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At least 811 records · Page 45

The ICF syndrome protein CDCA7 harbors a unique DNA binding domain that recognizes a CpG dyad in the context of a non-B DNA

CDCA7, encoding a protein with a carboxyl-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, a disease related to hypomethylation of juxtacentromeric satellite DNA. How CDCA7 directs DNA methylation to juxtacentromeric regions is unknown. Here, we show that the CDCA7 CRD adopts a unique zinc-binding structure that recognizes a CpG dyad in a non-B DNA formed by two sequence motifs. CDCA7, but not ICF mutants, preferentially binds the non-B DNA with strand-specific CpG hemi-methylation. The unmethylated sequence motif is highly enriched at centromeres of human chromosomes, whereas the methylated motif is distributed throughout the genome. At S phase, CDCA7, but not ICF mutants, is concentrated in constitutive heterochromatin foci, and the formation of such foci can be inhibited by exogenous hemi-methylated non-B DNA bound by the CRD. Binding of the non-B DNA formed in juxtacentromeric regions during DNA replication provides a mechanism by which CDCA7 controls the specificity of DNA methylation.

Science & Technology - Other Topics↗

Separate, separated, and together: the transcriptional program of the Clostridium acetobutylicum-Clostridium ljungdahlii syntrophy leading to interspecies cell fusion

ABSTRACT Syntrophic cocultures (hitherto assumed to be commensalistic) of Clostridium acetobutylicum and Clostridium ljungdahlii , whereby CO 2 and H 2 produced by the former feed the latter, result in interspecies cell fusion involving large-scale exchange of protein, RNA, and DNA between the two organisms. Although mammalian cell fusion is mechanistically dissected, the mechanism for such microbial-cell fusions is unknown. To start exploring this mechanism, we used RNA sequencing to identify genes differentially expressed in this coculture using two types of comparisons. One type compared coculture to the two monocultures, capturing the combined impact of interactions through soluble signals in the medium and through direct cell-to-cell interactions. The second type compared membrane-separated versus -unseparated cocultures, isolating the impact of interspecies physical contact. While we could not firmly identify specific genes that might drive cell fusion, consistent with our hypothesized model for this interspecies microbial cell fusion, we observed differential regulation of genes involved in C. ljungdahlii’s autotrophic Wood-Ljungdahl pathway metabolism and genes of the motility machinery. Unexpectedly, we also identified differential regulation of biosynthetic genes of several amino acids, and notably of arginine and histidine. We verified that they are produced by C. acetobutylicum and are metabolized by C. ljungdahlii to its growth advantage. These and other findings, and notably upregulation of C. acetobutylicum ribosomal-protein genes, paint a more complex syntrophic picture and suggest a mutualistic relationship, whereby beyond CO 2 and H 2 , C. acetobutylicum feeds C. ljungdahlii with growth-boosting amino acids, while benefiting from the H 2 utilization by C. ljungdahlii . IMPORTANCE The construction and study of synthetic microbial cocultures is a growing research area due to the untapped potential of defined multi-species industrial bioprocesses and the utility of defined cocultures for generating insight into complex, undefined, natural microbial consortia. Our previous work showed that coculturing C. acetobutylicum and C. ljungdahlii leads to a unique metabolic phenotype (production of isopropanol) and heterologous cell fusion events. Here, we used RNAseq to explore genes involved in and impacted by these fusions. First, we compared gene expression in coculture to each monoculture. Second, we utilized a transwell system to compare gene expression in mixed cocultures to cocultures with both species physically separated by a permeable membrane, isolating the impact of interspecies “touching” on the transcriptome. This study deepens our mechanistic understanding of the C. acetobutylicum-C. ljungdahlii coculture phenotype, laying the groundwork for reverse genetic studies of heterologous cell fusion in Clostridium cocultures.

Willis, Noah B. (ORCID:0009000689365955)↗

Three-dimensional Simulations of Massive Stars. II. Age Dependence

We present 3D full star simulations, reaching up to 90% of the total stellar radius, for three 7 M⊙ stars of different ages: zero-age main sequence (ZAMS), mid–main sequence (midMS), and terminal-age main sequence (TAMS). A comparison with several theoretical prescriptions shows that the generation spectra for all three ages are dominated by convective plumes. Two distinct overshooting layers are observed, with most plumes stopped within the layer situated directly above the convective boundary; overshooting to the second, deeper layer becomes progressively more infrequent with increasing stellar age. Internal gravity wave (IGW) propagation is significantly impacted in the midMS and TAMS models as a result of some IGWs getting trapped within their Brunt–Väisälä frequency spikes. A fundamental change in the wave structure across radius is also observed, driven by the effect of density stratification on IGW propagation causing waves to become evanescent within the radiative zone, with older stars being affected more strongly. We find that the steepness of the frequency spectrum at the surface increases from ZAMS to the older models, with older stars also showing more modes in their spectra.

79 ASTRONOMY AND ASTROPHYSICS↗

Oxygen isotopes in circumstellar Al203 grains from meteorites and stellar nucleosynthesis

We have found a approximately 3 micrometer Al2O3 grain (B39) in the Bishunpur LL3.1 chondrite that is enriched in 0-17 by a factor of approximately 6.8 (0-16/0-17 = 385 +/- 9) and depleted in 0-18 by almost 60% (0-16/0-18 = 853 +/- 30) relative to solar system oxygen and has an initial Al-26/Al-27 = 1.7 +/- 0.2 x 10 (exp 3), approximately 34 times greater than the initial solar system value. The isotopic compositions of B39 and two other Al2O3 grains previously reported from the Orgueil and Murchison meteorites show that these grains formed directly from the ejecta of low-mass AGB stars with C/O less than 1. A simple theoretical analysis is presented showing that the oxygen systematics of the grains are a natural consequence of main-sequence evolution followed by first dredge-up Al-26 is the result of third dredge-up. Circumstellar Al2O3 grains provide very precise isotopic data for stellar ejecta that complement spectroscopic observations of oxygen-rich stars. Isotopic differences indicate that the Al2O3 grains come from separate stars of different mass and intital oxygen composition that originated in molecular clouds different from the one in which the solar system formed.

Huss, Gary R.↗

Theoretical properties of Omega-loops in the convective zone of the Sun. 3: Extended updrafts

It was pointed out in an earlier paper that the continuing emergence of Omega-loops at localized sites on the surface of the Sun indicates a continuing updraft at those sites. The updraft evidently extends all the way from the base of the convective zone to somewhat near (approximately 10(exp 9)cm) the surface. We pointed out that such updrafts enhance the convective heat transport to the surface, accounting for a major part of the increased solar brightness or irradiance during times of solar activity. The problem is to work out, as much as possible, the dynamical nature of the extended updrafts, initiated as the wakes of successive rising Omega-loops and driven therafter by the convective forces. The question is, does the updraft take on a long-lived columnar form of its own, or does it never devlop beyond a sequence of rising wakes, resembling beads on a string? The dynamics of a columnar updraft is complicated by both the large Reynolds number and the strong stratication of the atmosphere, and by a total lack of direct observational information. Extended slender updrafts are not a spontaneous occurrence in numerical simulations of thermal convection in a stratified atmosphere, although slender concentrated downdrafts commonly occur. This paper examines several aspects of a columnar updrft in a convective atmosphere under various idealized circumstances to investigate to what extent that state can be maintained against the diminishing vorticity and expansion in the updraft. It appears that the successive passage of Omega-loops from the bottom to the top of the convective zone is an essential feature of the continuing existence of the updraft.

Parker, E. N.↗

Mission Operations of the Mars Exploration Rovers

A document describes a system of processes involved in planning, commanding, and monitoring operations of the rovers Spirit and Opportunity of the Mars Exploration Rover mission. The system is designed to minimize command turnaround time, given that inherent uncertainties in terrain conditions and in successful completion of planned landed spacecraft motions preclude planning of some spacecraft activities until the results of prior activities are known by the ground-based operations team. The processes are partitioned into those (designated as tactical) that must be tied to the Martian clock and those (designated strategic) that can, without loss, be completed in a more leisurely fashion. The tactical processes include assessment of downlinked data, refinement and validation of activity plans, sequencing of commands, and integration and validation of sequences. Strategic processes include communications planning and generation of long-term activity plans. The primary benefit of this partition is to enable the tactical portion of the team to focus solely on tasks that contribute directly to meeting the deadlines for commanding the rover s each sol (1 sol = 1 Martian day) - achieving a turnaround time of 18 hours or less, while facilitating strategic team interactions with other organizations that do not work on a Mars time schedule.

Bass, Deborah↗

Lidar Observations of Raman Scattering from S02 in a Power Plant Stack Plume

LIDAR techniques have been successfully applied to the detection of the Raman backscatter from S02 in the plume of a 200 megawatt coal-burning electrical- generating plant from a distance of 210 meters. The LIDAR system used consists of a 61-centimeter-diameter, f /4 Newtonian telescope and a 1.0-1.5-joules per pulse, 1-pulse-per-second ruby laser. Narrow band interference filters are used to select the 7546-angstrom v (sub 1) vibrational line of S02. The signal from a photomultiplier tube was sequentially applied to each 254-nanosecond-wide channel of a 15-cihannel photon counting system, resulting in a direct correlation between channel number and range increment. Photon counts were accumulated from the backscatter of a number of laser pulses (typically 50 or 100), and the accumulated counts per channel printed on paper tape. One sequence of measurements was made during a two-hour period while the plant electrical output was being reduced by approximately 50 percent. Although the Raman system had not been quantitatively calibrated, the LIDAR data correlated well with the varying plant electrical output. N2 scattering observations were also made and an approximate quantitative S02 concentration obtained by ratioing the S02 data to N2 data. This ratio compared well to the in-situ measurements made during the same period by Environmental Protection Agency sampling instruments.

Brumfield, M. L.↗

A molecular description of the evolution of resistance

BACKGROUND: In vitro evolution has been used to obtain nucleic acid molecules with interesting functional properties. The evolution process usually is carried out in a stepwise manner, involving successive rounds of selection, amplification and mutation. Recently, a continuous in vitro evolution system was devised for RNAs that catalyze the ligation of oligonucleotide substrates, allowing the evolution of catalytic function to be studied in real time. RESULTS: Continuous in vitro evolution of an RNA ligase ribozyme was carried out in the presence of a DNA enzyme that was capable of cleaving, and thereby inactivating, the ribozyme. The DNA concentration was increased steadily over 33.5 hours of evolution, reaching a final concentration that would have been sufficient to inactivate the starting population in one second. The evolved population of ribozymes developed resistance to the DNA enzyme, reducing their vulnerability to cleavage by 2000-fold but retaining their own catalytic function. Based on sequencing and kinetic analysis of the ribozymes, two mechanisms are proposed for this resistance. One involves three nucleotide substitutions, together with two compensatory mutations, that alter the site at which the DNA enzyme binds the ribozyme. The other involves enhancement of the ribozyme's ability to bind its own substrate in a way that protects it from cleavage by the DNA enzyme. CONCLUSIONS: The ability to direct the evolution of an enzyme's biochemical properties in response to the behavior of another macromolecule provides insight into the evolution of resistance and may be useful in developing enzymes with novel or enhanced function.

Non-NASA Center↗

Graph-Directed Approach for Downselecting Toxins for Experimental Structure Determination

Conotoxins are short, cysteine-rich peptides of great interest as novel therapeutic leads and of great concern as lethal biological agents due to their high affinity and specificity for various receptors involved in neuromuscular transmission. Currently, of the approximately 6000 known conotoxin sequences, only about 3% have associated structural characterization, which leads to a bottleneck in rapid high-throughput screening (HTS) for identification of potential leads or threats. In this work, we combine a graph-based approach with homology modeling to expand the library of conotoxin structures and to identify those conotoxin sequences that are of the greatest value for experimental structural characterization. The latter would allow for the rapid expansion of the known structural space for generating high quality template-based models. Our approach generalizes to other evolutionarily-related, short, cysteine-rich venoms of interest. Overall, we present and validate an approach for venom structure modeling and experimental guidance and employ it to produce a 290%-larger library of approximate conotoxin structures for HTS. We also provide a set of ranked conotoxin sequences for experimental structure determination to further expand this library.

59 BASIC BIOLOGICAL SCIENCES↗

A direct time series comparison between the La Jolla and Belfast radiocarbon records

For many years it has been widely assumed that the variations in the level of atmospheric carbon-14 were due to statistical fluctuations arising from experimental error. This is understandable since the signal/noise ratio is very low and the time sequences representing the variations are strongly stochastic. Interlaboratory comparisons show that baseline variations in the absolute value of the carbon-14 concentration do exist. However, assuming linearity, the delta 14C values are independent of these. The importance of assessing the quantitive reality of the delta 14C values is based upon their expression of the interplanetary cosmic ray source function, because in the range of 100 to 1000 year periods, there appears to be no evidence that the Earth's magnetic field is the source modulating function. Therefore the modulation is either due to changes in the solar atmosphere propagated out into the solar wind, or extra-heliospheric pressure effects, but these appear to be unlikely for the periods noted here. The recent availability of the new high quality Belfast time sequence of delta 14C now permits a simple mutual assessment of the several sequences which are available. Since the La Jolla record has been a standard for many years , these two were chosen for a simple comparison. Although differences exist, the close agreement between these two sequences, one carried out on White mountain Bristlecone pines, and the other done using Irish peat bog wood, is striking. This correlation between the two strongly reinforces the statistical view that the delta 14C record is that of real interplanetary modulation of the cosmic ray source leading to the generation of atmospheric 14C.

Sonett, C. P.↗

A Search for Coronal Emission at the Bottom of the Main-Sequence: Stars and Brown Dwarf Candidates with Spectral Types Later than M7 and the Rotation-Activity Relation

This program intended to test whether the lowest mass stars at the bottom end of the main sequence and the lower mass brown dwarfs have coronae. If they have coronae, what are the coronal characteristics and what drives them? In the classical dynamo picture, the closed magnetic loop structure is generated near the boundary of the convective envelope and the radiative core. Stars with mass below 0.30 Msun however are fully convective, and the nature of the dynamo responsible for the generation of the coronae in this regime is poorly understood. Previous results from the ROSAT mission (e.g., Fleming et al. 1993, 1995; Schmitt et al. 1995) had confirmed three very important characteristics of M-star coronae: (1) a very high percentage of all M dwarfs have coronae (of order 85% in the local 7 pc sample), (2) those M dwarfs showing high chromospheric activity, such as having the Balmer series in emission or large/numerous optical flaring, indeed exhibit the highest coronal activity, and (3) that the maximum saturation boundary in X-ray luminosity, which amounts to 0.0001-0.001 for Lx/Lbol for the dMe stars, extends down to the current detection limit, through spectral types M7. It was likely that the incompleteness noted for result (1) above was simply a detection limit problem; for more distant sources, the X-ray fainter dM stars will drop below detection thresholds before the more X-ray luminous dMe stars. The latest stars for which direct detection of the corona had been successful were of spectral type dM7 (e.g., VB8, LHS 3003). This program proposed to obtain ROSAT HRI observations for a large number of the coolest known (at that time) stars at the bottom of the main-sequence, which had spectral types of M9 or later. Three stars were approved for observations with ROSAT-HRI totaling 180 ksec. The goal was to obtain X-ray detections or low upper limits for the three approved stars.

Stringfellow, Guy↗

Structural basis for human ZBTB7A action at the fetal globin promoter

Elevated levels of fetal globin protect against β-hemoglobinopathies, such as sickle cell disease and β-thalassemia. Two zinc-finger (ZF) repressors, BCL11A and ZBTB7A/LRF, bind directly to the fetal globin promoter elements positioned at -115 and -200, respectively. Here, we describe X-ray structures of the ZBTB7A DNA-binding domain, consisting of four adjacent ZFs, in complex with the -200 sequence element, which contains two copies of four consecutive C:G base pairs. ZF1 and ZF2 recognize the 5' C:G quadruple, and ZF4 contacts the 3' C:G quadruple. Natural non-coding DNA mutations associated with hereditary persistence of fetal hemoglobin (HPFH) impair ZBTB7A DNA binding, with the most severe disruptions resulting from mutations in the base pairs recognized by ZF1 and ZF2. Our results firmly establish ZBTB7A/LRF as a key molecular regulator of fetal globin expression and inform genome-editing strategies that inhibit repressor binding and boost fetal globin expression to treat hemoglobinopathies.

59 BASIC BIOLOGICAL SCIENCES↗

Efficient 3D Molecular Design with an E(3) Invariant Transformer VAE

This work introduces a three-dimensional (3D) invariant graph-to-string transformer variational autoencoders (VAE) (Vagrant) for generating molecules with accurate density functional theory (DFT)-level properties. Vagrant learns to model the joint probability distribution of a 3D molecular structure and its properties by encoding molecular structures into a 3D-aware latent space. Directed navigation through this latent space implicitly optimizes the 3D structure of a molecule, and the latent embedding can be used to condition a generative transformer to predict the candidate structure as a one-dimensional (1D) sequence. Additionally, we introduce two novel sampling methods that exploit the latent characteristics of a VAE to improve performance. Here, we show that our method outperforms comparable 3D autoregressive and diffusion methods for predicting quantum chemical property values of novel molecules in terms of both sample quality and computational efficiency.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Quasiparticle Poisoning of Superconducting Qubits from Resonant Absorption of Pair-Breaking Photons

The ideal superconductor provides a pristine environment for the delicate states of a quantum computer: because there is an energy gap to excitations, there are no spurious modes with which the qubits can interact, causing irreversible decay of the quantum state. As a practical matter, however, there exists a high density of excitations out of the superconducting ground state even at ultralow temperature; these are known as quasiparticles. Observed quasiparticle densities are of order 1 μ m - 3 , tens of orders of magnitude greater than the equilibrium density expected from theory. Nonequilibrium quasiparticles extract energy from the qubit mode and can induce dephasing. Here we show that a dominant mechanism for quasiparticle poisoning is direct absorption of high-energy photons at the qubit junction. We use a Josephson junction-based photon source to controllably dose qubit circuits with millimeter-wave radiation, and we use an interferometric quantum gate sequence to reconstruct the charge parity of the qubit. We find that the structure of the qubit itself acts as a resonant antenna for millimeter-wave radiation, providing an efficient path for photons to generate quasiparticles. A deep understanding of this physics will pave the way to realization of next-generation superconducting qubits that are robust against quasiparticle poisoning.

Liu, Chuan-Hong↗

Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold

The FAM46 (also known as TENT5) proteins are noncanonical poly(A) polymerases (PAPs) implicated in regulating RNA stability. The regulatory mechanisms of FAM46 are poorly understood. Here, we report that the nuclear protein BCCIPα, but not the alternatively spliced isoform BCCIPβ, binds FAM46 and inhibits their PAP activity. Unexpectedly, our structures of the FAM46A/BCCIPα and FAM46C/BCCIPα complexes show that, despite sharing most of the sequence and differing only at the C-terminal portion, BCCIPα adopts a unique structure completely different from BCCIPβ. The distinct C-terminal segment of BCCIPα supports the adoption of the unique fold but does not directly interact with FAM46. The β sheets in BCCIPα and FAM46 pack side by side to form an extended β sheet. A helix-loop-helix segment in BCCIPα inserts into the active site cleft of FAM46, thereby inhibiting the PAP activity. Our results together show that the unique fold of BCCIPα underlies its interaction with and functional regulation of FAM46.

59 BASIC BIOLOGICAL SCIENCES↗

Data Analysis of X-ray Panels Used in X-ray CT Scientific Instruments

This report is a follow-up study on M. Skeate’s study on System Drift Detection for Health Monitoring (Skeate, 2023). The following report highlights analyses of the panel’s behavior with extended use. This includes effects of burn-in on the panel from over-use and bad pixels (defined in Methodology.) Using data-forward statistical analyses across a sequence of scans, and given that the other conditions present in the data can be replicated, this study show that overtime use of panels does not affect bad pixel count. Also, I present conclusive evidence of a direct relationship between the regions of the panel that are exposed to radiation and burn-in damage to that region overtime. Additionally, this study also highlights the effect of the duty cycle on the dark current change in the panel.

42 ENGINEERING↗

Feasibility of generating an artificial burst in a turbulent boundary layer

Artificial bursts were generated in laminar and turbulent boundary layers. The burst-like events were produced by withdrawing near-wall fluid from two minute holes separated in the spanwise direction or by pitching a miniature delta wing that was flush-mounted to the wall. Either of these actions generated streamwise vorticity and a low-speed streak that resembled a naturally occurring one. The resulting sequence of events occurred at a given location and at controlled times, allowing detailed examination and comparison with natural, random bursts by means of flow visualization and fast-response probe measurement techniques.

Gad-El-hak, M.↗

Coherent structures in a turbulent boundary layer. I - Generation of 'artificial' bursts

In an effort to better understand the physics and structure of coherent events in a turbulent boundary layer, an attempt is made to produce 'artificial' bursts. These are generated in a turbulent boundary layer developed on a flat plate towed in an 18 m water channel and thus with negligible freestream turbulence. The burstlike events are produced by either withdrawing near-wall fluid from two minute holes separated in the spanwise direction or by pitching a miniature delta wing that is flush-mounted to the wall. Either of these two actions generates a hairpinlike vortex and low-speed streak that resemble naturally occurring structures. The resulting sequence of events that occur at a given location can be uniquely controlled, thus allowing detailed examination via phase-locked measurements and flow visualization. In this paper, the proof of concept of artificial burst generation is established by comparing the artificial events with natural, random bursts using flow visualization and hot-film signals.

Gad-El-hak, M.↗