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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 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Tapping the treasure trove of atypical phages

With advancements in genomics technologies, a vast diversity of ‘atypical’ phages, that is, with single-stranded DNA or RNA genomes, are being uncovered from different ecosystems. Though these efforts have revealed the existence and prevalence of these nonmodel phages, computational approaches often fail to associate these phages with their specific bacterial host(s), while the lack of methods to isolate these phages has limited our ability to characterize infectivity pathways and new gene function. In this review, we call for the development of generalizable experimental methods to better capture this understudied viral diversity via isolation and study them through gene-level characterization and engineering. Establishing a diverse set of new ‘atypical’ phage model systems has the potential to provide many new biotechnologies, including potential uses of these atypical phages in halting the spread of antibiotic resistance and engineering of microbial communities for beneficial outcomes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Mechanistic basis of atypical TERT promoter mutations

Non-coding mutations in the TERT promoter (TERTp), typically at one of two bases -124 and -146 bp upstream of the start codon, are among the most prevalent driver mutations in human cancer. Several additional recurrent TERTp mutations have been reported but their functions and origins remain largely unexplained. Here, we show that atypical TERTp mutations arise secondary to canonical TERTp mutations in a two-step process. Canonical TERTp mutations create de novo binding sites for ETS family transcription factors that induce favourable conditions for DNA damage formation by UV light, thus creating a hotspot effect but only after a first mutational hit. In agreement, atypical TERTp mutations co-occur with canonical driver mutations in large cancer cohorts and arise subclonally specifically on the TERTp driver mutant chromosome homolog of melanoma cells treated with UV light in vitro. Our study gives an in-depth view of TERTp mutations in cancer and provides a mechanistic explanation for atypical TERTp mutations.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2007

Information Display System for Atypical Flight Phase

Method and system for displaying information on one or more aircraft flights, where at least one flight is determined to have at least one atypical flight phase according to specified criteria. A flight parameter trace for an atypical phase is displayed and compared graphically with a group of traces, for the corresponding flight phase and corresponding flight parameter, for flights that do not manifest atypicality in that phase.

Statler, Irving C.↗
NASA NTRS2005

Identification of atypical flight patterns

Method and system for analyzing aircraft data, including multiple selected flight parameters for a selected phase of a selected flight, and for determining when the selected phase of the selected flight is atypical, when compared with corresponding data for the same phase for other similar flights. A flight signature is computed using continuous-valued and discrete-valued flight parameters for the selected flight parameters and is optionally compared with a statistical distribution of other observed flight signatures, yielding atypicality scores for the same phase for other similar flights. A cluster analysis is optionally applied to the flight signatures to define an optimal collection of clusters. A level of atypicality for a selected flight is estimated, based upon an index associated with the cluster analysis.

Statler, Irving C.↗
DOE OSTI2022

Interwoven atypical quantum states in CeLiBi 2

Here we report the discovery of CeLiBi 2 , the first example of a material in the tetragonal CeTX 2 ( T = transition metal; X = pnictogen) family wherein an alkali cation replaces the typical transition metal. Magnetic susceptibility and neutron powder diffraction measurements are consistent with a crystal-field Γ 6 ground-state Kramers doublet that orders antiferromagnetically below T N = 3.4 K with an incommensurate propagation wave vector k = ( 0, 0.0724(4), 0.5) that generates a nanometric modulation of the magnetic structure. The best model of the ordered state is an elliptical cycloid with Ce moments primarily residing in the ab plane. This is highly unusual, as all other Γ 6 CeTX 2 members order ferromagnetically. Further, we observe an atypical hard-axis metamagnetic transition at 2 T in magnetostriction, magnetization, and resistivity measurements. CeLiBi 2 is a rare example of a highly conductive material with dominant skew scattering leading to a large anomalous Hall effect. Quantum oscillations with five frequencies arise in magnetostriction and magnetic susceptibility data to T = 30 K and μ 0 H = 55 T, which indicate small Fermi pockets of light carriers with effective masses as low as 0.07 m e . Density functional theory calculations indicate that square-net Dirac-like Bi-p bands are responsible for these ultralight carriers. Together, our results show that CeLiBi 2 enables multiple atypical magnetic and electronic properties in a single clean material.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Short incubation periods of atypical H-type BSE in cattle with EK211 and KK211 prion protein genotypes after intracranial inoculation

In 2006, a case of atypical H-type BSE (H-BSE) was found to be associated with a germline mutation in the PRNP gene that resulted in a lysine substitution for glutamic acid at codon 211 (E211K). The E211K amino acid substitution in cattle is analogous to E200K in humans, which is associated with the development of genetic Creutzfeldt-Jakob disease (CJD). In the present study, we aimed to determine the effect of the EK211 prion protein genotype on incubation time in cattle inoculated with the agent of H-BSE; to characterize the molecular profile of H-BSE in KK211 and EK211 genotype cattle; and to assess the influence of serial passage on BSE strain. Eight cattle, representing three PRNP genotype groups (EE211, EK211, and KK211), were intracranially inoculated with the agent of H-BSE originating from either a case in a cow with the EE211 prion protein genotype or a case in a cow with E211K amino acid substitution. All inoculated animals developed clinical disease; post-mortem samples were collected, and prion disease was confirmed through enzyme immunoassay, anti-PrP Sc immunohistochemistry, and western blot. Western blot molecular analysis revealed distinct patterns in a steer with KK211 H-BSE compared to EK211 and EE211 cattle. Incubation periods were significantly shorter in cattle with the EK211 and KK211 genotypes compared to the EE211 genotype. Inoculum type did not significantly influence the incubation period. This study demonstrates a shorter incubation period for H-BSE in cattle with the K211 genotype in both the homozygous and heterozygous forms.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Carbohydrate Deacetylase Unique to Gut Microbe Bacteroides Reveals Atypical Structure

Bacteroides are often the most abundant, commensal species in the gut microbiome of industrialized human populations. One of the most commonly detected species is Bacteroides ovatus. It has been linked to benefits like the suppression of intestinal inflammation but is also correlated with some autoimmune disorders, for example irritable bowel disorder (IBD). Bacterial cell surface carbohydrates, like capsular polysaccharides (CPS), may play a role in modulating these varied host interactions. Recent studies have begun to explore the diversity of CPS loci in Bacteroides; however, there is still much unknown. Here, we present structural and functional characterization of a putative polysaccharide deacetylase from Bacteroides ovatus (BoPDA) encoded in a CPS biosynthetic locus. We solved four high resolution crystal structures (1.36-1.56 Å) of the enzyme bound to divalent cations Co 2+ , Ni 2+ , Cu 2+ , or Zn 2+ and performed carbohydrate binding and deacetylase activity assays. Structural analysis of BoPDA revealed an atypical domain architecture that is unique to this enzyme, with a carbohydrate esterase 4 (CE4) superfamily catalytic domain inserted into a carbohydrate binding module (CBM). Additionally, BoPDA lacks the canonical CE4 His-His-Asp metal binding motif and our structures show it utilizes a noncanonical His-Asp dyad to bind metal ions. BoPDA is the first protein involved in CPS biosynthesis from B. ovatus to be characterized, furthering our understanding of significant biosynthetic processes in this medically relevant gut microbe.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Evidence of Atypical Structural Flexibility of the Active Site Surrounding of an [FeFe] Hydrogenase from Clostridium beijerinkii

[FeFe] hydrogenase from Clostridium beijerinkii (CbHydA1) is an unusual hydrogenase in that it can withstand prolonged exposure to O 2 by reversibly converting into an O 2 -protected, inactive state (Hinact). It has been indicated in the past that an atypical conformation of the “SC 367 CP” loop near the [2Fe] H portion of the six-iron active site (H-cluster) allows the Cys367 residue to adopt an “off-H + -pathway” orientation, promoting a facile transition of the cofactor to Hinact. Here, we investigated the electronic structure of the H-cluster in the oxidized state (H ox ) that directly converts to Hinact under oxidizing conditions and the related CO-inhibited state (H ox -CO). We demonstrate that both states exhibit two distinct forms in electron paramagnetic resonance (EPR) spectroscopy. The ratio between the two forms is pH-dependent but also sensitive to the buffer choice. Our IR and EPR analyses illustrate that the spectral heterogeneity is due to a perturbation of the coordination environment of the H-cluster’s [4Fe4S] H subcluster without affecting the [2Fe] H subcluster. Overall, we conclude that the observation of two spectral components per state is evidence of heterogeneity of the environment of the H-cluster likely associated with conformational mobility of the SCCP loop. Such flexibility may allow Cys367 to switch rapidly between off- and on-H + -pathway rotamers. Consequently, we believe such structural mobility may be the key to maintaining high enzymatic activity while allowing a facile transition to the O 2 -protected state.

08 HYDROGEN↗
DOE OSTI2025

Low Mutation Rate and Atypical Mutation Spectrum in Prasinoderma coloniale : Insights From an Early Diverging Green Lineage

Mutations are the ultimate source of genetic diversity on which natural selection and genetic drift act, playing a crucial role in evolution and long-term adaptation. At the molecular level, the spontaneous mutation rate (µ), defined as the number of mutations per base per generation, thus determines the adaptive potential of a species. Through a mutation accumulation experiment, we estimate the mutation rate and spectrum in Prasinoderma coloniale, a phytoplankton species from an early-branching lineage within the Archaeplastida, characterized by an unusually high genomic guanine-cytosine (GC) content (69.8%). We find that P. coloniale has a very low total mutation rate of µ = 2.00 × 10 -10 . The insertion–deletion mutation rate is almost 5 times lesser than the single nucleotide mutation rate with µ ID = 3.40 × 10 -11 and µ SNM = 1.62 × 10 -10 . Prasinoderma coloniale also exhibits an atypical mutational spectrum: While essentially all other eukaryotes show a bias toward GC to AT mutations, no evidence of this AT-bias is observed in P. coloniale. Since cytosine methylation is known to be mutagenic, we hypothesized that this may result from an absence of C-methylation. Surprisingly, we found high levels of C-methylation (14% in 5mC, 25% in 5mCG contexts). Methylated cytosines did not show increased mutation rates compared with unmethylated ones, not supporting the prevailing notion that C-methylation universally leads to higher mutation rates. Overall, P. coloniale combines a GC-rich genome with a low mutation rate and original mutation spectrum, suggesting the almost universal AT-bias may not have been present in the ancestor of the green lineage.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1997

Atypical form of Alzheimer's disease with prominent posterior cortical atrophy: a review of lesion distribution and circuit disconnection in cortical visual pathways

In recent years, the existence of visual variants of Alzheimer's disease characterized by atypical clinical presentation at onset has been increasingly recognized. In many of these cases post-mortem neuropathological assessment revealed that correlations could be established between clinical symptoms and the distribution of neurodegenerative lesions. We have analyzed a series of Alzheimer's disease patients presenting with prominent visual symptomatology as a cardinal sign of the disease. In these cases, a shift in the distribution of pathological lesions was observed such that the primary visual areas and certain visual association areas within the occipito-parieto-temporal junction and posterior cingulate cortex had very high densities of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in Alzheimer's disease. Previous quantitative analyses have demonstrated that in Alzheimer's disease, primary sensory and motor cortical areas are less damaged than the multimodal association areas of the frontal and temporal lobes, as indicated by the laminar and regional distribution patterns of neurofibrillary tangles and senile plaques. The distribution of pathological lesions in the cerebral cortex of Alzheimer's disease cases with visual symptomatology revealed that specific visual association pathways were disrupted, whereas these particular connections are likely to be affected to a less severe degree in the more common form of Alzheimer's disease. These data suggest that in some cases with visual variants of Alzheimer's disease, the neurological symptomatology may be related to the loss of certain components of the cortical visual pathways, as reflected by the particular distribution of the neuropathological markers of the disease.

Review↗
NASA NTRS2006

Discovering Atypical Flights in Sequences of Discrete Flight Parameters

This paper describes the results of a novel research and development effort conducted at the NASA Ames Research Center for discovering anomalies in discrete parameter sequences recorded from flight data. Many of the discrete parameters that are recorded during the flight of a commercial airliner correspond to binary switches inside the cockpit. The inputs to our system are records from thousands of flights for a given class of aircraft and destination. The system delivers a list of potentially anomalous flights as well as reasons why the flight was tagged as anomalous. This output can be analyzed by safety experts to determine whether or not the anomalies are indicative of a problem that could be addressed with a human factors intervention. The final goal of the system is to help safety experts discover significant human factors issues such as pilot mode confusion, i.e., a flight in which a pilot has lost situational awareness as reflected in atypicality of the sequence of switches that he or she throws during descent compared to a population of similar flights. We view this work as an extension of Integrated System Health Management (ISHM) where the goal is to understand and evaluate the combined health of a class of aircraft ar a given destination.

Budalakoti, Suratna↗
NASA NTRS2006

Statistical Detection of Atypical Aircraft Flights

A computational method and software to implement the method have been developed to sift through vast quantities of digital flight data to alert human analysts to aircraft flights that are statistically atypical in ways that signify that safety may be adversely affected. On a typical day, there are tens of thousands of flights in the United States and several times that number throughout the world. Depending on the specific aircraft design, the volume of data collected by sensors and flight recorders can range from a few dozen to several thousand parameters per second during a flight. Whereas these data have long been utilized in investigating crashes, the present method is oriented toward helping to prevent crashes by enabling routine monitoring of flight operations to identify portions of flights that may be of interest with respect to safety issues.

Statler, Irving↗
DOE OSTI2023

Mechanism of RanGTP priming H2A-H2B release from Kap114 in an atypical RanGTP•Kap114•H2A-H2B complex

Previously, we showed that the nuclear import receptor Importin-9 wraps around the H2A-H2B core to chaperone and transport it from the cytoplasm to the nucleus. However, unlike most nuclear import systems where RanGTP dissociates cargoes from their importins, RanGTP binds stably to the Importin-9•H2A-H2B complex, and formation of the ternary RanGTP•Importin-9•H2A-H2B complex facilitates H2A-H2B release to the assembling nucleosome. It was unclear how RanGTP and the cargo H2A-H2B can bind simultaneously to an importin, and how interactions of the three components position H2A-H2B for release. Here, we show cryo-EM structures of Importin-9•RanGTP and of its yeast homolog Kap114, including Kap114•RanGTP, Kap114•H2A-H2B, and RanGTP•Kap114•H2A-H2B, to explain how the conserved Kap114 binds H2A-H2B and RanGTP simultaneously and how the GTPase primes histone transfer to the nucleosome. In the ternary complex, RanGTP binds to the N-terminal repeats of Kap114 in the same manner as in the Kap114/Importin-9•RanGTP complex, and H2A-H2B binds via its acidic patch to the Kap114 C-terminal repeats much like in the Kap114/Importin-9•H2A-H2B complex. Ran binds to a different conformation of Kap114 in the ternary RanGTP•Kap114•H2A-H2B complex. Here, Kap114 no longer contacts the H2A-H2B surface proximal to the H2A docking domain that drives nucleosome assembly, positioning it for transfer to the assembling nucleosome or to dedicated H2A-H2B chaperones in the nucleus.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Antitoxin control of optimal transcriptional repression in the atypical HigB–HigA toxin–antitoxin system from Proteus vulgaris

Abstract Bacterial toxin–antitoxin (TA) pairs transcriptionally autoregulate their expression via a repression/derepression mechanism in response to changing environmental conditions. The structural diversity of TA systems influences the mechanisms of transcriptional regulation. Here, we define the molecular mechanism for the plasmid-encoded HigB–HigA TA pair originally identified in a post-operative infection with antibiotic-resistant Proteus vulgaris. We determine DNA binding and promoter activity by the HigB–HigA complex supported by structural biology and molecular dynamics simulations of an elusive DNA operator–TA repressor complex. To define the optimal oligomeric TA repressor–DNA operator complex required for derepression, we engineered a dedicated trimeric HigB–HigA2 complex that represses transcription more than 26-fold as compared to the tetrameric HigB2–HigA2. These results expand the known diversity of how the HigB–HigA TA family is autoregulated.

Biochemistry & Molecular Biology↗