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Functional classification of tauopathy strains reveals the role of protofilament core residues.
Sci Adv
January 2025
Center for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Distinct tau amyloid assemblies underlie diverse tauopathies but defy rapid classification. Cell and animal experiments indicate tau functions as a prion, as different strains propagated in cells cause unique, transmissible neuropathology after inoculation. Strain amplification requires compatibility of the monomer and amyloid template.
View Article and Find Full Text PDFMicroenvironment actuated CAR T cells improve solid tumor efficacy without toxicity.
Sci Adv
January 2025
Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2 normal mouse brain tissue. To improve the selectivity of the CAR T cell, we engineered a synthetic Notch receptor that selectively expresses the CAR upon binding to P-selectin, a cell adhesion protein overexpressed in tumor neovasculature.
View Article and Find Full Text PDFWWC proteins-mediated compensatory mechanism restricts schwannomatosis driven by loss of function.
Sci Adv
January 2025
Institute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
NF2-related schwannomatosis, previously known as neurofibromatosis type 2, is a genetic disorder characterized by nerve tumors due to gene mutations. Mice with deletion develop schwannomas slowly with low penetrance, hence inconvenient for preclinical studies. Here, we show that NF2, by recruiting E3 ubiquitin ligases β-TrCP1/2, promotes WWC1-3 ubiquitination and degradation.
View Article and Find Full Text PDFCreating coveted bioluminescence colors for simultaneous multi-color bioimaging.
Sci Adv
January 2025
Department of Biomolecular Science and Engineering, SANKEN, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
Bioluminescence, an optical marker that does not require excitation by light, allows researchers to simultaneously observe multiple targets, each exhibiting a different color. Notably, the colors of the bioluminescent proteins must sufficiently vary to enable simultaneous detection. Here, we aimed to introduce a method that can be used to expand the color variation by tuning dual-acceptor bioluminescence resonance energy transfer.
View Article and Find Full Text PDFMicroplastics in the bloodstream can induce cerebral thrombosis by causing cell obstruction and lead to neurobehavioral abnormalities.
Sci Adv
January 2025
State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, China.
Human health is being threatened by environmental microplastic (MP) pollution. MPs were detected in the bloodstream and multiple tissues of humans, disrupting the regular physiological processes of organs. Nanoscale plastics can breach the blood-brain barrier, leading to neurotoxic effects.
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