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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 1,135 records · Page 63
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Elucidating regulatory processes of intense physical activity by multi-omics analysis

Abstract Background Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment. Methods To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student’s t -test followed by pathway analysis and comparison between the different omics modalities. Results Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection. Conclusion This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Comparing western (Megascops kennicottii) and whiskered (M. trichopsis) screech-owl microbiomes in southern Arizona using a novel 16S rRNA sequencing method

Microbiomes are essential to a host’s physiology and health. Despite the overall importance of microbiomes to animal health, they remain understudied in wildlife. Microbiomes function as physical barriers to invading pathogens, and changes in the diversity or composition of microbes within a host may disrupt this barrier. In order to use microbiomes in wildlife ecology, knowledge of the natural variation within and among species is essential. We compare the diversity and composition of two avian species that share the same habitat and niche in our study area, the western screech-owl (Megascops kennicottii) and the whiskered screech-owl (M. trichopsis). We used a targeted 16S sequencing method to improve the taxonomic resolution of microbiomes. We found similar measures of alpha diversity between species and sample types (cloacal samples vs. fecal samples). However, there were significant differences in bacterial species richness among nestlings from different nest boxes, and the composition differed between the two bird species and among nestlings from different nest boxes. Western screech-owls had more variation in alpha diversity and composition and had fewer bacterial species in their core microbiome than whiskered screech-owls. Siblings are likely to yield similar findings for microbiomes; thus, sampling nestlings from different nests may be most informative for monitoring population-level changes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Nomenclatural issues concerning cultured yeasts and other fungi: why it is important to avoid unneeded name changes

The unambiguous application of fungal names is important to communicate scientific findings. Names are critical for (clinical) diagnostics, legal compliance, and regulatory controls, such as biosafety, food security, quarantine regulations, and industrial applications. Consequently, the stability of the taxonomic system and the traceability of nomenclatural changes is crucial for a broad range of users and taxonomists. The unambiguous application of names is assured by the preservation of nomenclatural history and the physical organisms representing a name. Fungi are extremely diverse in terms of ecology, lifestyle, and methods of study. Predominantly unicellular fungi known as yeasts are usually investigated as living cultures. Methods to characterize yeasts include physiological (growth) tests and experiments to induce a sexual morph; both methods require viable cultures. Thus, the preservation and availability of viable reference cultures are important, and cultures representing reference material are cited in species descriptions. Historical surveys revealed drawbacks and inconsistencies between past practices and modern requirements as stated in the International Code of Nomenclature for Algae, Fungi, and Plants (ICNafp). Improper typification of yeasts is a common problem, resulting in a large number invalid yeast species names. With this opinion letter, we address the problem that culturable microorganisms, notably some fungi and algae, require specific provisions under the ICNafp. We use yeasts as a prominent example of fungi known from cultures. But viable type material is important not only for yeasts, but also for other cultivable Fungi that are characterized by particular morphological structures (a specific type of spores), growth properties, and secondary metabolites. We summarize potential proposals which, in our opinion, will improve the stability of fungal names, in particular by protecting those names for which the reference material can be traced back to the original isolate.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Integration of Biorelevant Pediatric Dissolution Methodology into PBPK Modeling to Predict In Vivo Performance and Bioequivalence of Generic Drugs in Pediatric Populations: a Carbamazepine Case Study

This study investigated the impact of gastro-intestinal fluid volume and bile salt (BS) concentration on the dissolution of carbamazepine (CBZ) immediate release (IR) 100 mg tablets and to integrate these in vitro biorelevant dissolution profiles into physiologically based pharmacokinetic modelling (PBPK) in pediatric and adult populations to determine the biopredictive dissolution profile. Dissolution profiles of CBZ IR tablets (100 mg) were generated in 50–900 mL biorelevant adult fasted state simulated gastric and intestinal fluid (Ad-FaSSGF and Ad-FaSSIF), also in three alternative compositions of biorelevant pediatric FaSSGF and FaSSIF medias at 200 mL. This study found that CBZ dissolution was poorly sensitive to changes in the composition of the biorelevant media, where dissimilar dissolution (F2 = 46.2) was only observed when the BS concentration was changed from 3000 to 89 μM (Ad-FaSSIF vs Ped-FaSSIF 50% 14 BS). PBPK modeling demonstrated the most predictive dissolution volume and media composition to forecast the PK was 500 mL of Ad-FaSSGF/Ad-FaSSIF media for adults and 200 mL Ped-FaSSGF/FaSSIF media for pediatrics. A virtual bioequivalence simulation was conducted by using Ad-FaSSGF and/or Ad-FaSSIF 500 mL or Ped-FaSSGF and/or Ped-FaSSIF 200 mL dissolution data for CBZ 100 mg (reference and generic test) IR product. The CBZ PBPK models showed bioequivalence of the product. This study demonstrates that the integration of biorelevant dissolution data can predict the PK profile of a poorly soluble drug in both populations. Further work using more pediatric drug products is needed to verify biorelevant dissolution data to predict the in vivo performance in pediatrics.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Organogenetic transcriptomes of the Drosophila embryo at single cell resolution

To gain insight into the transcription programs activated during the formation of Drosophila larval structures, we carried out single cell RNA sequencing during two periods of Drosophila embryogenesis: stages 10-12, when most organs are first specified and initiate morphological and physiological specialization; and stages 13-16, when organs achieve their final mature architectures and begin to function. Our data confirm previous findings with regards to functional specialization of some organs – the salivary gland and trachea – and clarify the embryonic functions of another – the plasmatocytes. We also identify two early developmental trajectories in germ cells and uncover a potential role for proteolysis during germline stem cell specialization. We identify the likely cell type of origin for key components of the Drosophila matrisome and several commonly used Drosophila embryonic cell culture lines. Finally, we compare our findings with other recent related studies and with other modalities for identifying tissue-specific gene expression patterns. These data provide a useful community resource for identifying many new players in tissue-specific morphogenesis and functional specialization of developing organs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Metabolic Costs of Walking with Weighted Vests

ABSTRACT Introduction The US Army Load Carriage Decision Aid (LCDA) metabolic model is used by militaries across the globe and is intended to predict physiological responses, specifically metabolic costs, in a wide range of dismounted warfighter operations. However, the LCDA has yet to be adapted for vest-borne load carriage, which is commonplace in tactical populations, and differs in energetic costs to backpacking and other forms of load carriage. Purpose The purpose of this study is to develop and validate a metabolic model term that accurately estimates the effect of weighted vest loads on standing and walking metabolic rate for military mission-planning and general applications. Methods Twenty healthy, physically active military-age adults (4 women, 16 men; age, 26 ± 8 yr old; height, 1.74 ± 0.09 m; body mass, 81 ± 16 kg) walked for 6 to 21 min with four levels of weighted vest loading (0 to 66% body mass) at up to 11 treadmill speeds (0.45 to 1.97 m·s −1 ). Using indirect calorimetry measurements, we derived a new model term for estimating metabolic rate when carrying vest-borne loads. Model estimates were evaluated internally byk-fold cross-validation and externally against 12 reference datasets (264 total participants). We tested if the 90% confidence interval of the mean paired difference was within equivalence limits equal to 10% of the measured walking metabolic rate. Estimation accuracy, precision, and level of agreement were also evaluated by the bias, standard deviation of paired differences, and concordance correlation coefficient (CCC), respectively. Results Metabolic rate estimates using the new weighted vest term were statistically equivalent (P< 0.01) to measured values in the current study (bias, −0.01 ± 0.54 W·kg −1 ; CCC, 0.973) as well as from the 12 reference datasets (bias, −0.16 ± 0.59 W·kg −1 ; CCC, 0.963). Conclusions The updated LCDA metabolic model calculates accurate predictions of metabolic rate when carrying heavy backpack and vest-borne loads. Tactical populations and recreational athletes that train with weighted vests can confidently use the simplified LCDA metabolic calculator provided as Supplemental Digital Content to estimate metabolic rates for work/rest guidance, training periodization, and nutritional interventions.

Sport Sciences↗
DOE OSTI2021

Data from Managing Flowering Time in Miscanthus and Sugarcane to Facilitate Intra- and Intergeneric Crosses

Miscanthus is a close relative of saccharum and a potentially valuable genetic resource for improving sugarcane. Differences in flowering time within and between miscanthus and saccharum hinders intra- and interspecific hybridizations. A series of greenhouse experiments were conducted over three years to determine how to synchronize flowering time of saccharum and miscanthus genotypes. We found that day length was an important factor influencing when miscanthus and saccharum flowered. Sugarcane could be induced to flower in a central Illinois greenhouse using supplemental lighting to reduce the rate at which days shortened during the autumn and winter to 1 min d-1, which allowed us to synchronize the flowering of some sugarcane genotypes with Miscanthus genotypes primarily from low latitudes. In a complementary growth chamber experiment, we evaluated 33 miscanthus genotypes, including 28 M. sinensis , 2 M. floridulus , and 3 M. ×giganteus collected from 20.9° S to 44.9° N for response to three day lengths (10 h, 12.5 h, and 15 h). High latitude-adapted M. sinensis flowered mainly under 15 h days, but unexpectedly, short days resulted in short, stocky plants that did not flower; in some cases, flag leaves developed under short days but heading did not occur. In contrast, for M. sinensis and M. floridulus from low latitudes, shorter day lengths typically resulted in earlier flowering, and for some low latitude genotypes, 15 h days resulted in no flowering. However, the highest ratio of reproductive shoots to total number of culms was typically observed for 12.5 h or 15 h days. Latitude of origin was significantly associated with culm length, and the shorter the days, the stronger the relationship. Nearly all entries achieved maximal culm length under the 15 h treatment, but the nearer to the equator an accession originated, the less of a difference in culm length between the short-day treatments and the 15 h day treatment. Under short days, short culms for high-latitude accessions was achieved by different physiological mechanisms for M. sinensis genetic groups from the mainland in comparison to those from Japan; for mainland accessions, the mechanism was reduced internode length, whereas for Japanese accessions the phyllochron under short days was greater than under long days. Thus, for M. sinensis , short days typically hastened floral induction, consistent with the expectations for a facultative short-day plant. However, for high latitude accessions of M. sinensis , days less than 12.5 h also signaled that plants should prepare for winter by producing many short culms with limited elongation and development; moreover, this response was also epistatic to flowering. Thus, to flower M. sinensis that originates from high latitudes synchronously with sugarcane, the former needs day lengths >12.5 h (perhaps as high as 15 h), whereas that the latter needs day lengths <12.5 h.

Feedstock Production↗
DOE OSTI2022

Data for System Analysis of Lipomyces starkeyi During Growth on Various Plant‑Based Sugars

Oleaginous yeasts have received significant attention due to their substantial lipid storage capability. The accumulated lipids can be utilized directly or processed into various bioproducts and biofuels. Lipomyces starkeyi is an oleaginous yeast capable of using multiple plant-based sugars, such as glucose, xylose, and cellobiose. It is, however, a relatively unexplored yeast due to limited knowledge about its physiology. In this study, we have evaluated the growth of L. starkeyi on different sugars and performed transcriptomic and metabolomic analyses to understand the underlying mechanisms of sugar metabolism. Principal component analysis showed clear differences resulting from growth on different sugars. We have further reported various metabolic pathways activated during growth on these sugars. We also observed non-specific regulation in L. starkeyi and have updated the gene annotations for the NRRL Y-11557 strain. This analysis provides a foundation for understanding the metabolism of these plant-based sugars and potentially valuable information to guide the metabolic engineering of L. starkeyi to produce bioproducts and biofuels.

Conversion↗
DOE OSTI2021

Data for Integrating Transcriptomic and Metabolomic Analysis of the Oleaginous Yeast Rhodosporidium toruloides IFO0880 During Growth under Different Carbon Sources

Rhodosporidium toruloides is an oleaginous yeast capable of producing a variety of biofuels and bioproducts from diverse carbon sources. Despite numerous studies showing its promise as a platform microorganism, little is known about its metabolism and physiology. In this work, we investigated the central carbon metabolism in R. toruloides IFO0880 using transcriptomics and metabolomics during growth on glucose, xylose, acetate, or soybean oil. These substrates were chosen because they can be derived from plants. Significant changes in gene expression and metabolite concentrations were observed during growth on these four substrates. We mapped these changes onto the governing metabolic pathways to better understand how R. toruloides reprograms its metabolism to enable growth on these substrates. One notable finding concerns xylose metabolism, where poor expression of xylulokinase induces a bypass leading to arabitol production. Collectively, these results further our understanding of central carbon metabolism in R. toruloides during growth on different substrates. They may also help guide the metabolic engineering and development of better models of metabolism for R. toruloides .

Conversion↗
DOE OSTI2026

Data for "High-resolution microCT reveals relationships between stomata and interior leaf anatomy in Sorghum"

Includes three different types of stacks, in two folders: "REC_RAW_STACKS.zip" contains: (1) Raw gray-scale reconstructed microCT x-ray scans, in the form of individual stacks per sample. "ML_STACKS.zip" contains: (2) Stacks that have been labeled using a machine-learning mask-RCNN pipeline identifying epidermis, mesophyll, airspace, vascular bundle, and background. (3) Stacks that have stomata locations labeled using a small point. The three types of stacks were used to calculate a variety of anatomical and physiological traits, using ImageJ Macros provided on Github: https://github.com/leakey-lab/microCT-Macros-Fischer. Young leaves from WT and transgenic Sorghum plants. CSV "microCT_REC2_META.csv" contains metadata, including sample/sub-sample labels.

3D↗
DOE OSTI2022

Data for The Leaf Economics Spectrum of Triploid and Tetraploid C4 Grass Miscanthus x giganteus

The leaf economics spectrum (LES) describes multivariate correlations in leaf structural, physiological and chemical traits, originally based on diverse C3 species grown under natural ecosystems. However, the specific contribution of C4 species to the global LES is studied less widely. C4 species have a CO2 concentrating mechanism which drives high rates of photosynthesis and improves resource use efficiency, thus potentially pushing them towards the edge of the LES. Here, we measured foliage morphology, structure, photosynthesis, and nutrient content for hundreds of genotypes of the C4 grass Miscanthus × giganteus grown in two common gardens over two seasons. We show substantial trait variations across M. × giganteus genotypes and robust genotypic trait relationships. Compared to the global LES, M. × giganteus genotypes had higher photosynthetic rates, lower stomatal conductance, and less nitrogen content, indicating greater water and photosynthetic nitrogen use efficiency in the C4 species. Additionally, tetraploid genotypes produced thicker leaves with greater leaf mass per area and lower leaf density than triploid genotypes. By expanding the LES relationships across C3 species to include C4 crops, these findings highlight that M. × giganteus occupies the boundary of the global LES and suggest the potential for ploidy to alter LES traits.

Biomass Analytics↗
DOE OSTI2023

Data for Controlling Circuitry Underlies the Growth Optimization of Saccharomyces cerevisiae

Microbial growth emerges from coordinated synthesis of various cellular components from limited resources. In Saccharomyces cerevisiae , cyclic AMP (cAMP)-mediated signaling is shown to orchestrate cellular metabolism; however, it remains unclear quantitatively how the controlling circuit drives resource partition and subsequently shapes biomass growth. Here we combined experiment with mathematical modeling to dissect the signaling-mediated growth optimization of S. cerevisiae . We showed that, through cAMP-mediated control, the organism achieves maximal or nearly maximal steady-state growth during the utilization of multiple tested substrates as well as under perturbations impairing glucose uptake. However, the optimal cAMP concentration varies across cases, suggesting that different modes of resource allocation are adopted for varied conditions. Under settings with nutrient alterations, S. cerevisiae tunes its cAMP level to dynamically reprogram itself to realize rapid adaptation. Moreover, to achieve growth maximization, cells employ additional regulatory systems such as the GCN2-mediated amino acid control. This study establishes a systematic understanding of global resource allocation in S. cerevisiae , providing insights into quantitative yeast physiology as well as metabolic strain engineering for biotechnological applications.

Conversion↗
DOE OSTI2023

Data for Determining Mating Type and Ploidy in Rhodotorula toruloides and its Effect on Growth on Sugars from Lignocellulosic Biomass

Rhodotorula toruloides is being developed for the use in industrial biotechnology processes because of its favorable physiology. This includes its ability to produce and store large amounts of lipids in the form of intracellular lipid bodies. Nineteen strains were characterized for mating type, ploidy, robustness for growth, and accumulation of lipids on inhibitory switchgrass hydrolysate (SGH). Mating type was determined using a novel polymerase chain reaction (PCR)-based assay, which was validated using the classical microscopic test. Three of the strains were heterozygous for mating type (A1/A2). Ploidy analysis revealed a complex pattern. Two strains were triploid, eight haploid, and eight either diploid or aneuploid. Two of the A1/A2 strains were compared to their parents for growth on 75%v/v concentrated SGH. The A1/A2 strains were much more robust than the parental strains, which either did not grow or had extended lag times. The entire set was evaluated in 60%v/v SGH batch cultures for growth kinetics and biomass and lipid production. Lipid titers were 2.33–9.40 g/L with a median of 6.12 g/L, excluding the two strains that did not grow. Lipid yields were 0.032–0.131 (g/g) and lipid contents were 13.5–53.7% (g/g). Four strains had significantly higher lipid yields and contents. One of these strains, which had among the highest lipid yield in this study (0.131 ± 0.007 g/g), has not been previously described in the literature.

Conversion↗
DOE OSTI2023

Supporting information for Few-Shot Learning Enables Population-Scale Analysis of Leaf Traits in Populus trichocarpa

In this work, we use few-shot learning to segment the body and vein architecture of P. trichocarpa leaves from high-resolution scans obtained in the UC Davis common garden. Leaf and vein segmentation are formulated as separate tasks, in which convolutional neural networks (CNNs) are used to iteratively expand partial segmentations until reaching stopping criteria. Our leaf and vein segmentation approaches use just 50 and 8 manually traced images for training, respectively, and are applied to a set of 2,634 top and bottom leaf scans. We show that both methods achieve high segmentation accuracy, in some cases exceeding even human-level segmentation. The leaf and vein segmentations are subsequently used to extract 68 morphological traits using traditional open-source image processing tools, which are validated using real-world physical measurements. For a biological perspective, we perform a genome-wide association study using the vein density trait to discover novel genetic architectures associated with multiple physiological processes relating to leaf development and function. In addition to sharing all of the few-shot learning code (see https://github.com/jlager/few-shot-leaf-segmentation), we are releasing all images, manual segmentations, model predictions, 68 extracted leaf phenotypes, and a new set of SNPs called against the v4 P. trichocarpa genome for 1,419 genotypes. The data folder includes all images, ground truth segmentations, predicted segmentations, and extracted leaf traits. All images encode the sample ID in the file name by indicating the treatment, block, row, position, and leaf side, respectively. For example, the file, C_1_1_2_bot.jpeg, indicates the control treatment, block 1, row 1, position 2, and the bottom side of the leaf. Tabulated results include position IDs as well as the corresponding genotype IDs. The images folder includes the 2,906 high-resolution leaf scans taken in the field. The leaf_masks folder includes 50 ground truth segmentations used for training the leaf tracing algorithm. The leaf_preds folder includes the 2,906 predicted segmentations from the leaf tracing algorithm. The vein_masks folder includes 8 ground truth segmentations used for training the vein growing algorithm. The vein_preds folder includes the 1,453 predicted segmentations from the vein growing algorithm. The vein_probs folder includes the 1,453 predicted probability maps from the vein growing algorithm before thresholding. The genomes folder includes the set of SNPs called against the v4 P. trichocarpa genome for 1,419 genotypes with a README file detailing the steps taken. The results folder includes: (i) raw values of the 68 predicted leaf traits in digital_traits.tsv, (ii) manually measured values of petiole length and width in manual_traits.tsv, (iii) thin plate spline (TPS) adjusted values of the vein density trait in vein_density_tps_adj.tsv, (iv) best linear unbiased prediction (BLUP) adjusted values of the vein density trait in vein_density_blups.tsv, and (v) GWAS results for the vein density trait, including chromosome positions and corresponding P values, in gwas_results.csv.

09 BIOMASS FUELS↗
DOE OSTI2020

Better together: Elements of successful scientific software development in a distributed collaborative community

Many scientific disciplines rely on computational methods for data analysis, model generation, and prediction. Implementing these methods is often accomplished by researchers with domain expertise but without formal training in software engineering or computer science. This arrangement has led to underappreciation of sustainability and maintainability of scientific software tools developed in academic environments. Some software tools have avoided this fate, including the scientific library Rosetta. We use this software and its community as a case study to show how modern software development can be accomplished successfully, irrespective of subject area. Rosetta is one of the largest software suites for macromolecular modeling, with 3.1 million lines of code and many state-of-the-art applications. Since the mid 1990s, the software has been developed collaboratively by the RosettaCommons, a community of academics from over 60 institutions worldwide with diverse backgrounds including chemistry, biology, physiology, physics, engineering, mathematics, and computer science. Developing this software suite has provided us with more than two decades of experience in how to effectively develop advanced scientific software in a global community with hundreds of contributors. Here we illustrate the functioning of this development community by addressing technical aspects (like version control, testing, and maintenance), community-building strategies, diversity efforts, software dissemination, and user support. We demonstrate how modern computational research can thrive in a distributed collaborative community. The practices described here are independent of subject area and can be readily adopted by other software development communities

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2023

The genome-scale metabolic model for the purple non-sulfur bacterium Rhodopseudomonas palustris Bis A53 accurately predicts phenotypes under chemoheterotrophic, chemoautotrophic, photoheterotrophic, and photoautotrophic growth conditions

The purple non-sulfur bacterium Rhodopseudomonas palustris is recognized as a critical microorganism in the nitrogen and carbon cycle and one of the most common members in wastewater treatment communities. This bacterium is metabolically extremely versatile. It is capable of heterotrophic growth under aerobic and anaerobic conditions, but also able to grow photoautotrophically as well as mixotrophically. Therefore R . palustris can adapt to multiple environments and establish commensal relationships with other organisms, expressing various enzymes supporting degradation of amino acids, carbohydrates, nucleotides, and complex polymers. Moreover, R . palustris can degrade a wide range of pollutants under anaerobic conditions, e.g., aromatic compounds such as benzoate and caffeate, enabling it to thrive in chemically contaminated environments. However, many metabolic mechanisms employed by R . palustris to breakdown and assimilate different carbon and nitrogen sources under chemoheterotrophic or photoheterotrophic conditions remain unknown. Systems biology approaches, such as metabolic modeling, have been employed extensively to unravel complex mechanisms of metabolism. Previously, metabolic models have been reconstructed to study selected capabilities of R . palustris under limited experimental conditions. Here, we developed a comprehensive metabolic model (M-model) for R . palustris Bis A53 ( i DT1294) consisting of 2,721 reactions, 2,123 metabolites, and comprising 1,294 genes. We validated the model using high-throughput phenotypic, physiological, and kinetic data, testing over 350 growth conditions. i DT1294 achieved a prediction accuracy of 90% for growth with various carbon and nitrogen sources and close to 80% for assimilation of aromatic compounds. Moreover, the M-model accurately predicts dynamic changes of growth and substrate consumption rates over time under nine chemoheterotrophic conditions and demonstrated high precision in predicting metabolic changes between photoheterotrophic and photoautotrophic conditions. This comprehensive M-model will help to elucidate metabolic processes associated with the assimilation of multiple carbon and nitrogen sources, anoxygenic photosynthesis, aromatic compound degradation, as well as production of molecular hydrogen and polyhydroxybutyrate.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B

Chronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound frequently occurs following treatment interruption. Consequently, functional cure rates of chronic HBV infection remain low and there is increased interest in a novel treatment modality, capsid assembly modulators (CAMs). Here, we develop a multiscale mathematical model of CAM treatment in chronic HBV infection. By fitting the model to participant data from a phase I trial of the first-generation CAM vebicorvir, we estimate the drug’s dose-dependent effectiveness and identify the physiological mechanisms that drive the observed biphasic decline in HBV DNA and RNA, and mechanistic differences between HBeAg-positive and negative infection. Finally, we demonstrate analytically and numerically that the relative change of HBV RNA more accurately reflects the antiviral effectiveness of a CAM than the relative change in HBV DNA.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Redox poise in R. rubrum phototrophic growth drives large-scale changes in macromolecular pathways

During photoheterotrophic growth on organic substrates, purple nonsulfur photosynthetic bacteria like Rhodospirillum rubrum can acquire electrons by multiple means, including oxidation of organic substrates, oxidation of inorganic electron donors (e.g., H 2 ), and by reverse electron flow from the photosynthetic electron transport chain. These electrons are stored as reduced electron-carrying cofactors (e.g., NAD(P)H and ferredoxin). The overall ratio of oxidized to reduced cofactors (e.g., NAD(P)+:NAD(P)H), or ’redox poise’, is difficult to understand or predict, as are the cellular processes for dissipating these reducing equivalents. Using physics-based models that capture mass action kinetics consistent with the thermodynamics of reactions and pathways, a range of redox conditions for heterophototrophic growth are evaluated, from conditions in which the NADP+/NADPH levels approach thermodynamic equilibrium to conditions in which the NADP+/NADPH ratio is far above the typical physiological values. Modeling predictions together with experimental measurements indicate that the redox poise of the cell results in large-scale changes in the activity of biosynthetic pathways and, thus, changes in cell macromolecule levels (DNA, RNA, proteins, and fatty acids). Furthermore, modeling predictions indicate that during phototrophic growth, reverse electron flow from the quinone pool is a minor contributor to the production of reduced cofactors (e.g., NAD(P)H) compared to other oxidative processes (H 2 and carbon substrate oxidation). Instead, the quinone pool primarily operates to aid ATP production. The high level of ATP, in turn, drives reduction processes even when NADPH levels are relatively low compared to NADP+ by coupling ATP hydrolysis to the reductive processes. The model, in agreement with experimental measurements of macromolecule ratios of cells growing on different carbon substrates, indicates that the dynamics of nucleotide versus lipid and protein production is likely a significant mechanism of balancing oxidation and reduction in the cell.

59 BASIC BIOLOGICAL SCIENCES↗