Zygomycetes, Microsporidia, and the Evolutionary Ancestry of Sex Determination

Zygomycetes and their alleged sister taxon, the microsporidia, exclusively share the presence of a cluster of three genes encoding a sugar transporter, a high mobility group (HMG)-type transcription factor, and an RNA helicase. In zygomycetes, the HMG-type transcription factor acts as the sole sex determinant. This intimately ties the evolutionary history of this gene cluster to the evolution of sex determination. Here, we have unraveled the relationships of the two gene clusters by vicariously analyzing the sugar transporters and the RNA helicases. We show that if the two gene clusters share a common ancestry, it dates back to the early days of eukaryotic evolution. As a consequence, the zygomycete MAT locus would be old enough to represent the archetype of fungal and animal sex determination. However, the evolutionary scenario that has to be invoked is complex. An independent assembly of the two clusters deserves therefore consideration. In either case, shared ancestry or convergent evolution, the presence of the gene cluster in microsporidia and in zygomycetes represents at best a plesiomorphy. Hence, it is not phylogenetically informative. A further genome-wide reanalysis of gene order conservation reveals that gene order is not significantly more similar between microsporidia and zygomycetes than between microsporidia and any other fungal taxon or even humans. Consequently, the phylogenetic placement of microsporidia as sister to the zygomycetes needs to be reconsidered

The zinc finger antiviral protein ZAP restricts human cytomegalovirus and selectively binds and destabilizes viral UL4/UL5 transcripts

Interferon-stimulated gene products (ISGs) play a crucial role in early infection control. The ISG zinc finger CCCH-type antiviral protein 1 (ZAP/ZC3HAV1) antagonizes several RNA viruses by binding to CG-rich RNA sequences, whereas its effect on DNA viruses is less well understood. Here, we decipher the role of ZAP in the context of human cytomegalovirus (HCMV) infection, a β-herpesvirus that is associated with high morbidity in immunosuppressed individuals and newborns. We show that expression of the two major isoforms of ZAP, ZAP-S and ZAP-L, is induced during HCMV infection and that both negatively affect HCMV replication. Transcriptome and proteome analyses demonstrated that the expression of ZAP results in reduced viral mRNA and protein levels and decelerates the progression of HCMV infection. Metabolic RNA labeling combined with high-throughput sequencing (SLAM-seq) revealed that most of the gene expression changes late in infection result from the general attenuation of HCMV. Furthermore, at early stages of infection, ZAP restricts HCMV by destabilizing a distinct subset of viral mRNAs, particularly those from the previously uncharacterized HCMV gene locus. Through enhanced cross-linking immunoprecipitation and sequencing analysis (eCLIP-seq), we identified the transcripts expressed from this HCMV locus as the direct targets of ZAP. Moreover, our data show that ZAP preferentially recognizes not only CG, but also other cytosine-rich sequences, thereby expanding its target specificity. In summary, this report is the first to reveal direct targets of ZAP during HCMV infection, which strongly indicates that transcripts from the locus may play an important role for HCMV replication

The cytomegalovirus M35 protein directly binds to the interferon-β enhancer and modulates transcription of (Ifnb1) and other IRF3-driven genes

Induction of type I interferon (IFN) gene expression is among the first lines of cellular defense a virus encounters during primary infection. We previously identified the tegument protein M35 of murine cytomegalovirus (MCMV) as an essential antagonist of this antiviral system, showing that M35 interferes with type I IFN induction downstream of pattern-recognition receptor (PRR) activation. Here, we report structural and mechanistic details of M35's function. Determination of M35's crystal structure combined with reverse genetics revealed that homodimerization is a key feature for M35's immunomodulatory activity. In electrophoretic mobility shift assays (EMSAs), purified M35 protein specifically bound to the regulatory DNA element that governs transcription of the first type I IFN gene induced in nonimmune cells, (Ifnb1). DNA-binding sites of M35 overlapped with the recognition elements of interferon regulatory factor 3 (IRF3), a key transcription factor activated by PRR signaling. Chromatin immunoprecipitation (ChIP) showed reduced binding of IRF3 to the host (Ifnb1) promoter in the presence of M35. We furthermore defined the IRF3-dependent and the type I IFN signaling-responsive genes in murine fibroblasts by RNA sequencing of metabolically labeled transcripts (SLAM-seq) and assessed M35's global effect on gene expression. Stable expression of M35 broadly influenced the transcriptome in untreated cells and specifically downregulated basal expression of IRF3-dependent genes. During MCMV infection, M35 impaired expression of IRF3-responsive genes aside of (Ifnb1). Our results suggest that M35-DNA binding directly antagonizes gene induction mediated by IRF3 and impairs the antiviral response more broadly than formerly recognized. (IMPORTANCE) Replication of the ubiquitous human cytomegalovirus (HCMV) in healthy individuals mostly goes unnoticed but can impair fetal development or cause life-threatening symptoms in immunosuppressed or -deficient patients. Like other herpesviruses, CMV extensively manipulates its hosts and establishes lifelong latent infections. Murine CMV (MCMV) presents an important model system as it allows the study of CMV infection in the host organism. We previously showed that during entry into host cells, MCMV virions release the evolutionary conserved protein M35 protein to immediately dampen the antiviral type I interferon (IFN) response induced by pathogen detection. Here, we show that M35 dimers bind to regulatory DNA elements and interfere with recruitment of interferon regulatory factor 3 (IRF3), a key cellular factor for antiviral gene expression. Thereby, M35 interferes with expression of type I IFNs and other IRF3-dependent genes, reflecting the importance for herpesviruses to avoid IRF3-mediated gene induction

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Search for Eccentric Binary Black Hole Mergers with Advanced LIGO and Advanced Virgo during Their First and Second Observing Runs

When formed through dynamical interactions, stellar-mass binary black holes (BBHs) may retain eccentric orbits (e > 0.1 at 10 Hz) detectable by ground-based gravitational-wave detectors. Eccentricity can therefore be used to differentiate dynamically formed binaries from isolated BBH mergers. Current template-based gravitational-wave searches do not use waveform models associated with eccentric orbits, rendering the search less efficient for eccentric binary systems. Here we present the results of a search for BBH mergers that inspiral in eccentric orbits using data from the first and second observing runs (O1 and O2) of Advanced LIGO and Advanced Virgo. We carried out the search with the coherent WaveBurst algorithm, which uses minimal assumptions on the signal morphology and does not rely on binary waveform templates. We show that it is sensitive to binary mergers with a detection range that is weakly dependent on eccentricity for all bound systems. Our search did not identify any new binary merger candidates. We interpret these results in light of eccentric binary formation models. We rule out formation channels with rates ⪆100 Gpc-3 yr-1 for e > 0.1, assuming a black hole mass spectrum with a power-law index ≲2

GW190521 : A Binary Black Hole Merger with a Total Mass of 150 M_{⊙}

On May 21, 2019 at 03:02:29 UTC Advanced LIGO and Advanced Virgo observed a short duration gravitational-wave signal, GW190521, with a three-detector network signal-to-noise ratio of 14.7, and an estimated false-alarm rate of 1 in 4900 yr using a search sensitive to generic transients. If GW190521 is from a quasicircular binary inspiral, then the detected signal is consistent with the merger of two black holes with masses of 85_{-14}^{+21}  M_{⊙} and 66_{-18}^{+17}  M_{⊙} (90% credible intervals). We infer that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65  M_{⊙}. We calculate the mass of the remnant to be 142_{-16}^{+28}  M_{⊙}, which can be considered an intermediate mass black hole (IMBH). The luminosity distance of the source is 5.3_{-2.6}^{+2.4}  Gpc, corresponding to a redshift of 0.82_{-0.34}^{+0.28}. The inferred rate of mergers similar to GW190521 is 0.13_{-0.11}^{+0.30}  Gpc^{-3} yr^{-1}

Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA

We present our current best estimate of the plausible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next several years, with the intention of providing information to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals for the third (O3), fourth (O4) and fifth observing (O5) runs, including the planned upgrades of the Advanced LIGO and Advanced Virgo detectors. We study the capability of the network to determine the sky location of the source for gravitational-wave signals from the inspiral of binary systems of compact objects, that is binary neutron star, neutron star–black hole, and binary black hole systems. The ability to localize the sources is given as a sky-area probability, luminosity distance, and comoving volume. The median sky localization area (90% credible region) is expected to be a few hundreds of square degrees for all types of binary systems during O3 with the Advanced LIGO and Virgo (HLV) network. The median sky localization area will improve to a few tens of square degrees during O4 with the Advanced LIGO, Virgo, and KAGRA (HLVK) network. During O3, the median localization volume (90% credible region) is expected to be on the order of 105,106,107Mpc3 for binary neutron star, neutron star–black hole, and binary black hole systems, respectively. The localization volume in O4 is expected to be about a factor two smaller than in O3. We predict a detection count of 1-1+12(10-10+52) for binary neutron star mergers, of 0-0+19(1-1+91) for neutron star–black hole mergers, and 17-11+22(79-44+89) for binary black hole mergers in a one-calendar-year observing run of the HLV network during O3 (HLVK network during O4). We evaluate sensitivity and localization expectations for unmodeled signal searches, including the search for intermediate mass black hole binary mergers. © 2020, The Author(s)

GWTC-1: A Gravitational-Wave Transient Catalog of Compact Binary Mergers Observed by LIGO and Virgo during the First and Second Observing Runs

We present the results from three gravitational-wave searches for coalescing compact binaries with component masses above 1 Ma™ during the first and second observing runs of the advanced gravitational-wave detector network. During the first observing run (O1), from September 12, 2015 to January 19, 2016, gravitational waves from three binary black hole mergers were detected. The second observing run (O2), which ran from November 30, 2016 to August 25, 2017, saw the first detection of gravitational waves from a binary neutron star inspiral, in addition to the observation of gravitational waves from a total of seven binary black hole mergers, four of which we report here for the first time: GW170729, GW170809, GW170818, and GW170823. For all significant gravitational-wave events, we provide estimates of the source properties. The detected binary black holes have total masses between 18.6-0.7+3.2 Mâ™ and 84.4-11.1+15.8 Mâ™ and range in distance between 320-110+120 and 2840-1360+1400 Mpc. No neutron star-black hole mergers were detected. In addition to highly significant gravitational-wave events, we also provide a list of marginal event candidates with an estimated false-alarm rate less than 1 per 30 days. From these results over the first two observing runs, which include approximately one gravitational-wave detection per 15 days of data searched, we infer merger rates at the 90% confidence intervals of 110-3840 Gpc-3 y-1 for binary neutron stars and 9.7-101 Gpc-3 y-1 for binary black holes assuming fixed population distributions and determine a neutron star-black hole merger rate 90% upper limit of 610 Gpc-3 y-1. © 2019 authors. Published by the American Physical Society

Search for multimessenger sources of gravitational waves and high-energy neutrinos with advanced LIGO during its first observing run, ANTARES, and IceCube

Astrophysical sources of gravitational waves, such as binary neutron star and black hole mergers or core-collapse supernovae, can drive relativistic outflows, giving rise to non-thermal high-energy emission. High-energy neutrinos are signatures of such outflows. The detection of gravitational waves and high-energy neutrinos from common sources could help establish the connection between the dynamics of the progenitor and the properties of the outflow. We searched for associated emission of gravitational waves and high-energy neutrinos from astrophysical transients with minimal assumptions using data from Advanced LIGO from its first observing run O1, and data from the Antares and IceCube neutrino observatories from the same time period. We focused on candidate events whose astrophysical origins could not be determined from a single messenger. We found no significant coincident candidate, which we used to constrain the rate density of astrophysical sources dependent on their gravitational-wave and neutrino emission processes

Search for gravitational-wave signals associated with gamma-ray bursts during the second observing run of advanced LIGO and advanced Virgo

We present the results of targeted searches for gravitational-wave transients associated with gamma-ray bursts during the second observing run of Advanced LIGO and Advanced Virgo, which took place from 2016 November to 2017 August. We have analyzed 98 gamma-ray bursts using an unmodeled search method that searches for generic transient gravitational waves and 42 with a modeled search method that targets compact-binary mergers as progenitors of short gamma-ray bursts. Both methods clearly detect the previously reported binary merger signal GW170817, with p-values of <9.38 × 10−6 (modeled) and 3.1 × 10−4 (unmodeled). We do not find any significant evidence for gravitational-wave signals associated with the other gamma-ray bursts analyzed, and therefore we report lower bounds on the distance to each of these, assuming various source types and signal morphologies. Using our final modeled search results, short gamma-ray burst observations, and assuming binary neutron star progenitors, we place bounds on the rate of short gamma-ray bursts as a function of redshift for z ≤ 1. We estimate 0.07–1.80 joint detections with Fermi-GBM per year for the 2019–20 LIGO-Virgo observing run and 0.15–3.90 per year when current gravitational-wave detectors are operating at their design sensitivities