Influence of GluN2 subunit identity on NMDA receptor function

AbstractN-methyl-d-aspartate receptors (NMDARs) are ligand-gated ion channels (‘ionotropic’ receptors) activated by the major excitatory neurotransmitter, l-glutamate. While the term ‘the NMDAR’ is often used it obscures the fact that this class of receptor contains within it members whose properties are as different as they are similar. This heterogeneity was evident from early electrophysiological, pharmacological and biochemical assessments of the functional properties of NMDARs and while the molecular basis of this heterogeneity has taken many years to elucidate, it indicated from the outset that the diversity of NMDAR phenotypes could allow this receptor family to subserve a variety of functions in the mammalian central nervous system. In this review we highlight some recent studies that have identified structural elements within GluN2 subunits that contribute to the heterogeneous biophysical properties of NMDARs, consider why some recently described novel pharmacological tools may permit better identification of native NMDAR subtypes, examine the evidence that NMDAR subtypes differentially contribute to the induction of long-term potentiation and long-term depression and discuss how through the use of chimeric proteins additional insights have been obtained that account for NMDAR subtype-dependency of physiological and pathophysiological signalling.This article is part of the Special Issue entitled ‘Glutamate Receptor-Dependent Synaptic Plasticity’

Using Quality of Service surveys

SIGLEAvailable from British Library Document Supply Centre-DSC:6543.261(23) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Red Devonian trilobites with green eyes from Morocco and the silicification of the trilobite exoskeleton

Latest Emsian (Early Devonian) sediments at the famous mud−mound− and trilobite−locality Hamar Laghdad (Tafilalt, Morocco) yielded some red−coloured remains of phacopid trilobites. Closer examination revealed that the eyes of these phacopids are often greenish in colour. EDX−analyses showed that the lenses retained their original calcitic composition, possibly greenish due to Fe−impurities, while most of the exoskeleton was silicified. The silicified parts contain elevated concentrations of iron which causes the red colour. This phenomenon is explained by the porosity of the exoskeleton in contrast to the homogeneous and massive construction of the lenses and their Mg−content. These incompletely silicified trilobites enabled a reconstruction of the silicification process in trilobites. Their diagenetic alteration probably occurred as a result of events associated with the Cretaceous transgression

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence