Raising the bar on the type, size and timeline of a 'successful' decoupling

Peer reviewe

Decoupling for ecological sustainability : A categorisation and review of research literature

The idea of decoupling "environmental bads" from "economic goods" has been proposed as a path towards sustainability by organizations such as the OECD and UN. Scientific consensus reports on environmental impacts (e.g., greenhouse gas emissions) and resource use give an indication of the kind of decoupling needed for ecological sustainability: global, absolute, fast-enough and long-enough. This goal gives grounds for a categorisation of the different kinds of decoupling, with regard to their relevance. We conducted a survey of recent (1990-2019) research on decoupling on Web of Science and reviewed the results in the research according to the categorisation. The reviewed 179 articles contain evidence of absolute impact decoupling, especially between CO2 (and SOX) emissions and evidence on geographically limited (national level) cases of absolute decoupling of land and blue water use from GDP, but not of economy-wide resource decoupling, neither on national nor international scales. Evidence of the needed absolute global fast-enough decoupling is missing.Peer reviewe

Domain Swapping and Different Oligomeric States for the Complex Between Calmodulin and the Calmodulin-Binding Domain of Calcineurin A

BACKGROUND: Calmodulin (CaM) is a ubiquitously expressed calcium sensor that engages in regulatory interactions with a large number of cellular proteins. Previously, a unique mode of CaM target recognition has been observed in the crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A. METHODOLOGY/PRINCIPAL FINDINGS: We have solved a high-resolution crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A in a novel crystal form, which shows a dimeric assembly of calmodulin, as observed before in the crystal state. We note that the conformation of CaM in this complex is very similar to that of unliganded CaM, and a detailed analysis revels that the CaM-binding motif in calcineurin A is of a novel '1-11' type. However, using small-angle X-ray scattering (SAXS), we show that the complex is fully monomeric in solution, and a structure of a canonically collapsed CaM-peptide complex can easily be fitted into the SAXS data. This result is also supported by size exclusion chromatography, where the addition of the ligand peptide decreases the apparent size of CaM. In addition, we studied the energetics of binding by isothermal titration calorimetry and found them to closely resemble those observed previously for ligand peptides from CaM-dependent kinases. CONCLUSIONS/SIGNIFICANCE: Our results implicate that CaM can also form a complex with the CaM-binding domain of calcineurin in a 1 ratio 1 stoichiometry, in addition to the previously observed 2 ratio 2 arrangement in the crystal state. At the structural level, going from 2 ratio 2 association to two 1 ratio 1 complexes will require domain swapping in CaM, accompanied by the characteristic bending of the central linker helix between the two lobes of CaM

Charge Isomers of Myelin Basic Protein: Structure and Interactions with Membranes, Nucleotide Analogues, and Calmodulin

As an essential structural protein required for tight compaction of the central nervous system myelin sheath, myelin basic protein (MBP) is one of the candidate autoantigens of the human inflammatory demyelinating disease multiple sclerosis, which is characterized by the active degradation of the myelin sheath. In this work, recombinant murine analogues of the natural C1 and C8 charge components (rmC1 and rmC8), two isoforms of the classic 18.5-kDa MBP, were used as model proteins to get insights into the structure and function of the charge isomers. Various biochemical and biophysical methods such as size exclusion chromatography, calorimetry, surface plasmon resonance, small angle X-ray and neutron scattering, Raman and fluorescence spectroscopy, and conventional as well as synchrotron radiation circular dichroism were used to investigate differences between these two isoforms, both from the structural point of view, and regarding interactions with ligands, including calmodulin (CaM), various detergents, nucleotide analogues, and lipids. Overall, our results provide further proof that rmC8 is deficient both in structure and especially in function, when compared to rmC1. While the CaM binding properties of the two forms are very similar, their interactions with membrane mimics are different. CaM can be used to remove MBP from immobilized lipid monolayers made of synthetic lipids - a phenomenon, which may be of relevance for MBP function and its regulation. Furthermore, using fluorescently labelled nucleotides, we observed binding of ATP and GTP, but not AMP, by MBP; the binding of nucleoside triphosphates was inhibited by the presence of CaM. Together, our results provide important further data on the interactions between MBP and its ligands, and on the differences in the structure and function between MBP charge isomers

Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin

Structural changes in human serum albumin (HSA) induced by the pollutants 1-naphthol, 2-naphthol and 8-quinolinol were analyzed by circular dichroism, fluorescence spectroscopy and dynamic light scattering. The alteration in protein conformational stability was determined by helical content induction (from 55 to 75%) upon protein-pollutant interactions. Domain plasticity is responsible for the temperature-mediated unfolding of HSA. These findings were compared to HSA-hydrolase activity. We found that though HSA is a monomeric protein, it shows heterotropic allostericity for β-lactamase activity in the presence of pollutants, which act as K- and V-type non-essential activators. Pollutants cause conformational changes and catalytic modifications of the protein (increase in β-lactamase activity from 100 to 200%). HSA-pollutant interactions mediate other protein-ligand interactions, such as HSA-nitrocefin. Therefore, this protein can exist in different conformations with different catalytic properties depending on activator binding. This is the first report to demonstrate the catalytic allostericity of HSA through a mechanistic approach. We also show a correlation with non-microbial drug resistance as HSA is capable of self-hydrolysis of β-lactam drugs, which is further potentiated by pollutants due to conformational changes in HSA

Dual-channel remanufacturing closed-loop supply chains under carbon footprint and collection competition

Abstract Due to economic and environmental advantages, transferring from linear systems into circular economies has been accelerated, especially in developed countries, which affects companies’ relations. Among different tools and methodologies, the closed-loop supply chain (CLSC) model as an established approach has shown its efficiency in reflecting these relations regarding the consumers’ behavior. Because of the complexity, limited studies have considered the effects of different factors simultaneously on different CLSC network designs. This is the first attempt to study the effects of carbon emission and remanufacturing simultaneously on a dual-channel in both forward and reverse logistics, while there is competition on collection. Accordingly, a novel format for the demand function is suggested and employed. The decisions regarding the optimal pricing and collection strategies of CLSCs were investigated, within which the manufacturer is responsible for the remanufacturing process and selling the remanufactured products directly to the customer through the online channel. In contrast, new products are sold via the traditional retailer channel, imposing relevant costs. We explore the effect of different dual-collection settings when there is competition between collector parties under three possible options (i.e., Manufacturer-Retailer, Manufacturer-Third-party, and Retailer-Third-party). The considered demand for both new and remanufactured products addresses consumers who have different willingness to choose the remanufactured items and are sensitive to the produced products’ carbon footprint. The behavior of the formulated CLSC models is studied by game theory regarding decision variables, and each player's profit is discussed through systematic comparison. We analytically show that considering all the effects, third-party entry is not in the manufacturer's interest. The findings show that consumers’ willingness to choose remanufactured products is generally more influential on prices and profits than their sensitivity to the carbon footprint

Is there a recreational misuse potential for Pregabalin? : Analysis of anecdotal online reports in comparison with related Gabapentin and Clonazepam data

Original article can be found at: http://content.karger.com/ Copyright Karger.Background: Although pregabalin abuse potential is reportedly low, online data related to its recreational misuse potential have recently been identified. We aimed here at formally analysing pregabalin misuse web reports and comparing these with data pertaining to similar drugs, e.g. gabapentin and clonazepam, for which an abuse potential has already been identified. Methods: An 8-language analysis of the online information on pregabalin acquisition/misuse was carried out. An initial sample of 203 websites was considered and 108 relevant websites were monitored on a regular basis. To obtain material relating to gabapentin and clonazepam, an English-language search was carried out and 32 relevant websites were examined. Results: Misuse of pregabalin, which is commonly offered for sale online, was allegedly associated with sedative and/or psychedelic effects. This was associated with both higher dosages than clinically advised and idiosyncratic (i.e.: IV, rectal, intranasal) drug intake modalities. Although perceived as less powerful than pregabalin, gabapentin misuse was associated with similar sedative/psychedelic effects. Clonazepam allegedly induced either sedation or stimulation, depending on the dosage. Conclusions: Pregabalin experimenters might be profiled as individuals with a history of recreational polydrug misuse. Pregabalin misuse might be facilitated by easy online accessibility; potency; and peculiar, including anxiolytic, psychoactive effects. Physicians should carefully evaluate patients for history of drug abuse and observe them for signs of pregabalin/gabapentin/clonazepam misuse.Peer reviewe