The Upper Esophageal Sphincter Assist Device Is Associated With Symptom Response in Reflux-Associated Laryngeal Symptoms.

Reflux-associated laryngeal symptoms (RALS) is the process in which chronic laryngeal symptoms are related to gastroesophagopharyngeal reflux.1 Impairment of upper esophageal sphincter (UES) reflexes may predispose to esophagopharyngeal reflux.1 The novel noninvasive nonpharmacologic UES assist device (UESAD) applies external cricoid pressure to augment intraluminal UES pressure by 20 to 30 mm Hg and reduce esophagopharyngeal reflux events.2 This study aimed to assess the therapeutic efficacy of the UESAD in a pragmatic clinical setting, and to identify factors associated with symptom response among patients with suspected RALS.

Yeast Est2p affects telomere length by influencing association of Rap1p with telomeric chromatin.

In Saccharomyces cerevisiae, the sequence-specific binding of the negative regulator Rap1p provides a mechanism to measure telomere length: as the telomere length increases, the binding of additional Rap1p inhibits telomerase activity in cis. We provide evidence that the association of Rap1p with telomeric DNA in vivo occurs in part by sequence-independent mechanisms. Specific mutations in EST2 (est2-LT) reduce the association of Rap1p with telomeric DNA in vivo. As a result, telomeres are abnormally long yet bind an amount of Rap1p equivalent to that observed at wild-type telomeres. This behavior contrasts with that of a second mutation in EST2 (est2-up34) that increases bound Rap1p as expected for a strain with long telomeres. Telomere sequences are subtly altered in est2-LT strains, but similar changes in est2-up34 telomeres suggest that sequence abnormalities are a consequence, not a cause, of overelongation. Indeed, est2-LT telomeres bind Rap1p indistinguishably from the wild type in vitro. Taken together, these results suggest that Est2p can directly or indirectly influence the binding of Rap1p to telomeric DNA, implicating telomerase in roles both upstream and downstream of Rap1p in telomere length homeostasis.