The Molecular Exoskeleton of the Ring-like Planetary Nebula NGC 3132

We present Submillimeter Array (SMA) mapping of $^{12}$CO $J=2\rightarrow 1$, $^{13}$CO $J=2\rightarrow 1$, and CN $N=2\rightarrow 1$ emission from the Ring-like planetary nebula (PN) NGC 3132, one of the subjects of JWST Early Release Observation (ERO) near-infrared imaging. The $\sim$5$''$ resolution SMA data demonstrate that the Southern Ring's main, bright, molecule-rich ring is indeed an expanding ring, as opposed to a limb-brightened shell, in terms of its intrinsic (physical) structure. This suggests that NGC 3132 is a bipolar nebula viewed more or less pole-on (inclination $\sim$15--30$^\circ$). The SMA data furthermore reveal that the nebula harbors a second expanding molecular ring that is aligned almost orthogonally to the main, bright molecular ring. We propose that this two-ring structure is the remnant of an ellipsoidal molecular envelope of ejecta that terminated the progenitor star's asymptotic giant branch evolution and was subsequently disrupted by a series of misaligned fast, collimated outflows or jets resulting from interactions between the progenitor and one or more companions.Comment: 20 pages, 12 figures; accepted by The Astrophysical Journa

Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor

Class B GPCRs can activate multiple signalling effectors with the potential to exhibit biased agonism in response to ligand stimulation. Previously, we highlighted key TM domain polar amino acids that were crucial for the function of the GLP-1 receptor, a key therapeutic target for diabetes and obesity. Using a combination of mutagenesis, pharmacological characterisation, mathematical and computational molecular modelling, this study identifies additional highly conserved polar residues located towards the TM helical boundaries of Class B GPCRs that are important for GLP-1 receptor stability and/or controlling signalling specificity and biased agonism. This includes (i) three positively charged residues (R3.30227, K4.64288, R5.40310) located at the extracellular boundaries of TMs 3, 4 and 5 that are predicted in molecular models to stabilise extracellular loop 2, a crucial domain for ligand affinity and receptor activation; (ii) a predicted hydrogen bond network between residues located in TMs 2 (R2.46176), 6 (R6.37348) and 7 (N7.61406 and E7.63408) at the cytoplasmic face of the receptor that is important for stabilising the inactive receptor and directing signalling specificity, (iii) residues at the bottom of TM 5 (R5.56326) and TM6 (K6.35346 and K6.40351) that are crucial for receptor activation and downstream signalling; (iv) residues predicted to be involved in stabilisation of TM4 (N2.52182 and Y3.52250) that also influence cell signalling. Collectively, this work expands our understanding of peptide-mediated signalling by the GLP-1 receptor

Observations of gas flows inside a protoplanetary gap

Gaseous giant planet formation is thought to occur in the first few million years following stellar birth. Models predict that giant planet formation carves a deep gap in the dust component (shallower in the gas). Infrared observations of the disk around the young star HD142527, at ~140pc, found an inner disk ~10AU in radius, surrounded by a particularly large gap, with a disrupted outer disk beyond 140AU, indicative of a perturbing planetary-mass body at ~90 AU. From radio observations, the bulk mass is molecular and lies in the outer disk, whose continuum emission has a horseshoe morphology. The vigorous stellar accretion rate would deplete the inner disk in less than a year, so in order to sustain the observed accretion, matter must flow from the outer-disk into the cavity and cross the gap. In dynamical models, the putative protoplanets channel outer-disk material into gap-crossing bridges that feed stellar accretion through the inner disk. Here we report observations with the Atacama Large Millimetre Array (ALMA) that reveal diffuse CO gas inside the gap, with denser HCO+ gas along gap-crossing filaments, and that confirm the horseshoe morphology of the outer disk. The estimated flow rate of the gas is in the range 7E-9 to 2E-7 Msun/yr, which is sufficient to maintain accretion onto the star at the present rate

A mechanism for agonist activation of the glucagon-like peptide-1 (GLP-1) receptor through modelling & molecular dynamics

The receptor for glucagon-like peptide 1 (GLP-1R) is a validated drug target for the treatment of type 2 diabetes and obesity. Recently the first three structures of GLP-1R were published – an X-ray structure of the apo transmembrane domain in the inactive conformation; an X-ray structure of the full-length receptor bound to a truncated peptide agonist; and a cryo-EM structure of the full-length receptor bound with GLP-1 and coupled to the G protein Gs. Since the inactive structure was incomplete, and the two active-state structures shared significant differences, we utilised all available knowledge to build hybrid models of the full length active and inactive state receptors. The two models were simulated using molecular dynamics and the output trajectories analysed and compared to reveal insights into the mechanism for agonist-mediated receptor activation. His-7, Glu-9 and Asp-15 of GLP-1 act together to destabilise transmembrane helix 6 and extracellular loop 3 in order to generate an active conformation of GLP-1R