Search NASA⌕ Search

SEARCH · Search NASA

Results for “Mortality”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Multivariate environmental and trait-based controls of transpiration in the Central Amazon Rainforest

Tropical forest tree mortality is increasing due to more severe droughts, yet our understanding of how tree traits and life strategies are linked to drought stress has been limited by measurement scarcity. The BIONTE (BIOmass and NuTrient Experiment) near Manaus, Brazil hosts one of the world’s largest sap flow installations, with sensors in 90 canopy trees across a wood density gradient monitored since June 2022. The 2023 El Niño drought provided a unique opportunity to evaluate how water availability impacts tree transpiration. An interpretable machine learning framework was used to study the complex interactions between transpiration and multiple environmental variables such as soil water availability and vapor pressure deficit (VPD), and how these interactions vary with wood density and individual trees. We found varying responses of transpiration from different trees during the El Niño drought. Transpiration generally increased with temperature, with stronger effects in wetter areas and in trees with low to medium wood density. However, this response was modulated by stomatal sensitivity to VPD, which constrained transpiration under high atmospheric demand, particularly in intermediate-moisture area. The inflection in transpiration rate at high temperatures (>32°C) underscores the role of stomatal and hydraulic regulation in limiting water loss and protecting trees from excessive evaporative demand. Analysis of soil water contribution to transpiration revealed unimodal patterns in wetter area, with peak contributions near 0.45 cm 3 cm -3 of surface soil water and declining or flat responses beyond that threshold, suggesting a shift from water- to energy-limited transpiration. In contrast, drier areas exhibited limited transpiration sensitivity to soil water conditions and minimal trait-based variation in VPD responses, indicating supply-limited conditions. Despite higher wood density trees being generally more resilient, this study shows diverse tree drought resilience, prompting further investigation into the specific traits and dynamics between environmental variables in regulating transpiration and other physiological processes in trees.

Drought↗
DOE OSTI2025

Effects of PFOS on the behavior, growth, emergence, and predation susceptibility of larval mosquitoes ( Culex quinquefasciatus )

Per-/polyfluoroalkyl substances (PFAS) have been commonly used over several decades for a variety of products and are very persistent in the environment. However, not much is known about their direct effects on aquatic invertebrates and their ecosystems. We examined the survival, behavior, development, and predation susceptibility of mosquito larvae Culex quinquefasciatus exposed to concentrations of perfluorooctanesulfonic acid (PFOS) ranging from 0.02 to 453.7 µg/L. PFOS exposure resulted in reduced larval survival, with a 48 hour LC50 (concentration with 50 % mortality) of 255.99 µg/L. PFOS exposure also resulted in reduced developmental success and slower maturation to adulthood (and thus slower emergence from the water) compared to control larvae. PFOS also resulted in delays in reaction to prodding stimuli, which were meant to simulate a predator attack, and longer reactions to prodding. Larvae exposed to PFOS also spent more time at the bottom of the water column, rather than at the surface where respiration takes place. Effects of larval mosquito PFOS exposure on predation by unexposed damselfly naiads (genus Ischnura) were not detected. Overall, this research suggests that PFOS impacts mosquito larvae survival, behavior, development, and adult emergence, which could have important implications for food webs or public health given the role of mosquitos as disease vectors.

Food web dynamics↗
DOE OSTI2025

Enhancing carbon storage through proactively managing fire-prone coniferous mountain forests

Mountain ecosystems typically serve as carbon (C) sinks. However, studies also suggest that they could be C sources due to climate warming, drought and insect-related mortality, wildfires, and management actions. We applied the Lund-Potsdam-Jena General Ecosystem Simulator (LPJ-GUESS), a process-based dynamic vegetation-ecosystem model, to investigate the role of ecosystem management in C storage under Mediterranean climate over the 21 st century. We modified LPJ-GUESS to include implementing mechanical thinning by vegetation size classes, components, and types along with a new mechanistic fire-occurrence model that accounts for wind speed and lightning ignition. Simulations show that mechanical thinning or prescribed fire performed 5-20 years in advance of a high-severity wildfire reduced direct wildfire C emissions by 38-66 %. Our results also show that long-term management actions repeated every 5-20 years, including thinning relatively small trees (diameters up to 7 inches or ∼178 mm), can maintain stable C levels in the forest and lower dead-fuel amounts. We found that, although prescribed fire mitigated wildfire severity, ecosystem C storage from reduced wildfire emissions can be outweighed by the added emissions from the prescribed fire themselves. Thinning plus removing and sequestering the thinned biomass can ensure that forests act as net C sinks through the end of the 21 st century. However, addition of prescribed fire is needed to reduce understory and lower the projected extent of high-severity wildfire. Achieving the competing goals of reducing wildfire and making the Sierra Nevada long-term C sink can be advanced through carefully coordinated thinning, sequestration of thinned biomass, and prescribed fire.

Climate solutions↗
DOE OSTI2024

Health and air pollutant emission impacts of net zero CO2 by 2050 scenarios from the energy modeling forum 37 study

Carbon dioxide and non-greenhouse gas air pollutants are emitted from many of the same sources. Decarbonization actions thus typically yield air pollutant emission reductions, resulting in significant air quality benefits. Although several studies have highlighted this connection, including in the context of net zero carbon emission targets, substantial uncertainty remains regarding how alternative technological pathways to this goal will affect the spatial distribution and magnitude of air pollutants. Comprehensive multi-model and multi-scenario analyzes are needed to explore the relative impacts of alternative pathways. Here, our study begins to address this gap by leveraging the results from the recent Energy Modeling Forum 37 inter-model comparison exercise on U.S. decarbonization pathways. Comparing the results of the six teams who submitted air pollutant emissions suggests that strategies that target net zero U.S. carbon emissions would yield significant reductions in many air pollutants, and that this finding is generally robust across pathways. However, some energy sources, such as biomass and fossil fuels with carbon capture, will emit air pollutants and can potentially influence the magnitude, spatial distribution, and even sign of localized air pollutant emission changes. In the second part of this analysis, a simplified air quality and health impacts screening model is used to evaluate the air quality impacts in 2035 of sectoral emission changes from the three models that provided sectoral detail. Relative to a reference scenario, a net zero pathway is estimated to reduce fine particulate matter concentrations across the contiguous U.S., with health benefits from reduced mortality ranging from $\$$65 billion to $\$$250 billion in 2035 alone (2023$\$$s). These benefits would be expected to grow over time as the net zero trajectory becomes more stringent. Both the magnitude of potential benefits and the substantial variation of the projections across models underscore the need for an EMF-like inter-model comparison exercise focused on air quality.

Air pollutants↗
DOE OSTI2025

High-performance windows improve thermal survivability of occupants during cold snaps

Exposure to low indoor air temperature is a major contributor to temperature-related mortality during extreme cold events, especially when power outages disrupt operation of space heating systems. This study explores the impact of high-performance windows on the thermal resilience of residential buildings during extreme cold weather and grid power outages, as well as their long-term benefits through energy efficiency and reduced risk of property damage. Building performance simulations were conducted for reference residential buildings in three construction vintages and two major U.S. cities located in cold climate zones, considering two types of extreme cold events: short and severe, and long and milder. Our research found that even houses compliant with current energy codes struggle to maintain safe indoor temperatures for more than a few hours during power outages, necessitating rapid evacuations. High-performance windows can extend the thermal survivability time by up to 3.8 days within a 7-day cold snap and significantly reduce risk of bursting frozen water pipes, depending on the building’s insulation and infiltration level, cold event severity, and occupant vulnerability. This extended thermal safety time is crucial in scenarios where reduced mobility complicates emergency responses in senior housing. In addition to boosting thermal resilience, upgrading older homes with high-performance windows can reduce heating energy consumption by over 18% and cooling energy by 15%. Our findings highlight the need to incorporate thermal resilience assessments into new designs or major retrofits, including the use of typical and extreme weather scenarios and advanced technologies like high-performance windows.

Krelling, Amanda F↗
DOE OSTI2025

ARCH: Large-scale knowledge graph via aggregated narrative codified health records analysis

Objective: Electronic health record (EHR) systems contain a wealth of clinical data stored as both codified data and free-text narrative notes (NLP). The complexity of EHR presents challenges in feature representation, information extraction, and uncertainty quantification. Here, to address these challenges, we proposed an efficient Aggregated naRrative Codified Health (ARCH) records analysis to generate a large-scale knowledge graph (KG) for a comprehensive set of EHR codified and narrative features. Methods: Using data from 12.5 million Veterans Affairs patients, ARCH first derives embedding vectors and generates similarities along with associated p-values to measure the strength of relatedness between clinical features with statistical certainty quantification. Next, ARCH performs a sparse embedding regression to remove indirect linkage between features to build a sparse KG. Finally, ARCH was validated on various clinical tasks, including detecting known relationships between entity pairs, predicting drug side effects, disease phenotyping, as well as sub-typing Alzheimer’s disease patients. Results: ARCH produces high-quality clinical embeddings and KG for over 60,000 codified and narrative EHR concepts. The KG and embeddings are visualized in the R-shiny powered web-API.3 ARCH achieved high accuracy in detecting EHR concept relationships, with AUCs of 0.926 (codified) and 0.861 (NLP) for similar EHR concepts, and 0.810 (codified) and 0.843 (NLP) for related pairs. It detected drug side effects with a 0.723 AUC, which improved to 0.826 after fine-tuning. Using both codified and NLP features, the detection power increased significantly. Compared to other methods, ARCH has superior accuracy and enhances weakly supervised phenotyping algorithms’ performance. Notably, it successfully categorized Alzheimer’s patients into two subgroups with varying mortality rates. Conclusion: The proposed ARCH algorithm generates large-scale high-quality semantic representations and knowledge graph for both codified and NLP EHR features, useful for a wide range of predictive modeling tasks.

Electronic health records↗
DOE OSTI2025

Substituent size versus metal binding of inhibitors with variants of influenza endonuclease

The influenza virus causes a significant burden of illness each year. Although vaccination is the most effective method to prevent seasonal influenza infection, viral escape mechanisms make vaccine composition difficult to predict. Antivirals are crucial for decreasing rates of morbidity and mortality from influenza viral infection. The newest anti-influenza drugs target the RNA-dependent RNA polymerase acidic N-terminal (PA N ) endonuclease, a critical component of influenza viral replication machinery. This study examines the structure of inhibitors of PAN that utilize a hydroxypyridinone-based metal-binding pharmacophore (MBP). Specifically, this report explores how the size of substituent groups impacts the binding conformation and affinity of a series of compounds against both wild-type (WT) and resistance mutant strains, I38T and E23K. Co-crystal structures revealed that the distance between compounds and enzyme residue 38 was conserved to maintain strong interactions, resulting in deviations from ideal coordination geometries at the active site metal centers. This suggests the interactions with residue 38 with each compound is important and can impact inhibitor potency as a consequence of distortions in the metal binding geometry of the compounds.

Endonuclease↗
DOE OSTI2025

Velocity- and pressure-based metrics for estimating strike injuries during fish passage through hydro turbines

Hydropower is a crucial source of clean and reliable energy worldwide, and its importance will continue to grow. To enhance the environmental sustainability of hydropower development and operations, it is essential to predict the strike injury rates of fish passing through turbines accurately and cost-effectively. However, conventional experiments involving a large number of live fish are still commonly conducted in practice, and previous attempts mainly focused on the dose-response relationships at an individual level or relative comparisons of biological characterization between different conditions. Thus, this study proposes two novel strike metrics based on velocity and pressure (M V and M P ) measured by the cutting-edge Sensor Fish (SF) technology, designed to quantify the biological effects of strikes and collisions between fish and rigid hydraulic structures. SF measurements and 48-hour survival rates of live fish from a study conducted at the Ice Harbor Dam on the Snake River were used to establish thresholds for the two proposed metrics. These metrics and thresholds were then applied to three additional SF studies conducted at hydropower facilities featuring Kaplan turbines within the Columbia River basin. Results from the application of the strike metrics indicate that the estimated survival rates derived from both metrics agree well with previously reported live fish survival rates. Furthermore, the study identified specific passage regions with elevated risks of fish mortality due to strikes and collisions. Overall, the proposed strike metrics present a reliable and cost-effective approach to reducing reliance on live fish and lowering costs in fish passage studies.

Biological characterization↗
DOE OSTI2024

Protein data bank: From two epidemics to the global pandemic to mRNA vaccines and Paxlovid

Structural biologists and the open-access Protein Data Bank (PDB) played decisive roles in combating the COVID-19 pandemic. Global biostructure data were turned into global knowledge, allowing scientists and engineers to understand the inner workings of coronaviruses and develop effective countermeasures. Two mRNA vaccines, initially designed with guidance from PDB structures of the SARS-CoV-1 and MERS-CoV spike proteins, prevented infections entirely or reduced the likelihood of morbidity and mortality for more than five billion individual recipients worldwide. Structure-guided drug discovery by Pfizer, Inc (facilitated by PDB structures), initiated in the 2000s in response to SARS-CoV-1 and resumed in 2020, yielded nirmatrelvir (the active ingredient of Paxlovid) -- a potent, orally-bioavailable inhibitor of the SARS-CoV-2 main protease. You've got to love the Protein Data Bank!

Burley, Stephen K.↗
DOE OSTI2025

Propagating synthetic populations with dynamic Bayesian networks: a framework for long-horizon demographic forecasting

This study presents a dynamic demographic microsimulator using dynamic Bayesian networks to forecast long–term changes in household and individual life events. Leveraging longitudinal Panel Study of Income Dynamics (PSID) data, two networks for individuals and households were modeled to simulate transitions in employment, income, education, marriage, childbirth, leaving the parental home, home ownership, mortality, and household formation or dissolution. Across 1,000 simulation runs spanning 24 years, household–level outcomes remain highly accurate and individual–level predictions reasonable. Although accuracy naturally declines with projection horizon, performance remains promising at both levels. This study addresses a key limitation of existing population synthesis models, which typically generate only a single static snapshot of the population. In conclusion, by introducing a framework that propagates cross-sectional outputs into the future, the microsimulator enables the tracking of demographic evolution over time, enhances realism in population-based simulations, and supplies credible inputs to agent-based travel demand models.

Demographic modeling↗
DOE OSTI2026

Large-Scale Carbon Removal Will Create Public Health, Economic, and Climate Tradeoffs

Economy-wide efforts to achieve net-zero emissions offer both climate and air quality-related public health benefits from reducing fossil fuel combustion. We explore the expected costs and benefits if carbon dioxide removal (CDR) is deployed at scale in support of these efforts. Six leading forms of CDR at two levels of deployment are compared to a scenario with no U.S. climate action. We find that heavy reliance on CDR avoids a $2.5-5.8 trillion USD2020 in climate damages, provides $2.8-6.5 trillion USD2020 public health benefits, returns $5-6 trillion USD2020 in CDR revenues, but requires $11-13 trillion USD2020 CO2 mitigation cost, cumulatively by 2050 in the U.S. In contrast, lower reliance on CDR requires much deeper near-term fossil-fuel reductions, which increases mitigation costs by 52% but also creates 26% higher public health benefits from reductions in particulate matter- and ozone-related mortality and morbidity, preventing about 12,600 premature deaths by mid-century in the U.S.

Javadi, Parisa↗
DOE OSTI2025

Pseudomonas aeruginosa Adhesion and Biofilm Formation on Poly(l-lysine)-Tethered Hydrogels: Synergistic Effect of Substrate Stiffness and Positive Charge Density

Infections associated with antibacterial-resistant Pseudomonas aeruginosa (P. aeruginosa) are the major cause of morbidity and mortality of patients, presenting one of the greatest therapeutic challenges for treatment of community-acquired and nosocomial infections. To develop antimicrobial hydrogel coatings to control the adhesion and subsequent biofilm formation of P. aeruginosa, we have used photo-cross-linked poly(ethylene glycol) diacrylate (PEGDA) hydrogels with varied cross-linking densities and covalently grafted poly(l-lysine) (PLL) at different weight compositions (ϕ PLL ). Both surface stiffness and positive charge density of the hydrogels were efficiently tuned over a broad range to investigate their effects on two main strains of P. aeruginosa, PA01 and PA14. We found that both number and viability of attached cells were positively correlated with the hydrogel stiffness, leading to thicker and larger coverage of cell colonies at 72 h postseeding on the stiffer substrates. The dependence of both PA01 and PA14 strains on ϕ PLL , however, was nonmonotonic. Positive charges from dissociated amine groups in the grafted PLL chains significantly promoted initial adhesion and proliferation of both strains at low ϕ PLL and developed into the thickest biofilms on the stiffest hydrogels grafted with ϕ PLL of 1–2%. Nevertheless, on the softest hydrogels grafted with PLL at high ϕ PLL of 7–10%, the bacteria no longer attached or survived. These results not only improved our fundamental understanding of bacteria-material interactions but also provided a series of PLL-grafted PEGDA hydrogels with controlled stiffness and positive charge density as ideal surface coating materials to prevent bacterial infections.

bacteria↗
DOE OSTI2025

Antimicrobial Peptides Can Facilitate Whole Blood Safety from Bacteria: A Proof of Concept

With continuous improvements to blood donor deferrals and the availability of sensitive tests for donation screening for infectious agents, bacterial contamination of whole blood (WB) and blood components stored for transfusion is a rare event. Nonetheless, it still occurs and remains a transfusion-associated risk in terms of septic transfusion reactions (STRs) and transfusion-transmitted bacterial infections with morbidity and mortality outcomes. One of the risk mitigation strategies for bacterial contamination is to implement treatment with currently available proactive pathogen reduction technologies (PRTs) for these transfusion products. Here, as a proof of concept, we tested two recently developed unique cationic antimicrobial peptides (AMPs; D-CONGA and D-CONGA-Q7) for WB safety from bacterial contamination. In this study, WB was inoculated with Escherichia coli and Staphylococcus epidermidis and treated with the two peptides to evaluate their bactericidal efficacy. The results demonstrated that D-CONGA and D-CONGA-Q7 exhibit potent inhibitory activity against the bacteria with a minimal inhibitory concentration (MIC) range of 4–8 and 1–8 μM, respectively, depending on the bacterial species tested. Time-kill kinetics further confirmed that the peptides exhibit bactericidal efficacy at 8 μM by achieving a 5-log 10 reduction (99.999%) of the bacterial load in WB with a time-dependent killing profile. Furthermore, even at 20 μM, the AMPs did not negatively impact hemolysis or hemostatic properties. We have further demonstrated using a cationic exchange resin that the cationic AMPs can be separated and removed from WB after the peptide treatments. During 35-day WB storage at 2–8 °C, 4 μM D-CONGA-Q7 one-time treatment prevented S. epidermidis growth and preserved WB quality and integrity. Overall, the results described here provide the first proof of concept that certain AMPs, such as D-CONGA and D-CONGA-Q7, can facilitate WB safety from bacteria during storage.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

The Novel Carbapenem, JDB/PQ-1-219, Has Potent Broad Spectrum Activity against Multi-Drug Resistant Acinetobacter baumannii

Carbapenem resistance in Acinetobacter baumannii, driven largely by class D, along with class A and class B β- lactamases, has severely compromised the utility of these last resort antibiotics. As a result, infections caused by such pathogens are characterized by extremely high mortality rates. Here we describe the antimicrobial activity of the novel C5 methyl-substituted carbapenem JDB/PQ-1−219 against multidrug resistant A. baumannii and the mechanism of its interaction with its major carbapenemase, OXA-23. JDB/PQ-1-219 exhibits potent antimicrobial activity against A. baumannii producing various carbapenemases, with MICs that are all in the clinically susceptible range. The compound has unrestricted ingress through porins and avoids egress by efflux pumps, a unique property when compared to all commercial carbapenems. Kinetic experiments demonstrated that unlike for other carbapenems, acylation of OXA-23 by JDB/ PQ-1-219 is monophasic, and mass spectrometry studies showed that this results from the conversion of all enzyme into a reversible tetrahedral intermediate which gradually transitions into the stable acyl-enzyme complex. No deacylation of this complex is observed over a physiologically relevant time period, making JDB/PQ-1−219 an extremely potent inhibitor of OXA-23. Time-resolved crystallography revealed fine details of active site dynamics, leading to complete inhibition of the enzyme. Together, these studies identify JDB/PQ-1-219 as a uniquely effective novel carbapenem with clinically significant levels of activity against multidrug resistant A. baumannii.

Acinetobacter baumannii↗
DOE OSTI2025

Insights Into Nature-Based Climate Solutions: Managing Forests for Climate Resilience and Carbon Stability

Successful implementation of forest management as a nature-based climate solution is dependent on the durability of management-induced changes in forest carbon storage and sequestration. As forests face unprecedented stability risks in the face of ongoing climate change, much remains unknown regarding how management will impact forest stability, or how interactions with climate might shift the response of forests to management across spatiotemporal scales. Here, we used a process-based model to simulate multidecadal projections of forest dynamics in response to changes in management and climate. Simulations were conducted across gradients in forest type, edaphic factors, and management intensity under two alternate radiative forcing scenarios (RCP4.5 and RCP8.5). This allowed for the quantification of forest stability shifts in response to climate change, and the role of management in modulating that response, where ecosystem stability is characterized as the resilience and temporal stability of net primary production, aboveground biomass, and soil carbon. Our results indicate that forest structure is primarily shaped by management, but the same management strategy often produced divergent structures over time, due to interactions with regional climate change. We found that management can be used to increase stability and minimize the release of stored carbon by reducing mortality, but also highlight the regional dependency of management-induced changes in resilience to climate change.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Restoring Historic Forest Disturbance Frequency Would Partially Mitigate Droughts in the Central Sierra Nevada Mountains

Forest thinning and prescribed fire are expected to improve the climate resilience and water security of forests in the western U.S., but few studies have directly modeled the hydrological effects of multi-decadal landscape-scale forest disturbance. By updating a distributed process-based hydrological model (DHSVM) with vegetation maps from a distributed forest ecosystem model (LANDIS-II), we simulate the water resource impacts of forest management scenarios targeting partial or full restoration of the pre-colonial disturbance return interval in the central Sierra Nevada mountains. In a fully restored disturbance regime that includes fire, thinning, and insect mortality, reservoir inflow increases by 4%–9% total and 8%–14% in dry years. At sub-watershed scales (10–100 km2), thinning dense forests can increase streamflow by >20% in dry years. In a thinner forest, increased understory transpiration compensates for decreased overstory transpiration. Consequentially, 73% of streamflow gains are attributable to decreased overstory rain and snow interception loss. Thinner forests can increase headwater peak flows, but reservoir-scale peak flows are almost exclusively influenced by climate. Uncertainty in future precipitation causes high uncertainty in future water yield, but the additional water yield attributable to forest disturbance is about five times less sensitive to annual precipitation uncertainty. This partial decoupling of the streamflow disturbance response from annual precipitation makes disturbance especially valuable for water supply during dry years. Our study can increase confidence in the water resource benefits of restoring historic forest disturbance frequencies in the central Sierra Nevada mountains, and our modeling framework is widely applicable to other forested mountain landscapes.

Boardman, Eli N. [University of Nevada, Reno, NV (↗
DOE OSTI2025

Elevated Forest Canopy Loss After Wildfires in Moist and Cool Forests in the Pacific Northwest

Wildfire frequency, intensity, and rate of spread are increasing across the Western U.S, resulting in more severe ecosystem impacts. Significant tree mortality can occur years after fire events, but this has received little attention compared to the immediate tree loss during a fire. We overlapped forest cover loss data with burn severity maps in the U.S. Pacific Northwest and quantified the total and delayed forest canopy loss after fires. We found that wildfires resulted in total canopy loss fraction (CLF) of 84%, 53%, and 22% within 3 years in areas burned at high, moderate, and low severity, respectively. The delayed canopy loss accounted for approximately 1/3, 1/2, and 2/3 of the total canopy loss for high, moderate, and low severity burns. Delayed canopy loss was greater in moist and cool areas than in dry and warm areas, likely because tree species in wetter environments were less adapted to survive when fires did occur. Across all forests, delayed CLF doubled as temperature increased from the climatological mean to a hot anomaly and tripled as vapor pressure deficit increased from a wet anomaly to a dry anomaly. Fire impacts on forest ecosystems are likely to intensify under future climate scenarios as wildfires expand into areas that historically experienced infrequent fires. The impacts can also be exacerbated by more frequent compound extreme events, such as droughts, heatwaves, and fires. These findings highlight the urgent need for targeted forest management strategies, particularly in mesic forests, to mitigate future fire impacts.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Entire expressed peripheral blood transcriptome in pediatric severe malarial anemia

Abstract This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, compares the entire expressed whole blood host transcriptome between Kenyan children (3-48 mos.) with non-SMA (Hb ≥ 6.0 g/dL, n = 39) and SMA ( n = 18). Differential expression analyses reveal 1403 up-regulated and 279 down-regulated transcripts in SMA, signifying impairments in host inflammasome activation, cell death, and innate immune and cellular stress responses. Immune cell profiling shows decreased memory responses, antigen presentation, and immediate pathogen clearance, suggesting an immature/improperly regulated immune response in SMA. Module repertoire analysis of blood-specific gene signatures identifies up-regulation of erythroid genes, enhanced neutrophil activation, and impaired inflammatory responses in SMA. Enrichment analyses converge on disruptions in cellular homeostasis and regulatory pathways for the ubiquitin-proteasome system, autophagy, and heme metabolism. Pathway analyses highlight activation in response to hypoxic conditions [Hypoxia Inducible Factor (HIF)−1 target and Reactive Oxygen Species (ROS) signaling] as a central theme in SMA. These signaling pathways are also top-ranking in protein abundance measures and a Ugandan SMA cohort with available transcriptomic data. Targeted RNA-Seq validation shows strong concordance with our entire expressed transcriptome data. These findings identify key molecular themes in SMA pathogenesis, offering potential targets for new malaria therapies.

60 APPLIED LIFE SCIENCES↗