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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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11 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Microbiomes of frozen blood plasma samples reveal potential pathogens in wild birds and rodents

The lack of genomic data on pathogens from wildlife severely limits our ability to track transmission patterns and trace the origins of an outbreak. There are currently millions of wildlife samples in biobanks around the world, including blood samples. Blood has traditionally been viewed as a sterile environment in healthy individuals, but recent evidence suggests that this is not the case, especially for wild animals. Our goal was to determine whether frozen plasma samples can be surveyed using 16S sequencing to provide information about potential hosts for pathogens for a more complete understanding of disease systems. We sequenced blood plasma from wild North American deer mice ( Peromyscus maniculatus ) and American kestrels ( Falco sparverius ) that were cryogenically stored for 7 and 13 years, respectively, and compared two DNA extraction kits. The kestrel samples contained a very high number of reads that could not be identified to phylum compared to the mouse samples. The two kits differed in the phyla and genera that were detected, and the Zymo kit, which is optimized for plasma and serum, produced more high-quality reads for both kestrel and mouse samples. We identified several pathogenic genera, including Mycoplasma, Escherichia-Shigella , and Bartonella . Sequencing blood samples for pathogens could potentially have broad applications for identifying important reservoir hosts for pathogen transmission and provide a reduced set of species on which to follow up.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Proteomics Analysis of Human Contaminant Proteins

Complete characterization of unknowns via proteomics remains challenging. There exist regions of mass spectrometry-based proteomics data where empirical measurements are not attributed to peptides, and/or sequenced peptides from mass spectra are not attributed to any source. These uncharacterized regions are known as the “dark” proteome. Many proteomics tools rely on some a priori knowledge of sample composition; few tools allow for investigation of unknowns without relying on composition assumptions. Further, the potential low abundance of minor traces in these uncharacterized regions can make elucidation of the “dark” proteome challenging. Herein, we describe the development and evaluation of approaches to study the “dark” proteome and move towards an untargeted approach for more complete characterization, namely by studying minor human protein traces in non-human samples and combining that approach with non-human source organism identification without relying on assumptions. Human protein markers, in the form of genetically variant peptides, have been extensively examined in a variety of human matrices, including blood, plasma, and hair, but have yet to be investigated in non-human samples, such as cell cultures, as human contaminant traces. Genetically variant peptides are those that are found in proteins carrying single nucleotide polymorphisms. In this work, we aimed to (1) investigate the feasibility of detecting human contaminant genetically variant peptides (GVPs) in a diverse set of non-human organisms using public proteomics data and a computational pipeline, as well as to (2) develop a combined capability for untargeted source organism characterization and GVP detection. To our knowledge, this is the first report of applying these approaches towards a more complete proteomic characterization of unknowns. We successfully demonstrate the feasibility of broad human contaminant GVP detection in proteomics data, develop a better understanding of GVP detectability, characterize the sample-to-sample variability in GVP detection, and identify a core set of GVPs that can potentially be used as markers indicative of the human contaminant traces portion of the “dark” proteome. Further, we developed and evaluated a combined pipeline, MARLOWE-GVP, that enables both untargeted source organism characterization and GVP detection. We show high accuracy of correct source organism characterization and high degree of similarity of human contaminant GVP detection compared to the conventional approach. Success on both these efforts have allowed us to advance our understanding and characterization of the “dark” proteome.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

High-density Lipoprotein (HDL) Structure and Function Proteomics (JM-DP1)

The purpose of this experiment was to investigate how the interactions between APOA1 and APOA2 on the surface of high-density lipoproteins (HDL) impact particle function by studying the effect of exogenous APOA2 on HDL structure through limited proteolysis. Interactions were investigated on HDL isolated from human blood plasma using structural proteomics tools such as chemical cross-linking and limited proteolysis (LiP). The structural proteomics data was acquired using a Q-Exactive HF-X mass spectrometer and processed using MaxQuant software (v.1.6.17.0).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

PPI DataHub Project Data Package: High-density Lipoprotein (HDL) Structure and Function Proteomics

The purpose of this experiment was to investigate how the interactions between APOA1 and APOA2 on the surface of high-density lipoproteins (HDL) impact particle function. Interactions were investigated on HDL isolated from human blood plasma using structural proteomics tools such as chemical cross-linking and limited proteolysis (LiP). The structural proteomics data was acquired using a Q-Exactive HF-X mass spectrometer and data was processed and compiled using MaxQuant sofware (v.1.6.17.0). Processed datasets are openly accessible from the download button (~2.8 GB) and contain secondary processed LiP and global proteomic results files and supporting metadata materials. Processed data downloads include a sample naming key, processed MaxQuant results/parameters, and protein annotated relative abundance files.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

The impact of kidney function on Alzheimer’s disease blood biomarkers: implications for predicting amyloid-β positivity

Impaired kidney function has a potential confounding effect on blood biomarker levels, including biomarkers for Alzheimer’s disease (AD). Given the imminent use of certain blood biomarkers in the routine diagnostic work-up of patients with suspected AD, knowledge on the potential impact of comorbidities on the utility of blood biomarkers is important. We aimed to evaluate the association between kidney function, assessed through estimated glomerular filtration rate (eGFR) calculated from plasma creatinine and AD blood biomarkers, as well as their influence over predicting Aβ-positivity. We included 242 participants from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort, comprising cognitively unimpaired individuals (CU; n = 124), mild cognitive impairment (MCI; n = 58), AD dementia (n = 34), and non-AD dementia (n = 26) patients all characterized by [ 18 F] AZD-4694. Plasma samples were analyzed for Aβ42, Aβ40, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), tau phosphorylated at threonine 181 (p-tau181), 217 (p-tau217), 231 (p-tau231) and N-terminal containing tau fragments (NTA-tau) using Simoa technology. Kidney function was assessed by eGFR in mL/min/1.73 m 2 , based on plasma creatinine levels, age, and sex. Participants were also stratified according to their eGFR-indexed stages of chronic kidney disease (CKD). We evaluated the association between eGFR and blood biomarker levels with linear models and assessed whether eGFR provided added predictive value to determine Aβ-positivity with logistic regression models. Biomarker concentrations were highest in individuals with CKD stage 3, followed by stages 2 and 1, but differences were only significant for NfL, Aβ42, and Aβ40 (not Aβ42/Aβ40). All investigated biomarkers showed significant associations with eGFR except plasma NTA-tau, with stronger relationships observed for Aβ40 and NfL. However, after adjusting for either age, sex or Aβ-PET SUVr, the association with eGFR was no longer significant for all biomarkers except Aβ40, Aβ42, NfL, and GFAP. When evaluating whether accounting for kidney function could lead to improved prediction of Aβ-positivity, we observed no improvements in model fit (Akaike Information Criterion, AIC) or in discriminative performance (AUC) by adding eGFR to a base model including each plasma biomarker, age, and sex. While covariates like age and sex improved model fit, eGFR contributed minimally, and there were no significant differences in clinical discrimination based on AUC values. We found that kidney function seems to be associated with AD blood biomarker concentrations. However, these associations did not remain significant after adjusting for age and sex, except for Aβ40, Aβ42, NfL, and GFAP. While covariates such as age and sex improved prediction of Aβ-positivity, including eGFR in the models did not lead to improved prediction for any biomarker. Our findings indicate that renal function, within the normal to mild impairment range, does not seem to have a clinically relevant impact when using highly accurate blood biomarkers, such as p-tau217, in a biomarker-supported diagnosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

405 nm violet-blue light inactivates hepatitis C cell culture virus (HCVcc) in ex vivo human platelet concentrates and plasma

Abstract Added safety measures coupled with the development and use of pathogen reduction technologies (PRT) significantly reduces the risk of transfusion-transmitted infections (TTIs) from blood products. Current approved PRTs utilize chemical and/or UV-light based inactivation methods. While the effectiveness of these PRTs in reducing pathogens are well documented, these can cause tolerable yet unintended consequences on the quality and efficacy of the transfusion products. As an alternative to UV-based approaches, we have previously demonstrated that 405 nm violet-blue light exposure successfully inactivates a variety of pathogens, including bacteria, parasites, and viruses, in both platelet concentrates (PCs) and plasma. Herein, we show that 405 nm light treatment effectively inactivates hepatitis C cell culture virus (HCVcc) by up to ~ 3.8 log10 in small volumes of a variety of matrices, such as cell culture media, PBS, plasma, and PCs with 27 J/cm 2 of light exposure, and total inactivation of HCVcc after 162 J/cm 2 light exposure. Furthermore, we demonstrate that carry-over of media supplemented with fetal bovine serum enhances the production of reactive oxygen species (ROS), providing mechanistic insights to 405 nm light-mediated viral inactivation. Overall, 405 nm light successfully inactivates HCVcc, further strengthening this method as a novel PRT for platelets and plasma.

Science & Technology - Other Topics↗
DOE OSTI2024

Diagnosis of Alzheimer’s disease using plasma biomarkers adjusted to clinical probability

Abstract Recently approved anti-amyloid immunotherapies for Alzheimer’s disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five plasma biomarkers for amyloid-β pathology in cognitively impaired individuals in relation to clinical pretest probability. We observed that p-tau217 could rule in amyloid-β pathology in individuals with probable AD dementia (positive predictive value above 95%). In mild cognitive impairment, p-tau217 interpretation depended on patient age. Negative p-tau217 results could rule out amyloid-β pathology in individuals with non-AD dementia syndromes (negative predictive value between 90% and 99%). Our findings provide a framework for the individual-level interpretation of plasma biomarkers, suggesting that p-tau217 combined with clinical phenotyping can identify patients where amyloid-β pathology can be ruled in or out without the need for PET or CSF confirmatory testing.

Cell Biology↗
DOE OSTI2025

Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer’s disease spectrum

Abstract Plasma phosphorylated tau (p-tau) biomarkers open unprecedented opportunities for identifying carriers of Alzheimer’s disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment. To address this question, we included 103 cognitively unimpaired elderly and 40 cognitively impaired, amyloid-β-positive individuals from the TRIAD cohort, in addition to 336 cognitively unimpaired and 216 cognitively impaired, amyloid-β-positive older adults from the BioFINDER-2 cohort. Participants had tau PET scans, amyloid PET scans or amyloid CSF, p-tau217, p-tau181 and p-tau231 blood measures, structural T1-MRI and cognitive assessments. In this cross-sectional study, we used regression models and correlation analyses to assess the relationship between plasma biomarkers and cognitive scores. Furthermore, we applied receiver operating characteristic curves to assess cognitive impairment across plasma biomarkers. Finally, we categorized participants into amyloid (A), p-tau (T1) and tau PET (T2) positive (+) or negative (−) profiles and ran non-parametric comparisons to assess differences across cognitive domains. We found that plasma p-tau217 was more associated with cognitive performance than p-tau181 and p-tau231 and that this relationship was particularly strong for memory scores (TRIAD: βp-tau217 = −0.53, βp-tau181 = −0.35 and βp-tau231 = −0.24; BioFINDER-2: βp-tau217 = −0.52, βp-tau181 = −0.24 and βp-tau231 = −0.29). Associations in amyloid-β-positive participants resembled these results, but other cognitive scores also showed strong associations in cognitively impaired individuals. Moreover, plasma p-tau217 outperformed plasma p-tau181 and plasma p-tau231 in identifying memory impairment (area under the curve values for TRIAD: p-tau217 = 0.86, p-tau181 = 0.77 and p-tau231 = 0.75; and for BioFINDER-2: p-tau217 = 0.86, p-tau181 = 0.76 and p-tau231 = 0.81) and in identifying executive function impairment only in the BioFINDER-2 cohort (p-tau217 = 0.82, p-tau181 = 0.76 and p-tau231 = 0.76). Lastly, we showed that subtle memory deficits were present in A+T1+T2− participants for plasma p-tau217 (P = 0.007) and plasma p-tau181 (P = 0.01) in the TRIAD cohort and for all biomarkers across cognitive domains in A+T1+T2− and A+T1+T2− individuals (P < 0.001 in all) in the BioFINDER-2 cohort. The A+T1+T2− individuals showed cognitive deficits in both cohorts (P < 0.001 in all). Together, our results suggest that plasma p-tau217 stands out as a biomarker capable of identifying memory deficits attributable to Alzheimer’s disease and that memory impairment certainly occurs in amyloid-β- and plasma p-tau-positive individuals who have no significant amounts of tau in the neocortex.

Neurosciences & Neurology↗
DOE OSTI2024

Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation

Abstract Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species. After LPS stimulation, maximally different genes in resilient species included genes that detoxify LPS, diminish bacterial growth, discriminate sepsis from SIRS, and play roles in autophagy and apoptosis. The findings reveal the molecular landscape of species differences in inflammation. This may inform better selection of species for pre-clinical models and could lead to new therapeutic strategies that mimic mechanisms in inflammation-resilient species to limit inflammation without causing immunosuppression.

Biochemistry & Molecular Biology↗
DOE OSTI2026

Longitudinal Plasma Proteomic Profiling Reveals Divergent Immune Responses in Durably Cured and Relapsed Pulmonary Tuberculosis

Background: Predicting the risk of tuberculosis (TB) relapse is vital to improving treatment outcomes. Although clinical risk factors of relapse are well characterized, the biological mechanisms driving relapse, particularly host immune responses, remain poorly understood. Elucidating these mechanisms is necessary to better predict relapse risk. Methods: We conducted a longitudinal, global proteomic study on 60 participants with active pulmonary TB, half who were durably cured and half who relapsed. Plasma was collected at seven time-points: at treatment initiation (baseline), during therapy, and 52 weeks post-baseline. Samples were analyzed by high-resolution LC-MS/MS. Results: 2,418 proteins were identified across all samples, with 1,756 being differentially expressed relative to baseline (unadjusted p < 0.05). 956 proteins were differentially abundant between cured and relapsed participants. Relapsed participants showed heightened humoral immunity throughout treatment, as well as upregulated complement activation and HDL particles. Cured participants exhibited elevated recovery-related pathways by week 4, including downregulated epithelial invasion and upregulated oxygen transport. Conclusions: Heightened humoral and innate immune responses were associated with relapse, whereas recovery signatures were associated with durable cure. These findings advance our understanding of host responses to treatment and provide a basis for developing blood-based biomarkers to identify patients at increased risk of relapse.

LC-MS/MS↗
DOE OSTI2024

Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption

Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac 239 -infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8 + T cells in lymph nodes and reduced expression of BCL-2 in CD4 + T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4 + and CD8 + T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART.

60 APPLIED LIFE SCIENCES↗