Both positional and chemical variables control proteolytic cleavage of a presenilin ortholog.

Mechanistic details of intramembrane aspartyl protease (IAP) chemistry, which is central to many biological and pathogenic processes, remain largely obscure. Here, we investigated the kinetics of a microbial intramembrane aspartyl protease (mIAP) fortuitously acting on the renin substrate angiotensinogen and the C-terminal transmembrane segment of amyloid precursor protein (C100), which is cleaved by the presenilin subunit of γ-secretase, an Alzheimer disease (AD)-associated IAP. mIAP variants with substitutions in active-site and putative substrate-gating residues generally exhibit impaired, but not abolished, activity toward angiotensinogen and retain the predominant cleavage site (His-Thr).

Biliary and gallbladder dyskinesia.

Gallbladder and biliary dyskinesia are conditions that are becoming increasingly recognized due to improved technology. They are motility disorders that affect the gallbladder and sphincter of Oddi (SO), respectively. Gallbladder dyskinesia presents with typical biliary pain in the absence of gallstones.

Staging of esophageal cancer by EUS: staging accuracy revisited.

Background: EUS plays an important role in the preoperative staging of esophageal cancer. Recent data have called into question the staging accuracy of EUS, particularly in patients with early disease.

Objective: Our goals were to assess our institution's EUS staging accuracy by experienced endosonographers in a contemporary cohort of patients encompassing a wide range of disease stages and to assess staging accuracy after dilation of malignant strictures.

Contemporary Management of Biliary Tract Infections.

Biliary tract infections are a worldwide problem, with a large financial burden on health care. Biliary infections can result from multiple causes, but the most common culprit is cholelithiasis. In the past decade, our knowledge of the mechanism of disease, microbiology of infections, and management options has grown enormously.