Heterodox modeling: practicing well-tuned provisioning or commoning with networked multi-agent environments.

Market-driven, profit-oriented, mainstream neoclassical economics is increasingly being challenged by alternative approaches such as heterodox economics. This article contributes to broader discussions in this field, especially of social provisioning, and suggests that integrating perspectives from the overlapping fields of media history and history of economy could not only provide valuable insights and attract more supporters, but even initiate a bottom-up transformation process. Historical knowledge regarding how neoclassical economics gained mainstream status in the early postwar decades provides hints on how to popularize non-profit-driven, well-designed approaches to social provisioning, often referred to as commoning. More specifically, the article firstly addresses the necessity of a large-scale appropriation of computational methods, procedures, tools, media, and models to experiment with economic issues, which are usually applied mostly by mainstream profit-driven approaches. Secondly, it presents the implications of such a practice, which I tentatively refer to as heterodox modeling, while remembering the 1960s North American context of business simulation games and their role within the large-scale effort to educate and train the newly-defined class of "business managers." The article, thirdly, theorizes heterodox modeling as being based on a still imaginary, not-yet implemented, networked multi-agent online environment, which would integrate the modular programming of agent-based models, group exercises, role-playing, gaming, and testing of operations and processes within large-scale socio-ecological networks of commoning. Finally, the article argues not only to model heterodox economic theories, but at the same time to model in heterodox ways and highlight associated implications.

Mechanism of interdigitation formation at apical boundary of MDCK cell.

It has been reported that the MDCK cell tight junction shows stochastic fluctuation and forms the interdigitation structure, but the mechanism of the pattern formation remains to be elucidated. In the present study, we first quantified the shape of the cell-cell boundary at the initial phase of pattern formation. We found that the Fourier transform of the boundary shape shows linearity in the log-log plot, indicating the existence of scaling. Next, we tested several working hypotheses and found that the Edwards-Wilkinson equation, which consists of stochastic movement and boundary shortening, can reproduce the scaling property. Next, we examined the molecular nature of stochastic movement and found that myosin light chain puncta may be responsible. Quantification of boundary shortening indicates that mechanical property change may also play some role. Physiological meaning and scaling properties of the cell-cell boundary are discussed.

Catalytically inactive Cas9 impairs DNA replication fork progression to induce focal genomic instability.

Catalytically inactive Cas9 (dCas9) has become an increasingly popular tool for targeted gene activation/inactivation, live-cell imaging, and base editing. While dCas9 was reported to induce base substitutions and indels, it has not been associated with structural variations. Here, we show that dCas9 impedes replication fork progression to destabilize tandem repeats in budding yeast. When targeted to the CUP1 array comprising ∼16 repeat units, dCas9 induced its contraction in most cells, especially in the presence of nicotinamide. Replication intermediate analysis demonstrated replication fork stalling in the vicinity of dCas9-bound sites. Genetic analysis indicated that while destabilization is counteracted by the replisome progression complex components Ctf4 and Mrc1 and the accessory helicase Rrm3, it involves single-strand annealing by the recombination proteins Rad52 and Rad59. Although dCas9-mediated replication fork stalling is a potential risk in conventional applications, it may serve as a novel tool for both mechanistic studies and manipulation of genomic instability.

Myrsinoic acid E, an anti-inflammatory compound from Myrsine seguinii.

The methanolic extract of Myrsine seguinii yielded the novel anti-inflammatory compound, myrsinoic acid E (1), whose structure was elucidated to be 3,5-digeranyl-4-hydroxy benzoic acid. We synthesized 1- and its 3,5-diprenyl (2) and 3,5-difarnesyl analogues (3). Compounds 1-3 suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation of mouse ears by 59%, 14%, and 69% at a dose of 1.4 micromol.

Myrsinoic acids B, C and F, anti-inflammatory compounds from Myrsine seguinii.

The methanolic extract of Myrsine seguinii yielded three anti-inflammatory compounds, myrsinoic acids B, C and F, and their structures were elucidated from the spectroscopic data. These compounds suppressed the TPA-induced edema of mouse ear, myrsinoic acid F being the most active (IE 77% at a dose of 0.56 micromol).