Gene regulation is a complex non-equilibrium process. Here, we show that quantitating the temporal regulation of key gene states (transcriptionally inactive, active, and refractory) provides a parsimonious framework for analyzing gene regulation. Our theory makes two non-intuitive predictions. First, for transcription factors (TFs) that regulate transcription burst frequency, as opposed to amplitude or duration, weak TF binding is sufficient to elicit strong transcriptional responses. Second, refractoriness of a gene after a transcription burst enables rapid responses to stimuli. We validate both predictions experimentally by exploiting the natural, optogenetic-like responsiveness of the Neurospora GATA-type TF White Collar Complex (WCC) to blue light. Further, we demonstrate that differential regulation of WCC target genes is caused by different gene activation rates, not different TF occupancy, and that these rates are tuned by both the core promoter and the distance between TF-binding site and core promoter. In total, our work demonstrates the relevance of a kinetic, non-equilibrium framework for understanding transcriptional regulation.

The critical bottleneck of electrocatalytic CO 2 reduction reaction (CO 2 RR) lies in its low efficiency at high overpotential caused by competitive hydrogen evolution. It is challenging to develop an efficient catalyst achieving both high current density and high Faradaic efficiency (FE) for CO 2 RR. Herein, we synthesized fluorine-doped cagelike porous carbon (F-CPC) by purposely tailoring its structural properties. The optimized F-CPC possesses large surface area with moderate mesopore and abundant micropores as well as high electrical conductivity. When used as catalyst for CO 2 RR, F-CPC exhibits FE of 88.3% for CO at −1.0 V vs RHE with a current density of 37.5 mA•cm −2 . Experimental results and finite element simulations demonstrate that the excellent CO 2 RR performance of F-CPC at high overpotential should be attributed to its structure-enhanced electrocatalytic process stemming from its cagelike morphology.

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Both the temporal regularity and spatial regularity of gastric slow waves have negative correlations with gastric emptying, which suggests that the impaired gastric myoelectrical activity may be responsible for the delayed gastric emptying in patients with functional dyspepsia.

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Hematopoietic stem cells (HSCs) produce highly diverse cell lineages. Here, we chart native lineage pathways emanating from HSCs and define their physiological regulation by computationally integrating experimental approaches for fate mapping, mitotic tracking, and single-cell RNA sequencing. We find that lineages begin to split when cells leave the tip HSC population, marked by high Sca-1 and CD201 expression. Downstream, HSCs either retain high Sca-1 expression and the ability to generate lymphocytes, or irreversibly reduce Sca-1 level and enter into erythro-myelopoiesis or thrombopoiesis. Thrombopoiesis is the sum of two pathways that make comparable contributions in steady state, a long route via multipotent progenitors and CD48hi megakaryocyte progenitors (MkPs), and a short route from HSCs to developmentally distinct CD48−/lo MkPs. Enhanced thrombopoietin signaling differentially accelerates the short pathway, enabling a rapid response to increasing demand. In sum, we provide a blueprint for mapping physiological differentiation fluxes from HSCs and decipher two functionally distinct pathways of native thrombopoiesis.