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Traumatic brain injury (TBI) is one of the major causes of severe neurological disorders and long-term dysfunction in the nervous system. Besides inducing neurodegeneration, TBI alters stem cell activity and neurogenesis within primary neurogenic niches. However, the fate of dividing cells in other brain regions remains unclear despite offering potential targets for therapeutic intervention.

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Inducible protein switches are currently limited for use in tissues and organisms because common inducers cannot be controlled with precision in space and time in optically dense settings. Here, we introduce a protein that can be reversibly toggled with a small change in temperature, a stimulus that is both penetrant and dynamic. This protein, called Melt (Membrane localization using temperature) oligomerizes and translocates to the plasma membrane when temperature is lowered.

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Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted.

Nature

January 2025

School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, USA.

Tissue-resident memory CD8 T (T) cells provide protection from infection at barrier sites. In the small intestine, T cells are found in at least two distinct subpopulations: one with higher expression of effector molecules and another with greater memory potential. However, the origins of this diversity remain unknown.

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The forebrain is the most complex region of the vertebrate CNS, and its developmental organisation is controversial. We fate-mapped the embryonic chick forebrain using lipophilic dyes and Cre-recombination lineage tracing, and built a 4D model of brain growth. We reveal modular patterns of anisotropic growth, ascribed to progenitor regions through multiplex HCR.

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In-situ tumor vaccination remains challenging due to difficulties in the exposure and presentation of tumor-associated neoantigens (TANs). In view of the central role of lipid metabolism in cell fate determination and tumor-immune cell communication, here we report a photo-controlled lipid metabolism nanoregulator (PLMN) to achieve robust in-situ adjuvant-free vaccination, which is constructed through hierarchically integrating photothermal-inducible arachidonate 15-lipoxygenase (ALOX15)-expressing plasmids, cypate and FIN56 into cationic liposomes. Near-infrared light (NIR) stimulation triggers on-demand ALOX15 editing and causes excessive accumulation of downstream pro-ferroptosis lipid metabolites.

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