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PLOS Biology: New Articles

  • The suprachiasmatic nucleus regulates brown fat thermogenesis in male mice through an adrenergic receptor ADRB3-S100B signaling pathway

    by Yizhun Zeng, Xiaopeng Song, Qi Chen, Yue Gu, Jie Zhang, Tao Zhou, Zhihao Li, Tao Wang, Le Chang, Hongwei Yao, Yan Wang, Liyan Miao, Liujia Qian, Tiannan Guo, Yong Zhang, Sonia Rodriguez-Fernandez, Antonio Vidal-Puig, Ying Xu

    The suprachiasmatic nucleus (SCN), the central circadian pacemaker, orchestrates daily metabolic rhythms, yet its role in substrate selection and thermogenic adaptation under stress remains insufficiently understood. Here, we show that SCN lesioning abolishes the adaptive suppression of brown adipose tissue (BAT) thermogenesis typically observed during time-restricted feeding in subthermoneutral environments (TRF-STE), a paradigm that imposes concurrent nutrient and thermal stress. Contrary to wild-type responses, SCN-lesioned mice maintain elevated BAT thermogenic activity, despite impaired lipolysis, instead shifting toward glucose-driven heat production. This phenotype is accompanied by sustained sympathetic tone and β3-adrenergic receptor (ADRB3) signaling in BAT. Mechanistically, we identify a SCN-regulated ADRB3-S100B signaling axis underlying this metabolic reprogramming. S100B, a nutrient-sensitive calcium-binding protein, is upregulated in BAT following SCN disruption, where it promotes thermogenesis by stimulating brown adipocyte proliferation and suppressing senescence. Functional studies reveal that S100B is both necessary and sufficient for sustaining BAT thermogenesis under TRF-STE. Furthermore, diverse SCN disruption models, including light-induced circadian arrhythmia, N-Methyl-D-aspartic acid (NMDA) excitotoxicity, and Caspase-3-mediated ablation, consistently elevate S100B expression in BAT, reinforcing its role as a convergent effector of SCN-regulated metabolic adaptation. Thus, in intact animal, the SCN restrains the ADRB3-S100B module, gating BAT thermogenic output in accordance with energetic availability. Disruption of SCN output lifts this restraint, unmasking a latent ADRB3-S100B program that preserves thermogenesis when lipid fuel is limited. These findings reveal a previously unrecognized role of the SCN in governing thermogenic flexibility and fuel partitioning, and position the ADRB3-S100B axis as a potential target for mitigating circadian misalignment and metabolic disease.

  • How to integrate patient and carer perspectives, methodological rigor, and ethics into biomedical research funding

    by Hella Lichtenberg, Christina Müller, Henk Lindeman, Leila Ali, Anja Minheere, Monique van den Eijnden, Ulrich Dirnagl

    Patient and carer perspectives, methodological rigor, and ethical considerations can all be successfully integrated into the biomedical funding process. Drawing on experiences with ERA-NET NEURON, we present a structured, scalable, and transferable model for funders to follow. Patient and carer perspectives, methodological rigor and ethical considerations can all be successfully integrated into the biomedical funding process. This Community Page draws on experiences with ERA-NET NEURON to present a structured, scalable and transferable model for funders to follow.

  • Control of mitochondrial dynamics by the metabolic regulator dPGC1 limits Yorkie-induced oncogenic growth in Drosophila

    by Wei Qi Guinevere Sew, Maria Molano-Fernández, Zhiquan Li, Artim Lange, Nahia Pérez de Ciriza, Lene Juel Rasmussen, Hector Herranz

    Mitochondrial function and dynamics are essential for maintaining cellular homeostasis and overall health. Disruptions in these processes can contribute to various diseases, including cancer. The Hippo signaling pathway, a key regulator of tissue growth, plays a central role in cancer through its main effector, the Yes-associated protein (YAP), known as Yorkie (Yki) in Drosophila. In this model organism, Yki upregulation drives benign tissue overgrowth in imaginal discs. Our research demonstrates that the conserved metabolic regulator dPGC1 restricts Yki-driven tissue hyperplasia and helps maintain epithelial integrity in vivo. Combined Yki upregulation and dPGC1 depletion results in tumors characterized by enlarged mitochondria and the upregulation of genes promoting mitochondrial fusion, a condition that is both necessary and sufficient for Yki-driven oncogenic growth. We further demonstrate that mitochondrial enlargement is associated with increased levels of the cell cycle regulator Cyclin E, which plays a critical role in tumor development. These findings identify dPGC1 as a context-dependent tumor suppressor that coordinates mitochondrial dynamics and cell cycle regulation in response to oncogene activation, with implications for understanding cancer development in humans.

  • Variability in intrinsic promoter strength underlies the temporal hierarchy of the <i>Caulobacter</i> SOS response induction

    by Aditya Kamat, Asha Mary Joseph, Deeksha Rathour, Anjana Badrinarayanan

    Bacteria encode for gene regulatory networks crucial for sensing and repairing DNA damage. Upon exposure to genotoxic stress, these transcriptional networks are induced in a temporally structured manner. A case in point is of the highly conserved SOS response that is regulated by the LexA repressor. Studies have proposed that affinity of LexA towards promoters of SOS response genes is the primary determinant of its expression dynamics. Here, we describe an additional level of regulation beyond LexA box properties that modulates the SOS response gene expression pattern. Using transcriptomic analyses, we reveal a distinct temporal hierarchy in the induction of SOS-regulated genes in Caulobacter crescentus. We observe that LexA box properties are insufficient in predicting the temporal hierarchy of these genes. Instead, we find that intrinsic promoter strength underlies the order of gene activation, with differential sigma factor association as one of the factors modulating gene expression timing. Our findings highlight a novel regulatory layer in SOS dynamics and underscore the importance of promoter properties in shaping bacterial stress responses.

  • Are we over-conserving charismatic species?

    by Hai-Tao Shi, Yang Liu, Tien Ming Lee

    The prevalent strategy of conserving nonmegafauna charismatic species may be counterproductive, if conservation impact measures are oversimplistic and do not facilitate the restoration of long-term ecosystems and their functions. Is all conservation good? This Perspective argues that the prevalent strategy of focusing on charismatic species may be counterproductive if conservation impact measures are oversimplistic and do not facilitate the restoration of long-term ecosystems and their functions.