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Hibernation is an adaptation to extreme environmental seasonality that has been studied for almost 200 years, but our mechanistic understanding of the underlying physiological system remains lacking due to the partially observed nature of the system. During hibernation, small mammals, such as the Arctic ground squirrel, exhibit dramatic oscillations in body temperature, typically one of the only physiological states measured, of up to 40◦C. These spikes are known as interbout arousals and typically occur 10-20 times throughout hibernation. The physiological mechanism that drives interbout arousals is unknown, but two distinct mechanisms have been hypothesized. Using model selection for partially observed systems, we are able to differentiate between these two mechanistic hypotheses using only body temperature data recorded from a free-ranging Arctic ground squirrel. We then modify our discovered physiological model of Arctic ground squirrel to include environmental information and find that we can qualitatively match body temperature data recorded from a wide range of species, including a bird, a shrew, and a bear, which also dynamically modulate body temperature. Our results suggest that a universal, environmentally sensitive mechanism could regulate body temperature across a diverse range of species—a mechanistic restructuring of our current understanding of the physiological organization across species. While the findings presented here are applicable to thermophysiology, the general modeling procedure is applicable to time series data collected from partially observed biological, chemical, physical, mechanical, and cosmic systems for which the goal is to elucidate the underlying mechanism or control structure. 

SUMMARY Transcription factors (TFs) regulate gene expression despite constraints from chromatin structure and the cell cycle. Here we examine the concentration-dependent regulation ofhunchbackby the Bicoid morphogen through a combination of quantitative imaging, mathematical modeling and epigenomics inDrosophilaembryos. By live imaging of MS2 reporters, we find that, following mitosis, the timing of transcriptional activation driven by thehunchbackP2 (hbP2) enhancer directly reflects Bicoid concentration. We build a stochastic model that can explainin vivoonset time distributions by accounting for both the competition between Bicoid and nucleosomes athbP2 and a negative influence of DNA replication on transcriptional elongation. Experimental modulation of nucleosome stability alters onset time distributions and the posterior boundary ofhunchbackexpression. We conclude that TF-nucleosome competition is the molecular mechanism whereby the Bicoid morphogen gradient specifies the posterior boundary ofhunchbackexpression. 

Abstract Many eukaryotic photosynthetic organisms enhance their carbon uptake by supplying concentrated CO₂to the CO₂-fixing enzyme Rubisco in an organelle called the pyrenoid. Ongoing efforts seek to engineer this pyrenoid-based CO₂-concentrating mechanism (PCCM) into crops to increase yields. Here we develop a computational model for a PCCM on the basis of the postulated mechanism in the green algaChlamydomonas reinhardtii. Our model recapitulates allChlamydomonasPCCM-deficient mutant phenotypes and yields general biophysical principles underlying the PCCM. We show that an effective and energetically efficient PCCM requires a physical barrier to reduce pyrenoid CO₂leakage, as well as proper enzyme localization to reduce futile cycling between CO₂and HCO₃⁻. Importantly, our model demonstrates the feasibility of a purely passive CO₂uptake strategy at air-level CO₂, while active HCO₃⁻uptake proves advantageous at lower CO₂levels. We propose a four-step engineering path to increase the rate of CO₂fixation in the plant chloroplast up to threefold at a theoretical cost of only 1.3 ATP per CO₂fixed, thereby offering a framework to guide the engineering of a PCCM into land plants.