Adenosine, ‘pertussis-sensitive’ G-proteins, and K+ conductance in central mammalian neurones under energy deprivation

There is a striking similarity between the effects of adenosine and of hypoxia or glucose depletion on membrane potential and conductance of hippocampal neurones in tissue slices of rat brain. Both induce a membrane hyperpolarization by an increase in potassium conductance. It seemed likely, therefore, that a rise in extracellular adenosine concentration during energy deprivation may link neuronal metabolism with membrane K+ conductance. To test this hypothesis, we have now investigated the effects of hypoxia/glucose deprivation on hippocampal neurones from pertussis toxin-treated rats. In such slices adenosine had no effect on postsynaptic membrane potential and input resistance. Nevertheless, hypoxia or glucose depletion were as effective as in controls. These data provide evidence against adenosine as the main mediator between cell metabolism and potassium conductance

Evaluating electronic waste recycling systems : the influence of physical architecture on system performance

Thesis (S.M. in Technology and Policy)--Massachusetts Institute of Technology, Engineering Systems Division, Technology and Policy Program, 2008.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 63-68).Many different forms of electronic waste recycling systems now exist worldwide, and the amount of related legislation continues to increase. Numerous approaches have been proposed including landfill bans, extended producer responsibility (EPR) and advance recovery fee (ARF) funded recycling systems. In order for policymakers and system architects to establish the optimal recycling system for their location, they need to know how to evaluate the performance of existing systems, and furthermore, how to use this information to design new systems. This thesis addresses the question: How does the physical system architecture of e-waste systems influence system performance? Specifically, it focuses upon the physical system architecture of collection site density and distribution. This thesis presents a systematic methodology developed with the Materials Systems Laboratory for characterizing recycling systems. Case studies of existing e-waste systems operating in Switzerland, Sweden, the Netherlands, Norway, Belgium, the Canadian province of Alberta and the US States of California, Maine and Maryland are examined for correlations between the environmental and financial performance of existing systems with respect to both the context and the architectural options of those systems. The case study analysis furthermore informs the construction of a model of e-waste systems. This model, which examines architectural choices in collection, transport, processing and system management of e-waste, is used to predict the environmental and financial performance of theoretical e-waste systems for a given location. The model was intentionally developed to be both broad, in order to encompass all pieces of recycling systems, and general, such that many different types of systems, both real and hypothetical, can be analyzed. Following an application of the model to several different combinations of system architecture and context, policy recommendations are made regarding the construction and evaluation of e-waste systems in various locations.by Susan Fredholm.S.M.in Technology and Polic

Några mineralogiska iakttageher från trakten kring Nyköping

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The Practice of Thresholds: Autonomy in Clinical Education Explored Through Variation Theory and the Threshold Concepts Framework

This paper demonstrates a practical dimension to the discussion about threshold concepts. Threshold concepts have thus far mostly been acknowledged to elucidate learning processes mainly connected to theoretical concepts. By exploring situations that prompted experiences of autonomy and authenticity in clinical learning, findings showed how a practical experience could have the same power to transform thinking and identity as theoretical thresholds and serve as a trigger for transformational learning, therefore making the discussion about ‘practical thresholds' or thresholds in practice possible. The present study explores situations that prompted autonomy and authenticity, and offers context for and substance to these situations by adopting variation theory and the threshold concept framework. In order to learn more about situations that prompt experiences of autonomy and authenticity, and create prerequisites for such experiences, this paper examines how students discern and interpret these situations by analysing them through variation theory and the threshold concept framework

A Ketogenic Diet Suppresses Seizures in Mice through Adenosine A1 Receptors

A ketogenic diet (KD) is a high-fat, low-carbohydrate metabolic regimen; its effectiveness in the treatment of refractory epilepsy suggests that the mechanisms underlying its anticonvulsive effects differ from those targeted by conventional antiepileptic drugs. Recently, KD and analogous metabolic strategies have shown therapeutic promise in other neurologic disorders, such as reducing brain injury, pain, and inflammation. Here, we have shown that KD can reduce seizures in mice by increasing activation of adenosine A1 receptors (A1Rs). When transgenic mice with spontaneous seizures caused by deficiency in adenosine metabolism or signaling were fed KD, seizures were nearly abolished if mice had intact A1Rs, were reduced if mice expressed reduced A1Rs, and were unaltered if mice lacked A1Rs. Seizures were restored by injecting either glucose (metabolic reversal) or an A1R antagonist (pharmacologic reversal). Western blot analysis demonstrated that the KD reduced adenosine kinase, the major adenosine-metabolizing enzyme. Importantly, hippocampal tissue resected from patients with medically intractable epilepsy demonstrated increased adenosine kinase. We therefore conclude that adenosine deficiency may be relevant to human epilepsy and that KD can reduce seizures by increasing A1R-mediated inhibition

Conversion of a non-selective adenosine receptor antagonist into A3-selective high affinity fluorescent probes using peptide-based linkers

Advances in fluorescence-based imaging technologies have helped propel the study of real-time biological readouts and analysis across many different areas. In particular the use of fluorescent ligands as chemical tools to study proteins such as G protein-coupled receptors (GPCRs) has received ongoing interest. Methods to improve the efficient chemical synthesis of fluorescent ligands remain of paramount importance to ensure this area of bioanalysis continues to advance. Here we report conversion of the non-selective GPCR adenosine receptor antagonist Xanthine Amine Congener into higher affinity and more receptor subtype-selective fluorescent antagonists. This was achieved through insertion and optimisation of a dipeptide linker between the adenosine receptor pharmacophore and the fluorophore. Fluorescent probe 27 containing BODIPY 630/650 (pKD = 9.12 ± 0.05 [hA3AR]), and BODIPY FL-containing 28 (pKD = 7.96 ± 0.09 [hA3AR]) demonstrated clear, displaceable membrane binding using fluorescent confocal microscopy. From in silico analysis of the docked ligand-receptor complexes of 27, we suggest regions of molecular interaction that could account for the observed selectivity of these peptide-linker based fluorescent conjugates. This general approach of converting a non-selective ligand to a selective biological tool could be applied to other ligands of interest

Exercise-associated sudden death in Finnish standardbred and coldblooded trotters : - a case series with pedigree analysis

Exercise-associated sudden deaths (EASDs) are deaths occurring unexpectedly during or immediately after exercise. Sudden cardiac death (SCD) is one cause of EASD. Cardiac arrhythmias caused by genetic variants have been linked to SCD in humans. We hypothesize that genetic variants may be associated with SCD in animals, including horses. Genetic variants are transmitted to offspring and their frequency might increase within a family. Therefore, the frequency of such variants might increase with the inbreeding factor. Higher inbreeding could have a negative impact on racing performance. Pedigree data and career earnings from racehorses diagnosed with SCD between 2002 and 2017 were compared using non-parametric tests with 1) control horses that died due to catastrophic musculoskeletal injuries and 2) horses that raced during the same period without reported problems. Diagnosis of SCD was based on necropsy reports, including macroscopic and microscopic examinations. Death was registered in the study period for 61 horses. Eleven of these horses were excluded due to missing autopsy reports. In 25 cases, the diagnosis remained unknown and death was possibly caused by cardiac arrhythmia, in two cases cardiac disease was identified, in seven cases a rupture of a major vessel had occurred. In addition, 16 horses died or were euthanized due to severe musculoskeletal injuries. No significant differences in inbreeding coefficients or in career earnings were found between the groups or between horses with EASD compared with other horses racing during the same period. The study provides no evidence for increased inbreeding factor in Finnish racehorses with SCD. (c) 2021 Elsevier Inc. All rights reserved.Peer reviewe