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DOE OSTI2025

National serosurvey and risk mapping reveal widespread distribution of Coxiella burnetii in Kenya

Coxiella burnetii, the causative agent of Q fever, is an emerging pathogen that has the potential to cause severe chronic infections in animals and humans worldwide. The detrimental impact on public health is projected to be higher in the low- and middle-income countries given their lower capacity to sustain effective surveillance and response measures. We implemented a national serosurvey of cattle in Kenya to map the spatial distribution of the pathogen. The study used serum samples that were collected from randomly selected cattle in different ago-ecological zones across the country. These samples were screened for the pathogen using PrioCHECK Ruminant Q Fever AB Plate ELISA kit. The laboratory findings were analyzed using INLA package to identify risk factors for C. burnetii exposure from herd- and animal-level factors, area, and bioclimatic datasets accessed from online databases. A total of 6,593 cattle were recruited for the study; of these, 7.9% (95% CI; 7.2–8.5) were seropositive. Outputs from the multivariable analysis revealed that the animal age and some of the geographical variables including wind speed, area under shrubs and “petric calcisols” type of soil were significantly associated with C. burnetii seropositivity. Being a calf, weaner or subadult was associated with lower odds of exposure compared to being an adult by 0.24 (credibility interval: 2.5% and 97.5%), 0.41 (0.30–0.55) and 0.51 (0.38–0.69), respectively. In addition, a unit increase in the wind speed increased the odds of C. burnetii seropositivity by 1.27 (1.05–1.52) while an increase on the land area under shrubs was associated with lower odds of exposure (0.67 [0.47–0.69]). The effect of petric calcisols was non-linear; an increase of the land area with this soil type was associated with an exponential increase in C. burnetii seropositivity. This study provides new data on C. burnetii seroprevalence, information of its risk factors and a prevalence map that can be used for C. burnetii risk surveillance and control. The identification of environmental risk factors for C. burnetii exposure, and the increasing awareness of the zoonotic potential of the pathogen, calls for the need to enhance the existing collaborations for the surveillance and control of C. burnetii in line with the One Health framework. The evidence generated on the potential role of environmental factors can also be used to design nature-based interventions, such as replacement of vegetation in denuded areas, to reduce potential for the aerosolization of the pathogen. Livestock vaccination in the hotspots would also reduce animal infections and hence the contamination of the environment.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2006

Spacecraft Environment May Reduce Resistance To Infection

Living and working in a spacecraft exposes the crew to a unique environment. This environment includes microgravity, increased radiation, chemical and biological contamination, and a variety of stressors. Disturbances in this balance are often manifested by diminished immunity in astronauts/cosmonauts. Reactivation of Epstein- Barr virus (EBV), cytomegalovirus (CMV), and varicella-zoster virus (VZV) has been used as an indicator of immune status. Reactivation of EBV and VZV were detected and quantified in saliva. CMV was measured in urine. The DNA was extracted using a Qiagen Inc. kit and viral DNA was detected by real time polymerase chain reaction (PCR) based assay with Taqman 7700 (PE Biosystems). Patterns of Epstein-Barr virus (EBV) reactivation in 32 astronauts and 18 healthy age-matched control subjects were characterized by quantifying EBV shedding. Saliva samples were collected before, during, and after 10 space shuttle missions of 5 to 14 d duration. Of 1398 saliva specimens from 32 astronauts, 314 (23%) were positive for EBV DNA. Examination by flight phase showed that 29% of the saliva specimens collected from 28 astronauts before flight were positive for EBV DNA, as were 16% of those collected from 25 astronauts during flight and 16% of those collected after flight from 23 astronauts. The mean number of EBV copies/mL from samples taken during the flights was 417, ten-fold greater (p < 0.05) than the copies from the preflight (40) and post flight (44) phases. In contrast, the control subjects shed EBV DNA with a frequency of 3.7% and mean EBV copies of 40 per mL of saliva. Ten days before flight and on landing day, titers of antibody to EBV viral capsid antigen were significantly (p < 0.05) greater than baseline levels. Increases in the number of viral copies and in the amount of EBV-specific antibody were consistent with EBV reactivation before, during, and after space flight. Similarly, CMV and VZV reactivation increased in response to space flight conditions. Data indicates that space flight is a unique stress environment that may produce stress-induced changes in the host-microbe relationship resulting in increased risk of infection.

Pierson, Duane L.↗

DOE OSTI2025

Genome-wide association study of long COVID

Abstract Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association ofFOXP4with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4’s role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.

Genetics & Heredity↗

DOE OSTI2025

Antitoxin control of optimal transcriptional repression in the atypical HigB–HigA toxin–antitoxin system from Proteus vulgaris

Abstract Bacterial toxin–antitoxin (TA) pairs transcriptionally autoregulate their expression via a repression/derepression mechanism in response to changing environmental conditions. The structural diversity of TA systems influences the mechanisms of transcriptional regulation. Here, we define the molecular mechanism for the plasmid-encoded HigB–HigA TA pair originally identified in a post-operative infection with antibiotic-resistant Proteus vulgaris. We determine DNA binding and promoter activity by the HigB–HigA complex supported by structural biology and molecular dynamics simulations of an elusive DNA operator–TA repressor complex. To define the optimal oligomeric TA repressor–DNA operator complex required for derepression, we engineered a dedicated trimeric HigB–HigA2 complex that represses transcription more than 26-fold as compared to the tetrameric HigB2–HigA2. These results expand the known diversity of how the HigB–HigA TA family is autoregulated.

Biochemistry & Molecular Biology↗

NASA NTRS1998

2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

Non-NASA Center↗

DOE OSTI2026

Impact of Selenium and Vitamin E Deficiency on Zika Virus Pathogenesis and Immune Response in Mice

Micronutrient status is recognized to influence host susceptibility to viral infections, yet its impact on Zika virus (ZIKV) pathogenesis remains incompletely understood. We investigated the effects of dietary selenium and combined selenium plus vitamin E deficiency on ZIKV infection outcomes in a type I interferon α/β receptor knockout (Ifnar1 −/− ) murine model. Mice maintained on deficient diets exhibited significantly lower neutralizing antibody titers and reduced levels of key antiviral cytokines (IFN-γ, TNF-α, IFN-α, IFN-β, IL-12p70, CCL5) compared to controls. Correspondingly, higher viral RNA loads were detected in the brains of double-deficient mice, which also experienced greater weight loss and increased mortality. Deep sequencing revealed no major differences in overall viral genome diversity across diet groups; however, specific mutations, including V330L and D67E in the E gene, and V360I in the NS3 gene, were enriched or detected in nutritionally deficient animals. These findings suggest that antioxidant micronutrient deficiency impairs both humoral and cellular immune responses to ZIKV, potentially facilitating enhanced neuroinvasion. While the functional consequences of the identified mutations warrant further investigation, our results underscore the importance of adequate micronutrient intake for optimal antiviral defense. Further studies are needed to clarify the epidemiological significance of these observations.

Biological and medical sciences↗

NASA NTRS1973

Infectivity and egg production of Nematospiroides dubius as affected by space flight and ultraviolet irradiation

Nematospiroides dubius was tested to determine the infective potential of the third stage larvae and the egg-production and egg-viability rates of the resulting adults after they are exposed to space flight and solar ultraviolet irradiation. The results are indicative that space-flown larvae exposed to solar ultraviolet irradiation were rendered noninfective in C57 mice, whereas flight control larvae that received no solar ultraviolet irradiation matured at the same rate as the ground control larvae. However, depressed egg viability was evident in the flight control larvae.

Long, R. A.↗

NASA NTRS2007

Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the spaceflight environment has never been accomplished due to significant technological and logistical hurdles. Moreover, the effects of spaceflight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared to identical ground control cultures. Global microarray and proteomic analyses revealed 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground based microgravity culture model. Spaceflight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during spaceflight missions and provide novel therapeutic options on Earth.

Wilson, J. W.↗

DOE OSTI2025

Host-specific adaptation in Fusarium oxysporum correlates with distinct accessory chromosome content in human and plant pathogenic strains

ABSTRACT Fusarium oxysporumis a cross-kingdom pathogen. While some strains cause disseminated fusariosis and blinding corneal infections in humans, others are responsible for devastating vascular wilt diseases in plants. To better understand the distinct adaptations ofF. oxysporumto animal or plant hosts, we conducted a comparative phenotypic and genetic analysis of two strains: MRL8996 (isolated from a keratitis patient) and Fol4287 (isolated from a wilted tomato [Solanum lycopersicum]). Infection of mouse corneas and tomato plants revealed that, while both strains cause symptoms in both hosts, MRL8996 caused more severe corneal disease in mice, whereas Fol4287 induced more pronounced wilting symptoms in tomato plants.In vitroassays using abiotic stress treatments revealed that the human pathogen MRL8996 was better adapted to elevated temperatures, whereas the plant pathogen Fol4287 was more tolerant to osmotic and cell wall stresses. Both strains displayed broad resistance to antifungal treatment, with MRL8996 exhibiting the paradoxical effect of increased tolerance to higher concentrations of the antifungal caspofungin. We identified a set of accessory chromosomes (ACs) that encode genes with different functions and have distinct transposon profiles between MRL8996 and Fol4287. Interestingly, ACs from both genomes also encode proteins with shared functions, such as chromatin remodeling and post-translational protein modifications. Our phenotypic assays and comparative genomics analyses lay the foundation for future studies correlating genotypes with phenotype and for developing targeted antifungals for agricultural and clinical uses. IMPORTANCE Fusarium oxysporumis a cross-kingdom fungal pathogen that infects both plants and animals. In addition to causing many devastating wilt diseases, this group of organisms was recently recognized by the World Health Organization as a high-priority threat to human health. Climate change has increased the risk ofFusariuminfections, asFusariumstrains are highly adaptable to changing environments. Deciphering fungal adaptation mechanisms is crucial to developing appropriate control strategies. We performed a comparative analysis ofFusariumstrains using an animal (mouse) and plant (tomato) host andin vitroconditions that mimic abiotic stress. We also performed comparative genomics analyses to highlight the genetic differences between human and plant pathogens and correlate their phenotypic and genotypic variations. We uncovered important functional hubs shared by plant and human pathogens, such as chromatin modification, transcriptional regulation, and signal transduction, which could be used to identify novel antifungal targets.

Microbiology↗

NASA NTRS1972

Remote sensing of changes in morphology and physiology of trees under stress

Previsual detection of Fomes annosus in pine plantations was studied. Detailed analyses of photographic imagery obtained over the Ann Arbor Test Site during 1969 and 1970 reveal that the Ektachrome Infrared film was superior to Ektachrome Aerographic, Infrared Aerographic, or Plus-X Aerographic films for detecting Fomes annosus damage. Of far more significance in controlling the accuracy of damage detection, however, was the experience of the photo interpreter. Ratio-processing of multispectral scanner data was investigated with data collected in June of 1970 and in June of 1972. Ratioing of the 1.5-1.8 and 1.0-1.4 micrometer channels gave good results at detecting openings in the crown canopy and adjacent infected trees. Combined level slicing of the 1.5-1.8 micrometer channel and the 1.5-1.8 to 1.0-1.4 micrometer ratio permitted separation and recognition of forest litter in the openings and stressed trees adjacent ot the openings.

Olson, C. F., Jr.↗

NASA NTRS2017

Effects of Simulated Microgravity on a Host-Pathogen System

While it has been shown that decades of astronauts and cosmonauts can suffer from illnesses both during and after spaceflight, the underlying causes are still poorly understood, due in part to the fact that there are so many variables to consider when investigating the human immune system in a complex environment. Invertebrates have become popular models for studying human disease because they are cheap, highly amenable to experimental manipulation, and have innate immune systems with a high genetic similarity to humans. Fruit flies (Drosophila melanogaster) have been shown to experience a dramatic shift in immune gene expression following spaceflight, but are still able to fight off infections when exposed to bacteria. However, the common bacterial pathogen Serratia marcescens was shown to become more lethal to fruit flies after being cultured in space, suggesting that not only do we need to consider host changes in susceptibility, but also changes in the pathogen itself after spaceflight conditions. Being able to simulate spaceflight conditions in a controlled environment on the ground gives us the ability to not only evaluate the effects of microgravity on the host immune system, but also how the microorganisms that cause immune disorders are being affected by these drastic environmental shifts. In this study, I use a ground-based simulated microgravity environment to examine the genetic changes associated with increased S. marcescens virulence in order to understand how microgravity is affecting this pathogen, as well as how these genetic changes influence and interact with the host immune system. This study will provide us with more directed approaches to studying the effects of spaceflight on human beings, with the ultimate goal of being able to counteract immune dysfunction in future space exploration.

Immunology↗

NASA NTRS2017

Studying the Effect of Radiation in the Context of Deep Space Travel

Bhattacharya, Sharmila↗

DOE OSTI2025

In vitro activity and in vivo efficacy of omadacycline against Plasmodium species

Abstract Background Doxycycline is currently the only tetracycline-class antibiotic recommended for malaria prophylaxis. Omadacycline, a semisynthetic aminomethylcycline approved for treatment of adults with community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections, has a well-established safety profile. This study evaluated the in vitro activity of omadacycline againstPlasmodium falciparumandPlasmodium cynomolgiand its in vivo efficacy againstPlasmodium bergheiin experimental malaria models to assess its potential as an antimalarial drug. Methods Fluorescence-based assays were used to assess the in vitro blood and liver stage activity of omadacycline and doxycycline againstP. falciparumandP. cynomolgilaboratory clones. In vivo liver and early-stage blood stage efficacy were evaluated in a murine model ofP. bergheiinfection, utilizing in vivo imaging of luciferase-expressingP. berghei(ANKA strain) sporozoites in female albino C57Bl/6 mice. Parasitaemia was monitored by flow cytometry for up to 30 days post-infection. Results Omadacycline demonstrated comparable in vitro activity to doxycycline against both drug-sensitive and drug-resistantP. falciparumclones, while doxycycline showed reduced activity against two drug-resistant clones. Notably, omadacycline exhibited superior anti-schizont activity in theP. cynomolgiliver stage assay. In theP. bergheimurine model, omadacycline was efficacious in both liver and early blood stages compared to the untreated control group, and demonstrated improved survival compared to doxycycline. Conclusions Omadacycline demonstrated enhanced antimalarial efficacy over doxycycline in vitro in liver stage activity and in overcoming resistance in the blood stage, and in survival in an in vivo model ofP. bergheiinfection. These findings support further investigation of omadacycline as a potential candidate for malaria prophylaxis and treatment.

Infectious Diseases↗

NASA NTRS2003

Human Peripheral Blood Mononuclear Cells Cultured in Normal and Hyperglycemic Media in Simulated Microgravity Using NASA Bioreactors

We sought answers to several questions this summer at NASA Johnson Space Center. Initial studies involved the in vitro culture of human peripheral blood mononuclear in cells in different conditioned culture media. Several human cancer clones were similarly studied to determine responses to aberrant glycosylation by the argon laser. The cells were grown at unit gravity in flasks and in simulated microgravity using NASA bioreactors. The cells in each instance were analyzed by flow cytometry. Cell cycle analysis was acquired by staining nuclear DNA with propidium iodide. Responses to the laser stimulation was measured by observing autofluorescence emitted in the green and red spectra after stimulation. Extent of glycosylation correlated with the intensity of the laser stimulated auto-fluorescence. Our particular study was to detect and monitor aberrant glycosylation and its role in etiopathogenesis. Comparisons were made between cells known to be neoplastic and normal cell controls using the same Laser Induced Autofluorescence technique. Studies were begun after extensive literature searches on using the antigen presenting potential of dendritic cells to induce proliferation of antigen specific cytotoxic T-cells. The Sendai virus served as the antigen. Our goal is to generate sufficient numbers of such cells in the simulated microgravity environment for use in autologous transplants of virally infected individuals including those positive for hepatitis and HIV.

Lawless, DeSales↗

NASA NTRS2025

The Microbiome of A Tomato Crop Grown Under Different Lighting Regimes on the International Space Station

The VEG-05 experiment presented here investigated the effect of red-rich and blue-rich light recipes in Veggie on the microbiome of the Veggie facility and the plant tissues of a dwarf tomato variety, Solanum lycopersicum cv. Red Robin. For food safety, the plants were screened using culture-based methods for potential human pathogens that may cause infection by consumption of the fruit. The microbiome was investigated using bacterial 16S and fungal ITS sequencing methods to enumerate and identify bacterial and fungal communities on tomato fruit, roots, leaves, rooting substrate, and Veggie facility surfaces grown under blue-rich or red-rich lighting. Comparisons of microbial communities were made between lighting treatments, as well as for flight and ground controls. This analysis determined the core microbiome and microbiological composition for tomato plants grown under a blue-rich or red-rich lighting treatment and microgravity conditions. Culture-based pathogen screening, corroborated by 16S and ITS sequencing, yielded negative results. Bacterial and fungal counts were lower for ground controls than in-flight samples. However, there were no differences in microbial counts between lighting treatments. Regardless of lighting treatment, plant components shared a core microbiome, although some differences were observed in genera between lighting treatments.

Veggie↗

NASA NTRS2015

Summer 2015 Internship Abstract

Green fluorescent protein (GFP) visually shows the expression of proteins by fluorescing when exposed to certain wavelengths of light. The GFP in this experiment was used to identify cells actively releasing viruses. The experiment focused on the effect of microgravity on the GFP expression of Akata B-cells infected with Epstein Barr Virus (EBV). Two flasks were prepared with 30 million cells each and two bioreactors were prepared with 50 million cells each. All four cultures were incubated for 16 days and fed every four days. Cellometer readings were taken on the feeding days to find cell size, viability, and GFP expression. In addition, the cells were treated with Propodium monoazide (PMA) and run through real time PCR to determine viral load on the feeding days. On the International Space Station air samples are taken to analyze the bacterial and fungal organisms in the air. The Sartorius Portable Airport is being investigated for potential use on the ISS to analyze for viral content in the air. Multiple samples were taken around Johnson Space Center building 37 and in Clear Lake Pediatric Clinic. The filter used was the gelatin membrane filter and the DNA was extracted directly from the filter. The DNA was then run through real time PCR for Varicella Zoster Virus (VZV) and EBV as well as GAPDH to test for the presence of DNA. The results so far have shown low DNA yield and no positive results for VZV or EBV. Further inquiry involves accurately replicating an atmosphere with high viral load from saliva as would be found on the ISS to run the air sampler in. Another line of research is stress hormones that may be correlated to the reactivation of latent viruses. The stress hormones from saliva samples are analyzed rather than blood samples. The quantity found in saliva shows the quantity of the hormones actually attached to cells and causing a reaction, whereas in the blood the quantity of hormones is the total amount released to cause a reaction. The particular hormones tested for were cortisol, alpha-amylase, and DHEA. The DHEA was very high in the two control samples tested. Regularly, samples came into the lab from local clinics to be tested for various viruses. Saliva, blood, body scrapes, and tears were received from the clinics and then run for VZV, EBV, and Human Simplex Virus 1 (HSV-1) with the results then reported back to the clinician. Blood, saliva, and urine from astronauts were also tested for viruses and logged. In addition, several cell cultures were brought up and grown, including adherent Human Lung Fibroblast (HFL) cells infected with VZV, and Akata B-cells infected with EBV.

Smith, Courtney↗

NASA NTRSDate not supplied

Preparation for and Performance of a Pseudomonas aeruginosa Biofilm Experiment On Board the International Space Station

Biofilms are a problem on Earth given their ability to degrade the materials upon which they grow and due to their relevance to infections. Remarkably, 65% and 80% of infections and chronic diseases on Earth are associated with biofilms, respectively. In space, these problems' impact is higher because the crew's lives and mission success depend on nominal operation of mechanical systems. Furthermore, the isolated confined environment nature of spaceflight may increase the rates of disease transmission. In the case of the International Space Station (ISS), biofilms are an identified problem on the Environmental Control and Life Support System (ECLSS), namely on the water processor assembly (WPA). In late 2019, the Space Biofilms experiment launched towards ISS to (i) characterize the mass, thickness, morphology, and gene expression of biofilms formed in space with respect to matched Earth controls, (ii) interrogate the expression of antimicrobial resistance genes, and (iii) test novel materials as potential biofilm control strategies for future ECLSS components. For this, 288 bacterial samples were prepared prior to the launch of the Northrop Grumman CRS-12 mission from NASA's Wallops Flight Facility. The samples were integrated into the spaceflight hardware, BioServe's Fluid Processing Apparatus (FPA) packed in sets of eight in Group Activation Packs (GAP). Half of these samples were activated and terminated on orbit by NASA astronauts Jessica Meir and Christina Koch, while the remaining half were processed equivalently on Earth. The spaceflight bacterial samples of Space Biofilms returned on board SpaceX' CRS-19 Dragon spacecraft, in early 2020. We here describe the test campaign implemented to verify the experiment design and confirm it would enable us to achieve the project's scientific goals. This campaign ended with the Experiment Verification Test (EVT), from which we here present example morphology and transcriptomic results. We describe in detail the sample preparation prior to flight, including cleaning and sterilization of the coupons of six materials (SS316, passivated-SS316, lubricant impregnated surface, catheter-grade silicone with and without a nanotopography, and cellulose membrane), loading and integration of growth media, bacterial inoculum, fixative and preservative to enable experiment termination on orbit. Additionally, we describe the performance of the experiment on board the ISS, including crew activities, use of assets, temperature profile, and experiment timeline; all leading to a successful spaceflight experiment.

Pamela Flores↗

NASA NTRS1999

Sustained Partial Sleep Deprivation: Effects on Immune Modulation and Growth Factors

The vulnerability to medical emergencies is greatest in space where there are real limits to the availability or effectiveness of ground based assistance. Moreover, astronaut safety and health maintenance will be of increasing importance as we venture out into space for extended periods of time. It is therefore critical to understand the mechanisms of the regulatory physiology of homeostatic systems (sleep, circadian, neuroendocrine, fluid and nutritional balance) and the key roles played in adaptation. This synergy project has combined aims of the "Human Performance Factors, Sleep and Chronobiology Team"; the "Immunology, Infection and Hematology Team"; and the "Muscle Alterations and Atrophy Team", to broadly address the effects of long term sleep reduction, as is frequently encountered in space exploration, on neuroendocrine, neuroimmune and circulating growth factors. Astronaut sleep is frequently curtailed to averages of between 4- 6.5 hours per night. There is evidence that this amount of sleep is inadequate for maintaining optimal daytime functioning. However, there is a lack of information concerning the effects of chronic sleep restriction, or reduction, on regulatory physiology in general, and there have been no controlled studies of the cumulative effects of chronic sleep reduction on neuroendocrine and neuroimmune parameters. This synergy project represents a pilot study designed to characterize the effects of chronic partial sleep deprivation (PSD) on neuroendocrine, neuroimmune and growth factors. This project draws its subjects from two (of 18) conditions of the larger NSBRI project, "Countermeasures to Neurobehavioral Deficits from Cumulative Partial Sleep Deprivation During Space Flight", one of the projects on the "Human Performance Factors, Sleep and Chronobiology Team ". For the purposes of this study, to investigate the effects of chronic sleep loss on neuroendocrine and neuroimmune function, we have focused on the two extreme sleep conditions from this larger study: a 4.2 hour per night condition, and a 8.2 hour per night condition. During space flight, muscle mass and bone density are reduced, apparently due to loss of GH and IGF-I, associated with microgravity. Since >70% of growth hormone (GH) is secreted at night in normal adults, we hypothesized that the chronic sleep restriction to 4 hours per night would reduce GH levels as measured in the periphery. In this synergy project, in collaboration with the "Muscle Alterations and Atrophy Team ", we are measuring insulin-like growth factor-I (IGF-I) in peripheral circulation to test the prediction that it will be reduced by chronic sleep restriction. In addition to stress modulation of immune function, recent research suggests that sleep is also involved. While we all have the common experience of being sleepy when suffering from infection, and being susceptible to infection when not getting enough sleep, the mechanisms involved in this process are not understood and until recently have gone largely overlooked. We believe that the immune function changes seen in spaceflight may also be related to the cumulative effects of sleep loss. Moreover, in space flight, the possibility of compromised immune function or of the reactivation of latent viruses are serious potential hazards for the success of long term missions. Confined living conditions, reduced sleep, altered diet and stress are all factors that may compromise immune function, thereby increasing the risks of developing and transmitting disease. Medical complications, which would not pose serious problems on earth, may be disastrous if they emerged in space.

Mullington, Janet M.↗