Variable peptide processing of a Conus (Asprella) neocostatus α-conotoxin generates bioactive toxiforms that are potent against distinct nicotinic acetylcholine receptor subtypes.

Conusvenoms are composed of peptides that are commonly post-translationally modified, increasing their chemical diversity beyond what is encoded in the genome and enhancing their potency and selectivity. This study describes how PTMs alter an α-conotoxin's selectivity for specific nAChR subtypes. Venom from the cone snailConus(Asprella)neocostatuswas fractionated using high-performance liquid chromatography and tested using a behavioral intracranial mouse bioassay and a cholinergic calcium imaging assay using SH-SY5Y neuroblastoma cells.

Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content.

Introduction: Extracellular vesicles (EVs) can potently inhibit inflammation yet there is a lack of understanding about the impact of donor characteristics on the efficacy of EVs. The goal of this study was to determine whether the sex and age of donor platelet-derived EVs (PEV) affected their ability to inhibit viral myocarditis.

Methods: PEV, isolated from men and women of all ages, was compared to PEV obtained from women under 50 years of age, which we termed premenopausal PEV (pmPEV).

Long-Term Seizure Reduction Associated with Vagal Nerve Stimulation in Dravet Syndrome.

variants cause a range of epilepsy syndromes, including Dravet syndrome, leading to early cognitive and functional impairment. Despite advances in medical management, drug-resistant epilepsy remains common. Vagal nerve stimulation (VNS) has been suggested reducing seizure frequency in these patients but there is a lack of long-term follow-up, quantitative analysis that corrected for confounding factors such as antiseizure medications (ASMs) and the impact of VNS settings on response.

Advancing Monogenic Diabetes Research and Clinical Care by Creating a Data Commons: The Precision Diabetes Consortium (PREDICT).

Monogenic diabetes mellitus (MDM) is a group of relatively rare disorders caused by pathogenic variants in key genes that result in hyperglycemia. Lack of identified cases, along with absent data standards, and limited collaboration across institutions have hindered research progress. To address this, the UChicago Monogenic Diabetes Registry (UCMDMR) and UChicago Data for the Common Good (D4CG) created a national consortium of MDM research institutions called the PREcision DIabetes ConsorTium (PREDICT).

Phase 1 study of the safety, tolerability, and pharmacokinetics of a synthetic macrocyclic peptide antibiotic (BRII-693) in healthy adult participants.

BRII-693 is a next-generation intravenous (IV)-administered synthetic macrocyclic peptide antibiotic for infections caused by drug-resistant gram-negative pathogens. This single-center, randomized, double-blind, placebo-controlled phase 1 study investigated the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending doses of BRII-693 in 104 healthy participants. In single-dose cohorts, 10-400 mg of BRII-693 was evaluated in eight participants (six active; two placebo) per cohort.