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A new study describes a microscope combining three-photon excitation and adaptive optics capable of high-resolution in vivo imaging of fine neuronal structures in the mouse cortex through the intact skull. The authors demonstrate the use of this platform to guide precise laser-mediated microsurgery and for accurate and sensitive functional calcium imaging.
RNA interference (RNAi) therapeutics can silence disease-causing gene transcripts, but extrahepatic delivery has been challenging. Conjugating short interfering RNAs (siRNAs) to a lipophilic alkyl chain enabled safe delivery and long-term mRNA silencing in the brain, eye and lung in animal models, thereby opening new applications for RNAi therapeutics.
Existing technologies can map the intricate spatial distribution of biomolecules and cell types within tissues, but not in specimens that remain alive and intact. This study introduces scission-accelerated fluorophore exchange (SAFE) bioorthogonal imaging tools that enable living cells and tissues to be deeply and serially profiled, revealing their biological dynamics across both space and time.
Our multidisciplinary team used novel perfusion technology to successfully keep an injured liver graft discarded by all other centers alive for several days, allowing proper graft evaluation and repair. The graft was successfully transplanted into a sick patient, who recovered quickly and enjoyed a normal life at one-year follow up.
Are major decisions in the cell made through pairs of interacting loci (enhancers and promoters) or larger teams of cooperating regulatory elements? A new genome-wide assay and algorithm answers this question and provides a scalable technology to link new dimensions of genome structure with cellular function.
By quantifying thousands of proteins in tumor cells in an unbiased manner, Deep Visual Proteomics uncovers mechanisms that drive tumor evolution and reveals new therapeutic targets. The method incorporates advanced microscopy, artificial intelligence and ultra-high-sensitivity proteomics to characterize individual cell identities.
The jellyfish-derived green fluorescent protein StayGold is bright and hardly fades, contributing to improving spatiotemporal resolution and dramatically extending the observation period. To fully benefit from the rich photon budget, we tried some unusual illumination modalities for sustainable, quantitative live-cell or volumetric imaging.
We developed EasyFuse, a computational machine learning pipeline that detects cancer-specific gene fusions with superior performance over existing tools. Individual gene fusions exhibit a high frequency of pre-established CD4+ and CD8+ T-cell responses and thus represent a previously untapped source of neo-antigens that can be exploited for personalized immunotherapies.
Using a combination of metagenomic big data and deep learning tools, small proteins that inhibit pathogens — and could be further developed into novel antibiotics — are mined en masse. Such methods could greatly improve the throughput of drug discovery and translational usage of the microbiome.
A new method uses synthetic introns to express therapeutic proteins selectively in cells bearing cancer-initiating mutations affecting RNA splicing factors, while healthy cells remain unaffected. This approach enabled the eradication of human leukemia, breast cancer and uveal melanoma cells in mouse models and significantly prolonged host survival.
