneuvers, LV Stroke Volume). Conclusions: This Study: 1) Addressed specific aspects of operational space medicine and space physiology, including assessment of circulating volume disturbances 2) Expanded the applications of diagnostic ultrasound imaging and Doppler techniques in microgravity. 3) Used respiratory maneuvers against the background of acute circulating volume manipulations which appear to enhance our ability to noninvasively detect volume-dependency in a number of cardiac and vascular parameters. 4) Determined that Tei index is not clinically changed therefore contractility not altered in the face of reduced preload. 5) Determined that increased Femoral Vein Area indicating blood being sequestered in lower extremities correlates with reduced preload and cardiac output. 6) That Braslet may be the only feasible means of acutely treating high pressure pulmonary edema in reduced gravity environments.
Hamilton, Douglas↗
Measured influence of overhead HVAC on exposure to airborne contaminants from simulated speaking in a meeting and a classroom
Tracer gas experiments were conducted in a 158 m 3 room with overhead supply diffusers to study dispersion of contaminants from simulated speaking in physically distanced meeting and classroom configurations. The room was contained within a 237 m 3 cell with open plenum return to the HVAC system. Heated manikins at desks and a researcher operating the tracer release apparatus presented 8-9 thermal plumes. Experiments were conducted under conditions of no forced air and neutral, cooled, or heated air supplied at 980-1100 cmh, and with/out 20% outdoor air. CO 2 was released at the head of one manikin in each experiment to simulate small (< 5 µm diameter) respiratory aerosols. The metric of exposure relative to perfectly mixed (ERM) is introduced to quantify impacts, based on measurements at manikin heads and at three heights in the center and corners of the room. Chilled or neutral supply air provided good mixing with ERMs close to one. Thermal stratification during heating produced higher ERMs at most manikins: 25% were ≥ 2.5 and the highest were > 5× perfectly mixed conditions. Operation of two within-zone air cleaners together moving ≥400 cmh vertically in the room provided enough mixing to mitigate elevated exposure variations.
54 ENVIRONMENTAL SCIENCES↗
PNNL DataHub Project: Omics Lethal Human Viruses Project Profiling of the Host Response to Influenza A Virus Infection, Processed Experimental Dataset Catalog
Influenza A virus (IAV) is a high risk biological agent, classified as a Category C priority pathogen (Orthomyxoviridae) by the National Institute of Allergy and Infectious Diseases (NIAID), and is known to cause severe respiratory disease with high mortality rates in humans. Lethal host-pathogen invasion mechanisms and the cellular intricacies behind these fatal infections still remain unclear. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013-2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. Herein, PNNL sub-projects provide a never before released comprehensive infectious disease collection of primary and secondary transformation multi-Omics data profiling a series of priority pathogen primary experimental studies for enhanced open-access to viral Omics datasets and project lifecycle metadata. Secondary host-pathogen viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics (P), metabolomics (M), lipidomics (L), and transcriptomics (T) dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific Influenza A virus [NCBITAXON:11320] experimental infection study. Host sample types include human lung adenocarcinoma cells ["Calu-3", BTO:0002750] and whole mouse lung [BTO:0000763] tissue collections.
59 BASIC BIOLOGICAL SCIENCES↗
Omics Lethal Human Viruses Project Profiling of the Host Response to MERS-CoV Infection, Processed Experimental Dataset Catalog
Middle East Respiratory Syndrome coronavirus (MERS-CoV) is classified as a Category C priority pathogen (Coronaviridae) by the National Institute of Allergy and Infectious Diseases (NIAID), and is known to cause severe respiratory disease with high mortality rates in humans. Lethal host-pathogen invasion mechanisms and the cellular intricacies behind these fatal infections still remain unclear. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013-2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. Herein, PNNL sub-projects provide a never before released comprehensive infectious disease collection of primary and secondary transformation multi-Omics data profiling a series of priority pathogen primary experimental studies for enhanced open-access to viral Omics datasets and project lifecycle metadata. Secondary host-pathogen viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics (P), metabolomics (M), lipidomics (L), and transcriptomics (T) dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific MERS-CoV [NCBITAXON:1335626] experimental infection study. Host sample types include human lung adenocarcinoma cells ["Calu-3", BTO:0002750], human bronchial epithelial cells ["Calu-3 clone 2B4"; BTO:0002022], primary human fibroblasts ["FB"; BTO:0000452], primary human airway epithelial cells ["HAE"; BTO:0005571], human microvascular endothelial cells ["HMVE"; BTO:0003123], and whole mouse lung [BTO:0000763] tissue collections.
59 BASIC BIOLOGICAL SCIENCES↗
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.↗
CO2-O2 interactions in extension of tolerance to acute hypoxia
Objectives and results of experimental projects a re summarized. The scope of information desired included (1) physiological and performance consequences of exposures to simulated microgravity, in rest and graded physical activity, (2) separate influences of graded degrees of atmospheric hypercapnia and hypoxia, and (3) composite effects of hypoxia and hypercapnia. The research objectives were selected for close relevance to existing quantitative information concerning interactions of hypercapnia and hypoxia on respiratory and brain circulatory control. They include: (1) to determine influences of normoxic immersion on interrelations of pulmonary ventilation, arterial PCO2 and PO2, and brain blood flow, in rest and physical work; (2) to determine influence of normoxic immersion on respiratory reactivity to atmospheric hypercapnia at rest; (3) to determine influence of atmospheric hypoxia on respiratory reactivity to hypercapnia at rest and in work; and (4) to provide physiological baselines of data concerning adaptations in acute exposures to aid in investigation of rates of adaptation or deteriorations in physiological or performance capability during subsequent multi-day exposures. A list of publications related to the present grant period is included along with an appendix describing the Performance Measurement System (human perceptual, cognitive and psychomotor functions).
Lambertsen, C. J.↗
Preparing for Planetary Surface Exploration by Measuring Habitat Dust Intrusion with Filter Tests During an Analogue Mars Mission
As humans venture deeper into space more issues related to operations will become apparent. While the perils ofdust particles may not be widely recognized, it is one of the major issues astronauts will face on the surface of theMoon and Mars. Dust particles present a problem for both astronaut health and equipment as revealed during theApollo era lunar surface missions. Dust particles cling to spacesuits and field gear, which upon ingress would begincirculating throughout the spacecraft or habitat. An astronaut's health is compromised by the dust particle's potentialto embed in the lungs and cause respiratory illnesses. The extreme abrasiveness and granularity of the particles makeit near impossible to completely shield a spacecraft or habitat from dust related damage. NASA's Glenn ResearchCenter collaborated with Crew 188 at the Mars Desert Research Station (MDRS) in Utah to measure how much dustentered the habitat during a series of extravehicular activities (EVAs), or surface excursions. A NASA GRCdeveloped multistage filter system, coined the Scroll Filter System, was tested, for its effectiveness in removing dustthat entered the airlock and habitat after the EVAs. An optical particle counter measured the ambient airlockparticulates five times including: before the start of operations; after the crew left for EVA; in the middle of the EVAwith the settled air; before the crew entered the airlock after EVA; and finally, after the crew simulated repressurizationand suit brushing off in the airlock. Data was also collected in several of the working environmentlocations around MDRS and outside the habitat in the wind. Data collected from this research will help establishfilter equipment for life support systems and prescribed operations for astronaut transition from a planetary surfaceinto a desired clean habitat. Measurements may aid in updating a baseline expected dust load for a surface habitatand further facilitate the mitigation of astronaut's exposure to dust particles on the surface of celestial bodies.
Kobrick, Ryan L.↗
The contribution of BvgR, RisA, and RisS to global gene regulation, intracellular cyclic-di-GMP levels, motility, and biofilm formation in Bordetella bronchiseptica
Bordetella bronchiseptica is a highly contagious respiratory bacterial veterinary pathogen. In this study the contribution of the transcriptional regulators BvgR, RisA, RisS, and the phosphorylation of RisA to global gene regulation, intracellular cyclic-di-GMP levels, motility, and biofilm formation were evaluated. Next Generation Sequencing (RNASeq) was used to differentiate the global gene regulation of both virulence-activated and virulence-repressed genes by each of these factors. The BvgAS system, along with BvgR, RisA, and the phosphorylation of RisA served in cyclic-di-GMP degradation. BvgR and unphosphorylated RisA were found to temporally regulate motility. Additionally, BvgR, RisA, and RisS were found to be required for biofilm formation.
59 BASIC BIOLOGICAL SCIENCES↗
Photosynthetic and respiratory activity in germfree higher plant species
Equipment developed for the study of gas exchange in germfree plants is described. The equipment includes a gas exchange chamber to house the plant under study, a gas feed assembly to introduce and remove gas from the chamber, and a clinostat to rotate the apparatus. Fluorescent and incandescent lights are used to illuminate the chamber and a sealed plastic barrier is used to isolate the potting soil from the chamber atmosphere. The gas outflow from the chamber can be diverted to an infrared CO2 analyzer. The performance of the system was evaluated.
Source record↗
Cardiovascular group
As a starting point, the group defined a primary goal of maintaining in flight a level of systemic oxygen transport capacity comparable to each individual's preflight upright baseline. The goal of maintaining capacity at preflight levels would seem to be a reasonable objective for several different reasons, including the maintenance of good health in general and the preservation of sufficient cardiovascular reserve capacity to meet operational demands. It is also important not to introduce confounding variables in whatever other physiological studies are being performed. A change in the level of fitness is likely to be a significant confounding variable in the study of many organ systems. The principal component of the in-flight cardiovascular exercise program should be large-muscle activity such as treadmill exercise. It is desirable that at least one session per week be monitored to assure maintenance of proper functional levels and to provide guidance for any adjustments of the exercise prescription. Appropriate measurements include evaluation of the heart-rate/workload or the heart-rate/oxygen-uptake relationship. Respiratory gas analysis is helpful by providing better opportunities to document relative workload levels from analysis of the interrelationships among VO2, VCO2, and ventilation. The committee felt that there is no clear evidence that any particular in-flight exercise regimen is protective against orthostatic hypotension during the early readaptation phase. Some group members suggested that maintenance of the lower body muscle mass and muscle tone may be helpful. There is also evidence that late in-flight interventions to reexpand blood volume to preflight levels are helpful in preventing or minimizing postflight orthostatic hypotension.
Blomqvist, Gunnar↗
Controlling Host Responses to Infection
Pathogen invasion of host cells causes a myriad of functional changes including alterations of chromatin accessibility often limiting defense responses, shunting of cellular resources to centers of viral replication, and rearrangement of intracellular membranes to facilitate genome reproduction and progeny release. Systems biology approaches provide global snapshots of pathogen induced changes following infection and provide a variety of tools to begin to define how cellular homeostasis is disrupted, but improvements on these tools are required to determine how cellular functions are altered post infection. Chromatin accessibility techniques, biochemical assays to assess the activity of epigenetic enzymes, scalable sample collection platforms, and activity-based probes were used to characterize how human respiratory viruses modify host responses in infected human lungs over time. These studies enhanced our knowledge of how pathogens usurp the host environment during infection and identify additional targets for future evaluations of medical countermeasures.
59 BASIC BIOLOGICAL SCIENCES↗
Control of Nitrogen Dioxide in Stack Emission by Reaction with Ammonia
The development of an acid base gas-phase reaction system which utilizes anhydrous ammonia as the reactant to remove nitrogen dioxide from hydrazine-nitrogen tetroxide rocket combustion exhaust is reported. This reaction reduced NO2 levels in exhaust emissions so that the resulting stack emission is completely white instead of the earlier observed typical reddish-brown coloration. Preliminary analyses indicate the importance of reaction time and ammonia concentration on removal efficiency and elimination of the health hazard to individuals with respiratory problems.
Metzler, A. J.↗
Results of examination of the nasal mucosa
The olfactory epithelium, but not the nasal respiratory epithelium, of the four pocket mice (Perognathus longimembris) that survived their flight on Apollo XVII showed both diffuse alterations and numerous disseminated focal lesions. The olfactory mucosa of the mouse that died during flight was also affected, but to a minor degree insofar as could be determined. All this was in contrast to the normal appearance of the olfactory mucosa of the numerous control animals. A number of possible causes were considered: systemic or regional infection; inhaled particulate material (seed dust); by-products from the KO2 bed in aerosol or particulate form; gas contaminants originating in the flight package; volatile substances from the dead mouse; weightlessness; and cosmic ray particle radiation. Where feasible, studies were conducted in an effort to rule in or rule out some of these potentially causative factors. No definitive conclusions were reached as to the cause of the lesions in the flight mice.
Kraft, L. M.↗