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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 325 records · Page 18
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Delivering Robust Proton-Only Sensing of Hyperpolarized [1,2- 13 C 2 ]-Pyruvate Using Broad-Spectral-Range Nuclear Magnetic Resonance Pulse Sequences

Hyperpolarized [1- 13 C]pyruvate is the leading hyperpolarized injectable contrast agent and is currently under evaluation in clinical trials for molecular imaging of metabolic diseases, including cardiovascular disease and cancer. One aspect limiting broad scalability of the technique is that hyperpolarized 13 C MRI requires specialized 13 C hardware and software that are not generally available on clinical MRI scanners, which employ proton-only detection. Here, we present an approach that uses pulse sequences to transfer 13 C hyperpolarization to methyl protons for detection of the 13 C– 13 C pyruvate singlet, employing proton-only excitation and detection only. The new pulse sequences are robust to the B 1 and B 0 magnetic field inhomogeneities. The work focuses on singlet-to-magnetization (S2M) and rotor-synchronized (R) pulses, both relying on trains of hard pulses with broad spectral width coverage designed to effectively transform hyperpolarized 13 C 2 -singlet hyperpolarization to 1 H polarization on the CH 3 group of [1,2- 13 C 2 ]pyruvate. Finally, this approach may enable a broader adoption of hyperpolarized MRI as a molecular imaging technique.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2026

Hierarchical Chiral Self-Assembly of Nanocylinders Composed of Sequence-Defined Mesogenic Dimers

Chiral ensembles can arise through supramolecular curvature that resolves geometric frustrations in the packing of bent, achiral molecular or colloidal building blocks. Here, we leverage orthogonal protection−deprotection click chemistry to create sequence-defined mesogenic heterodimers exhibiting emergent chirality. We compare the hierarchical self-assembly of the synthesized asymmetric, achiral heterodimers, which differ only in the position of a methyl substituent. Both dimers form chiral spherulites composed of nanocylinders. However, the detailed arrangement of nanocylinders depends on the position of the methyl substituent and the crystallization conditions. Despite the chemical similarity, in one dimer, two crystalline forms are optically active. They form conglomerates of dextrorotatory and levorotatory spherulites. The other dimer forms more highly anisotropic spherulites that mask circular birefringence arising from the misorientation of nanocylinders, while mapping of nanocylinder directors reveals a sense at the spherulite surface. We propose that differences in nanocylinder arrangements may arise from changes in nanocylinder curvature and dimensions dictated by the methyl substituent position, inducing chirality. These results demonstrate multiscale hierarchical assembly relevant to dense systems of tubular structures and highlight the role of sequence and molecular design in directing the bottom-up hierarchical self-assembly and chirality of mesogenic systems.

Alkyls↗
DOE OSTI2021

The Relationship Between Topography, Bedrock Weathering, and Water Storage Across a Sequence of Ridges and Valleys

Abstract Bedrock weathering regulates nutrient mobilization, water storage, and soil production. Relative to the mobile soil layer, little is known about the relationship between topography and bedrock weathering. Here, we identify a common pattern of weathering and water storage across a sequence of three ridges and valleys in the sedimentary Great Valley Sequence in Northern California that share a tectonic and climate history. Deep drilling, downhole logging, and characterization of chemistry and porosity reveal two weathering fronts. The shallower front is ∼7 m deep at the ridge of all three hillslopes, and marks the extent of pervasive fracturing and oxidation of pyrite and organic carbon. A deeper weathering front marks the extent of open fractures and discoloration. This front is 11 m deep under two ridges of similar ridge‐valley spacing, but 17.5 m deep under a ridge with nearly twice the ridge‐valley spacing. Hence, at ridge tops, the fraction of the hillslope relief that is weathered scales with hillslope length. In all three hillslopes, below this second weathering front, closed fractures and unweathered bedrock extend about one‐half the hilltop elevation above the adjacent channels. Neutron probe surveys reveal that seasonally dynamic moisture is stored to approximately the same depth as the shallow weathering front. Under the channels that bound our study hillslopes, the two weathering fronts coincide and occur within centimeters of the ground surface. Our findings provide evidence for feedbacks between erosion and weathering in mountainous landscapes that result in systematic subsurface structuring and water routing.

58 GEOSCIENCES↗
DOE OSTI2022

Creep fronts and complexity in laboratory earthquake sequences illuminate delayed earthquake triggering

Earthquakes occur in clusters or sequences that arise from complex triggering mechanisms, but direct measurement of the slow subsurface slip responsible for delayed triggering is rarely possible. We investigate the origins of complexity and its relationship to heterogeneity using an experimental fault with two dominant seismic asperities. The fault is composed of quartz powder, a material common to natural faults, sandwiched between 760 mm long polymer blocks that deform the way 10 meters of rock would behave. We observe periodic repeating earthquakes that transition into aperiodic and complex sequences of fast and slow events. Neighboring earthquakes communicate via migrating slow slip, which resembles creep fronts observed in numerical simulations and on tectonic faults. Utilizing both local stress measurements and numerical simulations, we observe that the speed and strength of creep fronts are highly sensitive to fault stress levels left behind by previous earthquakes, and may serve as on-fault stress meters.

58 GEOSCIENCES↗
DOE OSTI2025

Design of diverse, functional mitochondrial targeting sequences across eukaryotic organisms using variational autoencoder

Mitochondria play a key role in energy production and metabolism, making them a promising target for metabolic engineering and disease treatment. However, despite the known influence of passenger proteins on localization efficiency, only a few protein-localization tags have been characterized for mitochondrial targeting. To address this limitation, we leverage a Variational Autoencoder to design novel mitochondrial targeting sequences. In silico analysis reveals that a high fraction of the generated peptides (90.14%) are functional and possess features important for mitochondrial targeting. We characterize artificial peptides in four eukaryotic organisms and, as a proof-of-concept, demonstrate their utility in increasing 3-hydroxypropionic acid titers through pathway compartmentalization and improving 5-aminolevulinate synthase delivery by 1.62-fold and 4.76-fold, respectively. Moreover, we employ latent space interpolation to shed light on the evolutionary origins of dual-targeting sequences. Overall, our work demonstrates the potential of generative artificial intelligence for both fundamental research and practical applications in mitochondrial biology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Perfect and imperfect views of ultraconserved sequences

Across the human genome, there are nearly 500 'ultraconserved' elements: regions of at least 200 contiguous nucleotides that are perfectly conserved in both the mouse and rat genomes. Remarkably, the majority of these sequences are non-coding, and many can function as enhancers that activate tissue-specific gene expression during embryonic development. From their first description more than 15 years ago, their extreme conservation has both fascinated and perplexed researchers in genomics and evolutionary biology. The intrigue around ultraconserved elements only grew with the observation that they are dispensable for viability. Here, in this paper, we review recent progress towards understanding the general importance and the specific functions of ultraconserved sequences in mammalian development and human disease and discuss possible explanations for their extreme conservation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Ultraconserved enhancer function does not require perfect sequence conservation

Ultraconserved enhancer sequences show perfect conservation between human and rodent genomes, suggesting that their functions are highly sensitive to mutation. However, current models of enhancer function do not sufficiently explain this extreme evolutionary constraint. We subjected 23 ultraconserved enhancers to different levels of mutagenesis, collectively introducing 1,547 mutations, and examined their activities in transgenic mouse reporter assays. Overall, we find that the regulatory properties of ultraconserved enhancers are robust to mutation. Upon mutagenesis, nearly all (19/23, 83%) still functioned as enhancers at one developmental stage, as did most of those tested again later in development (5/9, 56%). Replacement of endogenous enhancers with mutated alleles in mice corroborated results of transgenic assays, including the functional resilience of ultraconserved enhancers to mutation. Furthermore, our findings show that the currently known activities of ultraconserved enhancers do not necessarily require the perfect conservation observed in evolution and suggest that additional regulatory or other functions contribute to their sequence constraint.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Genome sequencing of Rigidoporus microporus provides insights on genes important for wood decay, latex tolerance and interspecific fungal interactions

Fungal plant pathogens remain a serious threat to the sustainable agriculture and forestry, despite the extensive efforts undertaken to control their spread. White root rot disease is threatening rubber tree (Hevea brasiliensis) plantations throughout South and Southeast Asia and Western Africa, causing tree mortality and severe yield losses. Here, we report the complete genome sequence of the basidiomycete fungus Rigidoporus microporus, a causative agent of the disease. Our phylogenetic analysis confirmed the position of R. microporus among the members of Hymenochaetales, an understudied group of basidiomycetes. Our analysis further identified pathogen's genes with a predicted role in the decay of plant cell wall polymers, in the utilization of latex components and in interspecific interactions between the pathogen and other fungi. We also detected putative horizontal gene transfer events in the genome of R. microporus. The reported first genome sequence of a tropical rubber tree pathogen R. microporus should contribute to the better understanding of how the fungus is able to facilitate wood decay and nutrient cycling as well as tolerate latex and utilize resinous extractives.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Ni-catalysed dicarbofunctionalization for the synthesis of sequence-encoded cyclooctene monomers

The properties of polymeric materials can be modulated by factors such as sequence control or functional group modifications. However, the synthesis of new macromolecular scaffolds is limited by the accessibility of structurally diverse monomers. This work describes a one-step, nickel-catalysed synthesis of 5,6-diaryl cyclooctene monomers from the feedstock chemical 1,5-cyclooctadiene. The reaction proceeds in a modular, regio- and diastereoselective fashion, granting access to both homo- and hetero-diaryl cyclooctene monomers that smoothly undergo ring-opening metathesis polymerization (ROMP). The resulting 1,2-diaryl-substituted polymers possess sequences with head-to-head styrene dyads that have not been previously explored, giving rise to unique and tunable properties. Density functional theory calculations highlight mechanistic aspects of the nickel-catalysed diarylation reaction and the ruthenium-catalysed ROMP process, revealing a previously unappreciated role of the boronic ester in promoting migratory insertion, which was leveraged to provide enantioinduction.

Catalytic mechanisms↗
DOE OSTI2026

ALS mutations disrupt self-association between the ubiquilin STI1 hydrophobic groove and internal placeholder sequences

Ubiquilins are molecular chaperones that play multifaceted roles in proteostasis, with point mutations in UBQLN2 leading to altered phase-separation properties and amyotrophic lateral sclerosis (ALS). Our mechanistic understanding of this essential process has been hindered by a lack of structural information on the STI1 domain, which is essential for ubiquilin chaperone activity and phase separation. Here, we present the first crystal structure of a ubiquilin-family STI1 domain bound to a transmembrane domain (TMD), and show that ALS mutations disrupt the STI1-TMD interaction. We further demonstrate that ubiquilins contain multiple conserved internal sequences that bind to the STI1 domain, including the PXX-repeat region that is a hotspot for ALS mutations. We propose that these placeholder sequences prevent solvent exposure of the STI1 hydrophobic groove and contribute to the multivalency that drives ubiquilin phase-separation. Together, this work provides a new paradigm for understanding how STI1 domains modulate ubiquilin chaperone activity and phase separation, and offers insights into the molecular basis of ALS pathogenesis.

Onwunma, Joan [Univ. of Toledo, OH (United States)↗
DOE OSTI2020

DNA origami protection and molecular interfacing through engineered sequence-defined peptoids

DNA nanotechnology has established approaches for designing programmable and precisely controlled nanoscale architectures through specific Watson−Crick base-pairing, molecular plasticity, and intermolecular connectivity. In particular, superior control over DNA origami structures could be beneficial for biomedical applications, including biosensing, in vivo imaging, and drug and gene delivery. However, protecting DNA origami structures in complex biological fluids while preserving their structural characteristics remains a major challenge for enabling these applications. Here, we developed a class of structurally well-defined peptoids to protect DNA origamis in ionic and bioactive conditions and systematically explored the effects of peptoid architecture and sequence dependency on DNA origami stability. The applicability of this approach for drug delivery, bioimaging, and cell targeting was also demonstrated. A series of peptoids (PE1–9) with two types of architectures, termed as “brush” and “block,” were built from positively charged monomers and neutral oligo-ethyleneoxy monomers, where certain designs were found to greatly enhance the stability of DNA origami. Through experimental and molecular dynamics studies, we demonstrated the role of sequence-dependent electrostatic interactions of peptoids with the DNA backbone. We showed that octahedral DNA origamis coated with peptoid (PE2) can be used as carriers for anticancer drug and protein, where the peptoid modulated the rate of drug release and prolonged protein stability against proteolytic hydrolysis. Finally, we synthesized two alkyne-modified peptoids (PE8 and PE9), conjugated with fluorophore and antibody, to make stable DNA origamis with imaging and cell-targeting capabilities. Our results demonstrate an approach toward functional and physiologically stable DNA origami for biomedical applications.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Persistent minimal sequences of SARS-CoV-2

Abstract Motivation Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 14 million cases and more than half million deaths. Given the absence of implemented therapies, new analysis, diagnosis and therapeutics are of great importance. Results Analysis of SARS-CoV-2 genomes from the current outbreak reveals the presence of short persistent DNA/RNA sequences that are absent from the human genome and transcriptome (PmRAWs). For the PmRAWs with length 12, only four exist at the same location in all SARS-CoV-2. At the gene level, we found one PmRAW of size 13 at the Spike glycoprotein coding sequence. This protein is fundamental for binding in human ACE2 and further use as an entry receptor to invade target cells. Applying protein structural prediction, we localized this PmRAW at the surface of the Spike protein, providing a potential targeted vector for diagnostics and therapeutics. In addition, we show a new pattern of relative absent words (RAWs), characterized by the progressive increase of GC content (Guanine and Cytosine) according to the decrease of RAWs length, contrarily to the virus and host genome distributions. New analysis shows the same property during the Ebola virus outbreak. At a computational level, we improved the alignment-free method to identify pathogen-specific signatures in balance with GC measures and removed previous size limitations. Availability and implementation https://github.com/cobilab/eagle. Supplementary information Supplementary data are available at Bioinformatics online.

Pratas, Diogo↗
DOE OSTI2021

Optimal Bayesian supervised domain adaptation for RNA sequencing data

Abstract Motivation When learning to subtype complex disease based on next-generation sequencing data, the amount of available data is often limited. Recent works have tried to leverage data from other domains to design better predictors in the target domain of interest with varying degrees of success. But they are either limited to the cases requiring the outcome label correspondence across domains or cannot leverage the label information at all. Moreover, the existing methods cannot usually benefit from other information available a priori such as gene interaction networks. Results In this article, we develop a generative optimal Bayesian supervised domain adaptation (OBSDA) model that can integrate RNA sequencing (RNA-Seq) data from different domains along with their labels for improving prediction accuracy in the target domain. Our model can be applied in cases where different domains share the same labels or have different ones. OBSDA is based on a hierarchical Bayesian negative binomial model with parameter factorization, for which the optimal predictor can be derived by marginalization of likelihood over the posterior of the parameters. We first provide an efficient Gibbs sampler for parameter inference in OBSDA. Then, we leverage the gene-gene network prior information and construct an informed and flexible variational family to infer the posterior distributions of model parameters. Comprehensive experiments on real-world RNA-Seq data demonstrate the superior performance of OBSDA, in terms of accuracy in identifying cancer subtypes by utilizing data from different domains. Moreover, we show that by taking advantage of the prior network information we can further improve the performance. Availability and implementation The source code for implementations of OBSDA and SI-OBSDA are available at the following link. https://github.com/SHBLK/BSDA. Supplementary information Supplementary data are available at Bioinformatics online.

Biochemistry & Molecular Biology↗
DOE OSTI2023

Whole-genome sequencing distinguishes the two most common giant kelp ecomorphs

Abstract Giant kelp, Macrocystis pyrifera, exists as distinct morphological variants—or “ecomorphs”—in different populations, yet the mechanism for this variation is uncertain, and environmental drivers for either adaptive or plastic phenotypes have not been identified. The ecomorphs Macrocystis “pyrifera” and M. “integrifolia” are distributed throughout temperate waters of North and South America with almost no geographic overlap and exhibit an incongruous, non-mirrored, distribution across the equator. This study evaluates the degree of genetic divergence between M. “pyrifera” and M. “integrifolia” across 18 populations in Chile and California using whole-genome sequencing and single-nucleotide polymorphism markers. Our results based on a principal component analysis, admixture clustering by genetic similarity, and phylogenetic inference demonstrate that M. “pyrifera” and M. “integrifolia” are genetically distinguishable. Analyses reveal separation by Northern and Southern Hemispheres and between morphs within hemispheres, suggesting that the convergent “integrifolia” morphology arose separately in each hemisphere. This is the first study to use whole-genome sequencing to understand genetic divergence in giant kelp ecomorphs, identifying 83 potential genes under selection and providing novel insights about Macrocystis evolution that were not evident with previous genetic techniques. Future studies are needed to uncover the environmental forces driving local adaptation and presumed convergent evolution of these morphs.

Environmental Sciences & Ecology↗
DOE OSTI2021

The first sequenced Sphaerotilus natans bacteriophage– characterization and potential to control its filamentous bacterium host

ABSTRACT Bacteriophages (phages) are ubiquitous entities present in every conceivable habitat as a result of their bacterial parasitism. Their prevalence and impact in the ecology of bacterial communities and their ability to control pathogens make their characterization essential, particularly of new phages, improving knowledge and potential application. The isolation and characterization of a new lytic phage against Sphaerotilus natans strain DSM 6575, named vB_SnaP-R1 (SnaR1), is here described. Besides being the first sequenced genome of a Sphaerotilus natans infecting phage, 99% of its 41507 bp genome lacks homology with any other sequenced phage, revealing its uniqueness and previous lack of knowledge. Moreover, SnaR1 is the first Podoviridae phage described infecting this bacterium. Sphaerotilus natans is an important filamentous bacterium due to its deleterious effect on wastewater treatment plants (WWTP) and thus, phages may play a role as novel biotechnological tools against filamentous overgrowth in WWTP. The lytic spectrum of SnaR1 was restricted to its host strain, infecting only one out of three S. natans strains and infection assays revealed its ability to reduce bacterial loads. Results suggest SnaR1 as the prototype of a new phage genus and demonstrates its potential as a non-chemical alternative to reduce S. natans DSM 6575 cells.

Ferreira, Rute↗
DOE OSTI2021

Barcoded reciprocal hemizygosity analysis via sequencing illuminates the complex genetic basis of yeast thermotolerance

Decades of successes in statistical genetics have revealed the molecular underpinnings of traits as they vary across individuals of a given species. But standard methods in the field cannot be applied to divergences between reproductively isolated taxa. Genome-wide reciprocal hemizygosity mapping (RH-seq), a mutagenesis screen in an interspecies hybrid background, holds promise as a method to accelerate the progress of interspecies genetics research. Here, we describe an improvement to RH-seq in which mutants harbor barcodes for cheap and straightforward sequencing after selection in a condition of interest. As a proof of concept for the new tool, we carried out genetic dissection of the difference in thermotolerance between two reproductively isolated budding yeast species. Experimental screening identified dozens of candidate loci at which variation between the species contributed to the thermotolerance trait. Hits were enriched for mitosis genes and other housekeeping factors, and among them were multiple loci with robust sequence signatures of positive selection. Together, these results shed new light on the mechanisms by which evolution solved the problems of cell survival and division at high temperature in the yeast clade, and they illustrate the power of the barcoded RH-seq approach.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Annotated genome sequence of a fast-growing diploid clone of red alder ( Alnus rubra Bong.)

Abstract Red alder (Alnus rubra Bong.) is an ecologically significant and important fast-growing commercial tree species native to western coastal and riparian regions of North America, having highly desirable wood, pigment, and medicinal properties. We have sequenced the genome of a rapidly growing clone. The assembly is nearly complete, containing the full complement of expected genes. This supports our objectives of identifying and studying genes and pathways involved in nitrogen-fixing symbiosis and those related to secondary metabolites that underlie red alder's many interesting defense, pigmentation, and wood quality traits. We established that this clone is most likely diploid and identified a set of SNPs that will have utility in future breeding and selection endeavors, as well as in ongoing population studies. We have added a well-characterized genome to others from the order Fagales. In particular, it improves significantly upon the only other published alder genome sequence, that of Alnus glutinosa. Our work initiated a detailed comparative analysis of members of the order Fagales and established some similarities with previous reports in this clade, suggesting a biased retention of certain gene functions in the vestiges of an ancient genome duplication when compared with more recent tandem duplications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Discovering methylated DNA motifs in bacterial nanopore sequencing data with MIJAMP

Abstract Bacterial DNA methylation is involved in diverse cellular functions, including modulation of gene expression, DNA repair, and restriction–modification systems for defense against viruses and other foreign DNA. Restriction systems hinder efforts to engineer organisms to produce fuels and chemicals from waste and renewable feedstocks by degrading DNA during transformation. Methylome analysis allows identification of motifs within a bacterial chromosome that may be targeted by native restriction enzymes. Further expression of the corresponding methyltransferases in Escherichia coli allows plasmid DNA to be protected from restriction in the target organism, thereby drastically enhancing transformation efficiency. Nanopore sequencing can detect methylated bases, but software is needed to transform modified base coordinates into methylated motifs. Here, we develop MIJAMP (MIJAMP Is Just A MethylBED Parser), a software package that was developed to discover methylated motifs from the output of ONT’s Modkit or other data in the methylBED format. MIJAMP employs a human-driven refinement strategy that empirically validates all motifs against genome-wide methylation data, thus eliminating incorrect motifs. MIJAMP also reports methylation data on specific, user-defined motifs. Using MIJAMP, we determined the methylated motifs both in a control strain (wild-type E. coli) and in Synecococcus sp. strain PCC7002, laying the foundation for improved transformation in this organism. MIJAMP is available at https://code.ornl.gov/alexander-public/mijamp/. One Sentence Summary: Here we describe software written to discover DNA methylation motifs from nanopore sequencing data.

59 BASIC BIOLOGICAL SCIENCES↗