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NASA NTRS2016

Evaluation of Different MODIS AOD Retrieval Algorithms for PM (sub 2.5) Estimation in the Western, Midwestern and Southeastern United States with Implications for Public Health

This study was part of the research activities of the Center for Applied Atmospheric Research and Education (CAARE) funded by the NASA MUREP (Minority University Research and Education Project) Institutional Research Opportunity (MIRO) Program. Satellite measurements of Aerosol Optical Depth (AOD) have been shown to be correlated with ground measurements of fine particulate matter less than 2.5 microns PM (sub 2.5), which in turn has been linked to respiratory and heart diseases. The strength of the correlation between AOD and PM (sub 2.5) varies for different AOD retrieval algorithms and geographic regions. We evaluated several Moderate Resolution Imaging Spectrometer (MODIS) AOD products from different satellites (Aqua vs. Terra), retrieval algorithms (Dark Target versus Deep Blue), Collections (5.1 versus 6) and spatial resolutions (10-kilometers versus 3-kilometers) for cities in the Western, Midwestern and Southeastern U.S. We developed and validated PM (sub 2.5) prediction models using remotely-sensed AOD data, which were improved by incorporating meteorological variables (temperature, relative humidity, precipitation, wind speed, and wind direction) from the North American Land Data Assimilation System Phase 2 (NLDAS-2). Adding these meteorological data significantly improved the predictive power of all the PM (sub 2.5) models, especially in the Western U.S. Temperature, relative humidity and wind speed were the most significant meteorological variables throughout the year in the Western U.S. Wind speed was the most significant meteorological variable for the cold season while temperature was the most significant variable for the warm season in the Midwestern and Southeastern U.S. Our study re-establishes the connection between PM (sub 2.5) and public health concerns including respiratory and cardiovascular diseases (asthma, high blood pressure, coronary heart disease, heart attack, and stroke). Using PM (sub 2.5) data and health data from the Centers for Disease Control and Prevention (CDC)'s Behavioral Risk Factor Surveillance System (BRFSS), our statistical analysis showed that heart attack and stroke occurrences had the strongest correlations with PM (sub 2.5).

Environmental Public Health↗

NASA NTRS2002

Patterns of gene expression in atrophying skeletal muscles: response to food deprivation

During fasting and many systemic diseases, muscle undergoes rapid loss of protein and functional capacity. To define the transcriptional changes triggering muscle atrophy and energy conservation in fasting, we used cDNA microarrays to compare mRNAs from muscles of control and food-deprived mice. Expression of >94% of genes did not change, but interesting patterns emerged among genes that were differentially expressed: 1) mRNAs encoding polyubiquitin, ubiquitin extension proteins, and many (but not all) proteasome subunits increased, which presumably contributes to accelerated protein breakdown; 2) a dramatic increase in mRNA for the ubiquitin ligase, atrogin-1, but not most E3s; 3) a significant suppression of mRNA for myosin binding protein H (but not other myofibrillar proteins) and IGF binding protein 5, which may favor cell protein loss; 4) decreases in mRNAs for several glycolytic enzymes and phosphorylase kinase subunits, and dramatic increases in mRNAs for pyruvate dehydrogenase kinase 4 and glutamine synthase, which should promote glucose sparing and gluconeogenesis. During fasting, metallothionein mRNA increased dramatically, mRNAs for extracellular matrix components fell, and mRNAs that may favor cap-independent mRNA translation rose. Significant changes occurred in mRNAs for many growth-related proteins and transcriptional regulators. These transcriptional changes indicate a complex adaptive program that should favor protein degradation and suppress glucose oxidation in muscle. Similar analysis of muscles atrophying for other causes is allowing us to identify a set of atrophy-specific changes in gene expression.

Non-NASA Center↗

DOE OSTI2024

Ultraviolet Superradiance from Mega-Networks of Tryptophan in Biological Architectures

Networks of tryptophan (Trp)–an aromatic amino acid with strong fluorescence response–are ubiquitous in biological systems, forming diverse architectures in transmembrane proteins, cytoskeletal filaments, subneuronal elements, photoreceptor complexes, virion capsids, and other cellular structures. We analyze the cooperative effects induced by ultraviolet (UV) excitation of several biologically relevant Trp mega-networks, thus giving insights into novel mechanisms for cellular signaling and control. Our theoretical analysis in the single-excitation manifold predicts the formation of strongly superradiant states due to collective interactions among organized arrangements of up to >10 5 Trp UV-excited transition dipoles in microtubule architectures, which leads to an enhancement of the fluorescence quantum yield (QY) that is confirmed by our experiments. We demonstrate the observed consequences of this superradiant behavior in the fluorescence QY for hierarchically organized tubulin structures, which increases in different geometric regimes at thermal equilibrium before saturation, highlighting the effect’s persistence in the presence of disorder. Our work thus showcases the many orders of magnitude across which the brightest (hundreds of femtoseconds) and darkest (tens of seconds) states can coexist in these Trp lattices.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2025

bmdrc: Python package for quantifying phenotypes from chemical exposures with benchmark dose modeling

Though chemical exposures are known to potentially have negative impacts on health, including contributing to chronic diseases such as cancer, the quantitative contribution of risk is not fully understood for every chemical. A commonly used approach to quantify levels of risk is to measure the proportion of organisms (such as a total number of zebrafish on a plate or mice in a cage) with abnormal behavioral responses or morphology at increasing concentrations of chemical exposure. A particular challenge with processing the proportional data from these assays is the appropriate estimation of chemical concentration levels that result in malformations or acute toxicity, as these values typically vary between experimental measurements. The recommended approach by the Environmental Protection Agency (EPA) is to fit benchmark dose curves with specific filters and model fitting steps, which are crucial to properly processing the proportional data. Several tools exist for the fitting of benchmark dose response curves, but none are standalone Python libraries built to process both morphological and behavioral data as proportions with all the EPA recommended filters, filter parameters, models, and model parameters. Thus, here we present the benchmark dose response curve (bmdrc) Python library, which was built to closely follow these EPA guidelines with helpful visualizations of filters and fitted model curves, and reports for reproducibility purposes. bmdrc is open-source and has demonstrated utility as a support package to an existing web portal for information on chemicals (https://srp.pnnl.gov). Our package will support any toxicology analysis where the response is a proportional value at increasing levels of a concentration of a chemical or chemical mixture.

Superfund↗

DOE OSTI2023

Younger facial looks are associate with a lower likelihood of several age-related morbidities in the middle-aged to elderly

Abstract Background Looking older for one’s chronological age is associated with a higher mortality rate. Yet it remains unclear how perceived facial age relates to morbidity and the degree to which facial ageing reflects systemic ageing of the human body. Objectives To investigate the association between ΔPA and age-related morbidities of different organ systems, where ΔPA represents the difference between perceived age (PA) and chronological age. Methods We performed a cross-sectional analysis on data from the Rotterdam Study, a population-based cohort study in the Netherlands. High-resolution facial photographs of 2679 men and women aged 51.5–87.8 years of European descent were used to assess PA. PA was estimated and scored in 5-year categories using these photographs by a panel of men and women who were blinded for chronological age and medical history. A linear mixed model was used to generate the mean PAs. The difference between the mean PA and chronological age was calculated (ΔPA), where a higher (positive) ΔPA means that the person looks younger for their age and a lower (negative) ΔPA that the person looks older. ΔPA was tested as a continuous variable for association with ageing-related morbidities including cardiovascular, pulmonary, ophthalmological, neurocognitive, renal, skeletal and auditory morbidities in separate regression analyses, adjusted for age and sex (model 1) and additionally for body mass index, smoking and sun exposure (model 2). Results We observed 5-year higher ΔPA (i.e. looking younger by 5 years for one’s age) to be associated with less osteoporosis [odds ratio (OR) 0.76, 95% confidence interval (CI) 0.62–0.93], less chronic obstructive pulmonary disease (OR 0.85, 95% CI 0.77–0.95), less age-related hearing loss (model 2; B = −0.76, 95% CI −1.35 to −0.17) and fewer cataracts (OR 0.84, 95% CI 0.73–0.97), but with better global cognitive functioning (g-factor; model 2; B = 0.07, 95% CI 0.04–0.10). Conclusions PA is associated with multiple morbidities and better cognitive function, suggesting that systemic ageing and cognitive ageing are, to an extent, externally visible in the human face.

Mekić, Selma↗

NASA NTRS1997

Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in treating neurodegenerative disorders.

Sroufe, Angela E.↗

NASA NTRS1995

Neurochemical phenotype of corticocortical connections in the macaque monkey: quantitative analysis of a subset of neurofilament protein-immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices

The neurochemical characteristics of the neuronal subsets that furnish different types of corticocortical connections have been only partially determined. In recent years, several cytoskeletal proteins have emerged as reliable markers to distinguish subsets of pyramidal neurons in the cerebral cortex of primates. In particular, previous studies using an antibody to nonphosphorylated neurofilament protein (SMI-32) have revealed a consistent degree of regional and laminar specificity in the distribution of a subpopulation of pyramidal cells in the primate cerebral cortex. The density of neurofilament protein-immunoreactive neurons was shown to vary across corticocortical pathways in macaque monkeys. In the present study, we have used the antibody SMI-32 to examine further and to quantify the distribution of a subset of corticocortically projecting neurons in a series of long ipsilateral corticocortical pathways in comparison to short corticocortical, commissural, and limbic connections. The results demonstrate that the long association pathways interconnecting the frontal, parietal, and temporal neocortex have a high representation of neurofilament protein-enriched pyramidal neurons (45-90%), whereas short corticocortical, callosal, and limbic pathways are characterized by much lower numbers of such neurons (4-35%). These data suggest that different types of corticocortical connections have differential representation of highly specific neuronal subsets that share common neurochemical characteristics, thereby determining regional and laminar cortical patterns of morphological and molecular heterogeneity. These differences in neuronal neurochemical phenotype among corticocortical circuits may have considerable influence on cortical processing and may be directly related to the type of integrative function subserved by each cortical pathway. Finally, it is worth noting that neurofilament protein-immunoreactive neurons are dramatically affected in the course of Alzheimer's disease. The present results support the hypothesis that neurofilament protein may be crucially linked to the development of selective neuronal vulnerability and subsequent disruption of corticocortical pathways that lead to the severe impairment of cognitive function commonly observed in age-related dementing disorders.

Non-NASA Center↗

DOE OSTI2023

Elucidating regulatory processes of intense physical activity by multi-omics analysis

Abstract Background Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment. Methods To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student’s t -test followed by pathway analysis and comparison between the different omics modalities. Results Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection. Conclusion This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2003

Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice

Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the gamma-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.

NASA Discipline Regulatory Physiology↗

NASA NTRS2014

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↗

NASA NTRS2002

Low-Shear modeled microgravity alters the Salmonella enterica serovar typhimurium stress response in an RpoS-independent manner

We have previously demonstrated that low-shear modeled microgravity (low-shear MMG) serves to enhance the virulence of a bacterial pathogen, Salmonella enterica serovar Typhimurium. The Salmonella response to low-shear MMG involves a signaling pathway that we have termed the low-shear MMG stimulon, though the identities of the low-shear MMG stimulon genes and regulatory factors are not known. RpoS is the primary sigma factor required for the expression of genes that are induced upon exposure to different environmental-stress signals and is essential for virulence in mice. Since low-shear MMG induces a Salmonella acid stress response and enhances Salmonella virulence, we reasoned that RpoS would be a likely regulator of the Salmonella low-shear MMG response. Our results demonstrate that low-shear MMG provides cross-resistance to several environmental stresses in both wild-type and isogenic rpoS mutant strains. Growth under low-shear MMG decreased the generation time of both strains in minimal medium and increased the ability of both strains to survive in J774 macrophages. Using DNA microarray analysis, we found no evidence of induction of the RpoS regulon by low-shear MMG but did find that other genes were altered in expression under these conditions in both the wild-type and rpoS mutant strains. Our results indicate that, under the conditions of these studies, RpoS is not required for transmission of the signal that induces the low-shear MMG stimulon. Moreover, our studies also indicate that low-shear MMG can be added to a short list of growth conditions that can serve to preadapt an rpoS mutant for resistance to multiple environmental stresses.

Non-NASA Center↗

NASA NTRS2011

Can Functional Cardiac Age be Predicted from ECG in a Normal Healthy Population

In a normal healthy population, we desired to determine the most age-dependent conventional and advanced ECG parameters. We hypothesized that changes in several ECG parameters might correlate with age and together reliably characterize the functional age of the heart. Methods: An initial study population of 313 apparently healthy subjects was ultimately reduced to 148 subjects (74 men, 84 women, in the range from 10 to 75 years of age) after exclusion criteria. In all subjects, ECG recordings (resting 5-minute 12-lead high frequency ECG) were evaluated via custom software programs to calculate up to 85 different conventional and advanced ECG parameters including beat-to-beat QT and RR variability, waveform complexity, and signal-averaged, high-frequency and spatial/spatiotemporal ECG parameters. The prediction of functional age was evaluated by multiple linear regression analysis using the best 5 univariate predictors. Results: Ignoring what were ultimately small differences between males and females, the functional age was found to be predicted (R2= 0.69, P < 0.001) from a linear combination of 5 independent variables: QRS elevation in the frontal plane (p<0.001), a new repolarization parameter QTcorr (p<0.001), mean high frequency QRS amplitude (p=0.009), the variability parameter % VLF of RRV (p=0.021) and the P-wave width (p=0.10). Here, QTcorr represents the correlation between the calculated QT and the measured QT signal. Conclusions: In apparently healthy subjects with normal conventional ECGs, functional cardiac age can be estimated by multiple linear regression analysis of mostly advanced ECG results. Because some parameters in the regression formula, such as QTcorr, high frequency QRS amplitude and P-wave width also change with disease in the same direction as with increased age, increased functional age of the heart may reflect subtle age-related pathologies in cardiac electrical function that are usually hidden on conventional ECG.

Schlegel, Todd↗

DOE OSTI2024

Biallelic variants in SNUPN cause a limb girdle muscular dystrophy with myofibrillar-like features

Abstract Alterations in RNA-splicing are a molecular hallmark of several neurological diseases, including muscular dystrophies, where mutations in genes involved in RNA metabolism or characterized by alterations in RNA splicing have been described. Here, we present five patients from two unrelated families with a limb-girdle muscular dystrophy (LGMD) phenotype carrying a biallelic variant in SNUPN gene. Snurportin-1, the protein encoded by SNUPN, plays an important role in the nuclear transport of small nuclear ribonucleoproteins (snRNPs), essential components of the spliceosome. We combine deep phenotyping, including clinical features, histopathology and muscle MRI, with functional studies in patient-derived cells and muscle biopsies to demonstrate that variants in SNUPN are the cause of a new type of LGMD according to current definition. Moreover, an in vivo model in Drosophila melanogaster further supports the relevance of Snurportin-1 in muscle. SNUPN patients show a similar phenotype characterized by proximal weakness starting in childhood, restrictive respiratory dysfunction and prominent contractures, although inter-individual variability in terms of severity even in individuals from the same family was found. Muscle biopsy showed myofibrillar-like features consisting of myotilin deposits and Z-disc disorganization. MRI showed predominant impairment of paravertebral, vasti, sartorius, gracilis, peroneal and medial gastrocnemius muscles. Conservation and structural analyses of Snurportin-1 p.Ile309Ser variant suggest an effect in nuclear-cytosol snRNP trafficking. In patient-derived fibroblasts and muscle, cytoplasmic accumulation of snRNP components is observed, while total expression of Snurportin-1 and snRNPs remains unchanged, which demonstrates a functional impact of SNUPN variant in snRNP metabolism. Furthermore, RNA-splicing analysis in patients’ muscle showed widespread splicing deregulation, in particular in genes relevant for muscle development and splicing factors that participate in the early steps of spliceosome assembly. In conclusion, we report that SNUPN variants are a new cause of limb girdle muscular dystrophy with specific clinical, histopathological and imaging features, supporting SNUPN as a new gene to be included in genetic testing of myopathies. These results further support the relevance of splicing-related proteins in muscle disorders.

Iruzubieta, Pablo (ORCID:0000000303316222)↗

DOE OSTI2021

Testing at scale during the COVID-19 pandemic

Assembly and publication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome in January 2020 enabled the immediate development of tests to detect the new virus. This began the largest global testing programme in history, in which hundreds of millions of individuals have been tested to date. The unprecedented scale of testing has driven innovation in the strategies, technologies and concepts that govern testing in public health. In this Review, we describe the changing role of testing during the COVID-19 pandemic, including the use of genomic surveillance to track SARS-CoV-2 transmission around the world, the use of contact tracing to contain disease outbreaks and testing for the presence of the virus circulating in the environment. Despite these efforts, widespread community transmission has become entrenched in many countries and has required the testing of populations to identify and isolate infected individuals, many of whom are asymptomatic. The diagnostic and epidemiological principles that underpin such population-scale testing are also considered, as are the high-throughput and point-of-care technologies that make testing feasible on a massive scale.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1993

Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

NASA Discipline Musculoskeletal↗

DOE OSTI2021

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↗

NASA NTRS1996

Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure

OBJECTIVES. The present study was undertaken to further characterize changes in skeletal muscle morphology and histochemistry in congestive heart failure and to determine the relation of these changes to abnormalities of systemic and local muscle exercise capacity. BACKGROUND. Abnormalities of skeletal muscle appear to play a role in the limitation of exercise capacity in congestive heart failure, but information on the changes in muscle morphology and biochemistry and their relation to alterations in muscle function is limited. METHODS. Eighteen men with predominantly mild to moderate congestive heart failure (mean +/- SEM New York Heart Association functional class 2.6 +/- 0.2, ejection fraction 24 +/- 2%) and eight age- and gender-matched sedentary control subjects underwent measurements of peak systemic oxygen consumption (VO2) during cycle ergometry, resistance to fatigue of the quadriceps femoris muscle group and biopsy of the vastus lateralis muscle. RESULTS. Peak VO2 and resistance to fatigue were lower in the patients with heart failure than in control subjects (15.7 +/- 1.2 vs. 25.1 +/- 1.5 ml/min-kg and 63 +/- 2% vs. 85 +/- 3%, respectively, both p < 0.001). Patients had a lower proportion of slow twitch, type I fibers than did control subjects (36 +/- 3% vs. 46 +/- 5%, p = 0.048) and a higher proportion of fast twitch, type IIab fibers (18 +/- 3% vs. 7 +/- 2%, p = 0.004). Fiber cross-sectional area was smaller, and single-fiber succinate dehydrogenase activity, a mitochondrial oxidative marker, was lower in patients (both p < or = 0.034). Likewise, the ratio of average fast twitch to slow twitch fiber cross-sectional area was lower in patients (0.780 +/- 0.06 vs. 1.05 +/- 0.08, p = 0.019). Peak VO2 was strongly related to integrated succinate dehydrogenase activity in patients (r = 0.896, p = 0.001). Peak VO2, resistance to fatigue and strength also correlated significantly with several measures of fiber size, especially of fast twitch fibers, in patients. None of the skeletal muscle characteristics examined correlated with exercise capacity in control subjects. CONCLUSIONS. These results indicate that congestive heart failure is associated with changes in the characteristics of skeletal muscle and local as well as systemic exercise performance. There are fewer slow twitch fibers, smaller fast twitch fibers and lower succinate dehydrogenase activity. The latter finding suggests that mitochondrial content of muscle is reduced in heart failure and that impaired aerobic-oxidative capacity may play a role in the limitation of systemic exercise capacity.

Non-NASA Center↗

DOE OSTI2023

PNNL DataHub NIAID Program Project: Modeling Host Responses to Understand Severe Human Virus Infections, Multi-Omic Viral Dataset Catalog Collection

The National Institute of Allergy and Infectious Diseases (NIAID) "Modeling Host Responses to Understand Severe Human Virus Infections" program project was a highly integrated and comprehensive systems biology research core, funded by the National Institute of Health (U19AI106772) from 2013-06-01 to 2018-05-31, investigating the complex host response to category A, B, and C priority pathogen infections. Resulting project deliverables include an extensive comprehensive collections of linked primary and secondary transformation viral experimental infection data. Here we 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 lifecycle datasets and project metadata. Using a highly integrated and multidisciplinary approach, linked primary data and metadata supporting secondary normalization datasets, provide critical information necessary for research reproducibility and long-term preservation. Enabling on-demand data access for research community consumption and developer reuse, serves to support new mechanistic insights and discoveries into host-pathogen interactions for aiding future biohazard data preparedness efforts in emergency response to global health crises involving viral infection.

59 BASIC BIOLOGICAL SCIENCES↗