NilD CRISPR RNA contributes to Xenorhabdus nematophila colonization of symbiotic host nematodes

The bacterium Xenorhabdus nematophila is a mutualist of entomopathogenic Steinernema carpocapsae nematodes and facilitates infection of insect hosts. X. nematophila colonizes the intestine of S. carpocapsae which carries it between insects. In the X. nematophila colonization-defective mutant nilD6::Tn5, the transposon is inserted in a region lacking obvious coding potential. We demonstrate that the transposon disrupts expression of a single CRISPR RNA, NilD RNA. A variant NilD RNA also is expressed by X. nematophila strains from S. anatoliense and S. websteri nematodes. Only nilD from the S. carpocapsae strain of X. nematophila rescued the colonization defect of the nilD6::Tn5 mutant, and this mutant was defective in colonizing all three nematode host species. NilD expression depends on the presence of the associated Cas6e but not Cas3, components of the Type I-E CRISPR-associated machinery. While cas6e deletion in the complemented strain abolished nematode colonization, its disruption in the wild-type parent did not. Likewise, nilD deletion in the parental strain did not impact colonization of the nematode, revealing that the requirement for NilD is evident only in certain genetic backgrounds. Our data demonstrate that NilD RNA is conditionally necessary for mutualistic host colonization and suggest that it functions to regulate endogenous gene expression

Foregut microbiome in development of esophageal adenocarcinoma

Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has increased six fold in the past 30 years. This cannot currently be explained by the usual environmental or by host genetic factors. EA is the end result of a sequence of GERD-related diseases, preceded by reflux esophagitis (RE) and Barrett’s esophagus (BE). Preliminary studies by Pei and colleagues at NYU on elderly male veterans identified two types of microbiotas in the esophagus. Patients who carry the type II microbiota are >15 fold likely to have esophagitis and BE than those harboring the type I microbiota. In a small scale study, we also found that 3 of 3 cases of EA harbored the type II biota. The findings have opened a new approach to understanding the recent surge in the incidence of EA. 

Our long-term goal is to identify the cause of GERD sequence. The hypothesis to be tested is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in GERD sequence. We will conduct a case control study to demonstrate the microbiome disease association in every stage of GERD sequence, as well as analyze the trend in changes in the microbiome along disease progression toward EA, by two specific aims. Aim 1 is to conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence. Furthermore, spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Aim 2 is to define the distal esophageal metagenome and demonstrate its association with GERD sequence. Detailed analyses will include pathway-disease and gene-disease associations. Archaea, fungi and viruses, if identified, also will be correlated with the diseases. A significant association between the foregut microbiome and GERD sequence, if demonstrated, will be the first step for eventually testing whether an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiota through use of antibiotics, probiotics, or prebiotics. Causative therapy of GERD could prevent its progression and reverse the current trend of increasing incidence of EA

Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samples

We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples. Our method uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier and ribosomal RNA. This depletion step improves both the quality of data and quantity of informative reads in unbiased total RNA sequencing libraries. We have also developed a hybrid-selection protocol to further enrich the viral content of sequencing libraries. These protocols have enabled rapid deep sequencing of both Lassa and Ebola virus and are broadly applicable to other viral genomics studies. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0519-7) contains supplementary material, which is available to authorized users

CHIME Discovery of a Binary Pulsar with a Massive Non-Degenerate Companion

Of the more than 3000 radio pulsars currently known, only ∼300 are in binary systems, and only five of these consist of young pulsars with massive nondegenerate companions. We present the discovery and initial timing, accomplished using the Canadian Hydrogen Intensity Mapping Experiment (CHIME) telescope, of the sixth such binary pulsar, PSR J2108+4516, a 0.577 s radio pulsar in a 269 day orbit of eccentricity 0.09 with a companion of minimum mass 11 M⊙. Notably, the pulsar undergoes periods of substantial eclipse, disappearing from the CHIME 400–800 MHz observing band for a large fraction of its orbit, and displays significant dispersion measure and scattering variations throughout its orbit, pointing to the possibility of a circumstellar disk or very dense stellar wind associated with the companion star. Subarcsecond resolution imaging with the Karl G. Jansky Very Large Array unambiguously demonstrates that the companion is a bright, V ≃ 11 OBe star, EM* UHA 138, located at a distance of 3.26(14) kpc. Archival optical observations of EM* UHA 138 approximately suggest a companion mass ranging from 17.5 M⊙ < Mc < 23 M⊙, in turn constraining the orbital inclination angle to 50fdg3 ≲ i ≲ 58fdg3. With further multiwavelength follow-up, PSR J2108+4516 promises to serve as another rare laboratory for the exploration of companion winds, circumstellar disks, and short-term evolution through extended-body orbital dynamics

Comprehensive Bayesian analysis of FRB-like bursts from SGR 1935+2154 observed by CHIME/FRB

The bright millisecond-duration radio burst from the Galactic magnetar SGR 1935+2154 in 2020 April was a landmark event, demonstrating that at least some fast radio burst (FRB) sources could be magnetars. The two-component burst was temporally coincident with peaks observed within a contemporaneous short X-ray burst envelope, marking the first instance where FRB-like bursts were observed to coincide with X-ray counterparts. In this study, we detail five new radio burst detections from SGR 1935+2154, observed by the CHIME/FRB instrument between October 2020 and December 2022. We develop a fast and efficient Bayesian inference pipeline that incorporates state-of-the-art Markov chain Monte Carlo techniques and use it to model the intensity data of these bursts under a flexible burst model. We revisit the 2020 April burst and corroborate that both the radio sub-components lead the corresponding peaks in their high-energy counterparts. For a burst observed in 2022 October, we find that our estimated radio pulse arrival time is contemporaneous with a short X-ray burst detected by GECAM and HEBS, and Konus-Wind and is consistent with the arrival time of a radio burst detected by GBT. We present flux and fluence estimates for all five bursts, employing an improved estimator for bursts detected in the side-lobes. We also present upper limits on radio emission for X-ray emission sources which were within CHIME/FRB's field-of-view at trigger time. Finally, we present our exposure and sensitivity analysis and estimate the Poisson rate for FRB-like events from SGR 1935+2154 to be $0.005^{+0.082}_{-0.004}$ events/day above a fluence of $10~\mathrm{kJy~ms}$ during the interval from 28 August 2018 to 1 December 2022, although we note this was measured during a time of great X-ray activity from the source.Comment: 22 pages, 6 figures, 4 tables. To be submitted to Ap

Spitzer Follow-up of Extremely Cold Brown Dwarfs Discovered by the Backyard Worlds: Planet 9 Citizen Science Project

We present Spitzer follow-up imaging of 95 candidate extremely cold brown dwarfs discovered by the Backyard Worlds: Planet 9 citizen science project, which uses visually perceived motion in multiepoch Wide-field Infrared Survey Explorer (WISE) images to identify previously unrecognized substellar neighbors to the Sun. We measure Spitzer [3.6]–[4.5] color to phototype our brown dwarf candidates, with an emphasis on pinpointing the coldest and closest Y dwarfs within our sample. The combination of WISE and Spitzer astrometry provides quantitative confirmation of the transverse motion of 75 of our discoveries. Nine of our motion-confirmed objects have best-fit linear motions larger than 1'' yr⁻¹; our fastest-moving discovery is WISEA J155349.96+693355.2 (μ ≈ 2.”15 yr⁻¹), a possible T-type subdwarf. We also report a newly discovered wide-separation (~400 au) T8 comoving companion to the white dwarf LSPM J0055+5948 (the fourth such system to be found), plus a candidate late T companion to the white dwarf LSR J0002+6357 at 5 5 projected separation (~8700 au if associated). Among our motion-confirmed targets, five have Spitzer colors most consistent with spectral type Y. Four of these five have exceptionally red Spitzer colors suggesting types of Y1 or later, adding considerably to the small sample of known objects in this especially valuable low-temperature regime. Our Y dwarf candidates begin bridging the gap between the bulk of the Y dwarf population and the coldest known brown dwarf

Spitzer Follow-up of Extremely Cold Brown Dwarfs Discovered by the Backyard Worlds: Planet 9 Citizen Science Project

We present Spitzer follow-up imaging of 95 candidate extremely cold brown dwarfs discovered by the Backyard Worlds: Planet 9 citizen science project, which uses visually perceived motion in multi-epoch WISE images to identify previously unrecognized substellar neighbors to the Sun. We measure Spitzer [3.6]-[4.5] color to phototype our brown dwarf candidates, with an emphasis on pinpointing the coldest and closest Y dwarfs within our sample. The combination of WISE and Spitzer astrometry provides quantitative confirmation of the transverse motion of 75 of our discoveries. Nine of our motion-confirmed objects have best-fit linear motions larger than 1"/yr; our fastest-moving discovery is WISEA J155349.96+693355.2 (total motion ~2.15"/yr), a possible T type subdwarf. We also report a newly discovered wide-separation (~400 AU) T8 comoving companion to the white dwarf LSPM J0055+5948 (the fourth such system to be found), plus a candidate late T companion to the white dwarf LSR J0002+6357 at 5.5' projected separation (~8,700 AU if associated). Among our motion-confirmed targets, five have Spitzer colors most consistent with spectral type Y. Four of these five have exceptionally red Spitzer colors suggesting types of Y1 or later, adding considerably to the small sample of known objects in this especially valuable low-temperature regime. Our Y dwarf candidates begin bridging the gap between the bulk of the Y dwarf population and the coldest known brown dwarf.Comment: accepted for publication in The Astrophysical Journa

Pulmonary Endpoints (Lung Carcinomas and Asbestosis) Following Inhalation Exposure to Asbestos

Lung carcinomas and pulmonary fibrosis (asbestosis) occur in asbestos workers. Understanding the pathogenesis of these diseases is complicated because of potential confounding factors, such as smoking, which is not a risk factor in mesothelioma. The modes of action (MOA) of various types of asbestos in the development of lung cancers, asbestosis, and mesotheliomas appear to be different. Moreover, asbestos fibers may act differentially at various stages of these diseases, and have different potencies as compared to other naturally occurring and synthetic fibers. This literature review describes patterns of deposition and retention of various types of asbestos and other fibers after inhalation, methods of translocation within the lung, and dissolution of various fiber types in lung compartments and cells in vitro. Comprehensive dose-response studies at fiber concentrations inhaled by humans as well as bivariate size distributions (lengths and widths), types, and sources of fibers are rarely defined in published studies and are needed. Species-specific responses may occur. Mechanistic studies have some of these limitations, but have suggested that changes in gene expression (either fiber-catalyzed directly or by cell elaboration of oxidants), epigenetic changes, and receptor-mediated or other intracellular signaling cascades may play roles in various stages of the development of lung cancers or asbestosis

CHIME/FRB Discovery of 25 Repeating Fast Radio Burst Sources

We present the discovery of 25 new repeating fast radio burst (FRB) sources found among CHIME/FRB events detected between 2019 September 30 and 2021 May 1. The sources were found using a new clustering algorithm that looks for multiple events co-located on the sky having similar dispersion measures (DMs). The new repeaters have DMs ranging from $\sim$220 pc cm$^{-3}$ to $\sim$1700 pc cm$^{-3}$, and include sources having exhibited as few as two bursts to as many as twelve. We report a statistically significant difference in both the DM and extragalactic DM (eDM) distributions between repeating and apparently nonrepeating sources, with repeaters having lower mean DM and eDM, and we discuss the implications. We find no clear bimodality between the repetition rates of repeaters and upper limits on repetition from apparently nonrepeating sources after correcting for sensitivity and exposure effects, although some active repeating sources stand out as anomalous. We measure the repeater fraction and find that it tends to an equilibrium of $2.6_{-2.6}^{+2.9}$% over our exposure thus far. We also report on 14 more sources which are promising repeating FRB candidates and which merit follow-up observations for confirmation.Comment: Submitted to ApJ. Comments are welcome and follow-up observations are encouraged