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Structural basis for LZTR1 recognition of RAS GTPases for degradation

1 month 1 week ago
Science, Volume 389, Issue 6765, Page 1112-1117, September 2025.
Srisathiyanarayanan Dharmaiah, Daniel A. Bonsor, Stephanie P. Mo, Alvaro Fernandez-Cabrera, Albert H. Chan, Simon Messing, Matthew Drew, Martha Vega, Dwight V. Nissley, Dominic Esposito, Pau Castel, Dhirendra K. Simanshu

Genomic signatures indicate biodiversity loss in an endemic island ant fauna

1 month 1 week ago
Science, Volume 389, Issue 6765, Page 1133-1136, September 2025.
Cong Liu, Eli Sarnat, Jo Ann Tan, Julia Janicki, John Deyrup, Masako Ogasawara, Miquel L. Grau, Lijun Qiu, Francisco Hita Garcia, Georg Fischer, Akanisi Caginitoba, Nitish Narula, Clive T. Darwell, Yasuhiro Kubota, Naomi E. Pierce, Alexander S. Mikheyev,…

The role of the gut microbiota in neuropsychiatric disorders and therapy

1 month 1 week ago
The vast microbial community residing in the gut is known as the gut microbiota (GM). Alterations in the compositional equilibrium of the GM, a phenomenon termed GM dysbiosis, have been increasingly associated with the pathogenesis of various diseases, particularly neuropsychiatric disorders. The microbiota-gut-brain axis (MGBA) serves as a bidirectional communication system that connects the gut to the brain. Notably, several prevalent neuropsychiatric disorders, including depression,...
Fan Zhang

ABCA7 variants impact phosphatidylcholine and mitochondria in neurons

1 month 1 week ago
Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease^(1,2), yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism,...
Djuna von Maydell

Senescent-like border-associated macrophages regulate cognitive aging via migrasome-mediated induction of paracrine senescence in microglia

1 month 1 week ago
Aging is a major risk factor for various neurological disorders, including Alzheimer's disease, and is associated with the accumulation of senescent cells, which can themselves propagate the senescence process through paracrine signaling. Migrasomes are organelles that form during cellular migration, detach from parent cells and mediate intercellular communication. Here we demonstrate that border-associated macrophages (BAMs) acquire senescence-associated properties during early brain aging,...
Mengyan Hu

Plasma proteomic associations with Alzheimer's disease endophenotypes

1 month 1 week ago
Clinical Alzheimer's disease is currently characterized by cerebral β-amyloidosis associated with cognitive impairment. However, most cases of Alzheimer's disease are associated with multiple neuropathologies at autopsy. The peripheral protein changes associated with these disease endophenotypes are poorly understood. In this study, we analyzed the plasma proteomes of individuals from four cohorts (n = 2,139 participants) to identify proteins and pathways associated with cerebral β-amyloidosis...
Shiva Afshar

Oxidative-stress-induced telomere instability drives T cell dysfunction in cancer

1 month 1 week ago
The tumor microenvironment (TME) imposes immunologic and metabolic stresses sufficient to deviate immune cell differentiation into dysfunctional states. Oxidative stress originating in the mitochondria can induce DNA damage, most notably telomeres. Here, we show that dysfunctional T cells in cancer did not harbor short telomeres indicative of replicative senescence but rather harbored damaged telomeres, which we hypothesized arose from oxidative stress. Chemo-optogenetic induction of highly...
Dayana B Rivadeneira

Senolytic therapy increases replicative capacity by eliminating senescent endothelial cells

1 month 1 week ago
Aging is the greatest risk factor for cardiovascular diseases (CVD) and is characterized by inflammation, oxidative stress, and cellular senescence. Cellular senescence is a state of persistent cell cycle arrest triggered by stressors such as DNA damage and telomere attrition. Senescent endothelial cells (ECs) can impair vascular function and promote inflammation, thereby contributing to CVD progression. Senolytics, a class of drugs that selectively eliminate senescent cells, have been shown to...
Hossein Abdeahad