Crystal structures of four indole derivatives as possible cannabinoid allosteric antagonists

Acknowledgements We thank the EPSRC National Crystallography Service (University of Southampton) for the data collections and the EPSRC National Mass Spectrometry Service (University of Swansea) for the HRMS data. We thank John Low for carrying out the Cambridge Database survey.Peer reviewedPublisher PD

Climate change influences foliar nutrition and metabolism of red maple (Acer rubrum) trees in a northern hardwood forest

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Blagden, M., Harrison, J. L., Minocha, R., Sanders-DeMott, R., Long, S., & Templer, P. H. Climate change influences foliar nutrition and metabolism of red maple (Acer rubrum) trees in a northern hardwood forest. Ecosphere, 13(2), (2022): e03859. https://doi.org/10.1002/ecs2.3859.Mean annual air temperatures are projected to increase, while the winter snowpack is expected to shrink in depth and duration for many mid- and high-latitude temperate forest ecosystems over the next several decades. Together, these changes will lead to warmer growing season soil temperatures and an increased frequency of soil freeze–thaw cycles (FTCs) in winter. We took advantage of the Climate Change Across Seasons Experiment (CCASE) at the Hubbard Brook Experimental Forest in the White Mountains of New Hampshire, USA, to determine how these changes in soil temperature affect foliar nitrogen (N) and carbon metabolism of red maple (Acer rubrum) trees in 2015 and 2017. Earlier work from this study revealed a similar increase in foliar N concentrations with growing season soil warming, with or without the occurrence of soil FTCs in winter. However, these changes in soil warming could differentially affect the availability of cellular nutrients, concentrations of primary and secondary metabolites, and the rates of photosynthesis that are all responsive to climate change. We found that foliar concentrations of phosphorus (P), potassium (K), N, spermine (a polyamine), amino acids (alanine, histidine, and phenylalanine), chlorophyll, carotenoids, sucrose, and rates of photosynthesis increased with growing season soil warming. Despite similar concentrations of foliar N with soil warming with and without soil FTCs in winter, winter soil FTCs affected other foliar metabolic responses. The combination of growing season soil warming and winter soil FTCs led to increased concentrations of two polyamines (putrescine and spermine) and amino acids (alanine, proline, aspartic acid, γ-aminobutyric acid, valine, leucine, and isoleucine). Treatment-specific metabolic changes indicated that while responses to growing season warming were more connected to their role as growth modulators, soil warming + FTC treatment-related effects revealed their dual role in growth and stress tolerance. Together, the results of this study demonstrate that growing season soil warming has multiple positive effects on foliar N and cellular metabolism in trees and that some of these foliar responses are further modified by the addition of stress from winter soil FTCs.This research was supported by an NSF Long Term Ecological Research (LTER) Grant to Hubbard Brook (NSF 1114804 and 1637685) and an NSF CAREER grant to PHT (NSF DEB1149929). RSD was supported by NSF DGE0947950, a Boston University (BU) Dean's Fellowship, and the BU Program in Biogeoscience. Jamie Harrison was supported by a BU Dean's Fellowship. Megan Blagden was supported by a BU Undergraduate Research Opportunity Program fellowship. This manuscript is a contribution to the Hubbard Brook Ecosystem Study. Hubbard Brook is part of the LTER network, which is supported by the NSF

Crystal structures of four indole derivatives with a phenyl substituent at the 2-position and a carbonyl group at the 3-position : the C(6) N-H⋯O chain remains the same, but the weak reinforcing inter-actions are different

Acknowledgements We thank the EPSRC National Crystallography Service (University of Southampton) for the data collections and the EPSRC National Mass Spectrometry Service (University of Swansea) for the HRMS data.Peer reviewedPublisher PD

Weak interactions in the crystal structures of two indole derivatives

Acknowledgements We thank the EPSRC National Crystallography Service (University of Southampton) for the data collections and the EPSRC National Mass Spectrometry Service (University of Swansea) for the HRMS data.Peer reviewedPublisher PD

Different N—H···π interactions in two indole derivatives

Acknowledgements We thank the EPSRC National Crystallography Service (University of Southampton) for the data collections and the EPSRC National Mass Spectrometry Service (University of Swansea) for the HRMS dataPeer reviewedPublisher PD

Multiple Tyrosine Residues Contribute to GABA Binding in the GABA_C Receptor Binding Pocket

The ligand binding site of Cys-loop receptors is dominated by aromatic amino acids. In GABA_C receptors, these are predominantly tyrosine residues, with a number of other aromatic residues located in or close to the binding pocket. Here we examine the roles of these residues using substitution with both natural and unnatural amino acids followed by functional characterization. Tyr198 (loop B) has previously been shown to form a cation−π interaction with GABA; the current data indicate that none of the other aromatic residues form such an interaction, although the data indicate that both Tyr102 and Phe138 may contribute to stabilization of the positively charged amine of GABA. Tyr247 (loop C) was very sensitive to substitution and, combined with data from a model of the receptor, suggest a π–π interaction with Tyr241 (loop C); here again functional data show aromaticity is important. In addition the hydroxyl group of Tyr241 is important, supporting the presence of a hydrogen bond with Arg104 suggested by the model. At position Tyr102 (loop D) size and aromaticity are important; this residue may play a role in receptor gating and/or ligand binding. The data also suggest that Tyr167, Tyr200, and Tyr208 have a structural role while Tyr106, Trp246, and Tyr251 are not critical. Comparison of the agonist binding site “aromatic box” across the superfamily of Cys-loop receptors reveals some interesting parallels and divergences

John Schuster, Descartes-agonistes: Physico-mathematics, method and corpuscular-mechanism, 1618–1633

We report on a 10 ks simultaneous Chandra/HETG-NuSTAR observation of the Bursting Pulsar, GRO J1744-28, during its third detected outburst since discovery and after nearly 18 years of quiescence. The source is detected up to 60 keV with an Eddington persistent flux level. Seven bursts, followed by dips, are seen with Chandra, three of which are also detected with NuSTAR. Timing analysis reveals a slight increase in the persistent emission pulsed fraction with energy (from 10% to 15%) up to 10 keV, above which it remains constant. The 0.5-70 keV spectra of the persistent and dip emission are the same within errors, and well described by a blackbody (BB), a power-law with an exponential rolloff, a 10 keV feature, and a 6.7 keV emission feature, all modified by neutral absorption. Assuming that the BB emission originates in an accretion disc, we estimate its inner (magnetospheric) radius to be about 4x10^7 cm, which translates to a surface dipole field B~9x10^10 G. The Chandra/HETG spectrum resolves the 6.7 keV feature into (quasi-)neutral and highly ionized Fe XXV and Fe XXVI emission lines. XSTAR modeling shows these lines to also emanate from a truncated accretion disk. The burst spectra, with a peak flux more than an order of magnitude higher than Eddington, are well fit with a power-law with an exponential rolloff and a 10~keV feature, with similar fit values compared to the persistent and dip spectra. The burst spectra lack a thermal component and any Fe features. Anisotropic (beamed) burst emission would explain both the lack of the BB and any Fe components.Comment: 15 pages, 11 figures, Accepted in Ap

Under pressure: Response urgency modulates striatal and insula activity during decision-making under risk

When deciding whether to bet in situations that involve potential monetary loss or gain (mixed gambles), a subjective sense of pressure can influence the evaluation of the expected utility associated with each choice option. Here, we explored how gambling decisions, their psychophysiological and neural counterparts are modulated by an induced sense of urgency to respond. Urgency influenced decision times and evoked heart rate responses, interacting with the expected value of each gamble. Using functional MRI, we observed that this interaction was associated with changes in the activity of the striatum, a critical region for both reward and choice selection, and within the insula, a region implicated as the substrate of affective feelings arising from interoceptive signals which influence motivational behavior. Our findings bridge current psychophysiological and neurobiological models of value representation and action-programming, identifying the striatum and insular cortex as the key substrates of decision-making under risk and urgency