Reproductive aging impairs female fertility, and oocyte aging is considered a major driver of this phenotype, which manifests with increased aneuploidy and miscarriage risk, while no effective treatme...

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Temperature shapes the biochemistry of microbial proteins, and several amino acid compositional indices have been proposed to detect cold adaptation in microbial proteomes. Whether these indices capture cold adaptation in Archaea, which are abundant in cold marine environments such as the Arctic Ocean, has not been tested. We calculated six amino acid compositional indices (arginine to lysine ratio, acidic residue proportion, aliphatic index, aromaticity, grand average of hydropathicity, and proline residue proportion) across global protein families for 142 Marine Group I (MG-I; Thaumarchaeota) and 146 Euryarchaeota genomes from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC), together with three MG-I metagenome-assembled genomes (MAGs) recovered from the Western Arctic Ocean. The Arctic MAGs fell within the range of index and phylogenetic distances of the wider MG-I population, and no signature of cold adaptation was detected. Instead, index values differed between the two main MG-I phylogenetic groups and between freshwater and marine genomes, and the Euryarchaeota formed five index-based clusters consistent with phylogeny. A group of 19 MG-I MAGs associated with sea sponges had significantly higher arginine to lysine ratios than other MG-I, differed in the usage of all amino acids except alanine and lysine, and had distinct codon usage and higher GC content; their anomalous placement in the MG-I phylogeny is consistent with long-branch attraction. These results indicate that amino acid compositional indices developed for Bacteria have limited power to detect cold adaptation in Archaea, but reveal strong proteomic signatures associated with host adaptation in sponge-associated Thaumarchaeota. ### Competing Interest Statement The authors have declared no competing interest. Natural Sciences and Engineering Research Council, https://ror.org/01h531d29, RGPIN-2022-05280 Canada Research Chairs, https://ror.org/0517h6h17 Digital Research Alliance of Canada, https://ror.org/010r6td27

AbstractMicroglial inflammatory activation is accompanied by extensive molecular remodeling, yet proteomic, lipidomic, and metabolomic responses are often analyzed independently. Here, we applied a mass spectrometry-based multiomic workflow to characterize proteomic, lipidomic, and polar metabolomic remodeling from matched biological replicates of immortalized murine BV-2 microglial cells following stimulation with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Pro-inflammatory activation was confirmed by increased nitrite accumulation, elevated TNF-α and IL-6 secretion, and treatment-associated morphological changes. Discovery proteomics quantified 8,676 proteins and identified 562 significantly altered proteins, including 344 increased and 218 decreased proteins. Increased proteins were enriched for interferon-responsive, innate immune, inflammatory effector, and antigen-associated pathways, whereas decreased proteins were associated with cellular organization, protein biogenesis, vesicular trafficking, and metabolic regulation. Targeted lipidomics identified 237 significantly altered lipids, including increased triacylglycerols and diacylglycerols and broad remodeling of glycerophospholipids, lysophospholipids, and sphingolipid-related species. Targeted polar metabolomics identified 75 significantly altered metabolites, including changes in nucleotide/NAD-related metabolism, amino acid metabolism, methylation-associated metabolites, acylcarnitine abundance, phospholipid precursors, polyamine metabolism, arginine/nitric oxide-associated metabolism, and redox-associated metabolites. Process-level integration of significant features revealed coordinated remodeling of inflammatory protein programs with lipid storage, membrane remodeling, nucleotide metabolism, amino acid availability, phospholipid precursor abundance, nitric oxide-associated metabolism, and redox/osmolyte pathways. These findings demonstrate that IFN-γ and LPS-induced activation of BV-2 cells involves complementary immune, lipid, and metabolic adaptation rather than isolated induction of canonical inflammatory mediators. This multiomic framework provides a resource for investigating how lipid and metabolic remodeling regulate microglial inflammatory states.