Search

Glutamate binds to AMPA receptors within a deep cleft between two globular protein domains (domains 1 and 2). Once glutamate binds, the cleft closes, and agonist-bound structures of the isolated ligand binding core suggest that closure of the binding cleft is sufficiently complete that it essentially prevents ligand dissociation. There is also considerable evidence supporting the view that cleft closure is the initial conformational change that triggers receptor activation and desensitization, and it has been dearly demonstrated that there is a correlation between the degree of cleft closure and agonist efficacy. It is unknown, however, whether the stability of binding deft closure also influences receptor-channel properties. The crystallographic structures indicate that closed-cleft conformations are stabilized by the formation of hydrogen bonds that involve amino acid side chains of residues in domains 1 and 2. We show here that mutations that disrupt one such cross-deft hydrogen bond (in the AMPA receptor subunit GluR2) decrease both agonist affinity and efficacy. The same mutations also hasten recovery from desensitization. We conclude that the stability of binding cleft closure has a significant impact on AMPA receptor function and is a major determinant of the apparent affinity of agonists. The results suggest that the stability of cleft closure has been tuned so that glutamate dissociates as rapidly as possible yet remains a full agonist. [ABSTRACT FROM AUTHOR]

Background: The jellyfish green fluorescent protein (GFP) can be inserted into the middle of another protein to produce a functional, fluorescent fusion protein. Finding permissive sites for insertion, however, can be difficult. Here we describe a transposon-based approach for rapidly creating libraries of GFP fusion proteins. Results: We tested our approach on the glutamate receptor subunit, GluR1, and the G protein subunit, αs. All of the in-frame GFP insertions produced a fluorescent protein, consistent with the idea that GFP will fold and form a fluorophore when inserted into virtually any domain of another protein. Some of the proteins retained their signaling function, and the random nature of the transposition process revealed permissive sites for insertion that would not have been predicted on the basis of structural or functional models of how that protein works. Conclusion: This technique should greatly speed the discovery of functional fusion proteins, genetically encodable sensors, and optimized fluorescence resonance energy transfer pairs. [ABSTRACT FROM AUTHOR]

Investigates the role of N-methyl-D-aspartate receptors in O-2A glial precursor cells in regulating polysialic acid-neural cell adhesion molecule expression and cell migration. Myelin formation; Interactions between ionotropic receptors, intracellular signaling and cell adhesion molecule; Cell surface properties.

Purpose: The purpose of this study was to compare lung image quality obtained with ultra-high resolution (UHR) spectral photon-counting CT (SPCCT) with that of dual-layer CT (DLCT), at standard and low dose levels using an image quality phantom and an anthropomorphic lung phantom., Methods: An image quality phantom was scanned using a clinical SPCCT prototype and an 8 cm collimation DLCT from the same manufacturer at 10 mGy. Additional acquisitions at 6 mGy were performed with SPCCT only. Images were reconstructed with dedicated high-frequency reconstruction kernels, slice thickness between 0.58 and 0.67 mm, and matrix between 512 2 and 1024 2 mm, using a hybrid iterative algorithm at level 6. Noise power spectrum (NPS), task-based transfer function (TTF) for iodine and air inserts, and detectability index (d') were assessed for ground-glass and solid nodules of 2 mm to simulate highly detailed lung lesions. Subjective analysis of an anthropomorphic lung phantom was performed by two radiologists using a five-point quality score., Results: At 10 mGy, noise magnitude was reduced by 29.1 % with SPCCT images compared to DLCT images for all parameters (27.1 ± 11.0 [standard deviation (SD)] HU vs. 38.2 ± 1.0 [SD] HU, respectively). At 6 mGy with SPCCT images, noise magnitude was reduced by 8.9 % compared to DLCT images at 10 mGy (34.8 ± 14.1 [SD] HU vs. 38.2 ± 1.0 [SD] HU, respectively). At 10 mGy and 6 mGy, average NPS spatial frequency (f av ) was greater for SPCCT images (0.75 ± 0.17 [SD] mm -1 ) compared to DLCT images at 10 mGy (0.55 ± 0.04 [SD] mm -1 ) while remaining constant from 10 to 6 mGy. At 10 mGy, TTF at 50 % (f 50 ) was greater for SPCCT images (0.92 ± 0.08 [SD] mm -1 ) compared to DLCT images (0.67 ± 0.06 [SD] mm -1 ) for both inserts. At 6 mGy, f 50 decreased by 1.1 % for SPCCT images, while remaining greater compared to DLCT images at 10 mGy (0.91 ± 0.06 [SD] mm -1 vs. 0.67 ± 0.06 [SD] mm -1 , respectively). At both dose levels, d' were greater for SPCCT images compared to DLCT for all clinical tasks. Subjective analysis performed by two radiologists revealed a greater median image quality for SPCCT (5; Q1, 4; Q3, 5) compared to DLCT images (3; Q1, 3; Q3, 3)., Conclusion: UHR SPCCT outperforms DLCT in terms of image quality for lung imaging. In addition, UHR SPCCT contributes to a 40 % reduction in radiation dose compared to DLCT., Competing Interests: Declaration of competing interest Hugo Lacombe and Marjorie Villien are employees of Philips Healthcare. The other authors have no relevant conflicts of interest or industry support for the project to declare., (Copyright © 2024. Published by Elsevier Masson SAS.)

In recent years, computed tomography (CT) has undergone a number of developments to improve radiological care. The most recent major innovation has been the development of photon-counting detectors. By comparison with the energy-integrating detectors traditionally used in CT, these detectors offer better dose efficiency, eliminate electronic noise, improve spatial resolution and have intrinsic spectral sensitivity. These detectors also allow the energy of each photon to be counted, thus improving the sampling of the X-ray spectrum in multiple energy bins, to better distinguish between photoelectric and Compton attenuation coefficients, resulting in better spectral images and specific color K-edge images. The purpose of this article was to make the reader more familiar with the basic principles and techniques of new photon-counting CT systems equipped with photon-counting detectors and also to describe the currently available devices that could be used in clinical practice., Competing Interests: Declaration of competing interest The authors have no relevant conflict of interest to disclose in relation with this article., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Cyclobis[n]helicenes (n=3 or 5) are chiral D 2 -symmetric π-conjugated macrocycles with stable lemniscular, or figure-eight, shapes. The conformational analysis of five different cyclobis[n]helicenes revealed that these molecules can only exist as their lemniscular conformers with high barriers to enantiomerization (>200 kJ mol -1 ). The enantiomers of a cyclobis[5]helicene were resolved by HPLC and their unusual chiroptical properties were attributed to the inherent chirality of their macrocyclic figure-eight., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)