The dual-gate model for pentameric ligand-gated ion channels activation and desensitization

Abstract

Pentameric ligand-gated ion channels (pLGICs) mediate fast neurotransmission in the nervous system. Their dysfunction is associated with psychiatric, neurological and neurodegenerative disorders such as schizophrenia, epilepsy and Alzheimer's disease. Understanding their biophysical and pharmacological properties, both at the functional and structural levels, thus holds many therapeutic promises. In addition to their agonist-elicited activation, most pLGICs display another key allosteric property, namely desensitization, in which they enter a shut state refractory to activation upon sustained agonist binding. While the activation mechanisms of several pLGICs have been revealed at near-atomic resolution, the structural foundation of desensitization has long remained elusive. Recent structural and functional data now suggest that the activation and desensitization gates are distinct, and are located at both sides of the ion channel. Such a "dual gate mechanism" accounts for the marked allosteric effects of channel blockers, a feature illustrated herein by theoretical kinetics simulations. Comparison with other classes of ligand- and voltage-gated ion channels show that this dual gate mechanism emerges as a common theme for the desensitization and inactivation properties of structurally unrelated ion channels.

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Response to letter to the editor by Finn et al. (2018)

Abstract

In their letter to the editor regarding our recent paper, Finn and colleagues, propose that the heightened motoneurone responsiveness in chronic hypoxia (CH) compared to acute hypoxia (AH) may relate primarily to greater peripheral fatigue in AH than CH, rather than motoneuronal adaptations to hypoxia.

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Airborne gamma-ray spectra processing: Extracting photopeaks

Publication date: July 2018
Source:Journal of Environmental Radioactivity, Volume 187
Author(s): Eugene Druker
The acquisition of information from the airborne gamma-ray spectra is based on the ability to evaluate photopeak areas in regular spectra from natural and other sources. In airborne gamma-ray spectrometry, extraction of photopeaks of radionuclides from regular one-second spectra is a complex problem. In the region of higher energies, difficulties are associated with low signal level, i.e. low count rates, whereas at lower energies difficulties are associated with high noises due to a high signal level. In this article, a new procedure is proposed for processing the measured spectra up to and including the extraction of evident photopeaks. The procedure consists of reducing the noise in the energy channels along the flight lines, transforming the spectra into the spectra of equal resolution, removing the background from each spectrum, sharpening the details, and transforming the spectra back to the original energy scale. The resulting spectra are better suited for examining and using the photopeaks. No assumptions are required regarding the number, locations, and magnitudes of photopeaks. The procedure does not generate negative photopeaks. The resolution of the spectrometer is used for the purpose. The proposed methodology, apparently, will contribute also to study environmental problems, soil characterization, and other near-surface geophysical methods.



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Anesthesia of thoracic surgery in children

Summary

Providing anesthesia in children with thoracic disease is a challenging task. The effects of the underlying disease, the surgical interventions, and preexisting condition of the patient need to be considered when planning perioperative care. The perioperative care for children undergoing thoracic surgery requires specific techniques adapted to the pediatric physiology and anatomy. This review is focused on anesthetic strategies for thoracic surgery with an emphasis on perioperative analgesia including neuraxial techniques.

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Intentional tracheoesophageal fistula cannulation for gastric decompression in type C esophageal atresia

Summary

We describe a nonsurgical technique for managing gastric distention in infants with type C esophageal atresia, involving intubating the trachea with an umbilical catheter and entering the stomach through the fistula as soon as a flexible bronchoscope found its wide-open orifice. This technique might have a special role when gastric distention precedes other commonly used preventive measures.

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Distances from vocal cords to mid-trachea for optimizing endotracheal tubes depth markers according to gestational age

Summary

Background

Adequate endotracheal tube positioning in preterm infants is complicated by the short length of the airway. Distal markers were designed to help with the insertion of endotracheal tubes at an appropriate depth below the vocal cords. However, those markers are not standardized between manufacturers, each tube size displays only one (sometimes 2) markers to provide information for infants of various gestational ages, and indicated distances are often too long for extremely preterm infants.

Aims

The study aims to describe vocal cords to mid-tracheal distance for different gestational ages and determine if depth markers should be adjusted accordingly.

Methods

Half the tracheal length added to the height of the posterior lamina of the cricoids approximates the distance between vocal cords and mid-trachea. Those dimensions were retrospectively retrieved from a database of laryngo-tracheal measurements obtained during autopsies of fetuses and newborn infants free of upper airway malformations. The equation of correlation between gestational age and distance from vocal cords to mid-trachea was used to calculate those distances for different gestational ages.

Results

Data were derived from 114 patients. Vocal cords to mid-trachea distance is linearly correlated with gestational age (r = .90; distance = 2.831 + 0.6208 × gestational age). We suggest depth markers at 17.7, 19.0, 20.8, 22.7, 24.6, and 26.4 mm for gestational ages of 24, 26, 29, 32, 35, and 38 weeks, respectively, indicated by contrasting colors.

Conclusion

The linear relationship between laryngo-tracheal size and gestational age offers the opportunity to revise endotracheal tube depth markers for the smallest patients. Trials comparing those suggested markers with those currently in use are needed before implementation.

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Deficiency of the BMP Type I receptor ALK3 partly protects mice from anemia of inflammation

Inflammatory stimuli induce the hepatic iron regulatory hormone hepcidin, which contributes to anaemia of inflammation (AI). Hepcidin expression is regulated by the bone morphogenetic protein (BMP) and the int...

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