(1S,5R,7R,30S)-14-De­oxy­isogarcinol

The title compound, C38H50O5 {systematic name: 10-(3-hy­droxy­benzo­yl)-2,2,7,7-tetra­methyl-3,6,8-tris­(3-methyl­but-2-en­yl)-3,4,4a,5,6,7-hexa­hydro-4a,8-methano-2H-cyclo­octa­[b]pyran-9,11(8H)-dione}, is a polyisoprenylated benzophenone, isolated for the first time from the fruits of Garcinia indica during our investigation of bioactive compounds from this plant and their large-scale extraction. The relative configuration of the title compound was chosen based on comparison of its spectroscopic and optical rotation data with that of the isomorphous and isostructural compound isogarcinol, whose absolute configuration is known. The crystal packing features O—H⋯O hydrogen bonds. A Cambridge Structural Database analysis revealed that the crystal structure reported here is isomorphous and isostructural with that of isogarcinol

Crystal and Molecular Structure of Secoisolariciresinol

The R,R-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]-1,4-butandiol lignan secoisolariciresinol (1) is a constituent of Gymnosperms used in the treatment of benign prostatic hyperplasya. The results of crystallographic and ab initio theoretical studies are reported and discussed. In the crystal, the molecule of (1) assumes a clustered conformation, characterized by the facing of the two phenyl rings. This geometry is stabilized by the formation of a network of hydrogen bonds. Theoretical calculations indicate that: i) the intramolecular hydrogen bond O1−H1⋅⋅⋅O1\u27 is the major factor dictating the facing of the two phenyl groups, while intermolecular hydrogen bonds and crystal packing have smaller effects; ii) the 1−4O⋅⋅⋅O non-bonded interactions in the vanillyl groups are important in determining the most stable conformation; iii) calculations with two explicit water molecules in the model give a good simulation of the local effects of a water solvent and indicate that (1) probably assumes a clustered conformation also in polar solvents

Magnetars as Astrophysical Laboratories of Extreme Quantum Electrodynamics: The Case for a Compton Telescope

A next generation of Compton and pair telescopes that improve MeV-band detection sensitivity by more than a decade beyond current instrumental capabilities will open up new insights into a variety of astrophysical source classes. Among these are magnetars, the most highly magnetic of the neutron star zoo, which will serve as a prime science target for a new mission surveying the MeV window. This paper outlines the core questions pertaining to magnetars that can be addressed by such a technology. These range from global magnetar geometry and population trends, to incisive probes of hard X-ray emission locales, to providing cosmic laboratories for spectral and polarimetric testing of exotic predictions of QED, principally the prediction of the splitting of photons and magnetic pair creation. Such fundamental physics cannot yet be discerned in terrestrial experiments. State of the art modeling of the persistent hard X-ray tail emission in magnetars is presented to outline the case for powerful diagnostics using Compton polarimeters. The case highlights an inter-disciplinary opportunity to seed discovery at the interface between astronomy and physics.Comment: 11 pages, 4 figures, Astro2020 Science White Paper submitted to the National Academies of Science

Fortilin potentiates the peroxidase activity of Peroxiredoxin-1 and protects against alcohol-induced liver damage in mice

Fortilin, a pro-survival molecule, inhibits p53-induced apoptosis by binding to the sequence-specific DNA-binding domain of the tumor suppressor protein and preventing it from transcriptionally activating Bax. Intriguingly, fortilin protects cells against ROS-induced cell death, independent of p53. The signaling pathway through which fortilin protects cells against ROS-induced cell death, however, is unknown. Here we report that fortilin physically interacts with the antioxidant enzyme peroxiredoxin-1 (PRX1), protects it from proteasome-mediated degradation, and keeps it enzymatically active by blocking its deactivating phosphorylation by Mst1, a serine/threonine kinase. At the whole animal level, the liver-specific overexpression of fortilin reduced PRX1 phosphorylation in the liver, enhanced PRX1 activity, and protected the transgenic animals against alcohol-induced, ROS-mediated, liver damage. These data suggest the presence of a novel oxidative-stress-handling pathway where the anti-p53 molecule fortilin augments the peroxidase PRX1 by protecting it against degradation and inactivation of the enzyme. Fortilin-PRX1 interaction in the liver could be clinically exploited further to prevent acute alcohol-induced liver damage in humans

Magnetars as Astrophysical Laboratories of Extreme Quantum Electrodynamics: The Case for a Compton Telescope

A next generation of Compton and pair telescopes that improve MeV-band detection sensitivity by more than a decade beyond current instrumental capabilities will open up new insights into a variety of astrophysical source classes. Among these are magnetars, the most highly magnetic of the neutron star zoo, which will serve as a prime science target for a new mission surveying the MeV window. This paper outlines the core questions pertaining to magnetars that can be addressed by such a technology. These range from global magnetar geometry and population trends, to incisive probes of hard X-ray emission locales, to providing cosmic laboratories for spectral and polarimetric testing of exotic predictions of QED, principally the prediction of the splitting of photons and magnetic pair creation. Such fundamental physics cannot yet be discerned in terrestrial experiments. State of the art modeling of the persistent hard X-ray tail emission in magnetars is presented to outline the case for powerful diagnostics using Compton polarimeters. The case highlights an inter-disciplinary opportunity to seed discovery at the interface between astronomy and physics

The Colocalization Potential of HIV-Specific CD8+ and CD4+ T-Cells is Mediated by Integrin β7 but Not CCR6 and Regulated by Retinoic Acid

CD4+ T-cells from gut-associated lymphoid tissues (GALT) are major targets for HIV-1 infection. Recruitment of excess effector CD8+ T-cells in the proximity of target cells is critical for the control of viral replication. Here, we investigated the colocalization potential of HIV-specific CD8+ and CD4+ T-cells into the GALT and explored the role of retinoic acid (RA) in regulating this process in a cohort of HIV-infected subjects with slow disease progression. The expression of the gut-homing molecules integrin β7, CCR6, and CXCR3 was identified as a “signature” for HIV-specific but not CMV-specific CD4+ T-cells thus providing a new explanation for their enhanced permissiveness to infection in vivo. HIV-specific CD8+ T-cells also expressed high levels of integrin β7 and CXCR3; however CCR6 was detected at superior levels on HIV-specific CD4+ versus CD8+ T-cells. All trans RA (ATRA) upregulated the expression of integrin β7 but not CCR6 on HIV-specific T-cells. Together, these results suggest that HIV-specific CD8+ T-cells may colocalize in excess with CD4+ T-cells into the GALT via integrin β7 and CXCR3, but not via CCR6. Considering our previous findings that CCR6+CD4+ T-cells are major cellular targets for HIV-DNA integration in vivo, a limited ability of CD8+ T-cells to migrate in the vicinity of CCR6+CD4+ T-cells may facilitate HIV replication and dissemination at mucosal sites

GWTC-2.1: Deep extended catalog of compact binary coalescences observed by LIGO and Virgo during the first half of the third observing run

The second Gravitational-Wave Transient Catalog, GWTC-2, reported on 39 compact binary coalescences observed by the Advanced LIGO and Advanced Virgo detectors between 1 April 2019 15 ∶ 00 UTC and 1 October 2019 15 ∶ 00 UTC. Here, we present GWTC-2.1, which reports on a deeper list of candidate events observed over the same period. We analyze the final version of the strain data over this period with improved calibration and better subtraction of excess noise, which has been publicly released. We employ three matched-filter search pipelines for candidate identification, and estimate the probability of astrophysical origin for each candidate event. While GWTC-2 used a false alarm rate threshold of 2 per year, we include in GWTC-2.1, 1201 candidates that pass a false alarm rate threshold of 2 per day. We calculate the source properties of a subset of 44 high-significance candidates that have a probability of astrophysical origin greater than 0.5. Of these candidates, 36 have been reported in GWTC-2. We also calculate updated source properties for all binary black hole events previously reported in GWTC-1. If the eight additional high-significance candidates presented here are astrophysical, the mass range of events that are unambiguously identified as binary black holes (both objects ≥ 3 M⊙ ) is increased compared to GWTC-2, with total masses from ∼ 14 M ⊙ for GW190924_021846 to ∼ 182 M⊙ for GW190426_190642. Source properties calculated using our default prior suggest that the primary components of two new candidate events (GW190403_051519 and GW190426_190642) fall in the mass gap predicted by pair-instability supernova theory. We also expand the population of binaries with significantly asymmetric mass ratios reported in GWTC-2 by an additional two events (the mass ratio is less than 0.65 and 0.44 at 90% probability for GW190403_051519 and GW190917_114630 respectively), and find that two of the eight new events have effective inspiral spins χeff > 0 (at 90% credibility), while no binary is consistent with χeff < 0 at the same significance. We provide updated estimates for rates of binary black hole and binary neutron star coalescence in the local Universe