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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

The Eco-Bio-Social Factors That Modulate Aedes aegypti Abundance in South Texas Border Communities

Aedes aegypti control requires dedicated resources that are usually scarce, limiting the reach and sustainability of vector control programs. This generates a need to focus on areas at risk of disease transmission and also understand the factors that might modulate local mosquito abundance. We evaluated the eco-bio-social factors that modulate indoor and outdoor relative abundance of female Ae. aegypti in communities of South Texas. We conducted housing quality and Knowledge Attitudes and Practices surveys in households that were part of a weekly mosquito surveillance program in November of 2017 and 2018. Our results showed widespread knowledge of mosquitoes and Zika virus by our participants. However, less than 35% considered them as serious problems in this region. The presence of window-mounted air conditioning units increased the risk of female mosquito relative abundance indoors. An increase in outdoor relative abundance was associated with larger properties and a higher number of children between 6 to 17 years of age. Interestingly, we observed that an increasing number of children <5 years of age modulated both indoor and outdoor relative abundance, with a 52% increase indoors and 30% decrease outdoors. The low perception of mosquito and disease risk highlights engagement needs for vector-borne disease prevention in this region. The identified risk factors can help guide public health officials in their efforts to reduce human and vector contact.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

The increasing threat of Rift Valley fever virus globalization: strategic guidance for protection and preparation

Rift Valley fever virus (RVFV) (Bunyavirales: Phlebovirus) is a prominent vector-borne zoonotic disease threat to global agriculture and public health. Risks of introduction into nonendemic regions are tied to changing climate regimes and other dynamic environmental factors that are becoming more prevalent, as well as virus evolutionary factors and human/animal movement. Endemic to the African continent, RVFV has caused large epizootics at the decadal scale since the early 20th century but has spread to the Arabian Peninsula and shows increasing patterns of interepizootic transmission on the annual scale. This virus can be transmitted by mosquitoes as well as through direct contact with infected tissues and can cause sporadic to widespread morbidity and mortality in domestic ungulate livestock as well as humans. High viremias in infected livestock moved for legal and illegal trade as well as in infected mosquitoes or human travelers can spread this virus worldwide. With increasing global commerce, it is likely RVFV will be introduced to new areas with suitable hosts, mosquito vector species, and environments. However, the strong mosquito component of RVFV epidemiology combined with advancements in vaccines, diagnostics, and virus evolutionary factors create opportunities for strategies to leverage models of connectivity among potential source and emerging regions to target surveillance and mitigation activities to reduce the risk of RVFV introduction, or contain the virus should it be introduced, into new regions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

A non-traditional crystal-based compound screening method targeting the ATP binding site of Plasmodium falciparum GRP78 for identification of novel nucleoside analogues

Drug resistance to front-line malarial treatments represents an ongoing threat to control malaria, a vector borne infectious disease. The malarial parasite, Plasmodium falciparum has developed genetic variants, conferring resistance to the current standard therapeutic artemisinin and its derivatives commonly referred to as artemisinin-combination therapies (ACTs). Emergence of multi-drug resistance parasite genotypes is a warning of potential treatment failure, reaffirming the urgent and critical need to find and validate alternate drug targets to prevent the spread of disease. An attractive and novel drug target includes glucose-regulated protein 78 kDa (GRP78, or BiP), an essential molecular chaperone protein involved in the unfolded protein response that is upregulated in ACT treated P. falciparum parasites. We have shown that both sequence and structure are closely related to human GRP78 (hGRP78), a chaperone belonging to the HSP70 class of ATPase proteins, which is often upregulated in cellular stress responses and cancer. By screening a library of nucleoside analogues, we identified eight ‘hit’ compounds binding at the active site of the ATP binding domain of P. falciparum GRP78 using a high-throughput ligand soaking screen using x-ray crystallography. These compounds were further evaluated using protein thermal shift assays to assess target binding activity. The nucleoside analogues identified from our screen provide a starting point for the development of more potent and selective antimalarial inhibitors. In addition, we have established a well-defined, high-throughput crystal-based screening approach that can be applied to many crystallizable P. falciparum proteins for generating anti-Plasmodium specific compounds.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Evaluation of the 2022 West Nile virus forecasting challenge, USA

Abstract Background West Nile virus (WNV) is the most common cause of mosquito-borne disease in the continental USA, with an average of ~1200 severe, neuroinvasive cases reported annually from 2005 to 2021 (range 386–2873). Despite this burden, efforts to forecast WNV disease to inform public health measures to reduce disease incidence have had limited success. Here, we analyze forecasts submitted to the 2022 WNV Forecasting Challenge, a follow-up to the 2020 WNV Forecasting Challenge. Methods Forecasting teams submitted probabilistic forecasts of annual West Nile virus neuroinvasive disease (WNND) cases for each county in the continental USA for the 2022 WNV season. We assessed the skill of team-specific forecasts, baseline forecasts, and an ensemble created from team-specific forecasts. We then characterized the impact of model characteristics and county-specific contextual factors (e.g., population) on forecast skill. Results Ensemble forecasts for 2022 anticipated a season at or below median long-term WNND incidence for nearly all (> 99%) counties. More counties reported higher case numbers than anticipated by the ensemble forecast median, but national caseload (826) was well below the 10-year median (1386). Forecast skill was highest for the ensemble forecast, though the historical negative binomial baseline model and several team-submitted forecasts had similar forecast skill. Forecasts utilizing regression-based frameworks tended to have more skill than those that did not and models using climate, mosquito surveillance, demographic, or avian data had less skill than those that did not, potentially due to overfitting. County-contextual analysis showed strong relationships with the number of years that WNND had been reported and permutation entropy (historical variability). Evaluations based on weighted interval score and logarithmic scoring metrics produced similar results. Conclusions The relative success of the ensemble forecast, the best forecast for 2022, suggests potential gains in community ability to forecast WNV, an improvement from the 2020 Challenge. Similar to the previous challenge, however, our results indicate that skill was still limited with general underprediction despite a relative low incidence year. Potential opportunities for improvement include refining mechanistic approaches, integrating additional data sources, and considering different approaches for areas with and without previous cases. Graphical Abstract

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

A Self-Assembling Pfs230D1-Ferritin Nanoparticle Vaccine Has Potent and Durable Malaria Transmission-Reducing Activity

Malaria is caused by eukaryotic protozoan parasites of the genus Plasmodium. There are 249 million new cases and 608,000 deaths annually, and new interventions are desperately needed. Malaria vaccines can be divided into three categories: liver stage, blood stage, or transmission-blocking vaccines. Transmission-blocking vaccines prevent the transmission of disease by the mosquito vector from one human to another. Pfs230 is one of the leading transmission-blocking vaccine antigens for malaria. Here, we describe the development of a 24-copy self-assembling nanoparticle vaccine comprising domain 1 of Pfs230 genetically fused to H. pylori ferritin. The single-component Pfs230D1-ferritin construct forms a stable and homogenous 24-copy nanoparticle with good production yields. The nanoparticle is highly immunogenic, as two low-dose vaccinations of New Zealand White rabbits elicited a potent and durable antibody response with high transmission-reducing activity when formulated in two distinct adjuvants suitable for translation to human use. This single-component 24-copy Pfs230D1-ferritin nanoparticle vaccine has the potential to improve production pipelines and the cost of manufacturing a potent and durable transmission-blocking vaccine for malaria control.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A short hepatitis C virus NS5A peptide expression by AAV vector modulates human T cell activation and reduces vector immunogenicity

Viral vector-mediated gene therapies have the potential to treat many human diseases; however, host immune responses against the vector and/or the transgene pose a safety risk to the patients and can negatively impact product efficacy. Thus, novel strategies to reduce vector immunogenicity are critical for the advancement of these therapies. T cell activation (TCA) is required for the development of immune responses during gene therapy. We hypothesized that modulation of TCA by incorporating a novel viral immunomodulatory factor into a viral vector may reduce unwanted TCA and immune responses during gene therapy. To test this hypothesis, we identified an immunomodulatory domain of the hepatitis C virus (HCV) NS protein 5A (NS5A) protein and studied the effect of viral vectors expressing NS5A peptide on TCA. Lentiviral vector-mediated expression of a short 20-mer peptide derived from the NS5A protein in human T cells was sufficient to inhibit TCA. Synthetic 20-mer NS5A peptide also inhibited TCA in primary human T cells. Mechanistically, the NS5A protein interacted with Lck and inhibited proximal TCR signaling. Importantly, NS5A peptide expression did not cause global T cell signaling dysfunction as distal T cell signaling was not inhibited. Finally, recombinant adeno-associated virus (AAV) vector expressing the 20-mer NS5A peptide reduced both the recall antigen and the TCR-mediated activation of human T cells and did not cause global T cell signaling dysfunction. Together, these data suggest that expression of a 20-mer NS5A peptide by an AAV vector may reduce unwanted TCA and may contribute to lower vector immunogenicity during gene therapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Identification of mosquito proteins that differentially interact with alphavirus nonstructural protein 3, a determinant of vector specificity

Chikungunya virus (CHIKV) and the closely related onyong-nyong virus (ONNV) are arthritogenic arboviruses that have caused significant, often debilitating, disease in millions of people. However, despite their kinship, they are vectored by different mosquito subfamilies that diverged 180 million years ago (anopheline versus culicine subfamilies). Previous work indicated that the nonstructural protein 3 (nsP3) of these alphaviruses was partially responsible for this vector specificity. To better understand the cellular components controlling alphavirus vector specificity, a cell culture model system of the anopheline restriction of CHIKV was developed along with a protein expression strategy. Mosquito proteins that differentially interacted with CHIKV nsP3 or ONNV nsP3 were identified. Six proteins were identified that specifically bound ONNV nsP3, ten that bound CHIKV nsP3 and eight that interacted with both. In addition to identifying novel factors that may play a role in virus/vector processing, these lists included host proteins that have been previously implicated as contributing to alphavirus replication.

Byers, Nathaniel M. (ORCID:0000000157725940)↗
DOE OSTI2021

Risk assessment of engineering diseases of embankment–bridge transition section for railway in permafrost regions

Abstract The embankment–bridge transition section (EBTS) is one of the zones where railway diseases occur frequently in permafrost regions. Disease risk assessment of EBTSs can provide guidance for maintenance. In this study, considering the engineering geological conditions, climate characteristics, and embankment structure types along the Qinghai–Tibet Railway (QTR) as well as based on the disease inventory of the QTR from 2010 to 2019, the logistic regression (LR), support vector machine (SVM), and combination‐weight‐based gay relation analysis (GRA) were used for disease risk assessment of the EBTSs along the QTR in permafrost regions. The results indicate that the LR and SVM models have a better capability for EBTS disease prediction than the GRA model, and the SVM model can select more disease samples in relatively larger regions than the LR model. Based on the SVM and LR models, the risk level of EBTSs is divided into four classes: low‐ (29.9%), moderate‐ (39.6%), high‐ (22.1%), and very high (8.4%) risk. Finally, we selected 272 EBTSs in high‐ and very‐high‐risk classes for key observation during the maintenance of the QTR in permafrost regions. This study provides a reference for the risk assessment of railways built in permafrost regions using data‐driven methods.

Zhang, Saize↗
DOE OSTI2020

Predicting Future Disease Burden in a Rapidly Changing Climate

The interplay of a rapidly changing climate and infectious disease occurrence is emerging as a critical topic, requiring investigation of possible direct, as well as indirect, connections between disease processes and climate-related variation and phenomena. First, we introduce and overview three infectious disease exemplars (dengue, influenza, valley fever) representing different transmission classes (insect-vectored, human-to-human, environmentally-transmitted) to illuminate the complex and significant interplay between climate disease processes, as well as to motivate discussion of how Sandia can transform the field, and change our understanding of climate-driven infectious disease spread. We also review state-of-the-art epidemiological and climate modeling approaches, together with data analytics and machine learning methods, potentially relevant to climate and infectious disease studies. We synthesize the modeling and disease exemplars information, suggesting initial avenues for research and development (R&D) in this area, and propose potential sponsors for this work. Whether directly or indirectly, it is certain that a rapidly changing climate will alter global disease burden. The trajectory of climate change is an important control on this burden, from local, to regional and global scales. The efforts proposed herein respond to the National Research Councils call for the creation of a multidisciplinary institute that would address critical aspects of these interlocking, cascading crises.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Transboundary determinants of avian zoonotic infectious diseases: challenges for strengthening research capacity and connecting surveillance networks

As the climate changes, global systems have become increasingly unstable and unpredictable. This is particularly true for many disease systems, including subtypes of highly pathogenic avian influenzas (HPAIs) that are circulating the world. Ecological patterns once thought stable are changing, bringing new populations and organisms into contact with one another. Wild birds continue to be hosts and reservoirs for numerous zoonotic pathogens, and strains of HPAI and other pathogens have been introduced into new regions via migrating birds and transboundary trade of wild birds. With these expanding environmental changes, it is even more crucial that regions or counties that previously did not have surveillance programs develop the appropriate skills to sample wild birds and add to the understanding of pathogens in migratory and breeding birds through research. For example, little is known about wild bird infectious diseases and migration along the Mediterranean and Black Sea Flyway (MBSF), which connects Europe, Asia, and Africa. Focusing on avian influenza and the microbiome in migratory wild birds along the MBSF, this project seeks to understand the determinants of transboundary disease propagation and coinfection in regions that are connected by this flyway. Through the creation of a threat reduction network for avian diseases (Avian Zoonotic Disease Network, AZDN) in three countries along the MBSF (Georgia, Ukraine, and Jordan), this project is strengthening capacities for disease diagnostics; microbiomes; ecoimmunology; field biosafety; proper wildlife capture and handling; experimental design; statistical analysis; and vector sampling and biology. Here, we cover what is required to build a wild bird infectious disease research and surveillance program, which includes learning skills in proper bird capture and handling; biosafety and biosecurity; permits; next generation sequencing; leading-edge bioinformatics and statistical analyses; and vector and environmental sampling. Creating connected networks for avian influenzas and other pathogen surveillance will increase coordination and strengthen biosurveillance globally in wild birds.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

Ribavirin targets sugar transporter 6 to suppress acquisition and transmission of rice stripe tenuivirus by its vector Laodelphax striatellus

Abstract BACKGROUND Rice stripe tenuivirus (RSV) is one of the most destructive pathogens of rice and other cereal crops. The virus is transmitted by the small brown planthopper (SBPH, Laodelphax striatellus ) in a circulative‐propagative manner. Thus, blocking transmission by the insect vector would provide an effective strategy to prevent epidemic outbreaks of the disease. RESULTS In this study, we explored the effect of ribavirin on acquisition and transmission of the virus by specifically inhibiting the expression of sugar transporter 6 (LsSt‐6), which was recently reported as a key vector component for RSV transmission. Ribavirin at the highest concentration tested (250 μmol L ‐1 ) significantly reduced RSV acquisition and transmission efficiency by SBPHs through inhibiting LsSt‐6 messenger RNA (mRNA) level. Survival of the model insect Spodoptera frugiperda cell line (Sf9) was 95.0 ± 2.2 and 85.6 ± 2.1% after exposure to 250 μmol L ‐1 ribavirin or 8‐azaguanine, respectively. Further study confirmed that 250 μmol L ‐1 ribavirin also significantly reduced LsSt‐6 mRNA and protein levels in Sf9 cells. However, 8‐azaguanine did not significantly inhibit viral infectivity and LsSt‐6 mRNA levels in SBPH or the Sf9 cell line. CONCLUSION This result provides evidence that ribavirin has the potential to disrupt LsSt‐6 expression but not others like viral RNAs to prevent acquiring RSV, which leads to less viral accumulation in SBPH tissues and thereby lower transmission efficiency. © 2020 Society of Chemical Industry

Hajano, Jamal‐U‐Ddin↗
DOE OSTI2022

Using X-ray Micro-Computed Tomography to Three-Dimensionally Visualize the Foregut of the Glassy-Winged Sharpshooter ( Homalodisca vitripennis )

Dissecting the heads of small insects belonging to the order Hemiptera for detailed anatomical investigation with light or scanning electron microscopy is difficult, time-consuming, and destructive, often resulting in sample preparation artifacts. Nevertheless, the structural details of these insects often hold critical information regarding their interactions with bacterial pathogens. For example, the glassy-winged sharpshooter (GWSS) is an efficient vector of the bacterium Xylella fastidiosa, the causal agent of Pierce’s disease in grape vines, but the foregut of this species is exceptionally difficult to dissect. Here, we describe a simple, non-destructive method to investigate the structure of the anterior gut of GWSS using high-resolution micro-computed X-ray tomography (microCT). The use of microCT eliminates the need for destructive dissection and reveals the morphology of small insects in three dimensions, allowing the user to virtually dissect the sample. The use of microCT imaging is a promising and powerful tool in the entomological sciences for studying the structures of vector insects, especially for difficult-to-dissect regions such as the foregut.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Climate change, malaria and neglected tropical diseases: a scoping review

Abstract To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Genomic Characterization and Wetland Occurrence of a Novel Campylobacter Isolate from Canada Geese

Populations of resident, non-migratory Canada geese are rapidly increasing. Canada geese are known to transmit viral and bacterial diseases, posing a possible threat to human health. The most prevalent pathogens vectored by geese are Campylobacter species, yet the current understanding of the identity and virulence of these pathogens is limited. In our previous study, we observed a high prevalence of Campylobacter spp. in the Banklick Creek wetland—a constructed treatment wetland (CTW) located in northern KY (USA) used to understand sources of fecal contamination originating from humans and waterfowl frequenting the area. To identify the types of Campylobacter spp. found contaminating the CTW, we performed genetic analyses of Campylobacter 16s ribosomal RNA amplified from CTW water samples and collected fecal material from birds frequenting those areas. Our results showed a high occurrence of a Campylobacter canadensis-like clade from the sampling sites. Whole-genome sequence analyses of an isolate from Canada goose fecal material, called MG1, were used to confirm the identity of the CTW isolates. Further, we examined the phylogenomic position, virulence gene content, and antimicrobial resistance gene profile of MG1. Lastly, we developed an MG1-specific real-time PCR assay and confirmed the presence of MG1 in Canada goose fecal samples surrounding the CTW. Our findings reveal that the Canada goose-vectored Campylobacter sp. MG1 is a novel isolate compared to C. canadensis that possesses possible zoonotic potential, which may be of human health concern.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Xylella fastidiosa modulates exopolysaccharide polymer length and the dynamics of biofilm development with a β-1,4-endoglucanase

Xylella fastidiosa is a Gram-negative bacterium that causes disease in many economically important crops. It colonizes the plant host xylem and the mouthparts of its insect vectors where it produces exopolysaccharide (EPS) and forms robust biofilms. Typically, the ability to form a biofilm enhances virulence, but X. fastidiosa does not fit neatly into that paradigm. Instead, X. fastidiosa enters into biofilms to attenuate its movement in the xylem, which, in turn, slows disease progression. In most of its over 600 known plant hosts, X. fastidiosa behaves as a benign commensal, but in some hosts like Vitis vinifera grapevines, it acts as a pathogen. Its ability to attenuate its own virulence in susceptible hosts may be a remnant of its commensal lifestyle in other hosts. Here, we demonstrate that X. fastidiosa utilizes a β-1,4 endoglucanase to cleave its self-produced β-1,4-glucan exopolysaccharide polymer to process it from a higher molecular weight to a lower molecular weight polymer. This processing mediates surface adherence of the cells and ultimately governs overall biofilm architecture, indicating enzymatic pruning of the EPS plays a key role in biofilm-mediated attenuation of X. fastidiosa in planta and, thus, is a key vestige that links its commensal behaviors to its parasitic behaviors in specific hosts.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

A Metabolomics Assay to Diagnose Citrus Huanglongbing Disease and to Aid in Assessment of Treatments to Prevent or Cure Infection

Citrus greening disease, or Huanglongbing (HLB), has devastated citrus crops globally in recent years. The causal bacterium, ‘ Candidatus Liberibacter asiaticus’, presents a sampling issue for qPCR diagnostics and results in a high false negative rate. In this work, we compared six metabolomics assays to identify HLB-infected citrus trees from leaf tissue extracted from 30 control and 30 HLB-infected trees. A liquid chromatography-mass spectrometry-based assay was most accurate. A final partial least squares-discriminant analysis (PLS-DA) model was trained and validated on 690 leaf samples with corresponding qPCR measures from three citrus varieties (Rio Red grapefruit, Hamlin sweet orange, and Valencia sweet orange) from orchards in Florida and Texas. Trees were naturally infected with HLB transmitted by the insect vector Diaphorina citri. In a randomized validation set, the assay was 99.9% accurate to classify diseased from nondiseased samples. This model was applied to samples from trees receiving plant defense-inducer compounds or biological treatments to prevent or cure HLB infection. From two trials, HLB-related metabolite abundances and PLS-DA scores were tracked longitudinally and compared with those of control trees. We demonstrate how our assay can assess tree health and the efficacy of HLB treatments and conclude that no trialed treatment was efficacious.

Plant Sciences↗
DOE OSTI2023

A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticle

Malaria transmission-blocking vaccines (TBVs) reduce disease transmission by breaking the continuous cycle of infection between the human host and the mosquito vector. Domain 1 (D1) of Pfs230 is a leading TBV candidate and comprises the majority of transmission-reducing activity (TRA) elicited by Pfs230. Here we show that the fusion of Pfs230D1 to a 60-copy multimer of the catalytic domain of dihydrolipoyl acetyltransferase protein (E2p) results in a single-component nanoparticle composed of 60 copies of the fusion protein with high stability, homogeneity, and production yields. The nanoparticle presents a potent human transmission-blocking epitope within Pfs230D1, indicating the antigen is correctly oriented on the surface of the nanoparticle. Two vaccinations of New Zealand White rabbits with the Pfs230D1 nanoparticle elicited a potent and durable antibody response with high TRA when formulated in two distinct adjuvants suitable for translation to human use. This single-component nanoparticle vaccine may play a key role in malaria control and has the potential to improve production pipelines and the cost of manufacturing of a potent and durable TBV.

60 APPLIED LIFE SCIENCES↗