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At least 145 records · Page 8

Recent Advances in Understanding the Role of Genomic and Epigenomic Factors in Noncommunicable Diseases

The NGS based whole genome and exome sequencing endeavors have identified a plethora of mutations in the coding regions of the human genome that are held responsible as the causative factors for various human noncommunicable diseases including cancer. These mutations encompass various nonsynonymous nucleotide substitutions causing missense, nonsense, and frameshift changes in the protein-coding genes. For these types of mutations it is easier to establish a causal link between these mutations and disease phenotypes as they tend to change the amino acids in the proteins resulting in their loss-of-function (of tumor suppressor genes) or gain-of-function (of oncogenes) which might be directly responsible for the disease such as cancer. Apart from these disease-causing mutations, vast majority (more than 80%) of single-nucleotide polymorphisms were distributed throughout the human genome, mostly in the noncoding regions such as introns and intergenic regions. Large body of evidence suggested that variants in the noncoding regions can be considered as genetic predisposition to many noncommunicable diseases including cancer.

59 BASIC BIOLOGICAL SCIENCES↗

The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease

Here, we used digital spatial profiling (DSP) to describe the glomerular transcriptomic signatures that may characterize the complex molecular mechanisms underlying progressive kidney disease in Alport syndrome, focal segmental glomerulosclerosis, and membranous nephropathy. Our results revealed significant transcriptional heterogeneity among diseased glomeruli, and this analysis showed that histologically similar glomeruli manifested different transcriptional profiles. Using glomerular pathology scores to establish an axis of progression, we identified molecular pathways with progressively decreased expression in response to increasing pathology scores, including signal recognition particle–dependent cotranslational protein targeting to membrane and selenocysteine synthesis pathways. We also identified a distinct signature of upregulated and downregulated genes common to all the diseases investigated when compared with nondiseased tissue from nephrectomies. These analyses using DSP at the single-glomerulus level could help to increase insight into the pathophysiology of kidney disease and possibly the identification of biomarkers of disease progression in glomerulopathies.

60 APPLIED LIFE SCIENCES↗

A comprehensive method on black-legged tick larvae and nymph feeding on mice to study Lyme disease transmission and acquisition

Tick-borne diseases are a growing public health concern in the United States, with cases rising steadily each year. Lyme borreliosis, or Lyme disease, remains the most prevalent, affecting approximately 476,000 individuals annually. Human-driven changes in climate and ecosystems have expanded the habitat of pathogen-carrying ticks, facilitating the spread of these infections. Additionally, increased instances of tick-borne diseases transmission through human tissues have been reported. Despite ongoing efforts to manage these infections, their incidence continues to rise. To develop effective control measures against these diseases and prevent the transmission of tick-borne infections through human and animal tissues, it is very important to develop detection assays and understand the transmission mechanisms of tick-borne infections. In this study, we provide detailed descriptions and visual references for larval and nymphal tick feeding on mice, focusing on the transmission and acquisition ofBorrelia burgdorferi(sensu stricto). These methodologies can be applied to study other tick-borne diseases, tick vectorial capacity, and tick biology, aiding in the development of detection strategies to combat these infections.

Microbiology↗

Non-Thermal Plasma as a Novel Strategy for Treating or Preventing Viral Infection and Associated Disease

Pathogenic viruses cause many human, animal, and plant diseases that are associated with substantial morbidity, mortality and socio-economic impact. Although effective strategies for combatting virus transmission and associated disease are available, global outbreaks of viral pathogens such as the virus responsible for the COVID-19 pandemic demonstrate that there is still a critical need for new approaches that can be used to interrupt the chain of viral infection and mitigate virus-associated pathogenesis. Recent studies point to non-thermal plasma (NTP), a partly ionized gas comprised of a complex mixture of reactive oxygen and nitrogen species along with physical effectors, as the potential foundation for new antiviral approaches. A more thorough understanding of the antiviral properties and safety of NTP has stimulated explorations of NTP as the basis for treatments of viral diseases. The recently described immunomodulatory properties of NTP are also being evaluated for potential use in immunotherapies of viral diseases as well as in antiviral vaccination strategies. In this review, we present the current state-of-the-art in addition to compelling arguments that NTP merits further exploration for use in the prevention and management of viral infections and associated diseases.

60 APPLIED LIFE SCIENCES↗

Image-based time series analysis to establish differential disease progression for two Fusarium head blight pathogens in oat spikelets with variable resistance

Oat-based value-added products have increased their value as healthy foodstuff. Fusarium head blight (FHB) infections and the mycotoxins accumulated to the oat seeds, however, pose a challenge to oat production. The FHB infections are predicted to become more prevalent in the future changing climates and under more limited use of fungicides. Both these factors increase the pressure for breeding new resistant cultivars. Until now, however, genetic links in oats against FHB infection have been difficult to identify. Therefore, there is a great need for more effective breeding efforts, including improved phenotyping methods allowing time series analysis and the identification of molecular markers during disease progression. To these ends, dissected spikelets of several oat genotypes with different resistance profiles were studied by image-based methods during disease progression by Fusarium culmorum or F. langsethiae species. The chlorophyll fluorescence of each pixel in the spikelets was recorded after inoculation by the two Fusarium spp., and the progression of the infections was analyzed by calculating the mean maximum quantum yield of PSII (F v /F m ) values for each spikelet. The recorded values were (i) the change in the photosynthetically active area of the spikelet as percentage of its initial size, and (ii) the mean of F v /F m values of all fluorescent pixels per spikelet post inoculation, both indicative of the progression of the FHB disease. The disease progression was successfully monitored, and different stages of the infection could be defined along the time series. The data also confirmed the differential rate of disease progression by the two FHB causal agents. In addition, oat varieties with variable responses to the infections were indicated.

oats↗

Transcriptomic Analysis of Arachidonic Acid Pathway Genes Provides Mechanistic Insight into Multi-Organ Inflammatory and Vascular Diseases

Arachidonic acid (AA) metabolites have been associated with several diseases across various organ systems, including the cardiovascular, pulmonary, and renal systems. Lipid mediators generated from AA oxidation have been studied to control macrophages, T-cells, cytokines, and fibroblasts, and regulate inflammatory mediators that induce vascular remodeling and dysfunction. AA is metabolized by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) to generate anti-inflammatory, pro-inflammatory, and pro-resolutory oxidized lipids. As comorbid states such as diabetes, hypertension, and obesity become more prevalent in cardiovascular disease, studying the expression of AA pathway genes and their association with these diseases can provide unique pathophysiological insights. In addition, the AA pathway of oxidized lipids exhibits diverse functions across different organ systems, where a lipid can be both anti-inflammatory and pro-inflammatory depending on the location of metabolic activity. Therefore, we aimed to characterize the gene expression of these lipid enzymes and receptors throughout multi-organ diseases via a transcriptomic meta-analysis using the Gene Expression Omnibus (GEO) Database. In our study, we found that distinct AA pathways were expressed in various comorbid conditions, especially those with prominent inflammatory risk factors. Comorbidities, such as hypertension, diabetes, and obesity appeared to contribute to elevated expression of pro-inflammatory lipid mediator genes. Our results demonstrate that expression of inflammatory AA pathway genes may potentiate and attenuate disease; therefore, we suggest further exploration of these pathways as therapeutic targets to improve outcomes.

59 BASIC BIOLOGICAL SCIENCES↗

Echocardiographic assessment of cardiac disease

The physical principles and current applications of echocardiography in assessment of heart diseases are reviewed. Technical considerations and unresolved points relative to the use of echocardiography in various disease states are stressed. The discussion covers normal mitral valve motion, mitral stenosis, aortic regurgitation, atrial masses, mitral valve prolapse, and idiopathic hypertrophic subaortic stenosis. Other topics concern tricuspic valve abnormalities, aortic valve disease, pulmonic valve, pericardial effusion, intraventricular septal motion, and left ventricular function. The application of echocardiography to congenital heart disease diagnosis is discussed along with promising ultrasonic imaging systems. The utility of echocardiography in quantitative evaluation of cardiac disease is demonstrated.

Popp, R. L.↗

The role of plant disease in the development of controlled ecological life support systems

Plant diseases could be important factors affecting growth of higher plants in Closed Ecological Life Support Systems (CELSS). Disease control, therefore, will be needed to maintain healthy plants. The most important controls should be aimed at preventing the introduction, reproduction and spread of pathogens and preventing plant infection. An integrared ease control program will maximize that approach. In the design and operation of CELSS, plant disease should be considered an important aspect of plant growth. The effects of plant diseases are reviewed and several disease control measures are discussed.

Nelson, B.↗

Triazolopyrimidine (trapidil), a platelet-derived growth factor antagonist, inhibits parathyroid bone disease in an animal model for chronic hyperparathyroidism

Parathyroid bone disease in humans is caused by chronic hyperparathyroidism (HPT). Continuous infusion of PTH into rats results in histological changes similar to parathyroid bone disease, including increased bone formation, focal bone resorption, and severe peritrabecular fibrosis, whereas pulsatile PTH increases bone formation without skeletal abnormalities. Using a cDNA microarray with over 5000 genes, we identified an association between increased platelet-derived growth factor-A (PDGF-A) signaling and PTH-induced bone disease in rats. Verification of PDGF-A overexpression was accomplished with a ribonuclease protection assay. Using immunohistochemistry, PDGF-A peptide was localized to mast cells in PTH-treated rats. We also report a novel strategy for prevention of parathyroid bone disease using triazolopyrimidine (trapidil). Trapidil, an inhibitor of PDGF signaling, did not have any effect on indexes of bone turnover in normal rats. However, dramatic reductions in marrow fibrosis and bone resorption, but not bone formation, were observed in PTH-treated rats given trapidil. Also, trapidil antagonized the PTH-induced increases in mRNA levels for PDGF-A. These results suggest that PDGF signaling is important for the detrimental skeletal effects of HPT, and drugs that target the cytokine or its receptor might be useful in reducing or preventing parathyroid bone disease.

NASA Discipline Cell Biology↗

Prediction of coronary artery disease in patients undergoing operations for mitral valve degeneration

OBJECTIVES: We sought to develop and validate a model that estimates the risk of obstructive coronary artery disease in patients undergoing operations for mitral valve degeneration and to demonstrate its potential clinical utility. METHODS: A total of 722 patients (67% men; age, 61 +/- 12 years) without a history of myocardial infarction, ischemic electrocardiographic changes, or angina who underwent routine coronary angiography before mitral valve prolapse operations between 1989 and 1996 were analyzed. A bootstrap-validated logistic regression model on the basis of clinical risk factors was developed to identify low-risk (< or =5%) patients. Obstructive coronary atherosclerosis was defined as 50% or more luminal narrowing in one or more major epicardial vessels, as determined by means of coronary angiography. RESULTS: One hundred thirty-nine (19%) patients had obstructive coronary atherosclerosis. Independent predictors of coronary artery disease include age, male sex, hypertension, diabetes mellitus,and hyperlipidemia. Two hundred twenty patients were designated as low risk according to the logistic model. Of these patients, only 3 (1.3%) had single-vessel disease, and none had multivessel disease. The model showed good discrimination, with an area under the receiver-operating characteristic curve of 0.84. Cost analysis indicated that application of this model could safely eliminate 30% of coronary angiograms, corresponding to cost savings of $430,000 per 1000 patients without missing any case of high-risk coronary artery disease. CONCLUSION: A model with standard clinical predictors can reliably estimate the prevalence of obstructive coronary atherosclerosis in patients undergoing mitral valve prolapse operations. This model can identify low-risk patients in whom routine preoperative angiography may be safely avoided.

Non-NASA Center↗

Spatial Analysis of Environmental Factors Related to Lyme Disease in Alabama by Means of NASA Earth Observation Systems

This slide presentation reviews the epidemiology of Lyme Disease that accounts for more than 95% or vector borne diseases in the United States. The history, symptoms and the life cycle of the tick, the transmitting agent of Lyme Disease, a map that shows the cases reported to the CDC between1990 and 2006 and the number of cases in Alabama by year from 1986 to 2007. A NASA project is described, the goals of which are to (1) Demonstrate the presence of the chain of infection of Lyme disease in Alabama (2) Identify areas with environmental factors that support tick population using NASA Earth Observation Systems data in selected areas of Alabama and (3) Increase community awareness of Lyme disease and recommend primary and secondary prevention strategies. The remote sensing methods included: Analyzed Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and DigitalGlobe Quickbird satellite imagery from summer months and Performed image analyses in ER Mapper 7.1. Views from the ASTER and Quickbird land cover are shown, the Normalized Difference Vegetation Index (NDVI) algorithm was applied to all ASTER and Quickbird imagery. The use of the images to obtain the level of soil moisture is reviewed, and this analysis was used along with the NDVI, was used to identify the areas that support the tick population.

Renneboog, Nathan↗

Infectious Disease Risk Associated with Space Flight

This slide presentation opens with views of the shuttle in various stages of preparation for launch, a few moments after launch prior to external fuel tank separation, a few pictures of the earth,and several pictures of astronomical interest. The presentation reviews the factors effecting the risks of infectious disease during space flight, such as the crew, water, food, air, surfaces and payloads and the factors that increase disease risk, the factors affecting the risk of infectious disease during spaceflight, and the environmental factors affecting immunity, such as stress. One factor in space infectious disease is latent viral reactivation, such as herpes. There are comparisons of the incidence of viral reactivation in space, and in other analogous situations (such as bed rest, or isolation). There is discussion of shingles, and the pain and results of treatment. There is a further discussion of the changes in microbial pathogen characteristics, using salmonella as an example of the increased virulence of microbes during spaceflight. A factor involved in the risk of infectious disease is stress.

Pierson, Duane L.↗

Sensitivity Analysis of Median Lifetime on Radiation Risks Estimates for Cancer and Circulatory Disease amongst Never-Smokers

Radiation risks are estimated in a competing risk formalism where age or time after exposure estimates of increased risks for cancer and circulatory diseases are folded with a probability to survive to a given age. The survival function, also called the life-table, changes with calendar year, gender, smoking status and other demographic variables. An outstanding problem in risk estimation is the method of risk transfer between exposed populations and a second population where risks are to be estimated. Approaches used to transfer risks are based on: 1) Multiplicative risk transfer models -proportional to background disease rates. 2) Additive risk transfer model -risks independent of background rates. In addition, a Mixture model is often considered where the multiplicative and additive transfer assumptions are given weighted contributions. We studied the influence of the survival probability on the risk of exposure induced cancer and circulatory disease morbidity and mortality in the Multiplicative transfer model and the Mixture model. Risks for never-smokers (NS) compared to the average U.S. population are estimated to be reduced between 30% and 60% dependent on model assumptions. Lung cancer is the major contributor to the reduction for NS, with additional contributions from circulatory diseases and cancers of the stomach, liver, bladder, oral cavity, esophagus, colon, a portion of the solid cancer remainder, and leukemia. Greater improvements in risk estimates for NS s are possible, and would be dependent on improved understanding of risk transfer models, and elucidating the role of space radiation on the various stages of disease formation (e.g. initiation, promotion, and progression).

Chappell, Lori J.↗

Climate Change and Vector Borne Diseases on NASA Langley Research Center

Increasing global temperature, weather patterns with above average storm intensities, and higher sea levels have been identified as phenomena associated with global climate change. As a causal system, climate change could contribute to vector borne diseases in humans. Vectors of concern originate from the vicinity of Langley Research Center include mosquitos and ticks that transmit disease that originate regionally, nationwide, or from outside the US. Recognizing changing conditions, vector borne diseases propagate under climate change conditions, and understanding the conditions in which they may exist or propagate, presents opportunities for monitoring their progress and mitigating their potential impacts through communication, continued monitoring, and adaptation. Personnel comprise a direct and fundamental support to NASA mission success, continuous and improved understanding of climatic conditions, and the resulting consequence of disease from these conditions, helps to reduce risk in terrestrial space technologies, ground operations, and space research. This research addresses conditions which are attributed to climatic conditions which promote environmental conditions conducive to the increase of disease vectors. This investigation includes evaluation of local mosquito population count and rainfall data for statistical correlation and identification of planning recommendations unique to LaRC, other NASA Centers to assess adaptation approaches, Center-level planning strategies.

Cole, Stuart K.↗

Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease

When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

Parsons-Wingerter, Patricia↗

Cardiovascular Disease Risk in NASA Astronauts Across the Lifespan: Historical Cohort Studies

Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in space flight activities are potentially associated with cardiovascular disease risk factors (e.g., altered dietary and exercise habits, physical and emotional stress, circadian shifts, radiation). Further, astronauts who travel into space multiple times may be at an increased risk across their lifespan. However, comparing the risk of cardiovascular disease in astronauts to other large cohorts is difficult. For example, comparisons between astronauts and large national cohorts, such as the National Health and Nutrition Examination Survey and the National Health Information Survey, are hampered by significant differences in health status between astronauts and the general population, and most of these national studies fail to provide longitudinal data on population health. To address those limitations, NASA's Longitudinal Study of Astronaut Health previously sought to compare the astronauts to a cohort of civil servants employed at the Johnson Space Center. However, differences between the astronauts and civil servants at the beginning of the study, as well as differential follow up, limited the ability to interpret the results. To resolve some of these limitations, two unique cohorts of healthy workers, U.S. Air Force aviators and Cooper Center Longitudinal Study participants, have been identified as potential comparison populations for the astronaut corps. The Air Force cohort was chosen due to similarities in health at selection, screening, and some occupational exposures that Air Force aviators endure, many of which mirror that of the astronaut corps. The Cooper Clinic cohort, a generally healthy prevention cohort, was chosen for the vast array of clinical cardiovascular measures collected in a longitudinal manner complementary to those collected on astronauts, for a large number of subjects since 1971. The purpose of this study is to understand the incidence of cardiovascular disease outcomes and risk factors in the astronaut corps and determine whether the rates of disease are different than these two cohorts. The research questions are: 1. Are there differences in the incidence of CVD outcomes (MI, revascularization, and stroke) between each cohort and the NASA Astronaut cohort? 2. Are there differences in the incidence of CVD risks (hypertension, hyperlipidemia, arrhythmias, and diabetes) between each cohort and the NASA Astronaut cohort? 3. Are there differences between each cohort and the NASA Astronaut cohort in how CVD risk factors (e.g., lipids, behaviors) change across time? Collectively, results from these studies will enhance our understanding of how cardiovascular disease outcomes and risk factors change across time in astronauts compared to other longitudinally-studied healthy cohorts and determine if there are interactions between or additive effects of the occupational health effects of spaceflight exposure and normal aging.

Charvat, Jacqueline M.↗

Determination of the Risk of Radiation-Associated Circulatory and Cancer Disease Mortality in a NASA Early Astronaut Cohort

Of the many possible health challenges posed during extended exploratory missions to space, the effects of space radiation on cardiovascular disease and cancer are of particular concern. There are unique challenges to estimating those radiation risks; care and appropriate and rigorous methodology should be applied when considering small cohorts such as the NASA astronaut population. The objective of this work was to determine if there was sufficient evidence for excess risk of cardiovascular disease and cancer in early NASA astronaut cohorts. NASA astronauts in selection groups 1-7 were chosen; this relatively homogeneous cohort consists of 73 white males, who unlike today's astronauts, maintained similar smoking and drinking habits to the general US population, and have published radiation doses. The participants flew in space on missions Mercury through Shuttle and received space radiation doses between 0-74.1 milligrays. Cause of death information was obtained from the Lifetime Surveillance of Astronaut Health (LSAH) program at NASA Johnson Space Center. Mortality was compared with the US male population. Trends of mortality with dose were assessed using a logistic model, fitted by maximum likelihood. Only 32 (43.84 percent) of the 73 early astronauts have died. Standard mortality ratios (SMRs) for cancer (n=7, SMR=43.4, 95 percent CI 17.8, 84.9), all circulatory disease (n=7, SMR=33.2, 95 percent CI 13.7, 65.0), and ischemic heart disease (IHD) (n=5, SMR=40.1, 95 percent CI 13.2, 89.4) were significantly lower than for the US white male population. For cerebrovascular disease, the upper confidence interval for SMR included 100, indicating it was not significantly different from the US population (n=2, SMR = 77.0, 95 percent CI 9.4, 268.2). The power of the study is low and remains below 10 percent even when risks 10 times those reported in the literature are assumed. Due to small sample size, there is currently insufficient statistical power to evaluate space radiation exposure effects on mortality in NASA astronauts. In addition to a comprehensive longitudinal study of NASA astronauts, a research strategy of low dose epidemiology data integration with cell and animal studies should be utilized for space radiation risk assessment in the astronauts.

Elgart, S. R.↗

Assessing Land Cover Change Dynamics in the Peruvian Amazon to Map Outbreak Risk and Inform Public Health Interventions for Zoonotic Disease Prevention

Dengue fever and leishmaniasis are two tropical diseases prevalent in Madre de Dios Region of Peru and have been associated with urbanization and road construction. Rapid land use changes such as mining, timber harvesting, and hydroelectric dam development lead to denser human presence in previously sparsely-populated areas which increases the proximity of human settlements to zoonotic disease vectors. In partnership with the Peruvian Ministries of Health (MINSA), the Environment (MINAM), and other in-country collaborators, a NASA DEVELOP team examined Land Use Land Cover (LULC) changes and reported dengue and leishmaniasis incidence in the Madre de Dios region. This sought to help MINSA and MINAM understand the spatial relationship between land use change and zoonotic disease incidence. We created a LULC classification script using Google Earth Engine (GEE) with Landsat 5 Thematic Mapper (TM) and Landsat 8 Operational Land Imager (OLI) imagery to classify land cover in 2010, 2015, and 2020 and evaluate changes over this time period. The team then compared the quantified results of the LULC assessment in conjunction with reported disease cases to evaluate disease incidence and key land cover changes across Madre de Dios’s 11 districts. Follow on work will use these products to develop more detailed outbreak risk maps. These products will allow MINSA, MINAM, and other partners to understand hotspots of land cover change in Peru and the relationship with outbreaks to inform public health decision makers and environmental policy.

Nataly Chacon-Buitrago↗