Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Freezing and rapid escape in response to aversive stimuli are instinctive behaviors common to most animals. High-throughput behavioral screening approaches identified small molecules that modulate a strobe light-induced fear response in zebrafish larvae described as "innate freezing" as well as small molecules that phenocopy the antipsychotic haloperidol. One class of compounds, the finazines, function partially through the σ1 receptor to cause both an escapelike response and an antipsychotic-like behavioral profile. Cover design by Erin Dewalt, based on image created by Andrea Velenich. Articles, pp552, 559; News & Views, p468.
Two independent high-throughput zebrafish behavioral screens of tens of thousands of compounds identify the 'finazines', a novel group of antipsychotics, and their endogenous genetic target, the σ1 receptor.
A phenotypic cell-based screen identifies an inhibitor of BET bromodomain transcriptional activity via inhibition of the alternative bromodomain-containing protein TAF1.
Non-apoptotic regulated cell death is not fully characterized, particularly for ferroptosis, the iron- and ROS-dependent form of regulated cell death. A systematic approach using modulatory profiling and cell line sensitivity analysis has unraveled the association of lipid metabolism with ferroptosis and enabled the discovery of a novel specific ferroptosis inducer.
Biomolecule-specific small-molecule probes, in contrast to genetically encoded tags, can visualize peptidoglycan, lipids, nucleic acids and glycans and have proven useful for imaging of the unique subcellular compartments and environment of bacteria.
Microarray analysis of butein-treated adipocytes results in the identification of the PR domain containing 4 (Prdm4) transcription factor, which stimulates WAT browning and lipolysis and protects against diet-induced obesity.
Metabolic tracer and free energy analysis of metabolic fluxes and pool sizes in E. coli, yeast and a mammalian cell line reveals a conservation of absolute metabolite concentrations that is constrained by thermodynamics and efficient enzyme utilization.
Crystal structure analysis of the Phd transcription factor bound to the DNA operator combined with biophysical studies reveal an interplay between intrinsically disordered regions and conditional cooperativity for operon binding and repression.
Modulatory profiling of lethal small-molecule compounds identified FIN56 as an inducer of ferroptosis. FIN56 promotes the degradation of glutathione peroxidase 4 and directly activates squalene synthase, an enzyme involved in cholesterol synthesis.
Chemical screening using a newly developed fluorescence-based assay for chromatin reactivation led to the identification of small-molecule inhibitors of the second bromodomain of TAF1 that synergize with BRD4 inhibitors.
A forward-genetic screen revealed that the mutations in DNA polymerase α (POLA1) are resistant to the effects of CD437. The direct interaction of CD437 and POLA1 blocks DNA replication and promotes cancer cell death.
Membrane anchoring protects metallo-β-lactamase NDM-1 from degradation while favoring its secretion into outer-membrane vesicles. This provides carbapenem resistance to bacteria that are sensitive to zinc starvation, which causes degradation of these enzymes.
A ubiquitin analog used as an activity-based probe of ubiquitin conjugation enzymes, E1, E2 and E3 covalently traps these enzymes without transfer to substrates. The probes can be used in structural and functional studies and to visualize enzyme activity in cells.
KDM5 histone demethylases promote the survival of drug-tolerant persister (DTP) cells in certain cancers. CPI-455, a chemical probe specific for KDM5, elevates cellular H3K4 methylation levels and reduces DTP cell numbers, suggesting that KDM5 is a viable target for cancer combination treatment.
X-ray crystallographic analyses of KDM5B provide a view of the enzyme's iron(II)- and 2-oxoglutarate-containing catalytic core, and structures of KDM5B complexes with small-molecule inhibitors reveal selectivity profiles for multiple compound chemotypes.
Human mitochondrial tRNAMet has a 5-formylcytidine (f5C) modification at the first anticodon position that is required for correct decoding of the AUA codon as methionine. The first step in the biosynthesis of f5C involves the S-adenosylmethionine-dependent methylation of cytidine 34 by the NSUN3 methyltransferase.
Small molecules identified in two high-throughput screens modulate a strobe-light-induced fear response in zebrafish larvae described as ‘innate freezing’. Some compounds cause escape-like behavior, including several that target the sigma-1 (σ1) receptor.
A screening approach involving ten larval zebrafish behavior assays and the similarity search tool, phenoBlast, for compounds that phenocopy the antipsychotic haloperidol identifies finazines that may work partially through the sigma-1 (σ1) receptor.
An siRNA screen of cells treated with a mitochondrial-targeted DNA oxidizing agent identifies proteins such as RAD23A, XRCC4, and POLθ that mediate mitochondrial DNA repair and replication.