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Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis.
Anim Microbiome
January 2025
Department of Large Animal Clinical Sciences, University of Florida, Gainesville, FL, 32610, USA.
Background: Cows that develop metritis experience dysbiosis of their uterine microbiome, where opportunistic pathogens overtake uterine commensals. An effective immune response is critical for maintaining uterine health. Nonetheless, periparturient cows experience immune dysregulation, which seems to be intensified by prepartum over-condition.
View Article and Find Full Text PDFDeveloping Topics.
Alzheimers Dement
December 2024
Alzheimer's Clinical Trial Consortium, Boston, MA, USA.
Background: Amyloid deposition occurs during the preclinical stages of Alzheimer's disease (AD) a decade or more before clinical symptoms emerge. We leveraged blood transcriptomics and positron emission tomography (PET) measures of amyloidosis to identify cell types and gene networks in the blood that relate to amyloid burden in the brain.
Method: Whole blood RNA sequencing and amyloid PET data were leveraged from 1771 participants (62% females, mean age 71, 32% amyloid+) in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study.
Drug Development.
Alzheimers Dement
December 2024
Good T Cells, Seoul, Mapo-gu, Korea, Republic of (South); YONSEI University, Seoul, Seodaemun-gu, Korea, Republic of (South).
Background: Neurodegenerative diseases, including Alzheimer's disease (AD), have been long thought to be independent of the peripheral immune system, but their pathogenesis status is functionally influenced by various T cell subsets in the periphery. Especially Treg cells are emerging as an important dynamic population in the brain, but the detailed immunological molecular and cellular processes are poorly characterized METHOD: We reported that the cell surface protein Lrig1 is enriched in Treg cells and is an essential regulator of the functions of Treg cells in vitro and in vivo. To evaluate the functional importance of Treg cells in AD pathogenesis, the modulating mAb specific to Lrig1 (GTC 310-01) via intravenous injection route was administered into 5xFAD or 6xTg mice, the genetic mouse model of AD, and the various AD symptoms were investigated.
View Article and Find Full Text PDFToll-like receptor adaptor protein TIRAP has specialized roles in signaling, metabolic control and leukocyte migration upon wounding in zebrafish larvae.
Int J Biol Sci
January 2025
Institute of Biology Leiden, Animal Science and Health, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
The TIRAP protein is an adaptor protein in TLR signaling which links TLR2 and TLR4 to the adaptor protein Myd88. The transcriptomic profiles of zebrafish larvae from a , and mutant and the corresponding wild type controls under unchallenged developmental conditions revealed a specific involvement of in calcium homeostasis and myosin regulation. Metabolomic profiling showed that the mutation results in lower glucose levels, whereas a mutation leads to higher glucose levels.
View Article and Find Full Text PDFWeakened Airway Epithelial Junctions and Enhanced Neutrophil Elastase Release Contribute to Age-Dependent Bacteremia Risk Following Pneumococcal Pneumonia.
Aging Cell
January 2025
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
Streptococcus pneumoniae (Sp; pneumococcus), the most common agent of community-acquired pneumonia, can spread systemically, particularly in the elderly, highlighting the need for adjunctive therapies. The airway epithelial barrier defends against bacteremia and is dependent upon apical junctional complex (AJC) proteins such as E-cadherin. After mouse lung challenge, pneumolysin (PLY), a key Sp virulence factor, stimulates epithelial secretion of an inflammatory eicosanoid, triggering the infiltration of polymorphonuclear leukocytes (PMNs) that secrete high levels of neutrophil elastase (NE), thus promoting epithelial damage and systemic infection.
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