Multilayer regulation underlies the functional precision and evolvability of the olfactory system.

Sensory neurons must be reproducibly specified to permit accurate neural representation of external signals but also able to change during evolution. We studied this paradox in the olfactory system by establishing a single-cell transcriptomic atlas of all developing antennal sensory lineages, including latent neural populations that normally undergo programmed cell death (PCD). This atlas reveals that transcriptional control is robust, but imperfect, in defining selective sensory receptor expression.

An implantable system for opioid safety.

Naloxone can effectively rescue victims from opioid overdose, but less than 5% survive due to delayed or absent first responder intervention. Current overdose reversal systems face key limitations, including low user adherence, false positive detection, and slow antidote delivery. Here, we describe a subcutaneously implanted robotic first responder to overcome these challenges.

Directed Evolution of Multicyclic Peptides Using Yeast Display for Sensitive and Selective Fluorescent Analysis of CD28 on the Cell Surface.

CD28 is a costimulatory receptor that provides the second signal necessary for T-cell activation and is associated with diseases, including rheumatoid arthritis, asthma, and cancer. Targeting CD28 is crucial for both functional bioanalysis and therapeutic development. Molecular probes, particularly fluorescent probes, can enhance our understanding of CD28's cellular roles.

A nucleotide code governs Lis1's ability to relieve dynein autoinhibition.

Dynein-1 is a microtubule motor responsible for the transport of cytoplasmic cargoes. Activation of motility requires it first overcome an autoinhibited state prior to its assembly with dynactin and a cargo adaptor. Studies suggest that Lis1 may relieve dynein's autoinhibited state.

Nde1 Promotes Lis1 Binding to Full-Length Autoinhibited Human Dynein-1.

Cytoplasmic dynein-1 (dynein) is the primary motor for the retrograde transport of intracellular cargoes along microtubules. The activation of the dynein transport machinery requires the opening of its autoinhibited Phi conformation by Lis1 and Nde1/Ndel1, but the underlying mechanism remains unclear. Using biochemical reconstitution and cryo-electron microscopy, we show that Nde1 significantly enhances Lis1 binding to autoinhibited dynein and facilitates the opening of Phi.