A gene cluster in Agrobacterium vitis homologous to polyketide synthase operons is associated with grape necrosis and hypersensitive response induction on tobacco

Here, we identify a cluster of eight genes on chromosome 2 of Agrobacterium vitis that is associated with the ability of the bacterium to cause a hypersensitive response on tobacco and a necrosis of grape shoot explants. Three of these genes share a high level of structural and sequence similarity to clusters of genes in other bacteria that encode the enzymes for biosynthesis of polyketides and long-chain polyunsaturated fatty acids. No similar gene clusters were discovered in sequenced genomes of other members of Rhizobiale

Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System

Exposure to space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized exposure to ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-week old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 mega electron volts per nucleon) or high-LET (sup 56) Fe ions (600 mega electron volts per nucleon) using either low (5 or 10 centigrays) or high (50 or 200 centigrays) doses at NASAs Space Radiation Lab at Brookhaven National Lab (NSRL/BNL). Tissues were harvested 5 weeks or 1 year after irradiation and bones were analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed for select groups by RT-PCR (Reverse Transcription-Polymerase Chain Reaction) during the proliferative phase or the mineralizing phase, and differentiation was analyzed by imaging mineralized nodules (percentage surface area). Representative genes were selected for expression analyses, including cell proliferation (PCNA, Cdk2, p21, p53), differentiation (Runx2, Alpl, Bglap), oxidative metabolism (Catalase, GPX, MnSOD, CuZnSOD, iNos, Foxo1), DNA-damage repair (Gadd45), or apoptosis (Caspase 3). As expected, a high dose (200 centigrays), but not low doses, of either (sup 56) Fe or protons caused a loss of cancellous bone volume per total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; (sup 56) Fe (200 centigrays) inhibited median nodule area by more than 90 percent at 5 weeks and 1 year post-irradiation, compared to controls. At 5 weeks post exposure, irradiation with protons or (sup 56) Fe caused few changes in gene expression levels during osteoblastogenesis, although a high dose of (sup 56) Fe (200 centigrays) increased levels of Catalase and Gadd45. In addition, supplementing cell culture media with SOD protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET ((sup 137) Cs gamma) if irradiated in vitro, but had limited protective effects on high-LET (sup 56) Fe-exposed cells. In sum, exposure of mice to either protons or (sup 56) Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET (sup 56) Fe increased expression of redox-related genes and inhibited osteoblastogenesis, albeit to a limited extent. We conclude that high-LET irradiation impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss

New Experimental Limits on Macroscopic Forces Below 100 Microns

Results of an experimental search for new macroscopic forces with Yukawa range between 5 and 500 microns are presented. The experiment uses 1 kHz mechanical oscillators as test masses with a stiff conducting shield between them to suppress backgrounds. No signal is observed above the instrumental thermal noise after 22 hours of integration time. These results provide the strongest limits to date between 10 and 100 microns, improve on previous limits by as much as three orders of magnitude, and rule out half of the remaining parameter space for predictions of string-inspired models with low-energy supersymmetry breaking. New forces of four times gravitational strength or greater are excluded at the 95% confidence level for interaction ranges between 200 and 500 microns.Comment: 25 Pages, 7 Figures: Minor Correction

The First Hour of Extra-galactic Data of the Sloan Digital Sky Survey Spectroscopic Commissioning: The Coma Cluster

On 26 May 1999, one of the Sloan Digital Sky Survey (SDSS) fiber-fed spectrographs saw astronomical first light. This was followed by the first spectroscopic commissioning run during the dark period of June 1999. We present here the first hour of extra-galactic spectroscopy taken during these early commissioning stages: an observation of the Coma cluster of galaxies. Our data samples the Southern part of this cluster, out to a radius of 1.5degrees and thus fully covers the NGC 4839 group. We outline in this paper the main characteristics of the SDSS spectroscopic systems and provide redshifts and spectral classifications for 196 Coma galaxies, of which 45 redshifts are new. For the 151 galaxies in common with the literature, we find excellent agreement between our redshift determinations and the published values. As part of our analysis, we have investigated four different spectral classification algorithms: spectral line strengths, a principal component decomposition, a wavelet analysis and the fitting of spectral synthesis models to the data. We find that a significant fraction (25%) of our observed Coma galaxies show signs of recent star-formation activity and that the velocity dispersion of these active galaxies (emission-line and post-starburst galaxies) is 30% larger than the absorption-line galaxies. We also find no active galaxies within the central (projected) 200 h-1 Kpc of the cluster. The spatial distribution of our Coma active galaxies is consistent with that found at higher redshift for the CNOC1 cluster survey. Beyond the core region, the fraction of bright active galaxies appears to rise slowly out to the virial radius and are randomly distributed within the cluster with no apparent correlation with the potential merger of the NGC 4839 group. [ABRIDGED]Comment: Accepted in AJ, 65 pages, 20 figures, 5 table

The sound of silence:Transgene silencing in mammalian cell engineering

To elucidate principles operating in native biological systems and to develop novel biotechnologies, synthetic biology aims to build and integrate synthetic gene circuits within native transcriptional networks. The utility of synthetic gene circuits for cell engineering relies on the ability to control the expression of all constituent transgene components. Transgene silencing, defined as the loss of expression over time, persists as an obstacle for engineering primary cells and stem cells with transgenic cargos. In this review, we highlight the challenge that transgene silencing poses to the robust engineering of mammalian cells, outline potential molecular mechanisms of silencing, and present approaches for preventing transgene silencing. We conclude with a perspective identifying future research directions for improving the performance of synthetic gene circuits.ISSN:2405-472

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Proteomic Analysis of Resistance of Gram-Negative Bacteria to Chlorhexidine and Impacts on Susceptibility to Colistin, Antimicrobial Peptides, and Ceragenins

Use of chlorhexidine in clinical settings has led to concerns that repeated exposure of bacteria to sub-lethal doses of chlorhexidine might result in chlorhexidine resistance and cross resistance with other cationic antimicrobials including colistin, endogenous antimicrobial peptides (AMPs) and their mimics, ceragenins. We have previously shown that colistin-resistant Gram-negative bacteria remain susceptible to AMPs and ceragenins. Here, we investigated the potential for cross resistance between chlorhexidine, colistin, AMPs and ceragenins by serial exposure of standard strains of Gram-negative bacteria to chlorhexidine to generate resistant populations of organisms. Furthermore, we performed a proteomics study on the chlorhexidine-resistant strains and compared them to the wild-type strains to find the pathways by which bacteria develop resistance to chlorhexidine. Serial exposure of Gram-negative bacteria to chlorhexidine resulted in four- to eight-fold increases in minimum inhibitory concentrations (MICs). Chlorhexidine-resistant organisms showed decreased susceptibility to colistin (8- to 32-fold increases in MICs) despite not being exposed to colistin. In contrast, chlorhexidine-resistant organisms had the same MICs as the original strains when tested with representative AMPs (LL-37 and magainin I) and ceragenins (CSA-44 and CSA-131). These results imply that there may be a connection between the emergence of highly colistin-resistant Gram-negative pathogens and the prevalence of chlorhexidine usage. Yet, use of chlorhexidine may not impact innate immune defenses (e.g., AMPs) and their mimics (e.g., ceragenins). Here, we also show that chlorhexidine resistance is associated with upregulation of proteins involved in the assembly of LPS for outer membrane biogenesis and virulence factors in Pseudomonas aeruginosa. Additionally, resistance to chlorhexidine resulted in elevated expression levels of proteins associated with chaperones, efflux pumps, flagella and cell metabolism. This study provides a comprehensive overview of the evolutionary proteomic changes in P. aeruginosa following exposure to chlorhexidine and colistin. These results have important clinical implications considering the continuous application of chlorhexidine in hospitals that could influence the emergence of colistin-resistant strains

The Atacama Cosmology Telescope: Cosmology from cross-correlations of unWISE galaxies and ACT DR6 CMB lensing

We present tomographic measurements of structure growth using cross-correlations of Atacama Cosmology Telescope (ACT) DR6 and Planck CMB lensing maps with the unWISE Blue and Green galaxy samples, which span the redshift ranges $0.2 \lesssim z \lesssim 1.1$ and $0.3 \lesssim z \lesssim 1.8$, respectively. We improve on prior unWISE cross-correlations not just by making use of the new, high-precision ACT DR6 lensing maps, but also by including additional spectroscopic data for redshift calibration and by analysing our measurements with a more flexible theoretical model. An extensive suite of systematic and null tests within a blind analysis framework ensures that our results are robust. We determine the amplitude of matter fluctuations at low redshifts ($z\simeq 0.2-1.6$), finding $S_8 \equiv \sigma_8 (\Omega_m / 0.3)^{0.5} = 0.813 \pm 0.021$ using the ACT cross-correlation alone and $S_8 = 0.810 \pm 0.015$ with a combination of Planck and ACT cross-correlations; these measurements are fully consistent with the predictions from primary CMB measurements assuming standard structure growth. The addition of Baryon Acoustic Oscillation data breaks the degeneracy between $\sigma_8$ and $\Omega_m$, allowing us to measure $\sigma_8 = 0.813 \pm 0.020$ from the cross-correlation of unWISE with ACT and $\sigma_8 = 0.813\pm 0.015$ from the combination of cross-correlations with ACT and Planck. These results also agree with the expectations from primary CMB extrapolations in $\Lambda$CDM cosmology; the consistency of $\sigma_8$ derived from our two redshift samples at $z \sim 0.6$ and $1.1$ provides a further check of our cosmological model. Our results suggest that structure formation on linear scales is well described by $\Lambda$CDM even down to low redshifts $z\lesssim 1$.Comment: 73 pages (incl. 30 pages of appendices), 50 figures, 16 tables, to be submitted to ApJ. Watch G. S. Farren and A. Krolewski discuss the analysis and results under https://cosmologytalks.com/2023/09/11/act-unwis

The Atacama Cosmology Telescope: Mitigating the impact of extragalactic foregrounds for the DR6 CMB lensing analysis

We investigate the impact and mitigation of extragalactic foregrounds for the CMB lensing power spectrum analysis of Atacama Cosmology Telescope (ACT) data release 6 (DR6) data. Two independent microwave sky simulations are used to test a range of mitigation strategies. We demonstrate that finding and then subtracting point sources, finding and then subtracting models of clusters, and using a profile bias-hardened lensing estimator, together reduce the fractional biases to well below statistical uncertainties, with the inferred lensing amplitude, $A_{\mathrm{lens}}$, biased by less than $0.2\sigma$. We also show that another method where a model for the cosmic infrared background (CIB) contribution is deprojected and high frequency data from Planck is included has similar performance. Other frequency-cleaned options do not perform as well, incurring either a large noise cost, or resulting in biased recovery of the lensing spectrum. In addition to these simulation-based tests, we also present null tests performed on the ACT DR6 data which test for sensitivity of our lensing spectrum estimation to differences in foreground levels between the two ACT frequencies used, while nulling the CMB lensing signal. These tests pass whether the nulling is performed at the map or bandpower level. The CIB-deprojected measurement performed on the DR6 data is consistent with our baseline measurement, implying contamination from the CIB is unlikely to significantly bias the DR6 lensing spectrum. This collection of tests gives confidence that the ACT DR6 lensing measurements and cosmological constraints presented in companion papers to this work are robust to extragalactic foregrounds.Comment: Companion paper to Qu et al and Madhavacheril et a

What does an interferometer really measure? Including instrument and data characteristics in the reconstruction of the 21cm power spectrum

Combining the visibilities measured by an interferometer to form a cosmological power spectrum is a complicated process in which the window functions play a crucial role. In a delay-based analysis, the mapping between instrumental space, made of per-baseline delay spectra, and cosmological space is not a one-to-one relation. Instead, neighbouring modes contribute to the power measured at one point, with their respective contributions encoded in the window functions. To better understand the power spectrum measured by an interferometer, we assess the impact of instrument characteristics and analysis choices on the estimator by deriving its exact window functions, outside of the delay approximation. Focusing on HERA as a case study, we find that observations made with long baselines tend to correspond to enhanced low-k tails of the window functions, which facilitate foreground leakage outside the wedge, whilst the choice of bandwidth and frequency taper can help narrow them down. With the help of simple test cases and more realistic visibility simulations, we show that, apart from tracing mode mixing, the window functions can accurately reconstruct the power spectrum estimator of simulated visibilities. We note that the window functions depend strongly on the chromaticity of the beam, and less on its spatial structure - a Gaussian approximation, ignoring side lobes, is sufficient. Finally, we investigate the potential of asymmetric window functions, down-weighting the contribution of low-k power to avoid foreground leakage. The window functions presented in this work correspond to the latest HERA upper limits for the full Phase I data. They allow an accurate reconstruction of the power spectrum measured by the instrument and can be used in future analyses to confront theoretical models and data directly in cylindrical space.Comment: 18 pages, 18 figures, submitted to MNRAS. Comments welcome