100 research outputs found
Predicting High-Flow Spinal CSF Leaks in Spontaneous Intracranial Hypotension Using a Spinal MRI-Based Algorithm: Have Repeat CT Myelograms Been Reduced?
ABSTRACT BACKGROUND AND PURPOSE: We adopted an imaging algorithm in 2011 in which extradural fluid on spinal MR imaging directs dynamic CT myelography. We assessed algorithm compliance and its effectiveness in reducing repeat or unnecessary dynamic CT myelograms
AMPA Receptors Commandeer an Ancient Cargo Exporter for Use as an Auxiliary Subunit for Signaling
Fast excitatory neurotransmission in the mammalian central nervous system is mainly mediated by ionotropic glutamate receptors of the AMPA subtype (AMPARs). AMPARs are protein complexes of the pore-lining α-subunits GluA1-4 and auxiliary β-subunits modulating their trafficking and gating. By a proteomic approach, two homologues of the cargo exporter cornichon, CNIH-2 and CNIH-3, have recently been identified as constituents of native AMPARs in mammalian brain. In heterologous reconstitution experiments, CNIH-2 promotes surface expression of GluAs and modulates their biophysical properties. However, its relevance in native AMPAR physiology remains controversial. Here, we have studied the role of CNIH-2 in GluA processing both in heterologous cells and primary rat neurons. Our data demonstrate that CNIH-2 serves an evolutionarily conserved role as a cargo exporter from the endoplasmic reticulum (ER). CNIH-2 cycles continuously between ER and Golgi complex to pick up cargo protein in the ER and then to mediate its preferential export in a coat protein complex (COP) II dependent manner. Interaction with GluA subunits breaks with this ancestral role of CNIH-2 confined to the early secretory pathway. While still taking advantage of being exported preferentially from the ER, GluAs recruit CNIH-2 to the cell surface. Thus, mammalian AMPARs commandeer CNIH-2 for use as a bona fide auxiliary subunit that is able to modify receptor signaling
The Biochemistry, Ultrastructure, and Subunit Assembly Mechanism of AMPA Receptors
The AMPA-type ionotropic glutamate receptors (AMPA-Rs) are tetrameric ligand-gated ion channels that play crucial roles in synaptic transmission and plasticity. Our knowledge about the ultrastructure and subunit assembly mechanisms of intact AMPA-Rs was very limited. However, the new studies using single particle EM and X-ray crystallography are revealing important insights. For example, the tetrameric crystal structure of the GluA2cryst construct provided the atomic view of the intact receptor. In addition, the single particle EM structures of the subunit assembly intermediates revealed the conformational requirement for the dimer-to-tetramer transition during the maturation of AMPA-Rs. These new data in the field provide new models and interpretations. In the brain, the native AMPA-R complexes contain auxiliary subunits that influence subunit assembly, gating, and trafficking of the AMPA-Rs. Understanding the mechanisms of the auxiliary subunits will become increasingly important to precisely describe the function of AMPA-Rs in the brain. The AMPA-R proteomics studies continuously reveal a previously unexpected degree of molecular heterogeneity of the complex. Because the AMPA-Rs are important drug targets for treating various neurological and psychiatric diseases, it is likely that these new native complexes will require detailed mechanistic analysis in the future. The current ultrastructural data on the receptors and the receptor-expressing stable cell lines that were developed during the course of these studies are useful resources for high throughput drug screening and further drug designing. Moreover, we are getting closer to understanding the precise mechanisms of AMPA-R-mediated synaptic plasticity
Kaldor-Verdoorn's Law and Increasing Returns to Scale: A Comparison Across Developed Countries
Sectoral capabilities and productive structure: An input-output analysis of the key sectors of the Brazilian economy
New animal models of progressive neurodegeneration: tools for identifying targets in predictive diagnostics and presymptomatic treatment
The genus <i>Cola</i> in southern Africa
The two species of Cola that occur in southern Africa are reviewed. C. natalensis Oliv. is endemic, but C. greenwayi Brenan has mainly a tropical east African distribution with the eastern Transvaal and northern Zululand speciÂmens being the most southerly records. A study o f the available material from tropical east Africa and southern Africa supports the view that C. microcarpa Brenan is synonymous with C. greenwayi
Revision of <i>Melhania</i> in southern Africa
The 13 species of Melhania in southern Africa are revised. Among the problems resolved is a long-standing one concerning the identities of M. rehmannii Szyszyl. and M. griquensis H. Bol., the latter in its strict sense being relegated to synonymy o f the former
The Genus <i>Crinum</i> in Southern Africa
The 21 species of Crinum recognized in southern Africa are reviewed and illustrated, mostly in colour. Five of these were described by the author during the last two decades. A key to the species and notes on the history, diagnostic features and distribution in southern Africa are provided
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