Webina: an open-source library and web app that runs AutoDock Vina entirely in the web browser.

MOTIVATION: Molecular docking is a computational technique for predicting how a small molecule might bind a macromolecular target. Among docking programs, AutoDock Vina is particularly popular. Like many docking programs, Vina requires users to download/install an executable file and to run that file from a command-line interface. Choosing proper configuration parameters and analyzing Vina output is also sometimes challenging. These issues are particularly problematic for students and novice researchers. RESULTS: We created Webina, a new version of Vina, to address these challenges. Webina runs Vina entirely in a web browser, so users need only visit a Webina-enabled webpage. The docking calculations take place on the user's own computer rather than a remote server. AVAILABILITY AND IMPLEMENTATION: A working version of the open-source Webina app can be accessed free of charge from http://durrantlab.com/webina. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

ProteinVR: Web-based molecular visualization in virtual reality.

Protein structure determines biological function. Accurately conceptualizing 3D protein/ligand structures is thus vital to scientific research and education. Virtual reality (VR) enables protein visualization in stereoscopic 3D, but many VR molecular-visualization programs are expensive and challenging to use; work only on specific VR headsets; rely on complicated model-preparation software; and/or require the user to install separate programs or plugins. Here we introduce ProteinVR, a web-based application that works on various VR setups and operating systems. ProteinVR displays molecular structures within 3D environments that give useful biological context and allow users to situate themselves in 3D space. Our web-based implementation is ideal for hypothesis generation and education in research and large-classroom settings. We release ProteinVR under the open-source BSD-3-Clause license. A copy of the program is available free of charge from http://durrantlab.com/protein-vr/, and a working version can be accessed at http://durrantlab.com/pvr/.

Orthognathic Correction in Prader-Willi Syndrome: Occlusion and Sleep Restored.

Children with Prader-Willi Syndrome (PWS) may present with a malocclusion and have a high propensity of developing obstructive sleep apnea (OSA). Obstructive sleep apnea is associated with short- and long-term adverse effects that negatively impact children with PWS. A case of a 15-year-old male with PWS, OSA, and a debilitating malocclusion is presented who underwent a combination of Le Fort 1 osteotomy, genioplasty, and tongue reduction to successfully treat his OSA and malocclusion. In select cases, orthognathic correction and other surgical therapies should be considered in patients with PWS.

Archean komatiite volcanism controlled by the evolution of early continents.

The generation and evolution of Earth's continental crust has played a fundamental role in the development of the planet. Its formation modified the composition of the mantle, contributed to the establishment of the atmosphere, and led to the creation of ecological niches important for early life. Here we show that in the Archean, the formation and stabilization of continents also controlled the location, geochemistry, and volcanology of the hottest preserved lavas on Earth: komatiites. These magmas typically represent 50-30% partial melting of the mantle and subsequently record important information on the thermal and chemical evolution of the Archean-Proterozoic Earth. As a result, it is vital to constrain and understand the processes that govern their localization and emplacement. Here, we combined Lu-Hf isotopes and U-Pb geochronology to map the four-dimensional evolution of the Yilgarn Craton, Western Australia, and reveal the progressive development of an Archean microcontinent. Our results show that in the early Earth, relatively small crustal blocks, analogous to modern microplates, progressively amalgamated to form larger continental masses, and eventually the first cratons. This cratonization process drove the hottest and most voluminous komatiite eruptions to the edge of established continental blocks. The dynamic evolution of the early continents thus directly influenced the addition of deep mantle material to the Archean crust, oceans, and atmosphere, while also providing a fundamental control on the distribution of major magmatic ore deposits.

Effect of femoral offset on pain and function after total hip arthroplasty.

The effects of altering patients' femoral offset (FO) during total hip arthroplasty on postoperative pain and function have not been well described. This study compared clinical outcomes as assessed by the Short Form 12 Health Survey and Western Ontario and McMaster University Osteoarthritis Index between patients who had their FOs restored to varying degrees (compared to the contralateral normal hip [CL]). We retrospectively measured postoperative FOs on standard anteroposterior pelvis radiographs and compared to the CL. Patients were categorized into one of 3 groups: decreased offset (< -5 mm compared to CL), normal offset (between -5 and +5 mm), and increased offset (> +5 mm). The decreased offset group exhibited Western Ontario and McMaster University Osteoarthritis Index Physical Function scores that were less than those of the normal offset and increased offset groups (72.03, 82.23, and 79.51, respectively [P = .019]). In conclusion, reducing a patients' native FO led to inferior functional outcome scores.

Capturing the Mechanism Underlying TOP mRNA Binding to LARP1.

The RNA-binding protein La-related protein 1 (LARP1) plays a central role in ribosome biosynthesis. Its C-terminal DM15 region binds the 7-methylguanosine (m7G) cap and 5' terminal oligopyrimidine (TOP) motif characteristic of transcripts encoding ribosomal proteins and translation factors. Under the control of mammalian target of rapamycin complex 1 (mTORC1), LARP1 regulates translation of these transcripts. Characterizing the dynamics of DM15-TOP recognition is essential to understanding this fundamental biological process. We use molecular dynamics simulations, biophysical assays, and X-ray crystallography to reveal the mechanism of DM15 binding to TOP transcripts. Residues C-terminal to the m7G-binding site play important roles in cap recognition. Furthermore, we show that the unusually static pocket that recognizes the +1 cytosine characteristic of TOP transcripts drives binding specificity. Finally, we demonstrate that the DM15 pockets involved in TOP-specific m7GpppC-motif recognition are likely druggable. Collectively, these studies suggest unique opportunities for further pharmacological development.

No evidence for high-pressure melting of Earth's crust in the Archean.

Much of the present-day volume of Earth's continental crust had formed by the end of the Archean Eon, 2.5 billion years ago, through the conversion of basaltic (mafic) crust into sodic granite of tonalite, trondhjemite and granodiorite (TTG) composition. Distinctive chemical signatures in a small proportion of these rocks, the so-called high-pressure TTG, are interpreted to indicate partial melting of hydrated crust at pressures above 1.5 GPa (>50 km depth), pressures typically not reached in post-Archean continental crust. These interpretations significantly influence views on early crustal evolution and the onset of plate tectonics. Here we show that high-pressure TTG did not form through melting of crust, but through fractionation of melts derived from metasomatically enriched lithospheric mantle. Although the remaining, and dominant, group of Archean TTG did form through melting of hydrated mafic crust, there is no evidence that this occurred at depths significantly greater than the ~40 km average thickness of modern continental crust.

Spontaneous Fractures of a Modern Modular Uncemented Femoral Stem.

BACKGROUND: Femoral stem fracture following total hip arthroplasty is an uncommon event that requires immediate revision surgery. QUESTIONS/PURPOSES: We report on four patients who experienced stem fractures of one design and a review of the US Food and Drug Administration adverse event reports on this design. METHODS: Fracture surfaces of four EMPERION™ (Smith & Nephew, Memphis, TN) femoral stems were analyzed under optical and scanning electron microscopy. A search of the FDA's Manufacturer and User Facility Device Experience (MAUDE) that reports on all EMPERION™ adverse events was completed. RESULTS: Fracture surfaces exhibited characteristics consistent with a fatigue fracture mechanism. Sixteen MAUDE reports claimed stem fracture or breakage of EMPERION™ stems. CONCLUSION: The four cases of EMPERION™ stem fractures were likely driven by small stem diameter, high offset, and high patient weight. Modular stem-sleeve femoral systems are susceptible to fatigue failure under high stress and should only be used in appropriate patients, whom are not considered obese.

Kinematics of passive flexion following balanced and overstuffed fixed bearing unicondylar knee arthroplasty.

INTRODUCTION: Progression of osteoarthritis in the unreplaced compartment following unicondylar knee arthroplasty (UKA) may be hastened if kinematics is disturbed following UKA implantation. The purpose of this study was to analyze tibiofemoral kinematics of the balanced and overstuffed UKA in comparison with the native knee during passive flexion since this is a common clinical assessment. METHODS: Ten cadaveric knees were mounted to robotic manipulator and underwent passive flexion from 0 to 90°. The kinematic pathway was recorded in the native knee and in the balanced, fixed bearing UKA. The medial UKA was implanted using a measured resection technique. Additionally, a one millimeter thicker tibial insert was installed to simulate the effects of overstuffing. Tibial kinematics in relation to the femur was recorded. RESULTS: Following UKA the tibia was externally rotated, and in valgus relative to the native knee near extension. In flexion, installing the UKA caused the knee to be translated medially and anteriorly. The tibia was translated distally through the entire range of flexion after UKA. Compared to the balanced UKA, overstuffing further increased valgus at full extension and distal translation of the tibia from full extension to 45° flexion. CONCLUSIONS: UKA implantation altered tibiofemoral kinematics in all planes. Differences were small; nevertheless, they may affect tibiofemoral loading patterns. CLINICAL RELEVANCE: Alterations in tibiofemoral kinematics following UKA might have implications for prosthesis failure and progression of osteoarthritis in the remaining compartment. Overstuffing should be avoided as it further increased valgus and did not improve the remaining kinematics.

Ingroup categorization affects the structural encoding of other-race faces: evidence from the N170 event-related potential.

The current research examined the influence of ingroup/outgroup categorization on brain event-related potentials measured during perceptual processing of own- and other-race faces. White participants performed a sequential matching task with upright and inverted faces belonging either to their own race (White) or to another race (Black) and affiliated with either their own university or another university by a preceding visual prime. Results demonstrated that the right-lateralized N170 component evoked by test faces was modulated by race and by social category: the N170 to own-race faces showed a larger inversion effect (i.e., latency delay for inverted faces) when the faces were categorized as other-university rather than own-university members; the N170 to other-race faces showed no modulation of its inversion effect by university affiliation. These results suggest that neural correlates of structural face encoding (as evidenced by the N170 inversion effects) can be modulated by both visual (racial) and nonvisual (social) ingroup/outgroup status.