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At least 37 records · Page 2

Structure of human NADK2 reveals atypical assembly and regulation of NAD kinases from animal mitochondria

All kingdoms of life produce essential nicotinamide dinucleotide NADP(H) using NAD kinases (NADKs). A panel of published NADK structures from bacteria, eukaryotic cytosol, and yeast mitochondria revealed similar tetrameric enzymes. Here, we present the 2.8-Å structure of the human mitochondrial kinase NADK2 with a bound substrate, which is an exception to this uniformity, diverging both structurally and biochemically from NADKs. We show that NADK2 harbors a unique tetramer disruptor/dimerization element, which is conserved in mitochondrial kinases of animals (EMKA) and absent from other NADKs. EMKA stabilizes the NADK2 dimer but prevents further NADK2 oligomerization by blocking the tetramerization interface. This structural change bears functional consequences and alters the activation mechanism of the enzyme. Whereas tetrameric NADKs undergo cooperative activation via oligomerization, NADK2 is a constitutively active noncooperative dimer. Thus, our data point to a unique regulation of NADP(H) synthesis in animal mitochondria achieved via structural adaptation of the NADK2 kinase.

59 BASIC BIOLOGICAL SCIENCES↗

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↗

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↗

Discordance of exercise thallium testing with coronary arteriography in patients with atypical presentations

Eighty-one patients with diagnostically difficult clinical presentations suggesting coronary artery disease underwent symptom-limited maximal-exercise treadmill testing (ETT) and exercise radionuclide scanning with thallium-201 followed by coronary angiography. Results showed that in nearly half of the patients (47%) these tests were in agreement, while either exercise thallium or ETT was positive in 94% of patients with coronary artery disease. It was found that agreement between exercise thallium and ETT tests predicted disease in 92% of the instances or excluded disease in 82% of the instances. It is concluded that despite frequent discord between these two tests in 53% of the cases, a significant gain in exclusive diagnostic capability is realized when applied to a patient population anticipated to have a disease prevalence equal to the 67% encountered in this study.

Bungo, M. W.↗

Atypical Particle Heating at a Supercritical Interplanetary Shock

We present the first observations at an interplanetary shock of large amplitude (> 100 mV/m pk-pk) solitary waves and large amplitude (approx.30 mV/m pk-pk) waves exhibiting characteristics consistent with electron Bernstein waves. The Bernstein-like waves show enhanced power at integer and half-integer harmonics of the cyclotron frequency with a broadened power spectrum at higher frequencies, consistent with the electron cyclotron drift instability. The Bernstein-like waves are obliquely polarized with respect to the magnetic field but parallel to the shock normal direction. Strong particle heating is observed in both the electrons and ions. The observed heating and waveforms are likely due to instabilities driven by the free energy provided by reflected ions at this supercritical interplanetary shock. These results offer new insights into collisionless shock dissipation and wave-particle interactions in the solar wind.

Wilson, Lynn B., III↗

A Pattern Dictionary Method for Anomaly Detection

In this paper, we propose a compression-based anomaly detection method for time series and sequence data using a pattern dictionary. The proposed method is capable of learning complex patterns in a training data sequence, using these learned patterns to detect potentially anomalous patterns in a test data sequence. The proposed pattern dictionary method uses a measure of complexity of the test sequence as an anomaly score that can be used to perform stand-alone anomaly detection. We also show that when combined with a universal source coder, the proposed pattern dictionary yields a powerful atypicality detector that is equally applicable to anomaly detection. The pattern dictionary-based atypicality detector uses an anomaly score defined as the difference between the complexity of the test sequence data encoded by the trained pattern dictionary (typical) encoder and the universal (atypical) encoder, respectively. We consider two complexity measures: the number of parsed phrases in the sequence, and the length of the encoded sequence (codelength). Specializing to a particular type of universal encoder, the Tree-Structured Lempel–Ziv (LZ78), we obtain a novel non-asymptotic upper bound, in terms of the Lambert W function, on the number of distinct phrases resulting from the LZ78 parser. This non-asymptotic bound determines the range of anomaly score. As a concrete application, we illustrate the pattern dictionary framework for constructing a baseline of health against which anomalous deviations can be detected.

97 MATHEMATICS AND COMPUTING↗

Physical and dynamical characterization of hyperbolic comet C/2017 U7 (PANSTARRS)

Here we present here a dynamical and observational study of the comet C/2017 U7 (PANSTARRS). This comet was discovered in 2017 and found to have a hyperbolic orbit. Our dynamical analysis shows that the object has probably originated in the Oort cloud, however an interstellar origin cannot be discarded. The observations were obtained in 2018 and 2019 using the Goodman High Throughput Spectrograph (GHTS) at the SOAR telescope. We obtained visible spectra covering the wavelength range of 0.5 - 0.9 μm and also images in the SDSS filters system. Both the low-resolution reflectance spectrum and the reflectance spectra derived from the SDSS filters show an atypical band at ~ 0.595 μm. We conducted a comparative study of the colors and reflectance spectra of different small body populations (e.g., comets, Centaurs, and trans-Neptunian objects or TNOs) from the literature and concluded that the spectra and the colors of this comet are atypical, showing only some overlap with those of some known members of the TNOs and Centaurs, within the large uncertainties of the measurements of those populations. It is found that the feature and overall spectral shape can be reproduced by laboratory spectra of kerite, a template for aliphatic-rich hydrocarbons that has been previously identified in NIR cometary spectra absorptions. It is tentatively proposed that the unusual spectral shape is the result of a particle size distribution of dust grains in the coma or on the surface that has arisen due to a low grain ejection velocity from the surface and large nucleus size.

79 ASTRONOMY AND ASTROPHYSICS↗

Imaging of Electrothermal Filament Formation in a Mott Insulator

Resistive switching—the current- and voltage-induced change of electrical resistance—is at the core of memristive devices, which play an essential role in the emerging field of neuromorphic computing. This study is about resistive switching in a Mott insulator, which undergoes a thermally driven metal-to-insulator transition. Two distinct switching mechanisms are reported for such a system: electric-field-driven resistive switching and electrothermal resistive switching. The latter results from an instability caused by Joule heating. Here, we present the visualization of the reversible resistive switching in a planar V 2 O 3 thin-film device using high-resolution wide-field microscopy in combination with electric transport measurements. We investigate the interaction of the electrothermal instability with the strain-induced spontaneous phase separation in the V 2 O 3 thin film at the Mott transition. The photomicrographs show the formation of a narrow metallic filament with a minimum width ≲500 nm. Although the filament formation and the overall shape of the current-voltage characteristics (IVCs) are typical of an electrothermal breakdown, we also observe atypical effects such as oblique filaments, filament splitting, and hysteretic IVCs with sawtoothlike jumps at high currents in the low-resistance regime. We are able to reproduce the experimental results in a numerical model based on a two-dimensional resistor network. This model demonstrates that resistive switching in this case is indeed electrothermal and that the intrinsic heterogeneity is responsible for the atypical effects. This heterogeneity is strongly influenced by strain, thereby establishing a link between switching dynamics and structural properties.

42 ENGINEERING↗

Phycocyanobilin biosynthesis in Galdieria sulphuraria requires isomerization of phycoerythrobilin synthesized by bilin reductases

Phycobiliproteins are essential components of the light-harvesting antennae in cyanobacteria and red algae, requiring covalently bound open-chain tetrapyrrole chromophores (bilins) for proper function. In the red alga Galdieria sulphuraria , the primary chromophore is phycocyanobilin (PCB), despite the apparent presence of only biosynthetic genes for phycoerythrobilin (PEB) biosynthesis (PEBA and PEBB). This observation suggests the presence of an alternative, atypical biosynthetic pathway for PCB. In this study, we confirmed the presence of PEB:PCB isomerase activity in an enriched protein fraction from G. sulphuraria . To further investigate this unusual pathway, we combined in silico analyses with biochemical assays. Phylogenetic analyses confirmed the placement of the G. sulphuraria ferredoxin-dependent bilin reductases within the PEBA and PEBB lineages, typically associated with PEB synthesis, whereas the related red alga Cyanidioschyzon merolae was found to contain only PCYA. This gene distribution presents a functional paradox. G. sulphuraria harbors PEB biosynthesis genes but no detectable PEB chromophores and lacks known PCB-synthesizing enzymes despite containing PCB. Functional characterization of recombinant GsPEBA (G. sulphuraria PEBA) and GsPEBB ( G. sulphuraria PEBB) confirmed their roles in PEB synthesis, demonstrating that these enzymes have not evolved to synthesize PCB or act as isomerases despite their phylogenetic placement. In contrast, Cm PCYA ( C. merolae PCYA) catalyzed direct PCB formation from biliverdin. Together, these findings reveal an atypical isomerase-based pathway for PCB biosynthesis in G. sulphuraria , expanding our understanding of bilin metabolism and providing new insight into the evolutionary flexibility of photosynthetic pigment biosynthesis in Rhodophyta.

14 SOLAR ENERGY↗

Progress Report on Mockup Irradiation Capsule Fuel Measurements at LANSCE

Irradiation tests are a key component of nuclear fuel development and identifying typical and atypical regions in the irradiated fuel volume relies on very few characterization techniques. The goal of the effort reported here is to provide complementary measurements adding to the available parameter space for post irradiation examination as well as to inform subsequent hot cell PIE examinations by identifying typical and atypical regions with respect to microstructure, tomographic data, or isotope densities. Pulsed neutrons, enabling diffraction as well as energy-resolved neutron imaging and neutron absorption resonance spectroscopy, offer unique capabilities for this purpose. Time-of-flight neutron diffraction has the potential to offer efficient, non-destructive and non-contact microstructural characterization of irradiated fuel specimen with spatial resolution of 1 mm 3 to 1 cm 3 while for energy-resolved neutron imaging (and by extension tomography) a resolution of 100 μm 3 was demonstrated. The potential results include crystallinity vs. amorphous volumes and microstructural information such as phase compositions, lattice strains (indicative of residual stresses or chemistry variations) and textures from the diffraction data as well as distances (e.g. pellet to cladding), cracks, and isotope densities of minor actinides, fission products as well as fission gas partial pressures e.g. in the plenum from energy resolved neutron imaging.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Ecology and thermal inactivation of microbes in and on interplanetary space vehicle components

Studies were made of atypical organisms found in Bacillus subtilis var. niger spore colonies. Efforts were aimed at: (1) determining the heat sensitivity of these atypical white spores treated under dry heat conditions and their influence on the nature of the survival curve, (2) preparing a new spore crop obtained from spore isolates by purification procedures, and (3) comparing spore crops obtained from Cape Kennedy (SSM-10) and Minnesota (Minn. sp. AAEF) with the old Cincinnati and new purified Cincinnati spore crop under dry heat conditions.

Campbell, J. E.↗

A comprehensive study of the X-ray structure and spectrum of IC 443

This paper presents the results of a comprehensive study of the X-ray emission from the supernova remnant IC 443, using the solid state spectrometer, IPC, and high-resolution images of the Einstein Observatory, and the medium-energy detector of the HEAO 1 A-2 experiment. A soft X-ray appearance was observed, highly atypical of a supernova remnant in the adiabatic phase, with little correlation between X-ray and optical or radio features. The best-fit models of the low-energy X-ray spectrum of the brightest area of the remnant suggest either that the remnant has not yet attained ionization equilibrium or that the X-rays arise in a multiphase medium. Pronounced soft X-ray spectral differences across the remnant are accounted for by variations in absorption by an intervening molecular cloud. The analysis suggests that, despite the atypical X-ray appearance, the X-ray emission in IC 443 is probably confined to a thin (0.1 pc) shell.

Petre, R.↗

The HST quasar absorption line key project. 4: HST faint-object spectrograph and ground-based observations of the unusual low-redshift broad absorption-line quasi-stellar object PG 0043+039

Hubble Space Telescope Faint Object Spectrograph (HST FOS) observations have shown that the spectrum of the low-redshift (z(sub em) approximately equal to 0.384) QSO PG 0043+039 exhibits weak broad absorption lines (BALs). The BALs were discovered during the course of UV spectrophotometry made for the HST Quasar Absorption Line Key Project. The HST data are analyzed along with ground-based optical and IUE spectrophotometry. The object is found to have a number of atypical properties relative to normal non-BAL QSOs. The observed continuum is atypical in the sense that it is much weaker than that of a normal optically selected QSO at rest wavelengths approximately less than 2200 A. Intrinsic reddening of E(B-V) approximately equal to 0.11 mag by dust similar to that found in the SMC at the redshift of PG 0043+039 conservatively accounts for the observed continuum shape moderately well. These observed characteristics are typical of low-ionization BAL QSOs, but convincing evidence for BALs due to low-ionization transitions of Mg II, Al III, Al II, or C II does not exist. Therefore, this object may be a misaligned BAL QSO having many of the characteristics of low-ionization BAL QSOs with the sight line passing through a putative dusty region, but evidently missing clouds of high enough column density to produce observable low-ionization BALs. If the intrinsic dust-extinction model is correct, the observations suggest that the dust is not confined to the presumably higher density, low-ionization BAL clouds, but that it has drifted to nearby high-ionization BAL regions. We also consider other possible mechanisms for producing the shape of the continuous energy distribution which cannot be ruled out. We compare the Fe II emission in PG 0043+039 with that in another Key Project QSO, NGC 2841-UB 3, which has optical Fe II emission comparable in strength to that in PG 0043+039, but has anomalously weak UV Fe II emission. In addition, from an analysis of UV and optical spectrophotometric data at 5 epochs over approximately 11 yr, there is tentative evidence that PG 0043+039 has varied in brightness by as much as 1.1 mag during this time interval. Two different interpretations of PG 0043+039 and the low-ionization BAL QSOs are considered. Various model scenarios for explaining the weak narrow-line (O III) emission are considered, but there is no definitive explanation.

Turnshek, David A.↗

Identification of a typical 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 a typicality 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.

Irving C Statler↗