The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation

Adipogenesis is mediated by the complex gene expression networks involving the posttranscriptional modifications. The natural compound rhein has been linked to the regulation of adipogenesis, but the underlying regulatory mechanisms remain elusive. Herein, we systematically analyzed the effects of rhein on adipogenesis at both the transcriptional and posttranscriptional levels. Rhein remarkably suppresses adipogenesis in the stage-specific and dose-dependent manners. Rhein has been identified to inhibit fat mass and obesity-associated (FTO) demethylase activity. Surprisingly, side-by-side comparison analysis revealed that the rhein treatment and Fto knockdown triggered the differential gene regulatory patterns, resulting in impaired adipocyte formation. Specifically, rhein treatment mildly altered the transcriptome with hundreds of genes dysregulated. N6-methyladenosine (m6A) methylome profile showed that, although the supply of rhein induced increased m6A levels on a small subset of messenger RNAs (mRNAs), few of them showed dramatic transcriptional response to this compound. Moreover, the specific rhein-responsive mRNAs, which are linked to mitotic pathway, are barely methylated or contain m6A peaks without dramatic response to rhein, suggesting separate regulation of global m6A pattern and adipogenesis mediated by rhein. Further identification of m6A-independent pathways revealed a positive regulator, receptor expressing-enhancing protein 3 (REEP3), in guidance of adipogenesis. Hence, this study provides the mechanistic view of the cellular actions of rhein in the modulation of adipogenesis and identifies a potential novel target for obesity therapeutic research.

Diet Mechanistic Philosophy

This chapter compares and contrasts the black-boxing approach with the “new wave of mechanistic philosophy.” Is the present treatment of black boxes novel and original? Or is it a rehashing of ideas that have been on the table since the turn of the new millennium? The black-boxing recipe fits in quite well with the depiction of science being in the business of discovering and modeling mechanisms. All three steps underlying the construction of a black box have been stressed, in some form or degree, in the extant literature. Nevertheless, the construction of black boxes, as presented here, dampens many of the ontological implications that characterize the contemporary landscape. This allows one to respond to some objections raised against the traditional mechanism. For this reason, the author provocatively refers to black-boxing as a “diet” mechanistic philosophy, with all the epistemic flavor of the old-fashioned mechanistic view, but hardly any metaphysical calories.

Applying mechanical philosophy to web science: The case of social machines

Social machines are a prominent focus of attention for those who work in the field of Web and Internet science. Although a number of online systems have been described as social machines (examples include the likes of Facebook, Twitter, Wikipedia, Reddit, and Galaxy Zoo), there is, as yet, little consensus as to the precise meaning of the term “social machine.” This presents a problem for the scientific study of social machines, especially when it comes to the provision of a theoretical framework that directs, informs, and explicates the scientific and engineering activities of the social machine community. The present paper outlines an approach to understanding social machines that draws on recent work in the philosophy of science, especially work in so-called mechanical philosophy. This is what might be called a mechanistic view of social machines. According to this view, social machines are systems whose phenomena (i.e., events, states, and processes) are explained via an appeal to (online) socio-technical mechanisms. We show how this account is able to accommodate a number of existing attempts to define the social machine concept, thereby yielding an important opportunity for theoretical integration.

A Systems View of Emotion in Socio-political Context

Most work to date in psychology and related sciences has examined simple, unidirectional causal processes of emotion affecting socio-political context or vice versa. In this classic, mechanistic view of science, each empirical observation stands on its own as a piece of some grander, not yet understandable, puzzle of nature. There have been repeated calls to eschew classic approaches in favor of systems meta-theory in psychology and related sciences. In this paper, we join these calls by arguing that systems meta-theory can better enable the study of emotions in socio-political contexts. We offer a brief primer on systems meta-theory, delineating three key beneficial features: multi-leveled, complex, and dynamic. Viewing emotion as a system of systems—within the person, their relationships (to others), and within the world (locally and globally)—enables fresh theory, method, and statistical analysis well suited to the study of emotion in a socio-political context.

WHY ECONOMICS IS AN EVOLUTIONARY, MATHEMATICAL SCIENCE: HOW COULD VEBLEN’S VIEW OF ECONOMICS HAVE BEEN SO DIFFERENT THAN PEIRCE’S?

More than a century ago, one of the most famous essays ever written in American economics appeared in the Quarterly Journal of Economics: “Why is Economics Not an Evolutionary Science?” There, Thorstein Veblen claimed that economics was too dominated by a mechanistic view to address the problems of economic life. Since the world and the economy had come to be viewed from an evolutionary perspective after Charles Darwin, it was rather straightforward to argue that the increasingly abstract mathematical character of economics was non-evolutionary. However, Veblen had studied with a first-rate intellect, Charles Sanders Peirce, attending his elementary logic class. If Peirce had written about the future of economics in 1898, it would have been very different than Veblen’s essay. Peirce could have written that economics should become an evolutionary mathematical science and that much of classical and neoclassical economics could be interpreted from an evolutionary perspective.

Role of the polycystins as mechanosensors of extracellular stiffness

Polycystin-1 has recently emerged as a possible receptor able to sense extracellular stiffness and to negatively control the cellular actomyosin contraction machinery. Here, we revisit a large body of literature on autosomal dominant polycystic kidney disease providing a new possible mechanistic view on the topic.

Linking population-level and microevolutionary processes to understand speciation dynamics at the macroevolutionary scale

Although speciation dynamics have been described for several taxonomic groups in distinct geographic regions, most macroevolutionary studies still lack a detailed mechanistic view on how or why speciation rates change. To help to partially fill this gap, we suggest that the interaction between the time taken by a species to geographically expand and the time populations take to evolve reproductive isolation should be considered when we are trying to understand macroevolutionary patterns. We introduce a simple conceptual index to guide our discussion on how demographic and microevolutionary processes might produce speciation dynamics at macroevolutionary scales. Our framework is developed under different scenarios: when speciation is mediated by geographical or resource-partitioning opportunities, and when diversity is limited or not. We also discuss how organismal intrinsic properties and different overall geographical settings can influence the tempo and mode of speciation. We argue that specific conditions observed at the micro scale might produce a pulse in speciation rates even without a pulse in either climate or physical barriers. We also propose a hypothesis to reconcile the apparent inconsistency between speciation measured at the micro and macro scales, and emphasize that diversification rates are better seen as an emergent property. We hope to bring the reader’s attention to interesting mechanisms to be further studied, to motivate the development of new theoretical models that connect micro and macroevolution, and to inspire new empirical and methodological approaches to more adequately investigate speciation dynamics either using neontological or paleontological data.