Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function.

Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, and aging. Because remyelination is often incomplete, better understanding endogenous remyelination and developing remyelination therapies that restore neural function are clinical imperatives. Here, we use in vivo two-photon microscopy and electrophysiology to study the dynamics of endogenous and therapeutic-induced cortical remyelination and functional recovery after cuprizone-mediated demyelination in mice.

BK channels mediate a presynaptic form of mGluR-LTD in the neonatal hippocampus.

BK channels can control neuronal function, but their functional relevance in activity-dependent changes of synaptic function remains elusive. Here, we report that repetitive low-frequency stimulation activates BK channels through 12(S)HPETE, an arachidonic acid metabolite, produced downstream of postsynaptic metabotropic glutamate receptors (mGluRs) to trigger long-term depression (LTD) at CA3-CA1 synapses in hippocampal slices from P7-P10 mice. Activation of BK channels is subunit specific, as paxilline but not iberiotoxin blocked mGluR-LTD.

A multiplex method for rapidly identifying viral protease inhibitors.

With current treatments addressing only a fraction of pathogens and new viral threats constantly evolving, there is a critical need to expand our existing therapeutic arsenal. To speed the rate of discovery and better prepare against future threats, we establish a high-throughput platform capable of screening compounds against 40 diverse viral proteases simultaneously. This multiplex approach is enabled by using cellular biosensors of viral protease activity combined with DNA-barcoding technology, as well as several design innovations that increase assay sensitivity and correct for plate-to-plate variation.

Development of small molecule non-covalent coronavirus 3CL protease inhibitors from DNA-encoded chemical library screening.

Variants of SARS-CoV-2 have continued to emerge across the world and cause hundreds of deaths each week. Due to the limited efficacy of vaccines against SARS-CoV-2 and resistance to current therapies, additional anti-viral therapeutics with pan-coronavirus activity are of high interest. Here, we screen 2.