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Visceral adipose tissue (VAT) is an energy store and endocrine organ critical for metabolic homeostasis. Regulatory T (T reg ) cells restrain inflammation to preserve VAT homeostasis and glucose tolerance. Here, we show that the VAT harbors two distinct T reg cell populations: prototypical serum stimulation 2-positive (ST2 + ) T reg cells that are enriched in males and a previously uncharacterized population of C-X-C motif chemokine receptor 3-positive (CXCR3 + ) T reg cells that are enriched in females. We show that the transcription factors GATA-binding protein 3 and peroxisome proliferator-activated receptor-γ, together with the cytokine interleukin-33, promote the differentiation of ST2 + VAT T reg cells but repress CXCR3 + T reg cells. Conversely, the differentiation of CXCR3 + T reg cells is mediated by the cytokine interferon-γ and the transcription factor T-bet, which also antagonize ST2 + T reg cells. Finally, we demonstrate that ST2 + T reg cells preserve glucose homeostasis, whereas CXCR3 + T reg cells restrain inflammation in lean VAT and prevent glucose intolerance under high-fat diet conditions. Overall, this study defines two molecularly and developmentally distinct VAT T reg cell types with unique context- and sex-specific functions., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Targeted nitric oxide production is relevant for maintaining cellular energy production, protecting against oxidative stress, regulating cell death, and promoting neuroprotection. This study aimed to characterize the putative interaction of nitric-oxide synthase with mitochondrial proteins. The primary finding of this study is that cytochrome c oxidase (CCO) subunit IV (CCOIV) is associated directly with NOS in brain mitochondria when calcium ions are present. The matrix side of CCOIV binds to the N -terminus of NOS, supported by the abrogation of the binding by antibodies towards the N -terminus of NOS. Evidence supporting the interaction between CCOIV and NOS was provided by the coimmunoprecipitation of NOS from detergent-solubilized whole rat brain mitochondria with antibodies to CCOIV and the coimmunoprecipitation of CCOIV from crude brain NOS preparations using antibodies to NOS. The CCOIV domain that interacts with NOS was identified using a series of overlapping peptides derived from the primary sequence of CCOIV. As calcium ions not only activate NOS, but also facilitate the docking of NOS to CCOIV, this study points to a dynamic mechanism of controlling the bioenergetics by calcium changes, thereby adapting bioenergetics to cellular demands.

As researchers develop computational models of neural systems with increasing sophistication and scale, it is often the case that fully de novo model development is impractical and inefficient. Thus arises a critical need to quickly find, evaluate, re-use, and build upon models and model components developed by other researchers. We introduce the NeuroML Database (NeuroML-DB.org), which has been developed to address this need and to complement other model sharing resources. NeuroML-DB stores over 1,500 previously published models of ion channels, cells, and networks that have been translated to the modular NeuroML model description language. The database also provides reciprocal links to other neuroscience model databases (ModelDB, Open Source Brain) as well as access to the original model publications (PubMed). These links along with Neuroscience Information Framework (NIF) search functionality provide deep integration with other neuroscience community modeling resources and greatly facilitate the task of finding suitable models for reuse. Serving as an intermediate language, NeuroML and its tooling ecosystem enable efficient translation of models to other popular simulator formats. The modular nature also enables efficient analysis of a large number of models and inspection of their properties. Search capabilities of the database, together with web-based, programmable online interfaces, allow the community of researchers to rapidly assess stored model electrophysiology, morphology, and computational complexity properties. We use these capabilities to perform a database-scale analysis of neuron and ion channel models and describe a novel tetrahedral structure formed by cell model clusters in the space of model properties and features. This analysis provides further information about model similarity to enrich database search., Competing Interests: The authors declare no competing interests., (Copyright: © 2023 Birgiolas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Competing interests: None declared.