Late-stage deuteration and tritiation through bioinspired cooperative hydrogenolysis
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Controlling noise with self-organized resetting
Biological systems often consist of a small number of constituents and are therefore inherently noisy. To function effectively, these systems must employ mechanisms to constrain the accumulation of noise. Such mechanisms have been extensively studied and comprise the constraint by external forces, nonlinear interactions, or the resetting of the system to a predefined state. Here, we propose a fourth paradigm for noise constraint: self-organized resetting, where the resetting rate and position emerge from self-organization through time-discrete interactions. We study general properties of self-organized resetting systems using the paradigmatic example of cooperative resetting, where random pairs of Brownian particles are reset to their respective average. We demonstrate that such systems undergo a delocalization phase transition, separating regimes of constrained and unconstrained noise accumulation. Additionally, we show that systems with self-organized resetting can adapt to external forces and optimize search behavior for reaching target values. Self-organized resetting has various applications in nature and technology, which we demonstrate in the context of sexual interactions in fungi and spatial dispersion in shared mobility services. This work opens routes into the application of self-organized resetting across various systems in biology and technology.
Increased early-season productivity drives earlier peak of vegetation photosynthesis across the Northern Hemisphere
Changes in vegetation carbon uptake are largely influenced by the timing and magnitude of the peak of the growing season (POS), when vegetation photosynthesis reaches its maximum. However, the factors controlling the timing of POS remain poorly understood, leaving us uncertain about its future trajectory. Using satellite observations and carbon flux measurements, we show that, in recent decades, increased early-season carbon uptake has been driven by both an earlier onset of the growing season and higher temperatures. In 93% of northern (>30°N) vegetation, these increases in early-season carbon uptake were associated with an advancement of POS. This ongoing shift suggests a developmental constraint on seasonal productivity, potentially limiting carbon uptake later in the season. Our findings provide a mechanistic explanation that reconciles previous observations linking earlier growing season onset, rising temperatures, and shifts in POS timing, and suggest a decrease in late-season carbon uptake with climate warming.
Rapid growth rate responses of terrestrial bacteria to field warming on the Antarctic Peninsula
Ice-free terrestrial environments of the western Antarctic Peninsula are expanding and subject to colonization by new microorganisms and plants, which control biogeochemical cycling. Measuring growth rates of microbial populations and ecosystem carbon flux is critical for understanding how terrestrial ecosystems in Antarctica will respond to future warming. We implemented a field warming experiment in early (bare soil; +2 °C) and late (peat moss-dominated; +1.2 °C) successional glacier forefield sites on the western Antarctica Peninsula. We used quantitative stable isotope probing with H218O using intact cores in situ to determine growth rate responses of bacterial taxa to short-term (1 month) warming. Warming increased the growth rates of bacterial communities at both sites, even doubling the number of taxa exhibiting significant growth at the early site. Growth responses varied among taxa. Despite that warming induced a similar response for bacterial relative growth rates overall, the warming effect on ecosystem carbon fluxes was stronger at the early successional site—likely driven by increased activity of autotrophs which switched the ecosystem from a carbon source to a carbon sink. At the late-successional site, warming caused a significant increase in growth rate of many Alphaproteobacteria, but a weaker and opposite gross ecosystem productivity response that decreased the carbon sink—indicating that the carbon flux rates were driven more strongly by the plant communities. Such changes to bacterial growth and ecosystem carbon cycling suggest that the terrestrial Antarctic Peninsula can respond fast to increases in temperature, which can have repercussions for long-term elemental cycling and carbon storage.
A neurocognitive mechanism for increased cooperation during group formation
How do group size changes influence cooperation within groups? To examine this question, we performed a dynamic, network-based prisoner’s dilemma experiment with fMRI. Across 83 human participants, we observed increased cooperation as group size increased. However, our computational modeling analysis of behavior and fMRI revealed that groups size itself did not increase cooperation. Rather, interaction between (1) participants’ stable prosocial tendencies, and (2) dynamic reciprocal strategy weighed by memory confidence, underlies the group size-modulated increase in cooperation because the balance between them shifts towards the prosocial tendency with higher memory demands in larger groups. We found that memory confidence was encoded in fusiform gyrus and precuneus, whereas its integration with prosocial tendencies was reflected in the left DLPFC and dACC. Therefore, interaction between recall uncertainty during reciprocal interaction (i.e., forgetting) and one’s individual prosocial preference is a core pillar of emergent cooperation in more naturalistic and dynamic group formation.
Targeting a chemo-induced adaptive signaling circuit confers therapeutic vulnerabilities in pancreatic cancer
Advanced pancreatic ductal adenocarcinomas (PDACs) respond poorly to all therapies, including the first-line treatment, chemotherapy, the latest immunotherapies, and KRAS-targeting therapies. Despite an enormous effort to improve therapeutic efficacy in late-stage PDAC patients, effective treatment modalities remain an unmet medical challenge. To change the status quo, we explored the key signaling networks underlying the universally poor response of PDAC to therapy. Here, we report a previously unknown chemo-induced symbiotic signaling circuit that adaptively confers chemoresistance in patients and mice with advanced PDAC. By integrating single-cell transcriptomic data from PDAC mouse models and clinical pathological information from PDAC patients, we identified Yap1 in cancer cells and Cox2 in stromal fibroblasts as two key nodes in this signaling circuit. Co-targeting Yap1 in cancer cells and Cox2 in stroma sensitized PDAC to Gemcitabine treatment and dramatically prolonged survival of mice bearing late-stage PDAC, whereas simultaneously inhibiting Yap1 and Cox2 only in cancer cells was ineffective. Mechanistically, chemotherapy triggers non-canonical Yap1 activation by nemo-like kinase in 14-3-3ζ-overexpressing PDAC cells and increases secretion of CXCL2/5, which bind to CXCR2 on fibroblasts to induce Cox2 and PGE2 expression, which reciprocally facilitate PDAC cell survival. Finally, analyses of PDAC patient data revealed that patients who received Statins, which inhibit Yap1 signaling, and Cox2 inhibitors (including Aspirin) while receiving Gemcitabine displayed markedly prolonged survival compared to others. The robust anti-tumor efficacy of Statins and Aspirin, which co-target the chemo-induced adaptive circuit in the tumor cells and stroma, signifies a unique therapeutic strategy for PDAC.
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