Search NASA⌕ Search

Engineering topics

Hayes, Andrew J.

Publications and source records attributed to Hayes, Andrew J..

The structural basis of bacterial manganese import

Metal ions are essential for all forms of life. In prokaryotes, ATP-binding cassette (ABC) permeases serve as the primary import pathway for many micronutrients including the first-row transition metal manganese. However, the structural features of ionic metal transporting ABC permeases have remained undefined. Here, we present the crystal structure of the manganese transporter PsaBC from Streptococcus pneumoniae in an open-inward conformation. The type II transporter has a tightly closed transmembrane channel due to “extracellular gating” residues that prevent water permeation or ion reflux. Below these residues, the channel contains a hitherto unreported metal coordination site, which is essential for manganese translocation. Mutagenesis of the extracellular gate perturbs manganese uptake, while coordination site mutagenesis abolishes import. These structural features are highly conserved in metal-specific ABC transporters and are represented throughout the kingdoms of life. Collectively, our results define the structure of PsaBC and reveal the features required for divalent cation transport.

59 BASIC BIOLOGICAL SCIENCES↗

Outcome of Primary Desmoid Tumors at All Anatomic Locations Initially Managed with Active Surveillance

Background: The behavior of desmoid tumors is unpredictable and varies from spontaneous remission to symptomatic and radiologic progression. This study aimed to evaluate the radiologic and symptomatic course of the disease in patients initially managed with active surveillance. Methods: Patients with a primary desmoid tumor at any anatomic location diagnosed between 1998 and 2016 were identified in a prospectively maintained database from a single sarcoma reference center in the United Kingdom. Inverse univariate Cox proportional hazard regression analyses were conducted to evaluate the course of the disease and indications for initiating treatment. Results: The study identified 168 patients with a primary desmoid tumor initially managed with active surveillance. The tumors were located in the abdominal wall (n = 61, 36%), an extremity (n = 51, 30%), chest wall (n = 30, 18%), intra-abdominal site (n = 15, 9%), or elsewhere (n = 11, 6%). Of all the patients, 36% experienced radiologic progressive disease, 36% had stable disease, and 27% regressed. The patients younger than 50 years were more likely to progress (p = 0.046), whereas the patients with chest wall or upper-extremity tumors reported significantly more pain (p = 0.01). Eventually, 46% of the patients proceeded to treatment. The median time to start of treatment after initial surveillance was 31 months, whereas the median follow-up time for the patients not receiving any treatment was 40.5 months. The indications for initiation of treatment were pain (32%), progression (31%), or both (13%). Conclusions: Patients with desmoid tumors can be managed with initial active surveillance, although almost half of patients may eventually need treatment. Pain, tumor progression, or both are the most common indications for the initiation of treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗