Burden of Wilson Disease among patients and care partners in the United States: results from a cross-sectional survey.

Objective: This study assessed the burden of Wilson Disease (WD) among patients and care partners (WD-CPs) in the US and compared it to a US general population of adults (GPs) and care partners (GP-CPs).

Methods: This cross-sectional, self-reported survey included patients with WD and WD-CPs aged ≥18 years recruited through the Wilson Disease Association (WDA), while data for GPs and GP-CPs were obtained from the 2022 National Health and Wellness Survey. GPs and GP-CPs were propensity score matched (3:1) with WD patients and WD-CPs for demographics and health characteristics.

Assembly of the 20S proteasome.

The proteasome is a cellular protease responsible for the selective degradation of the majority of the intracellular proteome. It recognizes, unfolds, and cleaves proteins that are destined for removal, usually by prior attachment to polymers of ubiquitin. This macromolecular machine is composed of two subcomplexes, the 19S regulatory particle (RP) and the 20S core particle (CP), which together contain at least 33 different and precisely positioned subunits.

Pioneering studies of the "morning-after" pill.

Yale School of Medicine produced the first proof-of-concept study on the viability of a "morning-after" pill for human use. This study was a result of a fruitful collaboration between a pair of Yale scientists, Drs. John M.

A conserved 20S proteasome assembly factor requires a C-terminal HbYX motif for proteasomal precursor binding.

Dedicated chaperones facilitate the assembly of the eukaryotic proteasome, but how they function remains largely unknown. Here we show that a yeast 20S proteasome assembly factor, Pba1-Pba2, requires a previously overlooked C-terminal hydrophobic-tyrosine-X (HbYX) motif for function. HbYX motifs in proteasome activators open the 20S proteasome entry pore, but Pba1-Pba2 instead binds inactive proteasomal precursors.

A multimeric assembly factor controls the formation of alternative 20S proteasomes.

The proteasome is the central regulatory protease of eukaryotic cells. Heteroheptameric alpha-subunit and beta-subunit rings stack to form the 20S proteasome, which associates with a 19S regulatory particle (RP). Here we show that two yeast proteins, Pba3 and Pba4, form a previously unidentified 20S proteasome-assembly chaperone.

Akt shows variable sensitivity to an Hsp90 inhibitor depending on cell context.

Hsp90 inhibitors are currently in clinical trials for cancer therapy based on their ability to promote proteasomal degradation of oncogenic protein kinases and nuclear receptors. Results from recent studies suggest that cancer cells are more sensitive to these inhibitors than cells from healthy tissues. We analyzed an immortalized cell line Ba/F3 for sensitivity to the Hsp90 inhibitor geldanamycin in the absence and presence of the oncogenic tyrosine fusion kinase NPM-ALK expressed from a retroviral vector.