scholarly journals Characterization of the subunit composition and structure of native adult glycine receptors

2021 ◽  
Author(s):  
Hailong Yu ◽  
Xiao-chen Bai ◽  
Weiwei Wang
Keyword(s):  
Nervous System ◽  
Glycine Receptor ◽  
Scaffolding Proteins ◽  
Β Subunit ◽  
Electrophysiological Properties ◽  
Assembly Mechanism ◽  
Composition And Structure ◽  
Cluster Properties ◽  
Functional States

The strychnine-sensitive pentameric Glycine Receptor (GlyR) mediates fast inhibitory neurotransmission in the mammalian nervous system. Only heteromeric GlyRs mediate synaptic transmission, since they contain the β subunit that permits clustering at the synapse through its interaction with scaffolding proteins. Here we show that α2 and β subunits assemble with an unexpected 4:1 stoichiometry to produce GlyR with native electrophysiological properties. We determined structures in multiple functional states at 3.6 - 3.8 Å resolutions and show α2β GlyR assembly mechanism. Furthermore, we show that one single β subunit in each GlyR gives rise to the characteristic electrophysiological properties of heteromeric GlyR, while more β subunits renders GlyR non-conductive. A single β subunit ensures a univalent GlyR-scaffold linkage, which means the scaffold alone regulates the cluster properties.

Fabrication and Characterization of Nife Thin Film Composition Modulated Alloys

1996 ◽  
Vol 451 ◽  
Author(s):  
S. D. Leith ◽  
D. T. Schwartz
Keyword(s):  
Rotation Rate ◽  
Stripping Voltammetry ◽  
Rotating Disk ◽  
Oscillation Period ◽  
Rotating Disk Electrode ◽  
Disk Rotation ◽  
Rate Oscillation ◽  
Composition And Structure ◽  
Spatially Periodic

ABSTRACTDescribed are results showing that an oscillating flow-field can induce spatially periodic composition variations in electrodeposited NiFe films. Flow-induced NiFe composition modulated alloys (CMA's) were deposited on the disk of a rotating disk electrode by oscillating the disk rotation rate during galvanostatic plating. Deposit composition and structure were investigated using potentiostatic stripping voltammetry and scanning probe microscopy. Results illustrate a linear relationship between the composition modulation wavelength and the flow oscillation period. CMA's with wavelengths less than 10 nm can be fabricated when plating with a disk rotation rate oscillation period less than 3 seconds.

Acid-Sensing Ion Channels

2020 ◽  
Author(s):  
Stefan Gründer
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Excitatory Synapses ◽  
Detailed Characterization ◽  
High Affinity ◽  
Acid Sensing Ion Channels ◽  
Long Time ◽  
Pathological Pain

Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. Being almost ubiquitously present in neurons of the vertebrate nervous system, their precise function remained obscure for a long time. Various animal toxins that bind to ASICs with high affinity and specificity have been tremendously helpful in uncovering the role of ASICs. We now know that they contribute to synaptic transmission at excitatory synapses as well as to sensing metabolic acidosis and nociception. Moreover, detailed characterization of mouse models uncovered an unanticipated role of ASICs in disorders of the nervous system like stroke, multiple sclerosis, and pathological pain. This review provides an overview on the expression, structure, and pharmacology of ASICs plus a summary of what is known and what is still unknown about their physiological functions and their roles in diseases.

scholarly journals Molecular Modeling of Histamine Receptors—Recent Advances in Drug Discovery

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1778
Author(s):  
Pakhuri Mehta ◽  
Przemysław Miszta ◽  
Sławomir Filipek
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Modeling ◽  
Molecular Targets ◽  
Histamine Receptors ◽  
Experimental Characterization ◽  
Complex Disorders ◽  
Theoretical Investigations ◽  
Recent Developments

The recent developments of fast reliable docking, virtual screening and other algorithms gave rise to discovery of many novel ligands of histamine receptors that could be used for treatment of allergic inflammatory disorders, central nervous system pathologies, pain, cancer and obesity. Furthermore, the pharmacological profiles of ligands clearly indicate that these receptors may be considered as targets not only for selective but also for multi-target drugs that could be used for treatment of complex disorders such as Alzheimer’s disease. Therefore, analysis of protein-ligand recognition in the binding site of histamine receptors and also other molecular targets has become a valuable tool in drug design toolkit. This review covers the period 2014–2020 in the field of theoretical investigations of histamine receptors mostly based on molecular modeling as well as the experimental characterization of novel ligands of these receptors.

scholarly journals Automated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ben R. Cairns ◽  
Benjamin Jevans ◽  
Atchariya Chanpong ◽  
Dale Moulding ◽  
Conor J. McCann
Keyword(s):  
Machine Learning ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Structural Changes ◽  
Computational Analysis ◽  
Confocal Imaging ◽  
Learning Approaches ◽  
Composition And Structure ◽  
Oxide Synthase ◽  
Computational Image Analysis

AbstractNeuronal nitric oxide synthase (nNOS) neurons play a fundamental role in inhibitory neurotransmission, within the enteric nervous system (ENS), and in the establishment of gut motility patterns. Clinically, loss or disruption of nNOS neurons has been shown in a range of enteric neuropathies. However, the effects of nNOS loss on the composition and structure of the ENS remain poorly understood. The aim of this study was to assess the structural and transcriptional consequences of loss of nNOS neurons within the murine ENS. Expression analysis demonstrated compensatory transcriptional upregulation of pan neuronal and inhibitory neuronal subtype targets within the Nos1−/− colon, compared to control C57BL/6J mice. Conventional confocal imaging; combined with novel machine learning approaches, and automated computational analysis, revealed increased interconnectivity within the Nos1−/− ENS, compared to age-matched control mice, with increases in network density, neural projections and neuronal branching. These findings provide the first direct evidence of structural and molecular remodelling of the ENS, upon loss of nNOS signalling. Further, we demonstrate the utility of machine learning approaches, and automated computational image analysis, in revealing previously undetected; yet potentially clinically relevant, changes in ENS structure which could provide improved understanding of pathological mechanisms across a host of enteric neuropathies.

scholarly journals Longitudinal Characterization of the Gut Bacterial and Fungal Communities in Yaks

2021 ◽  
Vol 7 (7) ◽  
pp. 559
Author(s):  
Yaping Wang ◽  
Yuhang Fu ◽  
Yuanyuan He ◽  
Muhammad Fakhar-e-Alam Kulyar ◽  
Mudassar Iqbal ◽  
...  
Keyword(s):  
Natural Aging ◽  
Fungal Communities ◽  
Significant Shift ◽  
Mature Adult ◽  
Bacterial Phyla ◽  
Development Stages ◽  
Composition And Structure ◽  
Intestinal Functions ◽  
Development Phases

Development phases are important in maturing immune systems, intestinal functions, and metabolism for the construction, structure, and diversity of microbiome in the intestine during the entire life. Characterizing the gut microbiota colonization and succession based on age-dependent effects might be crucial if a microbiota-based therapeutic or disease prevention strategy is adopted. The purpose of this study was to reveal the dynamic distribution of intestinal bacterial and fungal communities across all development stages in yaks. Dynamic changes (a substantial difference) in the structure and composition ratio of the microbial community were observed in yaks that matched the natural aging process from juvenile to natural aging. This study included a significant shift in the abundance and proportion of bacterial phyla (Planctomycetes, Firmicutes, Bacteroidetes, Spirochaetes, Tenericutes, Proteobacteria, and Cyanobacteria) and fungal phyla (Chytridiomycota, Mortierellomycota, Neocallimastigomycota, Ascomycota, and Basidiomycota) across all development stages in yaks. As yaks grew older, variation reduced, and diversity increased as compared to young yaks. In addition, the intestine was colonized by a succession of microbiomes that coalesced into a more mature adult, including Ruminococcaceae_UCG-005, Romboutsia, Prevotellaceae_UCG-004, Blautia, Clostridium_sensu_stricto_1, Ruminococcus_1, Ruminiclostridium_5, Rikenellaceae_RC9_gut_group, Alloprevotella, Acetitomaculum, Lachnospiraceae_NK3A20_group, Bacteroides, Treponema_2, Olsenella, Escherichia-Shigella, Candidatus_Saccharimonas, and fungal communities Mortierella, Lomentospora, Orpinomyces, and Saccharomyces. In addition, microorganisms that threaten health, such as Escherichia-Shigella, Mortierella, Lomentospora and Hydrogenoanaerobacterium, Corynebacterium_1, Trichosporon, and Coprinellus, were enriched in young and old yaks, respectively, although all yaks were healthy. The significant shifts in microflora composition and structure might reflect adaptation of gut microbiome, which is associated with physicochemical conditions changes and substrate availability in the gut across all development periods of yaks.

scholarly journals Immunological and Molecular Characterization of Goα-like Proteins in the Drosophila Central Nervous System

1989 ◽  
Vol 264 (31) ◽  
pp. 18552-18560 ◽  
Author(s):  
N C Thambi ◽  
F Quan ◽  
W J Wolfgang ◽  
A Spiegel ◽  
M Forte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Characterization
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