Zebrafish olfactory receptors ORAs differentially detect bile acids and bile salts

The fish olfactory receptor ORA family is orthologous to the mammalian vomeronasal receptors type 1. It consists of six highly conserved chemosensory receptors expected to be essential for survival and communication. We deorphanized the zebrafish ORA family in a heterologous cell system. The six receptors responded specifically to lithocholic acid (LCA) and closely related C24 5β-bile acids/salts. LCA attracted zebrafish as strongly as food in behavioral tests, whereas the less potent cholanic acid elicited weaker attraction, consistent with the in vitro results. The ORA-ligand recognition patterns were probed with site-directed mutagenesis guided by in silico modeling.We revealed the receptors' structure-function relationship underlying their specificity and selectivity for these compounds. Bile acids/salts are putative fish semiochemicals or pheromones sensed by the olfactory system with high specificity. This work identified their receptors and provided the basis for probing the roles of ORAs and bile acids/salts in fish chemosensation. © 2019 Cong et al.1

First low-frequency Einstein@Home all-sky search for continuous gravitational waves in Advanced LIGO data

We report results of a deep all-sky search for periodic gravitational waves from isolated neutron stars in data from the first Advanced LIGO observing run. This search investigates the low frequency range of Advanced LIGO data, between 20 and 100 Hz, much of which was not explored in initial LIGO. The search was made possible by the computing power provided by the volunteers of the Einstein@Home project. We find no significant signal candidate and set the most stringent upper limits to date on the amplitude of gravitational wave signals from the target population, corresponding to a sensitivity depth of 48.7 [1/root Hz]. At the frequency of best strain sensitivity, near 100 Hz, we set 90% confidence upper limits of 1.8 x 10(-25). At the low end of our frequency range, 20 Hz, we achieve upper limits of 3.9 x 10(-24). At 55 Hz we can exclude sources with ellipticities greater than 10(-5) within 100 pc of Earth with fiducial value of the principal moment of inertia of 10(38) kg m(2)

Search for intermediate mass black hole binaries in the first observing run of Advanced LIGO

During their first observational run, the two Advanced LIGO detectors attained an unprecedented sensitivity, resulting in the first direct detections of gravitational-wave signals produced by stellar-mass binary black hole systems. This paper reports on an all-sky search for gravitational waves (GWs) from merging intermediate mass black hole binaries (IMBHBs). The combined results from two independent search techniques were used in this study: the first employs a matched-filter algorithm that uses a bank of filters covering the GW signal parameter space, while the second is a generic search for GW transients (bursts). No GWs from IMBHBs were detected; therefore, we constrain the rate of several classes of IMBHB mergers. The most stringent limit is obtained for black holes of individual mass 100 M ⊙, with spins aligned with the binary orbital angular momentum. For such systems, the merger rate is constrained to be less than 0.93 Gpc−3yr−1 in comoving units at the 90% confidence level, an improvement of nearly 2 orders of magnitude over previous upper limits

Properties of the Binary Black Hole Merger GW150914

On September 14, 2015, the Laser Interferometer Gravitational-Wave Observatory (LIGO) detected a gravitational-wave transient (GW150914); we characterize the properties of the source and its parameters. The data around the time of the event were analyzed coherently across the LIGO network using a suite of accurate waveform models that describe gravitational waves from a compact binary system in general relativity. GW150914 was produced by a nearly equal mass binary black hole of masses 36+5−4M⊙ and 29+4−4M⊙; for each parameter we report the median value and the range of the 90% credible interval. The dimensionless spin magnitude of the more massive black hole is bound to be <0.7 (at 90% probability). The luminosity distance to the source is 410+160−180  Mpc, corresponding to a redshift 0.09+0.03−0.04 assuming standard cosmology. The source location is constrained to an annulus section of 610  deg2, primarily in the southern hemisphere. The binary merges into a black hole of mass 62+4−4M⊙ and spin 0.67+0.05−0.07. This black hole is significantly more massive than any other inferred from electromagnetic observations in the stellar-mass regime

Reverse chemical ecology in a moth: machine learning on odorant receptors identifies new behaviorally active agonists

The concept of reverse chemical ecology (exploitation of molecular knowledge for chemical ecology) has recently emerged in conservation biology and human health. Here, we extend this concept to crop protection. Targeting odorant receptors from a crop pest insect, the noctuid moth Spodoptera littoralis, we demonstrate that reverse chemical ecology has the potential to accelerate the discovery of novel crop pest insect attractants and repellents. Using machine learning, we first predicted novel natural ligands for two odorant receptors, SlitOR24 and 25. Then, electrophysiological validation proved in silico predictions to be highly sensitive, as 93% and 67% of predicted agonists triggered a response in Drosophila olfactory neurons expressing SlitOR24 and SlitOR25, respectively, despite a lack of specificity. Last, when tested in Y-maze behavioral assays, the most active novel ligands of the receptors were attractive to caterpillars. This work provides a template for rational design of new eco-friendly semiochemicals to manage crop pest populations

Integrative structural modeling reveals functional molecular switches of human G protein-coupled bittertaste receptors

On the human tongue, the bitter taste depends on a large family of 25 taste receptors type 2 (TAS2R) belonging to the G protein-coupled receptor (GPCR) family and classified distantly related to class A GPCR. To date, the experimental structures have not been determined for any TAS2R and key residues controlling their function are still under debate. Here we streamline the modeling of these receptors using an integrative approach combining sequence analysis, molecular modeling and site-directed mutagenesis followed by functional assays. We provide a general approach for modeling all mammal TAS2R and identify functional motifs or residues which are central to understand how we perceive bitterness. Above the protocol which is transposable to all TAS2R, the identification of functional molecular switches lays the groundwork for the rational design of chemical modulators of bitter taste receptors. Such ligands will be of broad interest beyond food science since bitter-taste receptors are ectopically expressed in other parts of the human body besides the tongue. Topin et al. Functional molecular switches of mammalian G protein-coupled bitter-taste receptors. Cell. Mol. Life Sci., 2021, 78, 7605-7615. Funding Acknowledgments: This work was supported by the French Ministry of Higher Education and Research [PhD Fellowship], by GIRACT (Geneva, Switzerland) [9th European PhD in Flavor Research Bursaries for first year students] and the Gen Foundation (Registered UK Charity No. 1071026) [a charitable trust which principally provides grants to students/researchers in natural sciences, in particular food sciences/technology]. This work has also been supported by the French government, through the UCAJEDI Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR15-IDEX-01. The authors are grateful to the OPAL infrastructure from Universite Cote drAzur and the Universite Cote drAzurrs Center for High-Performance Computing for providing resources and support. FCOI Declarations: Non

Metal Ions Activate the Human Taste Receptor TAS2R7

Divalent and trivalent salts exhibit a complex taste profile. They are perceived as being astringent/drying, sour, bitter, and metallic. We hypothesized that human bitter-taste receptors may mediate some taste attributes of these salts. Using a cell-based functional assay, we found that TAS2R7 responds to a broad range of divalent and trivalent salts, including zinc, calcium, magnesium, copper, manganese, and aluminum, but not to potassium, suggesting TAS2R7 may act as a metal cation receptor mediating bitterness of divalent and trivalent salts. Molecular modeling and mutagenesis analysis identified 2 residues, H943.37 and E2647.32, in TAS2R7 that appear to be responsible for the interaction of TAS2R7 with metallic ions. Taste receptors are found in both oral and extraoral tissues. The responsiveness of TAS2R7 to various mineral salts suggests it may act as a broad sensor, similar to the calcium-sensing receptor, for biologically relevant metal cations in both oral and extraoral tissues. © The Author(s) 2019. Published by Oxford University Press.1

Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software

Observing gravitational-wave transient GW150914 with minimal assumptions

The gravitational-wave signal GW150914 was first identified on September 14, 2015, by searches for short-duration gravitational-wave transients. These searches identify time-correlated transients in multiple detectors with minimal assumptions about the signal morphology, allowing them to be sensitive to gravitational waves emitted by a wide range of sources including binary black hole mergers. Over the observational period from September 12 to October 20, 2015, these transient searches were sensitive to binary black hole mergers similar to GW150914 to an average distance of ∼600  Mpc. In this paper, we describe the analyses that first detected GW150914 as well as the parameter estimation and waveform reconstruction techniques that initially identified GW150914 as the merger of two black holes. We find that the reconstructed waveform is consistent with the signal from a binary black hole merger with a chirp mass of ∼30  M[subscript ⊙] and a total mass before merger of ∼70  M[subscript ⊙] in the detector frame

All-sky search for periodic gravitational waves in the O1 LIGO data

We report on an all-sky search for periodic gravitational waves in the frequency band 20-475 Hz and with a frequency time derivative in the range of [-1.0, +0.1]e-8 Hz/s. Such a signal could be produced by a nearby spinning and slightly non-axisymmetric isolated neutron star in our galaxy. This search uses the data from Advanced LIGO's first observational run, O1. No periodic gravitational wave signals were observed, and upper limits were placed on their strengths. The lowest upper limits on worst-case (linearly polarized) strain amplitude h0 are 4e-25 near 170 Hz. For a circularly polarized source (most favorable orientation), the smallest upper limits obtained are 1.5e-25. These upper limits refer to all sky locations and the entire range of frequency derivative values. For a population-averaged ensemble of sky locations and stellar orientations, the lowest upper limits obtained for the strain amplitude are 2.5e-25.by Anand Sengupta et al.