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Mammalian parental care varies widely in investment and duration. While many species transition gradually from dependence on maternal care, others, such as the Northern elephant seal (Mirounga angustirostris), are abruptly weaned and endure prolonged fasting, relying solely on resources stored during nursing. Limited resources can lead to trade-offs between costly processes like growth and immune responses, which influence survival and fitness. Resource allocation reflects individual condition and species life-history, and may differ by sex if larger size benefits male lifetime fitness. We investigated inflammation and bacterial inhibition in Northern elephant seal pups immediately after weaning and one month into fasting, assessing whether responses were influenced by sex, growth, fatty reserves (body condition and blubber thickness), available energy (blood levels of glucose, triglycerides and total protein), nutritional stress (creatinine and δN), concurrent infections, and differences in maternal foraging (inferred from isotopic signals in pups' whiskers). Newly-weaned pups had stronger immune responses than later in fasting: bactericidal ability decreased by 8.76 % (95 % CI: 5.16-12.47) and inflammation by 36.37 % (95 % CI: 16.39-53.07), as resources became depleted. Although body length and mass did not differ by sex, females maintained higher body condition (mass per unit length) throughout fasting. Newly-weaned females inhibited bacterial growth better than males, but this advantage disappeared after a month. Fatty reserves and plasma proteins were associated with immune responses later in fasting, but maternal feeding site and trophic level were not. However, endogenous resource use (measured as δN values) was positively correlated with bacterial inhibition. Neutrophil counts and blood iron levels explained variation in inflammation. Our study shows that innate immune responses in a rapidly growing, capital-breeding mammal depend on maternal resources and reflect early sex differences and concurrent physiological challenges. Allocation of depleting resources during fasting drives trade-offs between immune function, growth, and development.
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http://dx.doi.org/10.1016/j.dci.2025.105413 | DOI Listing |
Arthritis Rheumatol
September 2025
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, 94305.
J Med Chem
September 2025
Department of Natural Products and Medicinal Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
Nitric oxide (NO) is a multifunctional signaling molecule in oncology, influencing tumor progression, apoptosis, and immune responses. In contrast, chlorambucil (Cbl), a DNA-alkylating chemotherapeutic, induces cytotoxicity through DNA damage. Here, we report a photoresponsive nanoparticle platform for sequential codelivery of NO and Cbl, where NO is released within 10 min of irradiation, followed by Cbl release within 30 min.
View Article and Find Full Text PDFJ Neurochem
September 2025
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Microglia, the resident immune cells of the central nervous system (CNS), are involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Dementia with Lewy Bodies (DLB), and Parkinson's disease (PD). 14-3-3 proteins act as molecular hubs to regulate protein-protein interactions, which are involved in numerous cellular functions, including cellular signaling, protein folding, and apoptosis. We previously revealed decreased 14-3-3 levels in the brains of human subjects with neurodegenerative diseases.
View Article and Find Full Text PDFMol Ther
September 2025
Department of Medicine, UMass Chan Medical School, Worcester, MA, USA; Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA; Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Li Weibo Institute for Rare Diseases Research, UMass Chan Medic
The interleukin (IL)-1 pathway is a key mediator of inflammation and innate immune responses. Its dysregulation contributes to rheumatoid arthritis (RA) and autoinflammatory diseases (AIDs). In this study, we develop a recombinant adeno-associated virus (rAAV)-based gene therapy to deliver an inflammation-inducible, secreted human IL-1 receptor antagonist (sIL-1Ra) as a complementary approach to existing IL-1 blockers.
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