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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 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Elucidating Mechanisms of Rust Pathogenesis for Engineering Resistance in Poplar

The overall objective of this research was to elucidate the molecular basis for the virulence of Melampsora larici-populina towards Populus spp. in order to address the formidable challenge of engineering durable resistance in poplar against leaf rust. Our original research plan was built on the technically innovative approach of using dual host systems and known host defense proteins and pathogen avirulent effectors along with genome-wide approaches to identify key pathogenesis effectors of Melampsora larici-populina that target poplar defense and nutrient acquisition. Our efforts focused on developing high-throughput experimental approaches and systems to enable us to address our overarching hypothesis that rust effectors with homology to other fungal effectors will either bypass the poplar immune system and/or suppress effector-triggered immunity through conserved mechanisms, and that an analysis of these interaction networks would provide for new approaches to develop rust-resistant poplar. Three main objectives were originally proposed: (1) mine key rust effectors that suppress host immunity; (2) elucidate interaction networks in poplar targeted by key rust effectors; (3) generate transgenic poplar resources for identification of genes involved in pathogen infection or host defense triggered by rust. Generally, we worked towards all three objectives by developing and applying complementary molecular, genomic, biochemical and plant transformation approaches.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Metabolomics Analysis of Bacterial Pathogen Burkholderia thailandensis and Mammalian Host Cells in Co-culture

The Tier 1 HHS/USDA Select Agent Burkholderia pseudomallei is a bacterial pathogen that is highly virulent when introduced into the respiratory tract and intrinsically resistant to many antibiotics. Transcriptomic- and proteomic-based methodologies have been used to investigate mechanisms of virulence employed by B. pseudomallei and Burkholderia thailandensis, a convenient surrogate; however, analysis of the pathogen and host metabolomes during infection is lacking. Changes in the metabolites produced can be a result of altered gene expression and/or post-transcriptional processes. Thus, metabolomics complements transcriptomics and proteomics by providing a chemical readout of a biological phenotype, which serves as a snapshot of an organism’s physiological state. However, the poor signal from bacterial metabolites in the context of infection poses a challenge in their detection and robust annotation. In this work, we coupled mammalian cell culture-based metabolomics with feature-based molecular networking of mono- and co-cultures to annotate the pathogen’s secondary metabolome during infection of mammalian cells. These methods enabled us to identify several key secondary metabolites produced by B. thailandensis during infection of airway epithelial and macrophage cell lines. Additionally, the use of in silico approaches provided insights into shifts in host biochemical pathways relevant to defense against infection. Using chemical class enrichment analysis, for example, we identified changes in a number of host-derived compounds including immune lipids such as prostaglandins, which were detected exclusively upon pathogen challenge. Taken together, our findings indicate that co-culture of B. thailandensis with mammalian cells alters the metabolome of both pathogen and host and provides a new dimension of information for in-depth analysis of the host–pathogen interactions underlying Burkholderia infection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

An automated workflow that generates atom mappings for large‐scale metabolic models and its application to Arabidopsis thaliana

SUMMARY Quantification of reaction fluxes of metabolic networks can help us understand how the integration of different metabolic pathways determines cellular functions. Yet, intracellular fluxes cannot be measured directly but are estimated with metabolic flux analysis (MFA), which relies on the patterns of isotope labeling of metabolites in the network. The application of MFA also requires a stoichiometric model with atom mappings that are currently not available for the majority of large‐scale metabolic network models, particularly of plants. While automated approaches such as the Reaction Decoder Toolkit (RDT) can produce atom mappings for individual reactions, tracing the flow of individual atoms of the entire reactions across a metabolic model remains challenging. Here we establish an automated workflow to obtain reliable atom mappings for large‐scale metabolic models by refining the outcome of RDT, and apply the workflow to metabolic models of Arabidopsis thaliana . We demonstrate the accuracy of RDT through a comparative analysis with atom mappings from a large database of biochemical reactions, MetaCyc. We further show the utility of our automated workflow by simulating 15 N isotope enrichment and identifying nitrogen (N)‐containing metabolites which show enrichment patterns that are informative for flux estimation in future 15 N‐MFA studies of A. thaliana . The automated workflow established in this study can be readily expanded to other species for which metabolic models have been established and the resulting atom mappings will facilitate MFA and graph‐theoretic structural analyses with large‐scale metabolic networks.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1997

Integrins, tensegrity, and mechanotransduction

Physical forces, such as those due to gravity, play an important role in tissue development and remodeling. Yet, little is known about how individual cells sense mechanical signals or how they transduce them into a chemical response. Rather than listing the numerous signal pathways that have been found to be sensitive to mechanical stimulation, we need to place potential molecular signaling mechanisms within the context of the entire cell. The model presented is based on the concept that cells use tensegrity architecture to organize their cytoskeleton and stabilize their form. Studies with stick and string tensegrity cell models predict that living cells are hard-wired to respond immediately to external mechanical stresses. This hard-wiring exists in the form of discrete cytoskeletal filament networks that mechanically couple specific cell surface receptors, such as integrins, to nuclear matrix scaffolds and to potential transducing molecules that physically associate with the cytoskeleton. If these signaling molecules do function in a "solid-state", then mechanical stresses may be transduced into biochemical responses through force-dependent changes in cytoskeletal geometry or through local alterations in thermodynamic or kinetic parameters. Changes in cytoskeletal tension (prestress) also may play a role in signal amplification and adaptation. Recent experimental results are described which provide direct support for the tensegrity theory.

Review↗
DOE OSTI2020

Phylogenetics-based identification and characterization of a superior 2,3-butanediol dehydrogenase for Zymomonas mobilis expression

Abstract Background Zymomonas mobilis has recently been shown to be capable of producing the valuable platform biochemical, 2,3-butanediol (2,3-BDO). Despite this capability, the production of high titers of 2,3-BDO is restricted by several physiological parameters. One such bottleneck involves the conversion of acetoin to 2,3-BDO, a step catalyzed by 2,3-butanediol dehydrogenase (Bdh). Several Bdh enzymes have been successfully expressed in Z. mobilis, although a highly active enzyme is yet to be identified for expression in this host. Here, we report the application of a phylogenetic approach to identify and characterize a superior Bdh, followed by validation of its structural attributes using a mutagenesis approach. Results Of the 11 distinct bdh genes that were expressed in Z. mobilis, crude extracts expressing Serratia marcescens Bdh ( Sm Bdh) were found to have the highest activity (8.89 µmol/min/mg), when compared to other Bdh enzymes (0.34–2.87 µmol/min/mg). The Sm Bdh crystal structure was determined through crystallization with cofactor (NAD + ) and substrate (acetoin) molecules bound in the active site. Active Sm Bdh was shown to be a tetramer with the active site populated by a Gln247 residue contributed by the diagonally opposite subunit. Sm Bdh showed a more extensive supporting hydrogen-bond network in comparison to the other well-studied Bdh enzymes, which enables improved substrate positioning and substrate specificity. This protein also contains a short α6 helix, which provides more efficient entry and exit of molecules from the active site, thereby contributing to enhanced substrate turnover. Extending the α6 helix to mimic the lower activity Enterobacter cloacae ( Ec Bdh) enzyme resulted in reduction of Sm Bdh function to nearly 3% of the total activity. In great contrast, reduction of the corresponding α6 helix of the Ec Bdh to mimic the Sm Bdh structure resulted in ~ 70% increase in its activity. Conclusions This study has demonstrated that Sm Bdh is superior to other Bdhs for expression in Z. mobilis for 2,3-BDO production. Sm Bdh possesses unique structural features that confer biochemical advantage to this protein. While coordinated active site formation is a unique structural characteristic of this tetrameric complex, the smaller α6 helix and extended hydrogen network contribute towards improved activity and substrate promiscuity of the enzyme.

09 BIOMASS FUELS↗
DOE OSTI2025

1000 Soils Pilot Dataset, version 8, May 2025

This record hosts data generated by the 1000 Soils Pilot. Data will be updated as more become available. Please see the most recent data upload for current data. A beta visualization tool is available for some data types at https://shinyproxy.emsl.pnnl.gov/app/1000soils. Please submit any suggestions or comments through the 'contact' tab. We are actively working to improve visualizations and value all feedback. Data completed include: Geochemistry, texture, respiration, and enzyme activities FTICR-MS organic matter chemistry Microbial biomass C and N TOC/TDN of water-extractable OM X-ray computed tomography (derived metrics available here, raw data available upon request) Metagenomes; a variety of data formats are available upon request Soil hydraulic properties Data in progress: LC-MS/MS in development, timeline TBD, inquire for status 1000S_processed_BGC_summary.csv contains all available biogeochemical data; microbial biomass C and N; and TOC/TDN of water-extractable OM; and 1000S_Tomography.xslx contains a summary of data generated via X-ray computed tomography. icr_v2_corems2.csv contains FTICR-MS data processed by CoreMS version 2. These data are merged by formula across instrument runs to enable cross-sample comparisons. Technical replicates are merged by retaining peaks present in 2 out of 3 replicates. 1000Soils_Metadata_Site_Mastersheet_v1.csv contains site information. Soil Hydraulics_corrected_02042025.xlsx contains soil hydraulics information. Readme File_v4.xlsx is the readme file. Please contact the MONet project (monet.emsl@pnnl.gov) or Emily Graham (emily.graham@pnnl.gov) with questions. The following file and all raw data are available upon request: icr_by_mass_for_single_sample_analysis_only.csv contains FTICR-MS data processed by CoreMS and is intended for usage in the calculation of biochemical transformations within samples only. These data are not acceptable for cross-sample comparison of masses because they are from multiple instrument runs. For more information, please see: https://www.emsl.pnnl.gov/monet and https://sc-data.emsl.pnnl.gov/monet Acknowledgment: Soil data were provided by the Molecular Observation Network (MONet) at the Environmental Molecular Sciences Laboratory (https://ror.org/04rc0xn13), a DOE Office of Science user facility sponsored by the Biological and Environmental Research program under Contract No. DE-AC05-76RL01830. The work (proposal: 10.46936/10.25585/60008970) conducted by the U.S. Department of Energy, Joint Genome Institute (https://ror.org/04xm1d337), a DOE Office of Science user facility, is supported by the Office of Science of the U.S. Department of Energy operated under Contract No. DE-AC02-05CH11231. The Molecular Observation Network (MONet) database is an open, FAIR, and publicly available compilation of the molecular and microstructural properties of soil. Data in the MONet open science database can be found at https://sc-data.emsl.pnnl.gov/.

biogeochemistry↗
DOE OSTI2024

Multisubstrate specificity shaped the complex evolution of the aminotransferase family across the tree of life

Aminotransferases (ATs) are an ancient enzyme family that play central roles in core nitrogen metabolism, essential to all organisms. However, many of the AT enzyme functions remain poorly defined, limiting our fundamental understanding of the nitrogen metabolic networks that exist in different organisms. Here, we traced the deep evolutionary history of the AT family by analyzing AT enzymes from 90 species spanning the tree of life (ToL). We found that each organism has maintained a relatively small and constant number of ATs. Mapping the distribution of ATs across the ToL uncovered that many essential AT reactions are carried out by taxon-specific AT enzymes due to wide-spread nonorthologous gene displacements. This complex evolutionary history explains the difficulty of homology-based AT functional prediction. Biochemical characterization of diverse aromatic ATs further revealed their broad substrate specificity, unlike other core metabolic enzymes that evolved to catalyze specific reactions today. Interestingly, however, we found that these AT enzymes that diverged over billion years share common signatures of multisubstrate specificity by employing different nonconserved active site residues. These findings illustrate that AT family enzymes had leveraged their inherent substrate promiscuity to maintain a small yet distinct set of multifunctional AT enzymes in different taxa. This evolutionary history of versatile ATs likely contributed to the establishment of robust and diverse nitrogen metabolic networks that exist throughout the ToL. The study provides a critical foundation to systematically determine diverse AT functions and underlying nitrogen metabolic networks across the ToL.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Community response of soil microorganisms to combined contamination of polycyclic aromatic hydrocarbons and potentially toxic elements in a typical coking plant

Both polycyclic aromatic hydrocarbons (PAHs) and potentially toxic elements (PTEs) of coking industries impose negative effects on the stability of soil ecosystem. Soil microbes are regarded as an essential moderator of biochemical processes and soil remediation, while their responses to PAHs-PTEs combined contamination are largely unknown. In the present study, soil microbial diversity and community composition in the typical coking plant under the chronic co-exposure of PAHs and PTEs were investigated and microbial interaction networks were built to reveal microbial co-occurrence patterns. The results indicated that the concentrations of PAHs in the soil inside the coking plant were significantly higher than those outside the plant. The mean concentration of ∑16PAHs was 2894.4 ng·g −1 , which is 5.58 times higher than that outside the plant. The average Hg concentration inside the coking plant was 22 times higher than the background value of Hebei province. The soil fungal community inside the coking plant showed lower richness compared with that of outside community, and there are significant difference in the bacterial and fungal community composition between inside and outside of coking plant ( p < 0.01). Predicted contribution of different environmental factors to each dominant species based on random forest identified 20 and 25 biomarkers in bacteria and fungi, respectively, that were highly sensitive to coking plant soil in operation, such as Betaproteobacteria，Sordariomycetes and Dothideomycetes . Bacterial and fungal communities were shaped by the soil chemical properties (pH), PTEs (Hg), and PAHs together in the coking plant soils. Furthermore, the bacterial and fungal interaction patterns were investigated separately or jointly by intradomain and interdomain networks. Competition is the main strategy based on the co-exclusion pattern in fungal community, and the competitive relationship inside the coking plant is more complex than that outside the plant. In contrast, cooperation is the dominant strategy in bacterial networks based on the co-occurrence pattern. The present study provided insights into microbial response strategies and the interactions between bacteria and fungi under long-term combined contamination.

Shen, Qihui↗
NASA NTRS2006

Mathematical Modeling of the Origins of Life

The emergence of early metabolism - a network of catalyzed chemical reactions that supported self-maintenance, growth, reproduction and evolution of the ancestors of contemporary cells (protocells) was a critical, but still very poorly understood step on the path from inanimate to animate matter. Here, it is proposed and tested through mathematical modeling of biochemically plausible systems that the emergence of metabolism and its initial evolution towards higher complexity preceded the emergence of a genome. Even though the formation of protocellular metabolism was driven by non-genomic, highly stochastic processes the outcome was largely deterministic, strongly constrained by laws of chemistry. It is shown that such concepts as speciation and fitness to the environment, developed in the context of genomic evolution, also held in the absence of a genome.

Pohorille, Andrew↗
DOE OSTI2021

Maize specialized metabolome networks reveal organ-preferential mixed glycosides

Despite the scientific and economic importance of maize, little is known about its specialized metabolism. Here, five maize organs were profiled using different reversed-phase liquid chromatography-mass spectrometry methods. The resulting spectral metadata, combined with candidate substrate-product pair (CSPP) networks, allowed the structural characterization of 427 of the 5,420 profiled compounds, including phenylpropanoids, flavonoids, benzoxazinoids, and auxin-related compounds, among others. Only 75 of the 427 compounds were already described in maize. Analysis of the CSPP networks showed that phenylpropanoids are present in all organs, whereas other metabolic classes are rather organ-enriched. Frequently occurring CSPP mass differences often corresponded with glycosyl- and acyltransferase reactions. The interplay of glycosylations and acylations yields a wide variety of mixed glycosides, bearing substructures corresponding to the different biochemical classes. For example, in the tassel, many phenylpropanoid and flavonoid-bearing glycosides also contain auxin-derived moieties. The characterized compounds and mass differences are an important step forward in metabolic pathway discovery and systems biology research.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Pore-scale observations of natural hydrate-bearing sediments via pressure core sub-coring and micro-CT scanning

Abstract Both intra-pore hydrate morphology and inter-pore hydrate distribution influence the physical properties of hydrate-bearing sediments, yet there has been no pore-scale observations of hydrate habit under pressure in preserved pressure core samples so far. We present for the first time a pore-scale micro-CT study of natural hydrate-bearing cores that were acquired from Green Canyon Block 955 in UT-GOM2-1 Expedition and preserved within hydrate pressure–temperature stability conditions throughout sub-sampling and imaging processes. Measured hydrate saturation in the sub-samples, taken from units expected to have in-situ saturation of 80% or more, ranges from 3 ± 1% to 56 ± 11% as interpreted from micro-CT images. Pore-scale observations of gas hydrate in the sub-samples suggest that hydrate in silty sediments at the Gulf of Mexico is pore-invasive rather than particle displacive, and hydrate particles in these natural water-saturated samples are pore-filling with no evidence of grain-coating. Hydrate can form a connected 3D network and provide mechanical support for the sediments even without cementation. The technical breakthrough to directly visualize particle-level hydrate pore habits in natural sediments reported here sheds light on future investigations of pressure- and temperature-sensitive processes including hydrate-bearing sediments, dissolved gases, and other biochemical processes in the deep-sea environment.

58 GEOSCIENCES↗
DOE OSTI2020

SNPeffect: identifying functional roles of SNPs using metabolic networks

Genetic sources of phenotypic variation have been a focus of plant studies aimed at improving agricultural yield and understanding adaptive processes. Genome-wide association studies identify the genetic background behind a trait by examining associations between phenotypes and single-nucleotide polymorphisms (SNPs). Although such studies are common, biological interpretation of the results remains a challenge; especially due to the confounding nature of population structure and the systematic biases thus introduced. Here, we propose a complementary analysis (SNPeffect) that offers putative genotype-to-phenotype mechanistic interpretations by integrating biochemical knowledge encoded in metabolic models. SNPeffect is used to explain differential growth rate and metabolite accumulation in A. thaliana and P. trichocarpa accessions as the outcome of SNPs in enzyme-coding genes. To this end, we also constructed a genome-scale metabolic model for Populus trichocarpa, the first for a perennial woody tree. As expected, our results indicate that growth is a complex polygenic trait governed by carbon and energy partitioning. The predicted set of functional SNPs in both species are associated with experimentally characterized growth-determining genes and also suggest putative ones. Functional SNPs were found in pathways such as amino acid metabolism, nucleotide biosynthesis, and cellulose and lignin biosynthesis, in line with breeding strategies that target pathways governing carbon and energy partition.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2026

Prediction of non-intuitive metabolic targets with bayesian metabolic control analysis to improve 3-hydroxypropionic acid production in Aspergillus niger

Development of efficient bioconversion processes is limited by the ability to predictably improve metabolic flux. Here we deployed Bayesian Metabolic Control Analysis as a platform to integrate multi-omics data with metabolic modeling and evaluated its ability to predict genetic interventions that improve metabolic flux. Global Metabolomics and proteomics data was collected from 17 Aspergillus niger strains engineered to produce the platform biochemical 3-hydroxypropionic acid from which seven actional genetic interventions were predicted from significant flux control coefficients. Of the suggested genetic interventions, two were present within the intuitively designed strains used for training (malonic semialdehyde dehydrogenase and pyruvate carboxylase) while five predicted targets were present within non-intuitive areas of the metabolic network including 5-formyltetrahydrofolate deformylase and four mitochondrial enzymes, alcohol dehydrogenase, succinyl-CoA ligase, aspartate aminotransferase, and malate dehydrogenase. Six of the targets were validated in the highest performing 3-HP strain used for multi-omics data generation which contained a prior disruption of the highest scoring target malonic semialdehyde dehydrogenase. Predicted directional perturbation of five of the six tested targets significantly improved titer and rate of 3-HP production and two significantly improved yield. The greatest improvements were observed following disruption of the non-intuitive target succinyl-CoA ligase which increased titer by 39% and yield by 29% (to 20.4 g/L 3-HP and 0.31 g 3-HP/g glucose) over the strains used for training. This study demonstrates the utility of Bayesian Metabolic Control Analysis and highlights the ability to predict meaningful genetic targets in unexpected areas of metabolism to improve engineered strains for bioconversion.

3-hydroxypropionic acid↗
NASA NTRS2017

Exploring Connectivity in Sequence Space of Functional RNA

Emergence of replicable genetic molecules was one of the marking points in the origin of life, evolution of which can be conceptualized as a walk through the space of all possible sequences. A theoretical concept of fitness landscape helps to understand evolutionary processes through assigning a value of fitness to each genotype. Then, evolution of a phenotype is viewed as a series of consecutive, single-point mutations. Natural selection biases evolution toward peaks of high fitness and away from valleys of low fitness. whereas neutral drift occurs in the sequence space without direction as mutations are introduced at random. Large networks of neutral or near-neutral mutations on a fitness landscape, especially for sufficiently long genomes, are possible or even inevitable. Their detection in experiments, however, has been elusive. Although a few near-neutral evolutionary pathways have been found, recent experimental evidence indicates landscapes consist of largely isolated islands. The generality of these results, however, is not clear, as the genome length or the fraction of functional molecules in the genotypic space might have been insufficient for the emergence of large, neutral networks. Thorough investigation on the structure of the fitness landscape is essential to understand the mechanisms of evolution of early genomes. RNA molecules are commonly assumed to play the pivotal role in the origin of genetic systems. They are widely believed to be early, if not the earliest, genetic and catalytic molecules, with abundant biochemical activities as aptamers and ribozymes, i.e. RNA molecules capable, respectively, to bind small molecules or catalyze chemical reactions. Here, we present results of our recent studies on the structure of the sequence space of RNA ligase ribozymes selected through in vitro evolution. Several hundred thousands of sequences active to a different degree were obtained by way of deep sequencing. Analysis of these sequences revealed several large clusters defined such that every sequence in a cluster can be reached from any other sequence in the same cluster through a series of single point mutations. Sequences in a single cluster appear to adopt more than one secondary structure. The mechanism of refolding within a single cluster was examined. To shed light on possible evolutionary paths in the space of ribozymes, the connectivity between clusters was investigated. The effect of length of RNA molecules on the structure of the fitness landscape and possible evolutionary paths was examined by way of comparing functional sequences of 20 and 80 nucleobases in length. It was found that sequences of different lengths shared secondary structure motifs that were presumed responsible for catalytic activity, with increasing complexity and global structural rearrangements emerging in longer molecules.

Wei, Chenyu↗
NASA NTRS1984

Information systems - Issues in global habitability

The present investigation is concerned with fundamental issues, related to information considerations, which arise in an interdisciplinary approach to questions of global habitability. Information system problems and issues are illustrated with the aid of an example involving biochemical cycling and biochemical productivity. The estimation of net primary production (NPP) as an important consideration in the overall global habitability issue is discussed. The NPP model requires three types of data, related to meteorological information, a land surface inventory, and the vegetation structure. Approaches for obtaining and processing these data are discussed. Attention is given to user requirements, information system requirements, workstations, network communications, hardware/software access, and data management.

Norman, S. D.↗
DOE OSTI2022

Protein cost minimization promotes the emergence of coenzyme redundancy

Metabolism relies on a small class of molecules (coenzymes) that serve as universal donors and acceptors of key chemical groups and electrons. Although metabolic networks crucially depend on structurally redundant coenzymes [e.g., NAD(H) and NADP(H)] associated with different enzymes, the criteria that led to the emergence of this redundancy remain poorly understood. Our combination of modeling and structural and sequence analysis indicates that coenzyme redundancy may not be essential for metabolism but could rather constitute an evolved strategy promoting efficient usage of enzymes when biochemical reactions are near equilibrium. Our work suggests that early metabolism may have operated with fewer coenzymes and that adaptation for metabolic efficiency may have driven the rise of coenzyme diversity in living systems.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

BCL10 Mutations Define Distinct Dependencies Guiding Precision Therapy for DLBCL

Activated B cell–like diffuse large B-cell lymphomas (ABC-DLBCL) have unfavorable outcomes and chronic activation of CARD11–BCL10–MALT1 (CBM) signal amplification complexes that form due to polymerization of BCL10 subunits, which is affected by recurrent somatic mutations in ABC-DLBCLs. Herein, we show that BCL10 mutants fall into at least two functionally distinct classes: missense mutations of the BCL10 CARD domain and truncation of its C-terminal tail. Truncating mutations abrogated a motif through which MALT1 inhibits BCL10 polymerization, trapping MALT1 in its activated filament-bound state. CARD missense mutations enhanced BCL10 filament formation, forming glutamine network structures that stabilize BCL10 filaments. Mutant forms of BCL10 were less dependent on upstream CARD11 activation and thus manifested resistance to BTK inhibitors, whereas BCL10 truncating but not CARD mutants were hypersensitive to MALT1 inhibitors. Therefore, BCL10 mutations are potential biomarkers for BTK inhibitor resistance in ABC-DLBCL, and further precision can be achieved by selecting therapy based on specific biochemical effects of distinct mutation classes.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2008

Utilizing Ion-Mobility Data to Estimate Molecular Masses

A method is being developed for utilizing readings of an ion-mobility spectrometer (IMS) to estimate molecular masses of ions that have passed through the spectrometer. The method involves the use of (1) some feature-based descriptors of structures of molecules of interest and (2) reduced ion mobilities calculated from IMS readings as inputs to (3) a neural network. This development is part of a larger effort to enable the use of IMSs as relatively inexpensive, robust, lightweight instruments to identify, via molecular masses, individual compounds or groups of compounds (especially organic compounds) that may be present in specific environments or samples. Potential applications include detection of organic molecules as signs of life on remote planets, modeling and detection of biochemicals of interest in the pharmaceutical and agricultural industries, and detection of chemical and biological hazards in industrial, homeland-security, and industrial settings.

Duong, Tuan↗