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  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
  • Burns, Tom, et al. (författare)
  • Paradigm Shift in Game Theory : Sociological Re-Conceptualization of Human Agency,Social Structure, and Agents' Cognitive-Normative Frameworks and Action Determination Modalities
  • 2018
  • Rapport (refereegranskat)abstract
    • This article aims to present some of the initial work of developing a social science grounded game theory—as a clear alternative to classical game theory. Two distinct independent initiatives in Sociology are presented: One, a systems approach, social systems game theory (SGT),and the other, Erving Goffman's interactionist approach (IGT). These approaches are presented and contrasted with classical theory. They focus on the social rules, norms, roles, role relationships,and institutional arrangements, which structure and regulate human behavior. While strategic judgment and instrumental rationality play an important part in the sociological approaches, they are not a universal or dominant modality of social action determination. Rule following is considered, generally speaking, more characteristic and more general. Sociological approaches, such as those outlined in this article provide a language and conceptual tools to more adequately and effectively than the classical theory describe, model, and analyze the diversity and complexity of human interaction conditions and processes: (1) complex cognitive rule based models of the interaction situation with which actors understand and analyze their situations; (2) value complex(es) with which actors operate, often with multiple values and norms applying in interaction situations;(3) action repertoires (rule complexes) with simple and complex action alternatives—plans, programs,established (sometimes highly elaborated) algorithms, and rituals; (4) a rule complex of action determination modalities for actors to generate and/or select actions in game situations; three actionmodalities are considered here; each modality consists of one or more procedures or algorithms for action determination: (I) following or implementing a rule or rule complex, norm, role, ritual,or social relation; (II) selecting or choosing among given or institutionalized alternatives according toa rule or principle; and (III) constructing or adopting one or more alternatives according to a value,guideline, or set of criteria. Such determinations are often carried out collectively. The paper identifies and illustrates in a concluding table several of the key differences between classical theory and the sociological approaches on a number of dimensions relating to human agency; social structure, norms, institutions, and cultural forms; patterns of game interaction and outcomes,the conditions of cooperation and conflict, game restructuring and transformation, and empirical relevance. Sociologically based game theory, such as the contributions outlined in this article suggest a language and conceptual tools to more adequately and effectively than the classical theory describe,model, and analyze the diversity, complexity, and dynamics of human interaction conditions and processes and, therefore, promises greater empirical relevance and scientific power. An Appendix provides an elaboration of SGT, concluding that one of SGT's major contributions is the rule based conceptualization of games as socially embedded with agents in social roles and role relationships and subject to cognitive-normative and agential regulation. SGT rules and rule complexes are based on contemporary developments relating to granular computing and Artificial Intelligence in general.
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