Hydroxycarboxylic acid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The hydroxycarboxylic acid family of receptors (ENSFM00500000271913, nomenclature as agreed by the NC-IUPHAR Subcommittee on Hydroxycarboxylic acid receptors [32, 10]) respond to organic acids, including the endogenous hydroxy carboxylic acids 3-hydroxy butyric acid and L-lactic acid, as well as the lipid lowering agents nicotinic acid (niacin), acipimox and acifran [47, 54, 57]. These receptors were provisionally described as nicotinic acid receptors, although nicotinic acid shows submicromolar potency at HCA2 receptors only and is unlikely to be the natural ligand [54, 57]

Hydroxycarboxylic acid receptors in GtoPdb v.2023.1

The hydroxycarboxylic acid family of receptors (ENSFM00500000271913, nomenclature as agreed by the NC-IUPHAR Subcommittee on Hydroxycarboxylic acid receptors [36, 12]) respond to organic acids, including the endogenous hydroxy carboxylic acids 3-hydroxy butyric acid and L-lactic acid, as well as the lipid lowering agents nicotinic acid (niacin), acipimox and acifran [53, 60, 65]. These receptors were provisionally described as nicotinic acid receptors, although nicotinic acid shows submicromolar potency at HCA2 receptors only and is unlikely to be the natural ligand [60, 65]

AGN STORM 2: V. Anomalous Behavior of the CIV Light Curve in Mrk 817

An intensive reverberation mapping campaign on the Seyfert 1 galaxy Mrk817 using the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope (HST) revealed significant variations in the response of the broad UV emission lines to fluctuations in the continuum emission. The response of the prominent UV emission lines changes over a $\sim$60-day duration, resulting in distinctly different time lags in the various segments of the light curve over the 14 months observing campaign. One-dimensional echo-mapping models fit these variations if a slowly varying background is included for each emission line. These variations are more evident in the CIV light curve, which is the line least affected by intrinsic absorption in Mrk817 and least blended with neighboring emission lines. We identify five temporal windows with distinct emission line response, and measure their corresponding time delays, which range from 2 to 13 days. These temporal windows are plausibly linked to changes in the UV and X-ray obscuration occurring during these same intervals. The shortest time lags occur during periods with diminishing obscuration, whereas the longest lags occur during periods with rising obscuration. We propose that the obscuring outflow shields the ultraviolet broad lines from the ionizing continuum. The resulting change in the spectral energy distribution of the ionizing continuum, as seen by clouds at a range of distances from the nucleus, is responsible for the changes in the line response.Comment: 20 pages, 8 figures, submitted to Ap

AGN STORM 2. IV. Swift X-ray and ultraviolet/optical monitoring of Mrk 817

The AGN STORM 2 campaign is a large, multiwavelength reverberation mapping project designed to trace out the structure of Mrk 817 from the inner accretion disk to the broad emission line region and out to the dusty torus. As part of this campaign, Swift performed daily monitoring of Mrk 817 for approximately 15 months, obtaining observations in X-rays and six UV/optical filters. The X-ray monitoring shows that Mrk 817 was in a significantly fainter state than in previous observations, with only a brief flare where it reached prior flux levels. The X-ray spectrum is heavily obscured. The UV/optical light curves show significant variability throughout the campaign and are well correlated with one another, but uncorrelated with the X-rays. Combining the Swift UV/optical light curves with Hubble UV continuum light curves, we measure interband continuum lags, $\tau(\lambda)$, that increase with increasing wavelength roughly following $\tau(\lambda) \propto \lambda^{4/3}$, the dependence expected for a geometrically thin, optically thick, centrally illuminated disk. Modeling of the light curves reveals a period at the beginning of the campaign where the response of the continuum is suppressed compared to later in the light curve - the light curves are not simple shifted and scaled versions of each other. The interval of suppressed response corresponds to a period of high UV line and X-ray absorption, and reduced emission line variability amplitudes. We suggest that this indicates a significant contribution to the continuum from the broad line region gas that sees an absorbed ionizing continuum.Comment: 20 pages, 13 figures, 3 tables, accepted for publication in Ap

Validation of ozone measurements from the Atmospheric Chemistry Experiment (ACE)

This paper presents extensive bias determination analyses of ozone observations from the Atmospheric Chemistry Experiment (ACE) satellite instruments: the ACE Fourier Transform Spectrometer (ACE-FTS) and the Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation (ACE-MAESTRO) instrument. Here we compare the latest ozone data products from ACE-FTS and ACE-MAESTRO with coincident observations from nearly 20 satellite-borne, airborne, balloon-borne and ground-based instruments, by analysing volume mixing ratio profiles and partial column densities. The ACE-FTS version 2.2 Ozone Update product reports more ozone than most correlative measurements from the upper troposphere to the lower mesosphere. At altitude levels from 16 to 44 km, the average values of the mean relative differences are nearly all within +1 to +8%. At higher altitudes (45 60 km), the ACE-FTS ozone amounts are significantly larger than those of the comparison instruments, with mean relative differences of up to +40% (about + 20% on average). For the ACE-MAESTRO version 1.2 ozone data product, mean relative differences are within +/- 10% (average values within +/- 6%) between 18 and 40 km for both the sunrise and sunset measurements. At higher altitudes (similar to 35-55 km), systematic biases of opposite sign are found between the ACE-MAESTRO sunrise and sunset observations. While ozone amounts derived from the ACE-MAESTRO sunrise occultation data are often smaller than the coincident observations (with mean relative differences down to -10%), the sunset occultation profiles for ACE-MAESTRO show results that are qualitatively similar to ACE-FTS, indicating a large positive bias (mean relative differences within +10 to +30%) in the 45-55 km altitude range. In contrast, there is no significant systematic difference in bias found for the ACE-FTS sunrise and sunset measurements

Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection

Stenotrophomonas maltophilia is a Gram-negative pathogen with emerging nosocomial incidence. Little is known about its pathogenesis and the genomic diversity exhibited by clinical isolates complicates the study of pathogenicity and virulence factors. Here, we present a strategy to identify such factors in new clinical isolates of S. maltophilia, incorporating an adult-zebrafish model of S. maltophilia infection to evaluate relative virulence coupled to 2D difference gel electrophoresis to explore underlying differences in protein expression. In this study we report upon three recent clinical isolates and use the collection strain ATCC13637 as a reference. The adult-zebrafish model shows discrimination capacity, i.e. from very low to very high mortality rates, with clinical symptoms very similar to those observed in natural S. maltophilia infections in fish. Strain virulence correlates with resistance to human serum, in agreement with previous studies in mouse and rat and therefore supporting zebrafish as a replacement model. Despite its clinical origin, the collection strain ATCC13637 showed obvious signs of attenuation in zebrafish, with null mortality. Multilocus-sequence-typing analysis revealed that the most virulent strains, UV74 and M30, exhibit the strongest genetic similitude. Differential proteomic analysis led to the identification of 38 proteins with significantly different abundance in the three clinical strains relative to the reference strain. Orthologs of several of these proteins have been already reported to have a role in pathogenesis, virulence or resistance mechanisms thus supporting our strategy. Proof of concept is further provided by protein Ax21, whose abundance is shown here to be directly proportional to mortality in the zebrafish infection model. Indeed, recent studies have demonstrated that this protein is a quorum-sensing-related virulence factor

Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Objectives Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5\u201374.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care

AGN STORM 2. I. First results: A Change in the Weather of Mrk 817

We present the first results from the ongoing, intensive, multiwavelength monitoring program of the luminous Seyfert 1 galaxy Mrk 817. While this active galactic nucleus was, in part, selected for its historically unobscured nature, we discovered that the X-ray spectrum is highly absorbed, and there are new blueshifted, broad, and narrow UV absorption lines, which suggest that a dust-free, ionized obscurer located at the inner broad-line region partially covers the central source. Despite the obscuration, we measure UV and optical continuum reverberation lags consistent with a centrally illuminated Shakura–Sunyaev thin accretion disk, and measure reverberation lags associated with the optical broad-line region, as expected. However, in the first 55 days of the campaign, when the obscuration was becoming most extreme, we observe a de-coupling of the UV continuum and the UV broad emission-line variability. The correlation recovered in the next 42 days of the campaign, as Mrk 817 entered a less obscured state. The short C IV and Lyα lags suggest that the accretion disk extends beyond the UV broad-line region. Unified