Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

Defective signaling, osteoblastogenesis, and bone remodeling in a mouse model of connexin43 C-terminal truncation

In skeletal tissue, loss or mutation of the gap junction protein, connexin43 (Cx43), in cells of the osteoblast-lineage leads to a profound cortical bone phenotype and defective tissue remodeling. There is mounting evidence in bone cells that the C-terminus (CT) of Cx43 is a docking platform for signaling effectors and is required for efficient downstream signaling. Here, we examined this function, using a mouse model of Cx43 CT-truncation (Gja1 K258Stop). Relative to Gja1+/− controls, male Gja1−/K258stop mice have a cortical bone phenotype that is remarkably similar to those reported for deletion of the entire Cx43 gene in osteoblasts. Further, we show that the Cx43 CT binds several signaling proteins that are required for optimal osteoblast function, including PKCδ, ERK, and β-catenin. Deletion of the Cx43 CT domain affects these signaling cascades, impacting osteoblast proliferation, differentiation, and collagen processing and organization. These data imply that, at least in bone, Cx43 gap junctions not only exchange signals, but also recruit the appropriate effector molecules to the Cx43 CT in order to efficiently activate signaling cascades that affect cell function and bone acquisition.</jats:p

Endoscopic posterior cordotomy for treatment of dyspnea due to vocal fold immobility

Introduction: Several surgical procedures have been described for the treatment of respiratory distress secondary to vocal fold immobility (VFI), but the contribution of posterior cordotomy (PC) to tracheostomy weaning or prevention has not been studied in depth, particularly in the acute setting. The objective of this study was to show the effectiveness of PC to relieve dyspnea, prevent the need for tracheostomy, and enable decannulation in patients with VFI. Methods: We conducted a retrospective study and reviewed the medical records of all patients whose dyspnea warranted surgical intervention from January 2013 to January 2018. Data were retrieved on epidemiology, etiology, and duration of VFI, tracheostomy dependence, success in decannulation from tracheostomy or respiratory relief, number of procedures until decannulation, and complications. Results: Twelve suitable patients were identified of whom eleven had bilateral VFI and one had unilateral VFI. Five were tracheostomy-dependent. Ten patients underwent unilateral PC, and two patients underwent bilateral PC. All the patients experienced respiratory relief, eleven after a single PC and one after two PCs. All tracheostomy-dependent patients were decannulated. The mean follow-up after PC was 24.55 months during which none of the patients required a re-tracheostomy and three patients required revision of the PC. There were no surgical complications. Postoperatively, eight patients (67%) experienced a breathy voice and three patients (25%) had dysphagia for fluids. No patient had aspiration pneumonia. Conclusions: We conclude that PC is an easy, safe, and effective procedure for tracheostomy weaning and respiratory relief in patients with VFI. A revision PC may be indicated in some patients. A breathy voice is to be expected, and a few patients will experience dysphagia to fluids that may be addressed by instructing the patient to use a fluid thickener and take small sips.</jats:p

Correction: Corrigendum: Determining crystal structures through crowdsourcing and coursework

Nature Communications 7: Article number:12549 (2016); Published 16 September 2016; Updated 25 October 2016 The original version of this Article contained an error in the spelling of a member of the University of Michigan students Consortium, Sam Lee, which was incorrectly given as Sam Lewe. This hasnow been corrected in both the PDF and HTML versions of the Article.</jats:p