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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
NASA NTRS1999

Ground Based Program for the Physical Analysis of Macromolecular Crystal Growth

In a reported period in situ atomic force microscopy was utilized in our laboratory to study mechanisms of growth and kinetics of crystallization of ten protein and virus crystals. These included canavalin, thaumatin, apoferritin, lipase, catalase, t-RNA, lysozyme, xylanase, turnip yellow mosaic virus (TYMV) and satellite tobacco mosaic virus (STMV). We have also designed and constructed in our laboratory both in situ conventional two-beam Michelson and phase shift Mach-Zenhder interferometers. Computer software for the processing of the interferometric images was developed as well. Interferometric techniques were applied for studies of growth kinetics and transport phenomena in crystallization of several macromolecular crystals. As a result of this work we have published 21 papers and have given many presentations at international and national meetings. A list of these publications and conference presentations is attached.

Malkin, Alexander J.↗
NASA NTRS2002

Tracking Avian Reservoirs of Arboviruses using Remote Sensing and Radiotelemetry

Encephalitis is caused by a virus that is transmitted by mosquitoes between mammalian hosts. The virus is closely related to the West Nile virus (WNV), which started in New York in 1999, and has since spread to 25 states. Like encephalitis, WNV is vectored by mosquitoes, and the primary hosts are birds; humans are accidental, or'dead-end' hosts. Very little is understood about the behavior of these bird populations, and how they intersect - both in time and in space - with mosquito populations. Exploring these relationships is the first step in developing models for encephalitis and WNV transmission risk. This project combines remotely sensed data with radiotelemetry to create a spatiotemporal map of encephalitis viral activity in bird and mosquito populations in the Sacramento Valley of California. Specifically, remote sensing (RS) and geographic information system (GIS) technologies were used to characterize habitats utilized by both avian viral reservoirs and the mosquitoes that vector encephalitis. Radiotelemetry and serosurveys (blood) were then used to spatially and temporally track the patterns of infection. The project uses Landsat ETM+ multitemporal satellite data to characterize habitats utilized by both birds and the mosquito vectors. Mist nets were used to sample members of individual flocks of blackbirds and cowbirds over a period of several months; these birds were then bled to assess their viral status, banded, and fitted with transmitters. Radiotelemetry was used to spatially and temporally track the distribution of banded birds and their associated flocks. The movement of these indicator flocks were compared with the location of remotely sensed (adult and larval) mosquito habitats to determine the intersection of bird's and vectors; this is key in understanding where and when transmission occurs from bird to bird, as well as from bird to mammal, via mosquito. The relationships found during the project are being used to generate a model of encephalitis transmission risk in California.

Beck, L.↗
NASA NTRS2002

Letting Our Cells Do the Fighting: Flight-Induced Changes in the Immune Response

The organisms that make us ill, such as bacteria, viruses, and fungi, are like attacking armies. We now know a great deal more about this unseen world of microscopic invaders. Fortunately for us, the human immune system is ever vigilant against them. Microorganisms such as bacteria, viruses, and fungi occupy almost every corner of the Earth, and even parts of the human body. Some organisms are beneficial to us, helping to produce milk, cheese or yogurt. Others are potentially harmful, yet we don#t always develop illnesses from them; they are kept in check by the sentinels of our immune system. Our immune system is routinely challenged by these organisms every day. When the immune response is diminished, our ability to fight off these "bugs" is lowered. And that's when we become ill. Space flight presents a challenge to the immune system. Scientists believe that the stressful conditions of space flight - launch into orbit, adapting to microgravity, heavy workloads, and isolation from family and friends, to name but a few - reduce the astronauts' immunity. This immune suppression makes them more susceptible to common illnesses from bacteria and to re-infections from latent viruses in the body. In addition, risk of spreading illness in the confined environment of the Space Shuttle is high. Understanding changes in immune function will help scientists develop ways to keep astronauts healthy in space. This knowledge can also benefit earthbound populations. This experiment will give scientists insight into the immune system by comparing how certain cells of astronauts' innate immune system - the first line of defense against invaders - function after flight compared to before flight.

Pierson, Duane↗
NASA NTRS1993

Three distinct cell phenotypes of induced-TNF cytotoxicity and their relationship to apoptosis

We have identified three distinct cell phenotypes with respect to the conditions under which cells became susceptible to TNF-mediated lysis. These conditions include: 1) treatment with the protein synthesis inhibitor, cycloheximide; 2) contact with activated macrophages, and 3) infection with vaccinia virus. Whereas vaccinia virus-infected 3T3 cells became sensitive to soluble TNF, F5b cells required contact with activated macrophages. We showed that the "macrophage-resistant" F5m cells did not become sensitive to TNF or to killing by activated macrophages after infection with vaccinia virus. Therefore, vaccinia infection does not sensitize all cells to TNF. We also determined the pathways of lysis for cells after sensitization. Whereas 3T3, LM929, and F5b cells were killed by the process of necrosis, F5m cells lysis was characterized by the release of low mol wt DNA fragments (apoptosis).

Non-NASA Center↗
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.↗
NASA NTRS2007

Assessment of Immune Status, Latent Viral Reactivation and Stress during Long Duration Bed Rest as an Analog for Spaceflight

As logistical access for in-flight space research becomes more limited, the use of ground based spaceflight analogs for life science studies will increase. These studies are particularly important as NASA progresses towards the Lunar and eventually Mars missions outlined in the 2005 Vision for Space Exploration. Countermeasures must be developed to mitigate the clinical risks associated with exploration class space missions. In an effort to coordinate studies across multiple disciplines, NASA has selected 90-day bed rest as the analog of choice, and initiated the Flight Analogs Project to implement research studies with or without the evaluation of countermeasures. Although bed rest is not the analog of choice to evaluate spaceflight-associated immune dysfunction, a standard Immune Assessment was developed for subjects participating in the 90-day bed best studies. The Immune Assessment consists of: leukocyte subset distribution, T cell functional responses, intracellular cytokine production profiles, latent viral reactivation, virus specific T cell levels, virus specific T cell function, stress hormone levels and a behavioral assessment using stress questionnaires. The purpose of the assessment during the initial studies (without countermeasure) is to establish control data against which future studies (with countermeasure) will be evaluated. It is believed that some of the countermeasures planned to be evaluated in future studies, such as exercise, pharmacologic intervention or nutritional supplementation, have the ability to impact immune function. Therefore immunity will likely be monitored during those studies. The data generated during the first three control studies showed that the subjects in general did not display altered peripheral leukocyte subsets, constitutive immune activation, significant latent viral reactivation (EBV, VZV) or altered T cell function. Interestingly, for some subjects the level of constitutively activated T cells (CD8+/CD69+) and virus-specific T cells (CMV and EBV) both decreased during the studies. This likely reflects the isolation of the subjects (from an immunological perspective) and absence of everyday subclinical challenges to the immune system. Cortisol levels (plasma and saliva) did not vary significantly during the studies. This probably reflects a lack of physiological stress during the study and the stress of readaptation to the 1xG environment at R+1. These data demonstrate the absence of significant immune alteration during 90-day bed rest, and establish control data against which future studies (including countermeasures) may be compared.

Crucian, Brian E.↗
NASA NTRS2011

Vitamin D Supplementation and Immune Response to Antarctic Winter

Maintaining vitamin D status without sunlight exposure is difficult without supplementation. This study was designed to better understand interrelationships between periodic cholecalciferol(vitamin D3) supplementation and immune function in Antarctic workers. The effect of 2 oral dosing regimens of vitamin D3 supplementation on vitamin D status and markers of immune function were evaluated in people in Antarctica with no ultraviolet light exposure for 6 mo. Participants were given a 2,000-IU (50 g) daily (n=15) or 10,000-IU (250 g) weekly (n=14) vitamin D3 supplement for 6 mo during a winter in Antarctica. Biological samples were collected at baseline and at 3 and 6 mo. Vitamin D intake, markers of vitamin D and bone metabolism, and latent virus reactivation were determined. After 6 mo the mean (SD) serum 25-hydroxyvitamin D3 concentration increased from 56 plus or minus 17 to 79 plus or minus 16 nmol/L and 52 plus or minus 10 to 69 plus or minus 9 nmol/L in the 2,000-IU/d and 10,000-IU/wk groups (main effect over time P less than 0.001). Participants with a greater BMI (participant BMI range = 19-43 grams per square meter) had a smaller increase in 25-hydroxyvitamin D3 after 6 mo supplementation (P less than 0.05). Participants with high serum cortisoland higher serum 25-hydroxyvitamin D3 were less likely to shed Epstein-Barr virus in saliva (P less than 0.05). The doses given raised vitamin D status in participants not exposed to sunlight for 6 mo, and the efficacy was influenced by baseline vitamin D status and BMI. The data also provide evidence that vitamin D, interacting with stress, can reduce risk of latent virus reactivation during the winter in Antarctica.

Zwart, S. R.↗
NASA NTRS2013

3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

Goodwin, Thomas J.↗
NASA NTRS2015

Municipality Level Simulations of Dengue Fever Incidence in Puerto Rico Using Ground Based and Remotely Sensed Climate Data

Dengue fever (DF) is caused by a virus transmitted between humans and Aedes genus mosquitoes through blood feeding. In recent decades incidence of the disease has drastically increased in the tropical Americas, culminating with the Pan American outbreak in 2010 which resulted in 1.7 million reported cases. In Puerto Rico dengue is endemic, however, there is significant inter‐annual, intraannual, and spatial variability in case loads. Variability in climate and the environment, herd immunity and virus genetics, and demographic characteristics may all contribute to differing patterns of transmission both spatially and temporally. Knowledge of climate influences on dengue incidence could facilitate development of early warning systems allowing public health workers to implement appropriate transmission intervention strategies. In this study, we simulate dengue incidence in several municipalities in Puerto Rico using population and meteorological data derived from ground based stations and remote sensing instruments. This data was used to drive a process based model of vector population development and virus transmission. Model parameter values for container composition, vector characteristics, and incubation period were chosen by employing a Monte Carlo approach. Multiple simulations were performed for each municipality and the results were compared with reported dengue cases. The best performing simulations were retained and their parameter values and meteorological input were compared between years and municipalities. Parameter values varied by municipality and year illustrating the complexity and sensitivity of the disease system. Local characteristics including the natural and built environment impact transmission dynamics and produce varying responses to meteorological conditions.

Remote Sensing↗
NASA NTRS2016

Mapping Past, Present, and Future Climatic Suitability for Invasive Aedes Aegypti and Aedes Albopictus in the United States: A Process-Based Modeling Approach Using CMIP5 Downscaled Climate Scenarios

The ongoing spread of the mosquitoes, Aedes aegypti and Aedes albopictus, in the continental United States leaves new areas at risk for local transmission of dengue, chikungunya, and Zika viruses. All three viruses have caused major disease outbreaks in the Americas with infected travelers returning regularly to the U.S. The expanding range of these mosquitoes raises questions about whether recent spread has been enabled by climate change or other anthropogenic influences. In this analysis, we used downscaled climate scenarios from the NASA Earth Exchange Global Daily Downscaled Projections (NEX GDDP) dataset to model Ae. aegypti and Ae. albopictus population growth rates across the United States. We used a stage-structured matrix population model to understand past and present climatic suitability for these vectors, and to project future suitability under CMIP5 climate change scenarios. Our results indicate that much of the southern U.S. is suitable for both Ae. aegypti and Ae. albopictus year-round. In addition, a large proportion of the U.S. is seasonally suitable for mosquito population growth, creating the potential for periodic incursions into new areas. Changes in climatic suitability in recent decades for Ae. aegypti and Ae. albopictus have occurred already in many regions of the U.S., and model projections of future climate suggest that climate change will continue to reshape the range of Ae. aegypti and Ae. albopictus in the U.S., and potentially the risk of the viruses they transmit.

process-based modeling↗
NASA NTRSDate not supplied

Method Development for In-situ Detection of Latent Herpesvirus DNA from Saliva using Nanopore Sequencing

Research toward latent herpesvirus reactivation has been intensively addressed through Space Shuttle and International Space Station (ISS) investigations. This work has provided the understanding that persistent reactivation of herpesviruses from asymptomatic crew can be detected through viral shedding in saliva, urine, and blood. Occasionally, viral reactivation from the latency stage can pose a threat to crew health (clinical manifestation) before, during, and after flight missions. Furthermore, previous work detailing correlations with immunity indicate that monitoring viral reactivation could be implemented to assess potential immune dysfunction. While in-flight monitoring is desirable, there is no well-established procedure or method for real-time evaluations, and research to date has relied on postflight, ground-based analysis. The development of portable molecular technologies like the miniPCR™ (miniPCR Bio) thermal cycler and the MinION™ sequencer (Oxford Nanopore Technologies) have confirmed that real-time monitoring is possible in extreme and low resource environments. These devices, combined with simple sample preparation methods, have been used to demonstrate bacterial identification onboard the ISS, as well as rapid viral detection in remote locations on Earth. The work here builds upon previous molecular advancements onboard the ISS toward the development and validation of a spaceflight-compatible method for viral detection from crew samples. Several herpesviruses can be detected in saliva, which provides a non-invasive means to collect samples for monitoring. While the basis for this method lies in previous spaceflight investigations, key points for method optimization include DNA extraction from saliva, viral primer selection, and bioinformatic processes for data analysis. To increase viral yield, numerous DNA extraction methods have been evaluated and will be discussed in detail. For initial development and testing, varicella-zoster virus (VZV) is being targeted though open reading frame 51 and 63 (ORF51, ORF63), as the replication origin-binding protein is highly expressed during latency. Optimization of the thermal cycling parameters has resulted in the ability to test the entire process. The full method has been tested with both viral VZV DNA standards and saliva spiked with varying concentrations of VZV. Viral sequence data were mapped to the reference sequence using minimap2. Prior to mapping, DNA sequencing reads were filtered for length and quality, barcodes were removed, and alignment identity calculated. Following further assessments, statistics were compared across multiple sequencing experiments and are being used to determine the success of the protocols. Forward work will include the incorporation of herpes simplex virus 1 (HSV-1) and Epstein-Barr virus (EBV) primers as well as the validation of results to the terrestrial qPCR standard assay. Upon full validation of the developed method, saliva will be collected from 20 healthy subjects and spiked with viral DNA. These samples will be split and assayed with the MinION and standard qPCR assay.

Hang N Nguyen↗
NASA NTRS2023

Broader Impacts and Outreach Videos on Ocean Physics and Biogeochemistry

This is just a preliminary NF1676 in advance of filming for a project....A convergent team of experts in biology, chemistry, physics, engineering, mathematics, and computational modeling examine how dynamic and coupled phytoplankton-pathogen-particle-predator linkages coalesce to explain the observed high spatial variability in the efficiency of the export of particulate organic carbon (POC) to the deep ocean. They elucidate and quantify the linkages between viruses and ballast minerals to increase understanding of carbon cycling in the oceanic biological carbon pump and the impact of viruses within it. By providing knowledge than can be used to improve the parameterization of carbon export in Earth system models, the project will help reduce uncertainty in regional marine biogeochemical projections, potentially improving marine ecosystem and fisheries management on timescales from seasons to decades. The project includes activities that provide teaching resources and hands-on training to educators within a ‘Tools of Science’ program that provides a simple and succinct way to communicate the process of scientific research to students in a way that is useful to teachers. The project couples laboratory-based experiments on model host-virus-grazer systems with extensive field based observational and manipulative studies on natural populations of diatoms and coccolithophores, the two phytoplankton groups that account for most of the estimated particulate organic matter flux to the deep ocean. Experiments and measurements integrate diagnostic biological and chemical controls on infection and particle coagulation theory with microscale physics and grazing to quantify links to each hypothesized export mechanism under field-relevant turbulent conditions. Cutting-edge engineering and analytical tools are used to diagnose and track infection dynamics while characterizing and quantifying particle aggregation and disaggregation, mineral dissolution, sinking dynamics, grazing rates, and fecal pellet production at unprecedented resolution and under well-defined, microscale physical regimes. Field campaigns elucidate the relative efficiency of hypothesized mechanisms in stimulating POC export in natural blooms, while providing bulk and size-resolved estimates of POC flux.

Daniel B Whitt↗
NASA NTRS2003

Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy

OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.

Non-NASA Center↗
NASA NTRS1997

Cortical neuronal cytoskeletal changes associated with FIV infection

HIV-1 infection is often complicated by central nervous system (CNS) dysfunction. Degenerative neuronal changes as well as neuronal loss have been documented in individuals with AIDS. Feline immunodeficiency virus (FIV) infection of cats provides a model for both the immune and the central nervous system manifestations of HIV infection of humans. In this study we have examined neurons in the frontal cortex of feline immunodeficiency virus-infected cats and controls for immunoreactivity with SMI 32, an antibody recognizing a non-phosphorylated epitope on neurofilaments. We noted a significant increase in the number of immunoreactive pyramidal cells in infected animals compared to controls. The changes seen in the neuronal cytoskeleton as a consequence of the inoculation with FIV were similar to those seen in humans undergoing the normal aging process as well as those suffering from neurological diseases, including Alzheimer's and dementia pugilistica. The changes we noted in the feline brain were also similar to that reported in animals with traumatic injuries or with spontaneously occurring or induced motor neuron diseases, suggesting that the increase in reactivity represents a deleterious effect of FIV on the central nervous system.

Non-NASA Center↗
NASA NTRS1972

Study of the effect of space cabin environment on susceptibility to disease

Decreased resistance to infections initiated by respiratory challenge with Klebsiella pneumoniae or influenza virus was observed in mice maintained in a simulated space cabin environment represented by 98% oxygen atmosphere and 27,000 ft altitude (5 psi). The reduced resistance was manifested by increased mortality rates as compared to those seen in mice maintained at ground level condition. However, an adaptation to the stress appeared to be present in mice exposed to the space cabin environment for extended time period, i.e. 36 days, and then challenged with the influenza virus. Reduced resistance was not observed when Salmonella typhimurium was used as the challenge agent. Histopathologic examination of lungs of mice indicated that the severity of damage appeared to be related to the duration of exposure to the simulated space cabin environment.

Source record↗
NASA NTRS1972

Microbial ecology measurement system

The sensitivity and potential rapidity of the PIA test that was demonstrated during the feasibility study warranted continuing the effort to examine the possibility of adapting this test to an automated procedure that could be used during manned missions. The effort during this program has optimized the test conditions for two important respiratory pathogens, influenza virus and Mycoplasma pneumoniae, developed a laboratory model automated detection system, and investigated a group antigen concept for virus detection. Preliminary tests on the handling of oropharygeal clinical samples for PIA testing were performed using the adenovirus system. The results obtained indicated that the PIA signal is reduced in positive samples and is increased in negative samples. Treatment with cysteine appeared to reduce nonspecific agglutination in negative samples but did not maintain the signal in positive samples.

Source record↗
NASA NTRS1972

Cytological studies of lunar treated tissue cultures

An electron microscopic study was made of botanical materials, particularly pine tissues, treated with lunar materials collected by Apollo 12 quarantine mission. Results show unusual structural changes within several of the treated tissues. The bodies, as yet unidentified, resemble virus particles observed within infected plant cells. Although the size and shape of the structures are comparable to rod shaped virus particles such as Tobacco mosaic, the numerical distribution, affinity for stains, and intercellular location are different.

Halliwell, R. S.↗
NASA NTRS1974

On a fundamental problem in radiation biology

Experimental evidence indicates that the radiation dose required to reduce a surviving population to a certain fraction of its original population is lower for vertebrate cells than for viruses. On the other hand, the number of ionizations per cell required to inactivate that cell is greater for vertebrate cells than for viruses. The apparent conflict between these two findings is investigated. It is found that the apparent contradiction is probably a result of the fractional power dependence of the radiation-dose value on the nucleic acid weight.

Dugan, V.↗