Generation of induced pluripotent stem cell line, NCHi027-A, from a female child with Posterior Cloaca (Type B).

Cloaca is an ultra-rare severe anorectal malformation in females where the gastrointestinal, genital, and urologic systems converge. Posterior Cloaca (Type B) is an extremely rare specific variant, where the urogenital sinus opens just anterior to the anus. NCHi027-A is an iPSC line derived from skin fibroblasts of a 4 year and 8-month-old female with Posterior Cloaca (Type B) using Sendai Virus reprogramming.

Reversible covalent c-Jun N-terminal kinase inhibitors targeting a specific cysteine by precision-guided Michael-acceptor warheads.

There has been a surge of interest in covalent inhibitors for protein kinases in recent years. Despite success in oncology, the off-target reactivity of these molecules is still hampering the use of covalent warhead-based strategies. Herein, we disclose the development of precision-guided warheads to mitigate the off-target challenge.

Targeting a key protein-protein interaction surface on mitogen-activated protein kinases by a precision-guided warhead scaffold.

For mitogen-activated protein kinases (MAPKs) a shallow surface-distinct from the substrate binding pocket-called the D(ocking)-groove governs partner protein binding. Screening of broad range of Michael acceptor compounds identified a double-activated, sterically crowded cyclohexenone moiety as a promising scaffold. We show that compounds bearing this structurally complex chiral warhead are able to target the conserved MAPK D-groove cysteine via reversible covalent modification and interfere with the protein-protein interactions of MAPKs.

Participant Personal Characteristics and Adherence to Oral Capsules: A Secondary Analysis of a Randomized Placebo-Controlled Trial of Antenatal Probiotics.

Background: Adherence to study interventions is critical to the conduct of randomized controlled trials (RCTs). The relationships between participant characteristics and intervention adherence are understudied in pregnant populations. The purpose of this study was to conduct a secondary analysis of adherence to study capsules in a double-masked, placebo-controlled RCT of a probiotic intervention to reduce antenatal Group B Streptococcus colonization, in relationship to participant characteristics.