Ferroptosis is a distinctive form of regulated cell death driven by iron-dependent phospholipid peroxidation. Its initiation and suppression are finely tuned by metabolic pathways, transcription facto...

Membrane protection against oxidative insults is achieved by the concerted action of glutathione peroxidase 4 (GPX4) and endogenous lipophilic antioxidants such as ubiquinone and vitamin E. Deficienci...

A new study identifies the aldehyde dehydrogenase ALDH7A1 as a key regulator of ferroptosis. ALDH7A1 generates a pool of membrane-associated NADH, which is used by ferroptosis suppressor protein 1 to ...

Mitochondrial ROS is necessary for the release of a critical anti-inflammatory cytokine.

Researchers are arguing over whether ‘disruptive’ or ‘novel’ science is waning – and how to remedy the problem.

The spatiotemporal organization of the postsynaptic density (PSD) is a fundamental determinant of synaptic transmission, information processing, and storage in the brain. The major bottleneck that prevents the direct and precise representation of the nanometer-scaled organization of excitatory glutamatergic synapses is the size of antibodies, nanobodies, and the genetically encoded fluorescent tags. Here, we introduce small, high affinity synthetic probes for simplified, high contrast visualization of excitatory synapses without the limitations of larger biomolecules. In vitro binding quantification together with microscopy-based evaluation identified eSylites, a series of fluorescent bivalent peptides comprising a dye, linker, and sequence composition that show remarkable cellular target selectivity. Applied on primary neurons or brain slices at nanomolar concentrations, eSylites specifically report PSD-95, the key orchestrator of glutamate receptor nanodomains juxtaposed to the presynaptic glutamate release sites that mediate fast synaptic transmission. The eSylite design minimizes a spatial dye offset and thereby enables visualization of PSD-95 with improved localization precision and further time-resolved discrimination. In particular, we find that individual dendritic spines can contain separate nanodomains enriched for either PSD-95 or its closest homologues, PSD-93 or SAP102. Collectively, these data establish eSylites as a broadly applicable tool for simplified excitatory synapse visualization, as well as a high-end microscopy compatible probe for resolving the PSD organization with unprecedented resolution.

HMCES, a recently discovered but ancient protein, covalently attaches to damaged single-stranded DNA and shields it from nucleases. Rua-Fernandez and colleagues now show that HMCES catalyzes its own recycling, permitting normal growth and non-mutagenic DNA repair.

8-oxoguanine (8-oxoG) is a common oxidative DNA lesion, which causes G>T substitutions that compose COSMIC single base substitution signature 18 (SBS18) in human cancers. Determinants of local and reg...