Neuronal influences are necessary to produce mitochondrial co-localization with glutamate transporters in astrocytes.

yesAbstract Recent evidence suggests that the predominant astrocyte glutamate transporter, GLT-1/ Excitatory Amino Acid Transporter 2 (EAAT2) is associated with mitochondria. We used primary cultures of mouse astrocytes to assess co-localization of GLT-1 with mitochondria, and tested whether the interaction was dependent on neurons, actin polymerization or the kinesin adaptor, TRAK2. Mouse primary astrocytes were transfected with constructs expressing V5-tagged GLT-1, pDsRed1-Mito with and without dominant negative TRAK2. Astrocytes were visualized using confocal microscopy and co-localization was quantified using Volocity software. Image analysis of confocal z-stacks revealed no co-localization between mitochondria and GLT-1 in pure astrocyte cultures. Co-culture of astrocytes with primary mouse cortical neurons revealed more mitochondria in processes and a positive correlation between mitochondria and GLT-1. This co-localization was not further enhanced after neuronal depolarization induced by 1 h treatment with 15 mM K+. In pure astrocytes, a rho kinase inhibitor, Y27632 caused the distribution of mitochondria to astrocyte processes without enhancing GLT-1/mitochondrial co-localization, however, in co-cultures, Y27632 abolished mitochondrial: GLT-1 co-localization. Disrupting potential mitochondrial: kinesin interactions using dominant negative TRAK2 did not alter GLT-1 distribution or GLT-1: mitochondrial co-localization. We conclude that the association between GLT-1 and mitochondria is modest, is driven by synaptic activity and dependent on polymerized actin filaments. Mitochondria have limited co-localization with the glutamate transporter GLT-1 in primary astrocytes in culture. Few mitochondria are in the fine processes where GLT-1 is abundant. It is necessary to culture astrocytes with neurones to drive a significant level of co-localization, but co-localization is not further altered by depolarization, manipulating sodium ion gradients or Na/K ATPase activity

Möbius and Hückel Cyclacenes with Dewar and Ladenburg Defects

Copyright © 2020 American Chemical Society. Cyclacene nanobelts have not been synthesized in over 60 years and remain one of the last unsynthesized building blocks of carbon nanotubes. Recent work has predicted that Hückel-cyclacenes containing Dewar benzenoid ring isomers are the most stable isomeric forms for several of the smaller sizes of cyclacene belts. Here, we give a more complete picture of the isomers that are possible within these nanobelt systems by simulating embedded Ladenburg (prismane) benzenoid rings in Hückel-[n]cyclacenes (n = 5-14) and embedded Dewar benzenoid rings in twisted Möbius-[n]cyclacenes (n = 9-14). The Möbius-[9]cyclacene isomer containing one Dewar benzenoid defect and the Hückel-[5]cyclacene isomer containing two maximally spaced Ladenburg benzenoid defects are found to be more stable than their conventional Kekulé benzenoid ring counterparts. The isomers that contain Dewar and Ladenburg benzenoid rings have larger electronic singlet-triplet energy gaps and lower polyradical character when compared with the conventional isomers

Dewar Benzenoids Discovered in Carbon Nanobelts

© 2020 American Chemical Society. The synthesis of cyclacene nanobelts remains an elusive goal dating back over 60 years. These molecules represent the last unsynthesized building block of carbon nanotubes and may be useful both as seed molecules for the preparation of structurally well-defined carbon nanotubes and for understanding the behavior and formation of zigzag nanotubes more broadly. Here we report the discovery that isomers containing two Dewar benzenoid rings are the preferred form for several sizes of cyclacene. The predicted lower polyradical character and higher singlet-triplet stability that these isomers possess compared with their pure benzenoid counterparts suggest that they may be more stable synthetic targets than the structures that have previously been identified. Our findings should facilitate the exploration of new routes to cyclacene synthesis through Dewar benzene chemistry

Genetic algorithm in ab initio protein structure prediction using low resolution model : a review

Proteins are sequences of amino acids bound into a linear chain that adopt a specific folded three-dimensional (3D) shape. This specific folded shape enables proteins to perform specific tasks. The protein structure prediction (PSP) by ab initio or de novo approach is promising amongst various available computational methods and can help to unravel the important relationship between sequence and its corresponding structure. This article presents the ab initio protein structure prediction as a conformational search problem in low resolution model using genetic algorithm. As a review, the essence of twin removal, intelligence in coding, the development and application of domain specific heuristics garnered from the properties of the resulting model and the protein core formation concept discussed are all highly relevant in attempting to secure the best solution

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Serotonin receptors on astrocytes in vitro and in vivo

Available from British Library Document Supply Centre-DSC:DXN009273 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Lack of localization of 5-HT6 receptors on cholinergic neurons: implication of multiple neurotransmitter systems in 5-HT6 receptor-mediated acetylcholine release

The involvement of the cholinergic system in learning and memory together with the cognitive enhancing properties of 5-HT6 receptor antagonists led us to study the relationship between 5-HT6 receptors and cholinergic neurotransmission. A selective cholinergic lesion, induced by injection of the immunotoxin 192-IgG-Saporin into the nucleus basalis magnocellularis, failed to alter the density of 5-HT6 receptor mRNA or protein expression in the deafferentated frontal cortex, suggesting that 5-HT6 receptors are not located on cholinergic neurons. The 5-HT6 receptor antagonist SB-357134 (0.001-1 microM) induced a concentration-dependant K+-evoked [3H]acetylcholine (ACh) release in vitro in rat cortical and striatal slices, which was blocked by tetrodotoxin. SB-357134, up to 1 microM, stimulated glutamate release in cortical and striatal slices. In the cortex, riluzole (1 microM) blocked the SB-357134-induced K+-stimulated [3H]ACh release, and simultaneous administration of MK-801 (1 microM) and SB-357134 (0.05 microM) elicited an increase in K+-evoked ACh release. In the striatum, SB-357134, 1 microM, decreased dopamine release, and the increase in K+-evoked [3H]ACh release induced by 5-HT6 receptor blockade was reversed by the D1 receptor antagonist, SCH23390 (1 microM). In both the frontal cortex and striatum, bicuculline, 1 microM, showed no effect on SB-357134-evoked [3H]ACh. These results are discussed in terms of neurochemical mechanisms involved in 5-HT6 receptor functions

Kernel Methods for Predicting Yields of Chemical Reactions

The use of machine learning methods for the prediction of reaction yield is an emerging area. We demonstrate the applicability of support vector regression (SVR) for predicting reaction yields, using combinatorial data. Molecular descriptors used in regression tasks related to chemical reactivity have often been based on time-consuming, computationally demanding quantum chemical calculations, usually density functional theory. Structure-based descriptors (molecular fingerprints and molecular graphs) are quicker and easier to calculate and are applicable to any molecule. In this study, SVR models built on structure-based descriptors were compared to models built on quantum chemical descriptors. The models were evaluated along the dimension of each reaction component in a set of Buchwald-Hartwig amination reactions. The structure-based SVR models outperformed the quantum chemical SVR models, along the dimension of each reaction component. The applicability of the models was assessed with respect to similarity to training. Prospective predictions of unseen Buchwald-Hartwig reactions are presented for synthetic assessment, to validate the generalizability of the models, with particular interest along the aryl halide dimension