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CRISPR gene activation and inhibition has become a powerful synthetic tool for influencing the expression of native genes for foundational studies, cellular reprograming, and metabolic engineering. Here the authors demonstrate near leak-free, inducible expression of a polycistronic array containing up to 24 gRNAs from two orthogonal CRISPR/Cas systems.
Continuous generation of reactive oxygen species is desirable in the advanced oxidation process. Here, the authors report a self-cycled photoFenton-like with a scalable artificial leaf for production of H2O2 from water with solar-to-H2O2 efficiency of 1.46%.
The study of tumour dormancy is limited by suitable in vivo models. Here the authors show that mammary intraductal breast cancer (BC) xenografts model estrogen receptor α-positive (ER+) BC dormancy and rapid metastatic progression characteristic of triple-negative (TN) BC. The dormant disseminated ER+ BC cells display characteristics of epithelial-mesenchymal plasticity and forced expression of E-cadherin allows them to overcome dormancy.
Tumor loss of IFN-γ signalling is a major mechanism of resistance to immune checkpoint blockers. Here the authors report that melanoma cells with knockout of IFNγR1 show constitutive JAK1/2 activation and that the JAK1/2 inhibitor ruxolitinib can overcome resistance to anti-CTLA-4 therapy.
Microenvironment localization and activation of L-TGF-β1 determine its specific function. Here, the authors elucidated the underlying mechanisms of specific presentation of L-TGF-β1 on the surface of myeloid lineage cells designated by LRRC33, and its activation by integrin αVβ8.
Hippo signalling is often deregulated in cancers. Here the authors show that CK2 enhances the cooperation of HHEX with YAP-TEAD complex to promote colorectal tumorigenesis.
Adipic acid is an important building block of polymers, although its production relies on harmful reagents. Here, authors examined surfactant-modified nickel hydroxide for adipic acid electrosynthesis coupled with hydrogen gas evolution.
Bivalves reveal that the subpolar North Atlantic destabilised and shows signs of having crossed a tipping point during the transition into the Little Ice Age.
Phosphorus (P) limitation is pervasive in tropical forests. Here the authors analyse the dependence of photosynthesis on leaf N and P in tropical forests, and show that incorporating leaf P constraints in a terrestrial biosphere model enhances its predictive power.
Cocaine is a tropane alkaloid produced by Erythroxylum novogranatense. Here the authors identify two polyketide synthases involved in cocaine biosynthesis and provide insight into the parallel evolution of these enzymes in tropane alkaloids-producing plants.
The ratio of predator-to-prey biomass is a key element in food webs. Here, the authors report a unified analysis of predator-prey biomass scaling in complex food webs, finding general patterns of sub-linear scaling across ecosystems and levels of organization.
Meshworks of claudin polymers control the paracellular transport and barrier properties of epithelial tight junctions. Here, the authors show different claudin nanoscale organization principles, finding that claudin segregation enables barrier formation and paracellular ion flux across tight junctions.
LSD1 inhibition blocks the neuroendocrine phenotype of some small cell lung cancers (SCLCs). Here, a genome-wide CRISPR/Cas9 LSD1 inhibitor resistance screen identifies the mRNA-binding protein ZFP36L1 as a gene repressed by LSD1 that when restored inhibits SCLC neuroendocrine differentiation.
The authors of this work characterize the effect of amino acid substitution on α-synuclein (α-Syn) aggregation. Residues 38 and 42 (in addition to 39) within the P1 region of α-Syn affect amyloid formation. The effect of substitution at position 38 is dependent on the amino-acid introduced, suggesting that specific interactions control α -Syn aggregation.
Ambient-stable solution-processed conductive materials with a low work function are essential to facilitate electron injection. Here, the authors design and synthesise polymer electrolyte with work function down to 2.2 eV for applications in high-performance light-emitting diodes and solar cells.
Minimally invasive procedures for tracking neural activity are important for understanding of neural networks. Here the authors describe microfabricated implants and windows that enable long-term recordings of motor circuit activity in Drosophila, allowing them to watch how neurons change their structure and activity over weeks.
Optoelectronic properties of van der Waals heterostructures can be tuned via strain. Here, authors demonstrate strong and localized luminescence in the ultraviolet region from interface bubbles between stacked multilayers of hexagonal boron nitride.
Hereditary tyrosinemia type 1 (HT1) is an inborn error of metabolism caused by a deficiency in fumarylacetoacetate hydrolase (FAH). Here, the authors show in an animal model that HT1 can be treated via in vivo portal vein administration of a lentiviral vector carrying the human FAH transgene.
Machine learning has been applied to problems in condensed matter physics, but its performance in an experimental setting needs testing. Zhang et al. study the effects of adversarial perturbations on a neural-network-based topological phase classifier, applied to experimental data from an NV center in diamond.
The development of antimalarials against the human liver and asexual blood stages is one of the top public health challenges. Here, the authors report a single-step biochemical assay for the characterization of prolyl-tRNA synthetase inhibitors, and develop high-affinity inhibitors for the enzyme, including elusive triple-site ligands.