ZMYND8 mediated liquid condensates spatiotemporally decommission the latent super-enhancers during macrophage polarization

Super-enhancers (SEs) govern macrophage polarization and function. However, the mechanism underlying the signal-dependent latent SEs remodeling in macrophages remains largely undefined. Here we show that the epigenetic reader ZMYND8 forms liquid compartments with NF-κB/p65 to silence latent SEs and restrict macrophage-mediated inflammation. Mechanistically, the fusion of ZMYND8 and p65 liquid condensates is reinforced by signal-induced acetylation of p65. Then acetylated p65 guides the ZMYND8 redistribution onto latent SEs de novo generated in polarized macrophages, and consequently, recruit LSD1 to decommission latent SEs. The liquidity characteristic of ZMYND8 is critical for its regulatory effect since mutations coagulating ZMYND8 into solid compartments disable the translocation of ZMYND8 and its suppressive function. Thereby, ZMYND8 serves as a molecular rheostat to switch off latent SEs and control the magnitude of the immune response. Meanwhile, we propose a phase separation model by which the latent SEs are fine-tuned in a spatiotemporal manner.

Current Understanding of Molecular Phase Separation in Chromosomes

Biomolecular phase separation denotes the demixing of a specific set of intracellular components without membrane encapsulation. Recent studies have found that biomolecular phase separation is involved in a wide range of cellular processes. In particular, phase separation is involved in the formation and regulation of chromosome structures at various levels. Here, we review the current understanding of biomolecular phase separation related to chromosomes. First, we discuss the fundamental principles of phase separation and introduce several examples of nuclear/chromosomal biomolecular assemblies formed by phase separation. We also briefly explain the experimental and computational methods used to study phase separation in chromosomes. Finally, we discuss a recent phase separation model, termed bridging-induced phase separation (BIPS), which can explain the formation of local chromosome structures.

Multicomponent Spiral Wound Membrane Separation Model for CO2 Removal from Natural Gas

A spiral wound membrane (SWM) is employed to separate acid gases (mainly CO2) from natural gas due to its robustness, lower manufacturing cost, and moderate packing density compared to hollow fiber membranes. Various mathematical models are available to describe the separation performance of SWMs under different operating conditions. Nevertheless, most of the mathematical models deal with only binary gas mixtures (CO2 and CH4) that may lead to an inaccurate assessment of separation performance of multicomponent natural gas mixtures. This work is aimed to develop an SWM separation model for multicomponent natural gas mixtures. The succession stage method is employed to discretize the separation process within the multicomponent SWM module for evaluating the product purity, hydrocarbon loss, stage cut, and permeate acid gas composition. Our results suggest that multicomponent systems tend to generate higher product purity, lower hydrocarbon loss, and augmented permeate acid gas composition compared to the binary system. Furthermore, different multicomponent systems yield varied separation performances depending on the component of the acid gas. The developed multicomponent SWM separation model has the potential to design and optimize the spiral wound membrane system for industrial application.

Formal Principles: Some Replies to Critics

One of the main theses of principles theory is that the rational application of constitutional rights presupposes proportionality analysis and that proportionality analysis necessarily includes balancing. The objection of over-constitutionalization has been raised to this thesis. Principles theory has attempted to reply to this objection with a theory of discretion in which formal principles, in particular, the principle of democracy, play a pivotal role. The theory of formal principles, however, has led in recent decades to more questions than answers. With respect to constitutional rights, two models have been and remain in competition: the combination model and the separation model. The first model balances formal principles in combination with substantive principles, whereas the second model separates the balancing of formal principles from the balancing of substantive principles. It is argued in this chapter that both models are mistaken, and an epistemic model is proposed that finds expression in the epistemic variables of the Weight Formula.