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All sourcesNASA NTRSDOE OSTI
NASA NTRS2010

Cosmic Infrared Background Fluctuations in Deep Spitzer Infrared Array Camera Images: Data Processing and Analysis

This paper provides a detailed description of the data reduction and analysis procedures that have been employed in our previous studies of spatial fluctuation of the cosmic infrared background (CIB) using deep Spitzer Infrared Array Camera observations. The self-calibration we apply removes a strong instrumental signal from the fluctuations that would otherwise corrupt the results. The procedures and results for masking bright sources and modeling faint sources down to levels set by the instrumental noise are presented. Various tests are performed to demonstrate that the resulting power spectra of these fields are not dominated by instrumental or procedural effects. These tests indicate that the large-scale ([greater, similar]30') fluctuations that remain in the deepest fields are not directly related to the galaxies that are bright enough to be individually detected. We provide the parameterization of these power spectra in terms of separate instrument noise, shot noise, and power-law components. We discuss the relationship between fluctuations measured at different wavelengths and depths, and the relations between constraints on the mean intensity of the CIB and its fluctuation spectrum. Consistent with growing evidence that the [approx]1-5 [mu]m mean intensity of the CIB may not be as far above the integrated emission of resolved galaxies as has been reported in some analyses of DIRBE and IRTS observations, our measurements of spatial fluctuations of the CIB intensity indicate the mean emission from the objects producing the fluctuations is quite low ([greater, similar]1 nW m-2 sr-1 at 3-5 [mu]m), and thus consistent with current [gamma]-ray absorption constraints. The source of the fluctuations may be high-z Population III objects, or a more local component of very low luminosity objects with clustering properties that differ from the resolved galaxies. Finally, we discuss the prospects of the upcoming space-based surveys to directly measure the epochs inhabited by the populations producing these source-subtracted CIB fluctuations, and to isolate the individual fluxes of these populations.

Arendt, Richard↗
NASA NTRS2014

A Classification Scheme for Young Stellar Objects Using the WIDE-FIELD INFRARED SURVEY EXPLORER ALLWISE Catalog: Revealing Low-Density Star Formation in the Outer Galaxy

We present an assessment of the performance of WISE and the AllWISE data release in a section of the Galactic Plane. We lay out an approach to increasing the reliability of point source photometry extracted from the AllWISE catalog in Galactic Plane regions using parameters provided in the catalog. We use the resulting catalog to construct a new, revised young star detection and classification scheme combining WISE and 2MASS near and mid-infrared colors and magnitudes and test it in a section of the Outer Milky Way. The clustering properties of the candidate Class I and II stars using a nearest neighbor density calculation and the two-point correlation function suggest that the majority of stars do form in massive star forming regions, and any isolated mode of star formation is at most a small fraction of the total star forming output of the Galaxy. We also show that the isolated component may be very small and could represent the tail end of a single mechanism of star formation in line with models of molecular cloud collapse with supersonic turbulence and not a separate mode all to itself.

WIDE-FIELD↗
DOE OSTI2020

WIYN Open Cluster Study LXXIX. M48 (NGC 2548) I. Radial Velocities, Rotational Velocities, and Metallicities of Stars in the Open Cluster M48 (NGC 2548)

WIYN/Hydra spectra (R ∼ 13,500, signal-to-noise pixel{sup −1} = 50–1000) of a 400 Å region around Li 6708 Å are used to determine radial and rotational velocities for 287 photometrically selected candidate members of the open cluster M48. The sample ranges from turnoff A stars to late-K dwarfs and eight giants. We combine our V {sub RAD} measurements and power spectrum analysis with parallax and proper motion data from Gaia DR2 to evaluate membership and multiplicity. We classify 152 stars as single cluster members, 11 as binary members, 16 as members of uncertain multiplicity, 56 as single nonmembers, 28 as single “likely” nonmembers, two as single “likely” members, one as a binary “likely” member, five as binary nonmembers, 10 as “likely” members of uncertain multiplicity, three as nonmembers of uncertain multiplicity, and three as “likely” nonmembers of uncertain multiplicity. From a subsample of 95 single members, we derive V {sub RAD} = 8.512 ± 0.087 km s{sup −1} (σ {sub μ}, and σ = 0.848 km s{sup −1}). Using 16 isolated Fe I lines for a subsample of 99 single members (that have σ{sub T{sub e{sub f{sub f}}}}<75 K (from 10 colors from UBVRI), v sin i < 25 km s{sup −1}, and well-behaved Fe I lines), [Fe/H]{sub M48} = −0.063 ± 0.007 dex (σ {sub μ}). [Fe/H] is independent of T {sub eff} over an unprecedentedly large range of 2500 K. The minimum cluster binary fraction is 11%–21%. M48 exhibits a clear but modest broadening of the main-sequence turnoff, and there is no correlation between color and v sin i.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2025

Cell-free synthetic biology for natural product biosynthesis and discovery

Natural products have applications as biopharmaceuticals, agrochemicals, and other high-value chemicals. However, there are challenges in isolating natural products from their native producers (e.g. bacteria, fungi, plants). In many cases, synthetic chemistry or heterologous expression must be used to access these important molecules. The biosynthetic machinery to generate these compounds is found within biosynthetic gene clusters, primarily consisting of the enzymes that biosynthesise a range of natural product classes (including, but not limited to ribosomal and nonribosomal peptides, polyketides, and terpenoids). Cell-free synthetic biology has emerged in recent years as a bottom-up technology applied towards both prototyping pathways and producing molecules. Recently, it has been applied to natural products, both to characterise biosynthetic pathways and produce new metabolites. This review discusses the core biochemistry of cell-free synthetic biology applied to metabolite production and critiques its advantages and disadvantages compared to whole cell and/or chemical production routes. Specifically, we review the advances in cell-free biosynthesis of ribosomal peptides, analyse the rapid prototyping of natural product biosynthetic enzymes and pathways, highlight advances in novel antimicrobial discovery, and discuss the rising use of cell-free technologies in industrial biotechnology and synthetic biology.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1992

Research in computational fluid dynamics and analysis of algorithms

Recently, higher-order compact schemes have seen increasing use in the DNS (Direct Numerical Simulations) of the Navier-Stokes equations. Although they do not have the spatial resolution of spectral methods, they offer significant increases in accuracy over conventional second order methods. They can be used on any smooth grid, and do not have an overly restrictive CFL dependence as compared with the O(N(exp -2)) CFL dependence observed in Chebyshev spectral methods on finite domains. In addition, they are generally more robust and less costly than spectral methods. The issue of the relative cost of higher-order schemes (accuracy weighted against physical and numerical cost) is a far more complex issue, depending ultimately on what features of the solution are sought and how accurately they must be resolved. In any event, the further development of the underlying stability theory of these schemes is important. The approach of devising suitable boundary clusters and then testing them with various stability techniques (such as finding the norm) is entirely the wrong approach when dealing with high-order methods. Very seldom are high-order boundary closures stable, making them difficult to isolate. An alternative approach is to begin with a norm which satisfies all the stability criteria for the hyperbolic system, and look for the boundary closure forms which will match the norm exactly. This method was used recently by Strand to isolate stable boundary closure schemes for the explicit central fourth- and sixth-order schemes. The norm used was an energy norm mimicking the norm for the differential equations. Further research should be devoted to BC for high order schemes in order to make sure that the results obtained are reliable. The compact fourth order and sixth order finite difference scheme had been incorporated into a code to simulate flow past circular cylinders. This code will serve as a verification of the full spectral codes. A detailed stability analysis by Carpenter (from the fluid Mechanics Division) and Gottlieb gave analytic conditions for stability as well as asymptotic stability. This had been incorporated in the code in form of stable boundary conditions. Effects of the cylinder rotations had been studied. The results differ from the known theoretical results. We are in the middle of analyzing the results. A detailed analysis of the effects of the heating of the cylinder on the shedding frequency had been studied using the above schemes. It has been found that the shedding frequency decreases when the wire was heated. Experimental work is being carried out to affirm this result.

Gottlieb, David↗
DOE OSTI2021

A panoramic view of the Local Group dwarf galaxy NGC 6822

ABSTRACT We present a panoramic survey of the isolated Local Group dwarf irregular galaxy NGC 6822. Our photometry reaches ∼2–3 mag deeper than most previous studies and spans the widest area around the dwarf compared to any prior work. We observe no stellar overdensities in the outskirts of NGC 6822 to V ∼ 30 mag arcsec−2 and a projected radius of 16.5 kpc. This indicates that NGC 6822 has not experienced any recent interaction with a companion galaxy, despite previous suggestions to the contrary. Similarly, we find no evidence for any dwarf satellites of NGC 6822 to a limiting luminosity MV ≈ −5. NGC 6822 contains a disc of H i gas and young stars, oriented at ∼60○ to an extended spheroid composed of old stellar populations. We observe no correlation between the distribution of young stars and spheroid members. Our imaging allows us to trace the spheroid to nearly 11 kpc along its major axis, commensurate with the extent of the NGC 6822 globular cluster system. We find that the spheroid becomes increasingly flattened at larger radii, and its position angle twists by up to 40○. We use Gaia EDR3 astrometry to measure a proper motion for NGC 6822, and then sample its orbital parameter space. While this galaxy has spent the majority of its life in isolation, we find that it likely passed within the virial radius of the Milky Way ∼3–4 Gyr ago. This may explain the apparent flattening and twisting observed in the outskirts of its spheroid.

79 ASTRONOMY AND ASTROPHYSICS↗
NASA NTRS2016

An Efficient, FPGA-Based, Cluster Detection Algorithm Implementation for a Strip Detector Readout System in a Time Projection Chamber Polarimeter

A fundamental challenge in a spaceborne application of a gas-based Time Projection Chamber (TPC) for observation of X-ray polarization is handling the large amount of data collected. The TPC polarimeter described uses the APV-25 Application Specific Integrated Circuit (ASIC) to readout a strip detector. Two dimensional photoelectron track images are created with a time projection technique and used to determine the polarization of the incident X-rays. The detector produces a 128x30 pixel image per photon interaction with each pixel registering 12 bits of collected charge. This creates challenging requirements for data storage and downlink bandwidth with only a modest incidence of photons and can have a significant impact on the overall mission cost. An approach is described for locating and isolating the photoelectron track within the detector image, yielding a much smaller data product, typically between 8x8 pixels and 20x20 pixels. This approach is implemented using a Microsemi RT-ProASIC3-3000 Field-Programmable Gate Array (FPGA), clocked at 20 MHz and utilizing 10.7k logic gates (14% of FPGA), 20 Block RAMs (17% of FPGA), and no external RAM. Results will be presented, demonstrating successful photoelectron track cluster detection with minimal impact to detector dead-time.

Polarimeter↗
DOE OSTI2022

A combined theoretical-experimental investigation of thermal transport in low-dose irradiated thorium dioxide

During reactor operation, nuclear fuels are subject to extreme temperature and irradiation conditions which can significantly degrade the fuel's thermal transport properties. The reduction in thermal conductivity of the fuel as a result of irradiation-induced lattice defects is arguably the most important fuel performance metric in regard to reactor efficiency and safety. Because thorium dioxide (ThO2) is suitable as a model system for more complex materials such as UO2 and its mixed oxides, we present a theoretical investigation of thermal conductivity reduction seen in defect-bearing thorium dioxide and compare directly to experimental measurements. Phonon-mediated thermal transport of the fuel is modeled by a solution to the Boltzmann transport equation (BTE) for phonons. A cluster dynamics (CD) model for lattice defect evolution during irradiation predicts defect densities which are used as input to the BTE for modeling phonon-defect scatterings. Phonon scatterings by lattice defects include those from point defects and vacancy clusters and interstitial clusters of various sizes. The CD model is benchmarked against structural defect characterization of irradiated thorium dioxide using electron microscopy. Thermal conductivity predicted by the BTE model is compared to measured values for irradiated thorium dioxide specimens below room temperature to isolate effects of phonon-defect scattering from intrinsic 3-phonon processes, which dominate at higher temperatures. The computed conductivity values are in partial agreement at temperatures close to room temperature while slight deviations are observed at the lowest measured temperatures, suggesting that implemented phonon-defect scattering cross-section expressions may not be adequate for low temperatures. The presented work provides a necessary investigation of the influence of irradiation induced defects on fuel performance and represents a first step toward a full characterization of phonon mediated thermal transport in irradiated materials with complex defect microstructure.

36 MATERIALS SCIENCE↗
DOE OSTI2024

An exopolysaccharide pathway from a freshwater Sphingomonas isolate

Bacteria embellish their cell envelopes with a variety of specialized polysaccharides. Biosynthesis pathways for these glycans are complex, and final products vary greatly in their chemical structures, physical properties, and biological activities. This tremendous diversity comes from the ability to arrange complex pools of monosaccharide building blocks into polymers with many possible linkage configurations. Due to the complex chemistry of bacterial glycans, very few biosynthetic pathways have been defined in detail. As part of an initiative to characterize novel polysaccharide biosynthesis enzymes, we isolated a bacterium from Lake Michigan called Sphingomonas sp. LM7 that is proficient in exopolysaccharide (EPS) production. We identified genes that contribute to EPS biosynthesis in LM7 by screening a transposon mutant library for colonies displaying altered colony morphology. A gene cluster was identified that appears to encode a complete wzy/wzx-dependent polysaccharide assembly pathway. Deleting individual genes in this cluster caused a non-mucoid phenotype and a corresponding loss of EPS secretion, confirming the role of this gene cluster in polysaccharide production. We extracted EPS from LM7 cultures and determined that it contains a linear chain of 3- and 4-linked glucose, galactose, and glucuronic acid residues. Finally, we show that the EPS pathway in Sphingomonas sp. LM7 diverges from that of sphingan-family EPSs and adhesive polysaccharides such as the holdfast that are present in other Alphaproteobacteria. Our approach of characterizing complete biosynthetic pathways holds promise for engineering polysaccharides with valuable properties.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Pangenomes suggest ecological-evolutionary responses to experimental soil warming

ABSTRACT Below-ground carbon transformations that contribute to healthy soils represent a natural climate change mitigation, but newly acquired traits adaptive to climate stress may alter microbial feedback mechanisms. To better define microbial evolutionary responses to long-term climate warming, we study microorganisms from an ongoing in situ soil warming experiment where, for over three decades, temperate forest soils are continuously heated at 5°C above ambient. We hypothesize that across generations of chronic warming, genomic signatures within diverse bacterial lineages reflect adaptations related to growth and carbon utilization. From our bacterial culture collection isolated from experimental heated and control plots, we sequenced genomes representing dominant taxa sensitive to warming, including lineages of Actinobacteria, Alphaproteobacteria, and Betaproteobacteria. We investigated genomic attributes and functional gene content to identify signatures of adaptation. Comparative pangenomics revealed accessory gene clusters related to central metabolism, competition, and carbon substrate degradation, with few functional annotations explicitly associated with long-term warming. Trends in functional gene patterns suggest genomes from heated plots were relatively enriched in central carbohydrate and nitrogen metabolism pathways, while genomes from control plots were relatively enriched in amino acid and fatty acid metabolism pathways. We observed that genomes from heated plots had less codon bias, suggesting potential adaptive traits related to growth or growth efficiency. Codon usage bias varied for organisms with similar 16S rrn operon copy number, suggesting that these organisms experience different selective pressures on growth efficiency. Our work suggests the emergence of lineage-specific trends as well as common ecological-evolutionary microbial responses to climate change. IMPORTANCE Anthropogenic climate change threatens soil ecosystem health in part by altering below-ground carbon cycling carried out by microbes. Microbial evolutionary responses are often overshadowed by community-level ecological responses, but adaptive responses represent potential changes in traits and functional potential that may alter ecosystem function. We predict that microbes are adapting to climate change stressors like soil warming. To test this, we analyzed the genomes of bacteria from a soil warming experiment where soil plots have been experimentally heated 5°C above ambient for over 30 years. While genomic attributes were unchanged by long-term warming, we observed trends in functional gene content related to carbon and nitrogen usage and genomic indicators of growth efficiency. These responses may represent new parameters in how soil ecosystems feedback to the climate system.

Choudoir, Mallory J. (ORCID:0000000291175150)↗
DOE OSTI2023

A symbiotic bacterium of Antarctic fish reveals environmental adaptability mechanisms and biosynthetic potential towards antibacterial and cytotoxic activities

Antarctic microbes are important agents for evolutionary adaptation and natural resource of bioactive compounds, harboring the particular metabolic pathways to biosynthesize natural products. However, not much is known on symbiotic microbiomes of fish in the Antarctic zone. In the present study, the culture method and whole-genome sequencing were performed. Natural product analyses were carried out to determine the biosynthetic potential. We report the isolation and identification of a symbiotic bacterium Serratia myotis L7-1, that is highly adaptive and resides within Antarctic fish, Trematomus bernacchii . As revealed by genomic analyses, Antarctic strain S. myotis L7-1 possesses carbohydrate-active enzymes (CAZymes), biosynthetic gene clusters (BGCs), stress response genes, antibiotic resistant genes (ARGs), and a complete type IV secretion system which could facilitate competition and colonization in the extreme Antarctic environment. The identification of microbiome gene clusters indicates the biosynthetic potential of bioactive compounds. Based on bioactivity-guided fractionation, serranticin was purified and identified as the bioactive compound, showing significant antibacterial and antitumor activity. The serranticin gene cluster was identified and located on the chrome. Furthermore, the multidrug resistance and strong bacterial antagonism contribute competitive advantages in ecological niches. Our results highlight the existence of a symbiotic bacterium in Antarctic fish largely represented by bioactive natural products and the adaptability to survive in the fish living in Antarctic oceans.

Xiao, Yu↗
NASA NTRS1999

Capella: Structure and Abundances

This grant covers the analysis of ASCA spectra of the cool star binary system Capella. This project has also required the analysis of simultaneous EUVE data. The ASCA spectrum of Capella could not be fit with standard models; by imposing models based on strong lines observed with EUVE, a problem wavelength region was identified. Correcting the problem required calculations of atomic collision strengths of higher principal quantum number than had ever been calculated, resulting in a paper in process by Liedahl and Brickhouse. With these new models applied to the ASCA spectrum, better fits were obtained. While solar abundance ratios are generally consistent with the ASCA data, the ratio of Ne/Fe is three to four times lower than solar photospheric values. Whether there is a general First Ionization Potential (FIP) effect or a specific neon anomaly cannot be determined from these data. Detailed discussion has been provided to NASA in the most recent annual report (1997). Two poster presentations have been made regarding modeling requirements. A substantial paper is in the final revision form, following review by six co-authors. The results of this work have wide implications, since the newly calculated emission lines almost certainly contribute to other problems in fitting not only other stellar spectra, but also composite supernova remnants, galaxies, and cooling flow clusters of galaxies. Furthermore, Liedahl and Brickhouse have identified other species for which lines of a similar nature (high principal quantum number) will contribute significant flux. For moderate resolution X-ray spectra, lines left out of the models in relatively isolated bands, will be attributed to continuum flux by spectral fitting engines, causing errors in line-to-continuum ratios. Thus addressing the general theoretical problem is of crucial importance.

Brickhouse, Nancy S.↗
NASA NTRS1994

A violent interaction between the dwarf galaxy UGC 7636 and the giant elliptical galaxy NGC 4472

We present new U, B, R, and H I imagery of the Virgo Cluster giant elliptical galaxy NGC 4472 and its interacting dwarf companion galaxy UGC 7636. Using a composite image reconstruction technique, we show that a trail of debris approx. 5 arcmin in length and approx. 1 arcmin in width (30x6 kpc for a Virgo cluster distance of 20 Mpc) is projected northward from the dwarf galaxy. A cloud of H I is projected along the northwest edge of the debris between the dwarf and gE. The dwarf's nuclear morphology is irregular and bow-shaped on what appears to be its leading edge. Apart from a number of isolated blue regions, most of of the trailing debris is similar in color to the dwarf's nucleus. Only a modest enhancement of star formation appears to have been induced by the interaction. Although separated by 15 kpc, the H I and stellar morphologies are remarkably similar. The stars and H I appear to have been tidally distorted in situ, prior to the cloud's removal by ram pressure. If the H I has maintained its shape by magnetic support, a magnetic field strength an order of magnitude larger than the galaxy's is required. Ram pressure deceleration due to the cloud's motion through NGC 4472's x-ray-emitting interstellar medium shold be sufficient for the cloud to become gravitationally bound to NGC 4472. The H I cloud is not self-gravitating and may fragment and be destroyed in the interaction. UGC 7636 will probably be disrupted by NGC 4472's strong tidal forces; the stellar debris will disperse into the Virgo cluster or become bound to NGC 4472's halo on eccentric orbits. The debris captured in the collision will have a negligible impact on NGC 4472's stellar and gaseous content. On the other hand, if similar interactions are common in giant elliptical galaxies, they could alter or deplete surrounding dwarf galaxy populations, fuel bursts of nuclear activity, and perhaps provide a source of magnetic energy to their interstellar media.

Mcnamara, Brian R.↗
DOE OSTI2022

Defensive Islanding to Enhance the Resilience of Distribution Systems Against Cyber-Induced Failures

The extensive integration of communication, computation, and control technologies into cyber-physical power systems (CPPSs) has increased the vulnerabilities of CPPSs to cyberattacks. This calls for developing solutions that assess and reduce the impacts of cyber-induced failures on CPPSs. This paper proposes a defensive islanding strategy to isolate impacted parts of the CPPS and form self-sufficient islanded grids with an objective of minimum load curtailment. The defensive islanding aims to split a power system into smaller grids to improve its resilience against a potential extreme event. A clustering approach that leverages the hierarchical spectral clustering method is utilized for the optimal defensive islanding. The proposed approach captures the fragility behavior and loading conditions of power system components due to cyber-induced failures. A graphical-based coupling framework is used to map the impacts of cyber failures into operation of power system components. The proposed method is demonstrated on a modified 33-node distribution feeder system integrated with distributed energy resources. The amount of load curtailment and radiality constraints have been used to evaluate the performance of the proposed clustering strategies. The results show the capability of the proposed algorithm to create islands considering the cyber-induced failures for enhanced resilience.

cyber-induced failures↗
NASA NTRS1988

A 21 cm survey of the Pisces-Perseus supercluster. III - The region north of +38 degrees

As part of a comprehensive survey of galaxies in the region of the Pisces-Perseus supercluster and its surroundings, 21-cm line observations obtained with the NRAO 91-m telescope are presented for 383 galaxies in the right ascension range from 22 to 10 hr and north of +38 deg declination. Recent improvements to the Green Bank receiver/feed system have dramatically raised detection rates at the distance of Pisces-Perseus (cz = +5000 km/s). The present study has contributed to double the number of known redshifts outside rich clusters in this section of the sky. The H I content of the current sample, as expressed in terms of the H I mass expected for a galaxy of the same optical size and morphology, matches the standard of normalcy established for isolated galaxies.

Haynes, Martha P.↗
DOE OSTI2022

‘Flux+Mutability’: a conditional generative approach to one-class classification and anomaly detection

Abstract Anomaly Detection is becoming increasingly popular within the experimental physics community. At experiments such as the Large Hadron Collider, anomaly detection is growing in interest for finding new physics beyond the Standard Model. This paper details the implementation of a novel Machine Learning architecture, called Flux+Mutability, which combines cutting-edge conditional generative models with clustering algorithms. In the ‘flux’ stage we learn the distribution of a reference class. The ‘mutability’ stage at inference addresses if data significantly deviates from the reference class. We demonstrate the validity of our approach and its connection to multiple problems spanning from one-class classification to anomaly detection. In particular, we apply our method to the isolation of neutral showers in an electromagnetic calorimeter and show its performance in detecting anomalous dijets events from standard QCD background. This approach limits assumptions on the reference sample and remains agnostic to the complementary class of objects of a given problem. We describe the possibility of dynamically generating a reference population and defining selection criteria via quantile cuts. Remarkably this flexible architecture can be deployed for a wide range of problems, and applications like multi-class classification or data quality control are left for further exploration.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2020

Activated KCNQ1 channel promotes fibrogenic response in hereditary gingival fibromatosis via clustering and activation of Ras

Abstract Background and Objective Activated potassium channels were found to be strongly correlated with gingival overgrowth (GO) phenotype as we reviewed syndromic hereditary gingival fibromatosis (HGF). Nevertheless, the functional roles of potassium channels in gingival fibrosis or gingival overgrowth remained uncovered. The aim of the present study was to explore the pathogenic role of aberrantly activated potassium channel in Hereditary Gingival Fibromatosis (HGF). Methods Gingival tissues were collected from 9 HGF patients and 15 normal controls. Expression of KCNQ1 was detected by immunohistochemistry. Gingival fibroblasts were isolated, and outward K + currents were detected by whole‐cell patch‐clamp analysis, transmembrane potential was determined by flow cytometry. Normal human gingival fibroblasts (NHGFs) were transfected with KCNQ1 adenovirus or treated with KCNQ1 selective agonist ML277 and antagonist chromanol 293B. Accumulation of Extracellular Matrix (ECM) was measured by Western blotting and Sircol Soluble Collagen Assay. Content of secreted TGF‐β1 was measured by ELISA. Active RAS pull‐down assay and cell immunofluorescence were utilized to verify RAS activation. Results KCNQ1 was upregulated in gingival tissues derived from HGF patients and HGF gingival fibroblasts presented increased outward K + currents than NHGFs. Overexpression of KCNQ1, or KCNQ1 agonist ML277, promoted fibrotic responses of NHGFs. TGF‐β1 and KCNQ1 channels formed a positive feed‐back loop. ML277 generated lateral clustering and activation of Ras on plasma membrane, followed by augmented MAPK/AP‐1 signaling pathway output. JNK or ERK1/2 inhibitors suppressed ML277‐induced AP‐1 and ECM upregulation. Conclusion Activation of KCNQ1 potassium channel promoted fibrogenic responses in NHGFs via Ras/MAPK/AP‐1 signaling.

Gao, Qian↗
DOE OSTI2021

Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential

The Antarctic marine ecosystem harbors a wealth of biological and chemical innovation that has risen in concert over millennia since the isolation of the continent and formation of the Antarctic circumpolar current. Scientific inquiry into the novelty of marine natural products produced by Antarctic benthic invertebrates led to the discovery of a bioactive macrolide, palmerolide A, that has specific activity against melanoma and holds considerable promise as an anticancer therapeutic. While this compound was isolated from the Antarctic ascidian Synoicum adareanum, its biosynthesis has since been hypothesized to be microbially mediated, given structural similarities to microbially produced hybrid nonribosomal peptide-polyketide macrolides. Here, we describe a metagenome-enabled investigation aimed at identifying the biosynthetic gene cluster (BGC) and palmerolide A-producing organism. A 74-kbp candidate BGC encoding the multimodular enzymatic machinery (hybrid type I-trans-AT polyketide synthase-nonribosomal peptide synthetase and tailoring functional domains) was identified and found to harbor key features predicted as necessary for palmerolide A biosynthesis. Surveys of ascidian microbiome samples targeting the candidate BGC revealed a high correlation between palmerolide gene targets and a single 16S rRNA gene variant (R = 0.83 to 0.99). Through repeated rounds of metagenome sequencing followed by binning contigs into metagenome-assembled genomes, we were able to retrieve a nearly complete genome (10 contigs) of the BGC-producing organism, a novel verrucomicrobium within the Opitutaceae family that we propose here as “Candidatus Synoicihabitans palmerolidicus.” The refined genome assembly harbors five highly similar BGC copies, along with structural and functional features that shed light on the host-associated nature of this unique bacterium.

59 BASIC BIOLOGICAL SCIENCES↗