Unusual radiographic progression of tumoral calcinosis along the anterior cruciate ligament in an adolescent male.

A 13-year-old boy was referred to orthopedic surgery for chronic intermittent pain and swelling of the left knee. Initial imaging was consistent with osteochondritis dissecans of the femoral condyle. Follow-up imaging demonstrated unexpected progression, with a mass extending into the notch, replacing the anterior cruciate ligament, and eroding the femoral and tibial condyles.

Eye Movement Differences in Contact Versus Non-Contact Olympic Athletes.

The purpose of this study was to investigate the difference in oculomotor functioning between Olympic-level contact and non-contact sports participants. In total, 67 male and female Olympic-level contact ( = 27) and non-contact ( = 40) athletes completed oculomotor tasks, including Horizontal Saccade (HS), Circular Smooth Pursuit (CSP), Horizontal Smooth Pursuit (HSP), and Vertical Smooth Pursuit (VSP) using a remote eye tracker. No significant differences for sex or age occurred.

Pathogenic mutations in UBQLN2 exhibit diverse aggregation propensity and neurotoxicity.

The ubiquitin-adaptor protein UBQLN2 promotes degradation of several aggregate-prone proteins implicated in neurodegenerative diseases. Missense UBQLN2 mutations also cause X-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previously we demonstrated that the liquid-like properties of UBQLN2 molecular assemblies are altered by a specific pathogenic mutation, P506T, and that the propensity of UBQLN2 to aggregate correlated with neurotoxicity.

Discovery of KB-0742, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of CDK9 for MYC-Dependent Cancers.

Transcriptional deregulation is a hallmark of many cancers and is exemplified by genomic amplifications of the MYC family of oncogenes, which occur in at least 20% of all solid tumors in adults. Targeting of transcriptional cofactors and the transcriptional cyclin-dependent kinase (CDK9) has emerged as a therapeutic strategy to interdict deregulated transcriptional activity including oncogenic MYC. Here, we report the structural optimization of a small molecule microarray hit, prioritizing maintenance of CDK9 selectivity while improving on-target potency and overall physicochemical and pharmacokinetic (PK) properties.