The tumor suppressor gene 101 (tsg101) regulates vesicular trafficking processes in yeast and mammals. We report a novel protein, Tal (Tsg101-associated ligase), whose RING finger is necessary for multiple monoubiquitylation of Tsg101. Bivalent binding of Tsg101 to a tandem tetrapeptide motif (PTAP) and to a central region of Tal is essential for Tal-mediated ubiquitylation of Tsg101. By studying endocytosis of the epidermal growth factor receptor and egress of the human immunodeficiency virus, we conclude that Tal regulates a Tsg101-associated complex responsible for the sorting of cargo into cytoplasm-containing vesicles that bud at the multivesicular body and at the plasma membrane.[Keywords: Endocytosis; growth factor; HIV; ubiquitin; signal transduction] Supplemental material is available at http://www.genesdev.org.

Our findings are in line with emerging evidence that the spectrum of interstitial damage caused by smoke includes not only Langerhans cell hystiocytosis, respiratory bronchiolitis or desquamative interstitial pneumonia but also advanced usual interstitial pneumonitis as well. We believe that in some patients smoking plays a destructive role by a variety of mechanisms and can cause emphysema, lung fibrosis as well as pulmonary vasculopathy and hypertension. Future studies are needed to define the genetics and pathophysiology of this uncommonly reported clinical syndrome.

Our study found a 9.9% prevalence of ovarian varices in the general population. Our findings suggest that more than half (59%) the patients with ovarian varices have pelvic congestion syndrome and that most (77%) of them might benefit from ovarian vein embolization or ligation.

US performed by a skilled operator is a reliable tool for adenoma localization prior to minimally invasive parathyroidectomy. If the US findings are inconclusive, a Tc-sestamibi scan should be used. If there is a high clinical suspicion of adenoma in the presence of negative imaging studies, bilateral neck exploration should be performed.