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Mammalian aldehyde oxidases (AOXs; EC1.2.3.1) are a group of conserved proteins belonging to the family of molybdo-flavoenzymes along with the structurally related xanthine dehydrogenase enzyme. AOXs are characterized by broad substrate specificity, oxidizing not only aromatic and aliphatic aldehydes into the corresponding carboxylic acids, but also hydroxylating a series of heteroaromatic rings. The number of AOX isoenzymes expressed in different vertebrate species is variable. The two extremes are represented by humans, which express a single enzyme (AOX1) in many organs and mice or rats which are characterized by tissue-specific expression of four isoforms (AOX1, AOX2, AOX3, and AOX4). In vertebrates each AOX isoenzyme is the product of a distinct gene consisting of 35 highly conserved exons. The extant species-specific complement of AOX isoenzymes is the result of a complex evolutionary process consisting of a first phase characterized by a series of asynchronous gene duplications and a second phase where the pseudogenization and gene deletion events prevail. In the last few years remarkable advances in the elucidation of the structural characteristics and the catalytic mechanisms of mammalian AOXs have been made thanks to the successful crystallization of human AOX1 and mouse AOX3. Much less is known about the physiological function and physiological substrates of human AOX1 and other mammalian AOX isoenzymes, although the importance of these proteins in xenobiotic metabolism is fairly well established and their relevance in drug development is increasing. This review article provides an overview and a discussion of the current knowledge on mammalian AOX.
During starch metabolism, the phosphorylation of glucosyl residues of starch, to be more precise of amylopectin, is a repeatedly observed process. This phosphorylation is mediated by dikinases, the glucan, water dikinase (GWD) and the phosphoglucan, water dikinase (PWD). The starch-related dikinases utilize ATP as dual phosphate donor transferring the terminal gamma-phosphate group to water and the beta-phosphate group selectively to either C6 position or C3 position of a glucosyl residue within amylopectin. By the collaborative action of both enzymes, the initiation of a transition of alpha-glucans from highly ordered, water-insoluble state to a less order state is realized and thus the initial process of starch degradation. Consequently, mutants lacking either GWD or PWD reveal a starch excess phenotype as well as growth retardation. In this review, we focus on the increased knowledge collected over the last years related to enzymatic properties, the precise definition of the substrates, the physiological implications, and discuss ongoing questions.
Discussions about the opening of science to society have led to the emergence of new fields such as sustainability science and transformative science. At the same time, the megatrend of stakeholder participation reached the academic world and thus scientific research processes. This challenges the way science is conducted and the tools, methods and theories perceived appropriate. Although researchers involve stakeholders, the scientific community still lacks comprehensive theoretical analysis of the practical processes behind their integration - for example what kind of perceptions scientists have about their roles, their objectives, the knowledge to gather, their understanding of science or the science-policy interface. Our paper addresses this research gap by developing four ideal types of stakeholder involvement in science - the technocratic, the functionalist, the neoliberal-rational and the democratic type. In applying the typology, which is based on literature review, interviews and practical experiences, we identify and discuss three major criticisms raised towards stakeholder involvement in science: the legitimacy of stakeholder claims, the question whether bargaining or deliberation are part of the stakeholder involvement process and the question of the autonomy of science. Thus, the typology helps scientists to better understand the major critical questions that stakeholder involvement raises and enables them to position themselves when conducting their research. (C) 2016 Elsevier Ltd. All rights reserved.
Background: First rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other "criterion A' symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia.
Widespread flooding in June 2013 caused damage costs of (sic)6 to 8 billion in Germany, and awoke many memories of the floods in August 2002, which resulted in total damage of (sic)11.6 billion and hence was the most expensive natural hazard event in Germany up to now. The event of 2002 does, however, also mark a reorientation toward an integrated flood risk management system in Germany. Therefore, the flood of 2013 offered the opportunity to review how the measures that politics, administration, and civil society have implemented since 2002 helped to cope with the flood and what still needs to be done to achieve effective and more integrated flood risk management. The review highlights considerable improvements on many levels, in particular (1) an increased consideration of flood hazards in spatial planning and urban development, (2) comprehensive property-level mitigation and preparedness measures, (3) more effective flood warnings and improved coordination of disaster response, and (4) a more targeted maintenance of flood defense systems. In 2013, this led to more effective flood management and to a reduction of damage. Nevertheless, important aspects remain unclear and need to be clarified. This particularly holds for balanced and coordinated strategies for reducing and overcoming the impacts of flooding in large catchments, cross-border and interdisciplinary cooperation, the role of the general public in the different phases of flood risk management, as well as a transparent risk transfer system. Recurring flood events reveal that flood risk management is a continuous task. Hence, risk drivers, such as climate change, land-use changes, economic developments, or demographic change and the resultant risks must be investigated at regular intervals, and risk reduction strategies and processes must be reassessed as well as adapted and implemented in a dialogue with all stakeholders.
Over the past decade, an increasing number of public organizations involved in marine governance in Europe have adapted their formal coordination structures for fisheries and marine environmental management. This study examines why the International Council for the Exploration of the Sea (ICES), DG FISH of the European Commission, the Norwegian Institute of Marine Research (IMR), and the Swedish Agency for Marine and Water Management (SwAM) have changed their sectoral structures into organizations with a geographical focus on marine ecosystems. The study finds that the gradual convergence of formal coordination structures for fisheries and marine environmental management is driven by coercive, normative and mimetic processes of isomorphism. The structural changes reflect an organizational adaptation to a changing institutional environment and an Ecosystem Approach to Management (EAM) focusing on regional marine areas, cross-sector integration and coordination. (C) 2016 Elsevier Ltd. All rights reserved.