Aggregator
Interferon-induced senescent CD8(+) T cells reduce anti-PD1 immunotherapy efficacy in early triple-negative breast cancer
Triple-negative breast cancers (TNBCs) lack predictive biomarkers to guide immunotherapy, especially during early-stage disease. To address this issue, we used single-cell RNA sequencing, bulk transcriptomics, and pathology assays on samples from 171 patients with early-stage TNBC receiving chemotherapy with or without immunotherapy. Our investigation identified an enriched subset of interferon (IFN)-induced CD8^(+) T cells in early TNBC samples, which predict immunotherapy nonresponsiveness....
The flexible stalk domain of sTREM2 modulates its interactions with brain-based phospholipids
The microglial surface protein Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) plays a critical role in mediating brain homeostasis and inflammatory responses in Alzheimer's disease (AD). The soluble form of TREM2 (sTREM2) exhibits neuroprotective effects in AD, though the underlying mechanisms remain elusive. Moreover, differences in ligand binding between TREM2 and sTREM2, which have major implications for their roles in AD pathology, remain unexplained. To address these knowledge...
Regulatory networks of KRAB zinc finger genes and transposable elements changed during human brain evolution and disease
Evidence indicates that transposable elements (TEs) can contribute to the evolution of new traits, with some TEs acting as deleterious elements while others are repurposed for beneficial roles in evolution. In mammals, some KRAB-ZNF proteins can serve as a key defense mechanism to repress TEs, offering genomic protection. Notably, the family of KRAB-ZNF genes evolves rapidly and exhibits diverse expression patterns in primate brains, where some TEs, including autonomous LINE-1 and non-autonomous...
Losses to Follow-Up in a Nationally Representative Study of Community-Living Older Americans: Two Approaches to Censoring and Implications for Mortality Outcomes
CONCLUSIONS: When evaluating mortality using the NHATS Sensitive files, investigators should consider censoring all participants who are lost to follow-up at the time of the last completed interview, recognizing potential trade-offs in terms of reductions in power and precision.