Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability

Mutations linked to neurodevelopmental disorders, such as intellectual disability (ID), are frequently found in genes that encode for proteins of the excitatory synapse. Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary proteins that regulate crucial aspects of receptor function. Here, we investigate a mutant form of the TARP family member stargazin, described in an ID patient. Molecular dynamics analyses predicted that the ID-associated stargazin variant, V143L, weakens the overall interface of the AMPAR:stargazin complex and impairs the stability of the complex. Knock-in mice harboring the V143L stargazin mutation manifest cognitive and social deficits and hippocampal synaptic transmission defects, resembling phenotypes displayed by ID patients. In the hippocampus of stargazin V143L mice, CA1 neurons show impaired spine maturation, abnormal synaptic transmission and long-term potentiation specifically in basal dendrites, and synaptic ultrastructural alterations. These data suggest a causal role for mutated stargazin in the pathogenesis of ID and unveil a new role for stargazin in the development and function of hippocampal synapses.This work was supported by a NARSAD Independent Investigator Grant (#23151) and a NARSAD Young Investigator Grant (#20733) from the Brain and Behavior Research Foundation, by a research grant from the Jérôme Lejeune Foundation (#1530), by “la Caixa” Foundation (ID 100010434), and FCT, I.P under the project code LCF/PR/HP20/52300003, by a Marie Curie Integration Grant (618525), by a Bial Foundation Grant (266/2016), by national funds through the Portuguese Science and Technology Foundation (FCT: UID/NEU/04539/2013, UIDB/04539/2020, POCI-01-0145-FEDER-28541, POCI-01-0145-FEDER-016682, PTDC/QUI-OUT/32243/2017 and CPCA/A0/7302/2020), and by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme, under project CENTRO-01-0145-FEDER-000008:BrainHealth 2020. GLC, NB, MVR, ME and CAVB were supported by FCT through Ph.D. scholarships SFRH/BD/51962/2012, SFRH/BD/144881/2019, SFRH/BD/129236/2017, SFRH/BD/51958/2012 and SFRH/BD/145457/2019, respectively. ASI and JG were supported by FCT through Postdoctoral fellowship SFRH/BPD122299/2016 and SFRH/BPD/120611/2016, respectively. RPG and RM received support from FCT/DGES, under the program “Verão com Ciência”

On the Model Performance of Composite CO2 Separation Membranes

A simple model on the performance of composite CO2 separation membranes (ceramic oxide-ion conductor and molten alkaline carbonates) is derived from an equivalent circuit comprising two interlinked cells, using the main electrical circuit component analogs of the electrochemical characteristics of each composite phase (thermodynamic voltages and ionic resistances) and surrounding gas phase activities of species involved in the surface reactions. A newly introduced graphical solution inspired in conventional corrosion diagrams is used to benchmark, map and discuss membrane performance, including the roles of cell inner ionic transport and surface/interface reaction processes. The impact of oxide phase composition (ZrO2, CeO2 and Bi2O3- based oxides), content (4090 vol%) and working temperature (873-973K) on membrane performance are assessed in detail, highlighting the limits of materials currently available. Selected examples of published data on membrane performance are used to demonstrate the efficacy of the suggested diagram and to comment on permeation kinetic constraints, namely phase tortuosity. (C) 2016 Elsevier Ltd. All rights reserved