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Preparation and use of SER/GLU-based DES as a novel and potent catalyst for the green synthesis of pyrazolopyranopyrimidines
A novel electrodeposited nanocatalyst of nickel nanoparticles and reduced graphene oxide doped with halogens for hydrogen evolution reaction
Analysis of preoperative serum cytokine levels in patients with oral squamous cell carcinoma
Effects of live black soldier fly and yellow mealworm larvae supplementation on slaughter performance and meat composition of Muscovy ducks
Utilizing genetic variation in perennial sorghum to improve host plant resistance to aphids
Identification of gene signatures associated with lactation for predicting prognosis and treatment response in breast cancer patients through machine learning
Development of an integrated reactor model package for optimizing the operating modes of the sulfur production unit
Association between statin use and cataract formation in a retrospective cohort study using Japanese health screening and claims data
Arena ice quality and perspectives on optimizing performance and addressing emerging challenges
Li+-migration influencing factors and non-destructive life extension of quasi-solid-state polymer electrolytes
Borylated strain rings synthesis via photorearrangements enabled by energy transfer catalysis
SNAP25-dependent membrane trafficking of the Kv1.5 channel regulates the onset of atrial fibrillation
Mechanosensing antagonizes ethylene signaling to promote root gravitropism in rice
Nickase fidelity drives EvolvR-mediated diversification in mammalian cells
Abstract In vivo genetic diversifiers have previously enabled efficient searches of genetic variant fitness landscapes for continuous directed evolution. However, existing genomic diversification modalities for mammalian genomic loci exclusively rely on deaminases to generate transition mutations within target loci, forfeiting access to most missense mutations. Here, we engineer CRISPR-guided error-prone DNA polymerases (EvolvR) to diversify all four nucleotides within genomic loci in mammalian cells. We demonstrate that EvolvR generates both transition and transversion mutations throughout a mutation window of at least 40 bp and implement EvolvR to evolve previously unreported drug-resistant MAP2K1 variants via substitutions not achievable with deaminases. Moreover, we discover that the nickase’s mismatch tolerance limits EvolvR’s mutation window and substitution biases in a gRNA-specific fashion. To compensate for gRNA-to-gRNA variability in mutagenesis, we maximize the number of gRNA target sequences by incorporating a PAM-flexible nickase into EvolvR. Finally, we find a strong correlation between predicted free energy changes underlying R-loop formation and EvolvR’s performance using a given gRNA. The EvolvR system diversifies all four nucleotides to enable the evolution of mammalian cells, while nuclease and gRNA-specific properties underlying nickase fidelity can be engineered to further enhance EvolvR’s mutation rates.
Epithelial cell competition is promoted by signaling from immune cells
Abstract In epithelial tissues, juxtaposition of cells of different phenotypes can trigger cell competition, a process whereby one type of cell drives death and extrusion of another. During growth and homeostasis, cell competition is thought to serve a quality control function, eliminating cells that are “less fit”. Tissues may also attack and eliminate newly arising tumor cells, exploiting mechanisms shared with other instances of cell competition, but that differ, reportedly, in the involvement of the immune system. Whereas immune cells have been shown to play a direct role in killing tumor cells, this has not been observed in other cases of cell competition, suggesting that tissues recognize and handle cancer cells differently. Here, we challenge this view, showing that, in the fruit fly Drosophila, innate immune cells play similar roles in cell killing during classical cell competition as in eliminating tumors. These findings suggest that immune suppression of cancer may exploit the same mechanisms as are involved in promoting phenotypic uniformity among epithelial cells.
Decoupled few-femtosecond phase transitions in vanadium dioxide
Abstract The nature of the insulator-to-metal phase transition in vanadium dioxide (VO2) is one of the longest-standing problems in condensed-matter physics. Ultrafast spectroscopy has long promised to determine whether the transition is primarily driven by the electronic or structural degree of freedom, but measurements to date have been stymied by their sensitivity to only one of these components and/or their limited temporal resolution. Here we use ultra-broadband few-femtosecond pump-probe spectroscopy to resolve the electronic and structural phase transitions in VO2 at their fundamental time scales. Our experiments show that the system transforms into a bad-metallic phase within 10 fs after photoexcitation, but requires another 100 fs to complete the transition, during which we observe electronic oscillations and a partial re-opening of the bandgap, signalling a transient semi-metallic state. Comparisons with tensor-network simulations and density-functional theory calculations show these features result from an unexpectedly fast structural transition, in which the vanadium dimers separate and untwist with two different timescales. Our results resolve the structural and electronic nature of the light-induced phase transition in VO2 and establish ultra-broadband few-femtosecond spectroscopy as a powerful tool for studying quantum materials out of equilibrium.