Optical interferometry of a thin film array of titanium dioxide (TiO2) nanotubes allows the label-free sensing of rabbit immunoglobulin G (IgG). A protein A capture probe is used, which is immobilized on the inner pore walls of the nanotubes by electrostatic adsorption. Control experiments using IgG from chicken (which does not bind to protein A) confirms the specificity of the protein A-modified TiO2 nanotube array sensor. The aqueous stability of the TiO2 nanotube array was examined and compared with porous silica (SiO2), a more extensively studied thin film optical biosensor. The TiO2 nanotube array is stable in the pH range 2 to 12, whereas the porous SiO2 sensor displays significant degradation at pH > 8.

Cystic fibrosis (CF) is the most common life-shortening genetic disease affecting ~1 in 3,500 of the Caucasian population. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. To date, more than 2,000 CFTR mutations have been identified, which produce a wide range of phenotypes. The CFTR protein, a chloride channel, is normally expressed on epithelial cells lining the lung, gut, and exocrine glands. Mutations in CFTR have led to pleiotropic effects in CF patients and have resulted in early morbidity and mortality. Research has focused on identifying small molecules, or modulators, that can restore CFTR function. In recent years, two modulators, ivacaftor (Kalydeco) and lumacaftor/ivacaftor (Orkambi), have been approved by the U.S. Food and Drug Administration to treat CF patients with certain CFTR mutations. The development of these modulators has served as proof-of-concept that targeting CFTR by modulators is a viable therapeutic option. Efforts to discover new modulators that could deliver a wider and greater clinical benefit are still ongoing. However, traditional randomized controlled trials (RCTs) require large numbers of patients and become impracticable to test the modulators' efficacy in CF patients with CFTR mutations at frequencies much lower than 1%, suggesting the need for personalized medicine in these CF patients.

No abstract

Background-Before endoscopy patients undergo an uncomfortable fluid fast to reduce the risk of gastric acid aspiration and to ensure good endoscopic views are obtained. However, fluids rapidly leave the stomach and thus a long fluid fast before endoscopy may not be required.

The World Health Organization(WHO) has reported a worldwide surge in cases of cholera caused by the intestinal pathogen , and, combined, such surges have claimed several million lives, mostly in early childhood. Elevated cAMP production in intestinal epithelial cells challenged with cholera toxin (CTX) results in diarrhea due to chloride transport by a cAMP-activated channel, the cystic fibrosis transmembrane conductance regulator (CFTR). However, the identity of the main cAMP-producing proteins that regulate CFTR in the intestine and may be relevant for secretory diarrhea is unclear. Here, using RNA-Seq to identify the predominant AC isoform in mouse and human cells and extensive biochemical analyses for further characterization, we found that the cAMP-generating enzyme adenylate cyclase 6 (AC6) physically and functionally associates with CFTR at the apical surface of intestinal epithelial cells. We generated epithelium-specific AC6 knockout mice and demonstrated that CFTR-dependent fluid secretion is nearly abolished in AC6 knockout mice upon CTX challenge in ligated ileal loops. Furthermore, loss of AC6 function dramatically impaired CTX-induced CFTR activation in human and mouse intestinal spheroids. Our finding that the CFTR-AC6 protein complex is the key mediator of CTX-associated diarrhea may facilitate development of antidiarrheal agents to manage cholera symptoms and improve outcomes.