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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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6 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Structure of the Inmazeb cocktail and resistance to Ebola virus escape

Monoclonal antibodies can provide important pre- or post-exposure protection against infectious disease for those not yet vaccinated or in individuals that fail to mount a protective immune response after vaccination. Inmazeb (REGN-EB3), a three-antibody cocktail against Ebola virus, lessened disease and improved survival in a controlled trial. Here, we present the cryo-EM structure at 3.1 Å of the Ebola virus glycoprotein, determined without symmetry averaging, in a simultaneous complex with the antibodies in the Inmazeb cocktail. This structure allows the modeling of previously disordered portions of the glycoprotein glycan cap, maps the non-overlapping epitopes of Inmazeb, and illuminates the basis for complementary activities and residues critical for resistance to escape by these and other clinically relevant antibodies. We further provide direct evidence that Inmazeb protects against the rapid emergence of escape mutants, whereas monotherapies even against conserved epitopes do not, supporting the benefit of a cocktail versus a monotherapy approach.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Auto-deconvolution and molecular networking of gas chromatography–mass spectrometry data

We engineered a machine learning approach, MSHub, to enable auto-deconvolution of gas chromatography–mass spectrometry (GC–MS) data. We then designed workflows to enable the community to store, process, share, annotate, compare and perform molecular networking of GC–MS data within the Global Natural Product Social (GNPS) Molecular Networking analysis platform. MSHub/GNPS performs auto-deconvolution of compound fragmentation patterns via unsupervised non-negative matrix factorization and quantifies the reproducibility of fragmentation patterns across samples.

47 OTHER INSTRUMENTATION↗
DOE OSTI2025

Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease

Elucidating the downstream impact of exogenous hormones on the aging brain will have far-reaching consequences for understanding why Alzheimer’s disease (AD) predominates in women almost twofold over men. We tested the extent to which menopausal hormone therapy (HT) use is associated with later-life amyloid-β (Aβ) and tau accumulation using PET onN = 146 baseline clinically normal women, aged 51 to 89 years. Women were scanned over a 4.5-year (SD, 2.1; range, 1.3 to 10.4) and 3.5-year (SD, 1.5; range, 1.2 to 8.1) period for Aβ and tau, respectively, ~14 years after the initiation of HT. In older women (aged >70 years), HT users exhibited faster regional tau accumulation relative to non-users, localized to the entorhinal cortex and the inferior temporal and fusiform gyri, with an indirect effect of HT on cognitive decline through regional tau accumulation. In younger women (aged <70 years), HT associations with tau accumulation were negligible. Findings are relevant for optimizing menopausal treatment guidelines.

Science & Technology - Other Topics↗
DOE OSTI2024

Variants in the MS4A cluster interact with soluble TREM2 expression on biomarkers of neuropathology

Recent evidence suggests that Alzheimer’s disease (AD) genetic risk variants (rs1582763 and rs6591561) of the MS4A locus are genome-wide significant regulators of soluble TREM2 levels such that the minor allele of the protective variant (rs1582763) is associated with higher sTREM2 and lower AD risk while the minor allele of (rs6591561) relates to lower sTREM2 and higher AD risk. Our group previously found that higher sTREM2 relates to higher Aβ 40 , worse blood–brain barrier (BBB) integrity (measured with the CSF/plasma albumin ratio), and higher CSF tau, suggesting strong associations with amyloid abundance and both BBB and neurodegeneration complicate interpretation. We expand on this work by leveraging these common variants as genetic tools to tune the interpretation of high CSF sTREM2, and by exploring the potential modifying role of these variants on the well-established associations between CSF sTREM2 as well as TREM2 transcript levels in the brain with AD neuropathology. Biomarker analyses leveraged data from the Vanderbilt Memory & Aging Project (n = 127, age = 72 ± 6.43) and were replicated in the Alzheimer’s Disease Neuroimaging Initiative (n = 399, age = 73 ± 7.39). Autopsy analyses were performed leveraging data from the Religious Orders Study and Rush Memory and Aging Project (n= 577, age = 89 ± 6.46). We found that the protective variant rs1582763 attenuated the association between CSF sTREM2 and Aβ 40 (β= -0.44, p-value= 0.017) and replicated this interaction in ADNI (β = -0.27, p = 0.017). We did not observe this same interaction effect between TREM2 mRNA levels and Aβ peptides in brain (Aβ total β = -0.14, p = 0.629; Aβ 1-38 , β = 0.11, p = 0.200). In contrast to the effects on Aβ, the minor allele of this same variant seemed to enhance the association with blood–brain barrier dysfunction (β = 7.0e-4, p = 0.009), suggesting that elevated sTREM2 may carry a much different interpretation in carriers vs. non-carriers of this allele. When evaluating the risk variant (rs6591561) across datasets, we did not observe a statistically significant interaction against any outcome in VMAP and observed opposing directions of associations in ADNI and ROS/MAP on Aβ levels. Together, our results suggest that the protective effect of rs1582763 may act by decoupling the associations between sTREM2 and amyloid abundance, providing important mechanistic insight into sTREM2 changes and highlighting the need to incorporate genetic context into the analysis of sTREM2 levels, particularly if leveraged as a clinical biomarker of disease in the future.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

CoSHA: Code for Stellar Properties Heuristic Assignment—for the MaStar Stellar Library

We introduce CoSHA: a Code for Stellar properties Heuristic Assignment. In order to estimate the stellar properties, CoSHA implements a Gradient Tree Boosting algorithm to label each star across the parameter space (T eff , $\mathrm{log}g$, [Fe/H], and [α/Fe]). We use CoSHA to estimate the stellar atmospheric parameters of 22,000 unique stars in the MaNGA Stellar Library (MaStar). To quantify the reliability of our approach, we run internal tests, using both the Göttingen Stellar Library (a theoretical library) and the first data release of MaStar, and external tests, by comparing the resulting distributions in the parameter space with the APOGEE estimates of the same properties. In summary, our parameter estimates span the ranges T eff = [2900, 12,000] K, $\mathrm{log}g=[-0.5,5.6]$, [Fe/H] = [-3.74, 0.81], and αM = [-0.22, 1.17]. We report internal (external) uncertainties of the properties of ${\sigma }_{{T}_{\mathrm{eff}}}\sim 43(240)$ K, ${\sigma }_{\mathrm{log}g}\sim 0.2(0.4)$, σ [Fe/H] ~ 0.16(0.24), and σ [α/Fe] ~ 0.09(0.08). These uncertainties are comparable to those of other methods with similar objectives. Despite the fact that CoSHA is not aware of the spatial distributions of these physical properties in the Milky Way, we are able to recover the main trends known in the literature. The catalog of physical properties for MaStar can be accessed online.

79 ASTRONOMY AND ASTROPHYSICS↗