Conformational Dynamics of Supramolecular Protein Assemblies in the EMDB

The Electron Microscopy Data Bank (EMDB) is a rapidly growing repository for the dissemination of structural data from single-particle reconstructions of supramolecular protein assemblies including motors, chaperones, cytoskeletal assemblies, and viral capsids. While the static structure of these assemblies provides essential insight into their biological function, their conformational dynamics and mechanics provide additional important information regarding the mechanism of their biological function. Here, we present an unsupervised computational framework to analyze and store for public access the conformational dynamics of supramolecular protein assemblies deposited in the EMDB. Conformational dynamics are analyzed using normal mode analysis in the finite element framework, which is used to compute equilibrium thermal fluctuations, cross-correlations in molecular motions, and strain energy distributions for 452 of the 681 entries stored in the EMDB at present. Results for the viral capsid of hepatitis B, ribosome-bound termination factor RF2, and GroEL are presented in detail and validated with all-atom based models. The conformational dynamics of protein assemblies in the EMDB may be useful in the interpretation of their biological function, as well as in the classification and refinement of EM-based structures.Comment: Associated online data bank available at: http://lcbb.mit.edu/~em-nmdb

Computational modeling approach to predicting the shape and mechanical properties of DNA-based nanostructures

This study also has implications that reach beyond the realm of mechanics and engineering. An increase in bone fracture risk generally occurs with age, due to both a loss of bone mass and bone quality (Ritchie et al. 2009). It is also common for the discs between individual vertebrae to degrade due to age or disease. Our work thus seeks to find an explanation for the loss of bone mass from the aspect of changing boundary conditions (degradation of the discs). In this way, our work serves two purposes: first to provide a better understanding of an optimal structure already present in nature and second to enhance our understanding of the change to our own bone structure that occurs with age

Interoperable Summary Description Model Using Dublin Core

This paper proposes an interoperable metadata model generating summary description for multimedia content using Dublin Core (DC). The motive is based on the fundamental concepts such as (1) Description information about the multimedia content is essential in multimedia content access, search and retrieval process (2) the existing metadata are too complicated to use in applications such as e-cataloguing and browsing of e-commerce. As an approach to solve the problem, summary description that may be optimally minimal descriptive elements set derived from existing metadata schemes (full descriptions) is described in this paper. The proposed summary description generator model is achieved using thesaurus approach built on the basis of DC and any existing various metadata schemes

Contributions to the anisotropic elasto-plastic analysis of shells

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2009.Includes bibliographical references (p. 133-142).Shells are probably the most widely used structural component in engineering and also in nature due to their high efficiency and excellent performance when properly designed. On the other hand, they can be very sensitive to changes in geometries, thicknesses, applied loads and boundary conditions. Hence much research effort has been devoted to the reliable and efficient analysis of shells. This work contributes to the anisotropic elasto-plastic analysis of shells by addressing key issues in developing shell elements for finite element analysis and an elasto-plasticity model considering anisotropy and its evolution. First we develop a shell element that models the three-dimensional (3D) effects of surface tractions. The element is the widely used MITC4 shell element enriched by the use of a fully 3D stress-strain description, appropriate through-the-thickness displacements to model surface tractions, and pressure degrees of freedom for incompressible analyses. The element formulation avoids instabilities and ill-conditioning. We also develop a triangular 6-node shell element that represents an important improvement over a recently published element. The element is spatially isotropic, passes the membrane and bending patch tests, contains no spurious zero energy mode, and is formulated without an artificial constant. In particular, the improved element does not show the instability sometimes observed with the earlier published element.(cont.) Finally we review a constitutive model for anisotropic elasto-plastic analysis which takes into account the anisotropy of both the elastic and plastic material behaviors, as well as their evolution with plastic strains. It is based on continuum energy considerations, the Lee decomposition of deformations and a stored energy function of the logarithmic strains. The present work focuses on giving some physical insight into the parameters of the model and their effects on the predictions in proportional and in non-proportional loading conditions.by Do-Nyun Kim.Ph.D

Sensitivity Analysis for the Mechanical Properties of DNA Bundles

In structural DNA nanotechnology, programming a three-dimensional shape into DNA bundles has been a primary design objective. However, the mechanical properties of these DNA bundle structures are another important factor to be considered in the design process. While the mechanics of the individual DNA double helix has been explored extensively and hence its properties are well known, the mechanical properties of structural motifs such as DNA junctions and strand breaks important to bundle mechanics have not been well characterized due to experimental limitations, rendering it difficult to predict the mechanical properties of DNA bundles. Here, we investigate the effect of these structural motifs on the global bundle rigidities by performing sensitivity analysis on a six-helix DNA bundle structure using the finite element modeling approach. Results reveal the primary structural features and their parametric values required to reproduce the experimental bundle rigidities

Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures

DNA nanotechnology enables the programmed synthesis of intricate nanometer-scale structures for diverse applications in materials and biological science. Precise control over the 3D solution shape and mechanical flexibility of target designs is important to achieve desired functionality. Because experimental validation of designed nanostructures is time-consuming and cost-intensive, predictive physical models of nanostructure shape and flexibility have the capacity to enhance dramatically the design process. Here, we significantly extend and experimentally validate a computational modeling framework for DNA origami previously presented as CanDo [Castro,C.E., Kilchherr,F., Kim,D.-N., Shiao,E.L., Wauer,T., Wortmann,P., Bathe,M., Dietz,H. (2011) A primer to scaffolded DNA origami. Nat. Meth., 8, 221–229.]. 3D solution shape and flexibility are predicted from basepair connectivity maps now accounting for nicks in the DNA double helix, entropic elasticity of single-stranded DNA, and distant crossovers required to model wireframe structures, in addition to previous modeling (Castro,C.E., et al.) that accounted only for the canonical twist, bend and stretch stiffness of double-helical DNA domains. Systematic experimental validation of nanostructure flexibility mediated by internal crossover density probed using a 32-helix DNA bundle demonstrates for the first time that our model not only predicts the 3D solution shape of complex DNA nanostructures but also their mechanical flexibility. Thus, our model represents an important advance in the quantitative understanding of DNA-based nanostructure shape and flexibility, and we anticipate that this model will increase significantly the number and variety of synthetic nanostructures designed using nucleic acids.MIT Faculty Start-up Fun

Lattice-free prediction of three-dimensional structure of programmed DNA assemblies

DNA can be programmed to self-assemble into high molecular weight 3D assemblies with precise nanometer-scale structural features. Although numerous sequence design strategies exist to realize these assemblies in solution, there is currently no computational framework to predict their 3D structures on the basis of programmed underlying multi-way junction topologies constrained by DNA duplexes. Here, we introduce such an approach and apply it to assemblies designed using the canonical immobile four-way junction. The procedure is used to predict the 3D structure of high molecular weight planar and spherical ring-like origami objects, a tile-based sheet-like ribbon, and a 3D crystalline tensegrity motif, in quantitative agreement with experiments. Our framework provides a new approach to predict programmed nucleic acid 3D structure on the basis of prescribed secondary structure motifs, with possible application to the design of such assemblies for use in biomolecular and materials science.United States. Office of Naval Research (ONR N000141210621)National Science Foundation (U.S.) (NSF-DMREF Program CMMI1334109

Peliosis hepatis presenting with massive hepatomegaly in a patient with idiopathic thrombocytopenic purpura

Peliosis hepatis is a rare condition that can cause hepatic hemorrhage, rupture, and ultimately liver failure. Several authors have reported that peliosis hepatis develops in association with chronic wasting disease or prolonged use of anabolic steroids or oral contraceptives. In this report we describe a case in which discontinuation of steroid therapy improved the condition of a patient with peliosis hepatis. Our patient was a 64-year-old woman with a history of long-term steroid treatment for idiopathic thrombocytopenic purpura . Her symptoms included abdominal pain and weight loss; the only finding of a physical examination was hepatomegaly. We performed computed tomography (CT) and magnetic resonance imaging (MRI) of the liver and a liver biopsy. Based on these findings plus clinical observations, she was diagnosed with peliosis hepatis and her steroid treatment was terminated. The patient recovered completely 3 months after steroid discontinuation, and remained stable over the following 6 months

Early Results from Posterior Cervical Fusion with a Screw-Rod System

PURPOSE: We performed 65 cases of posterior fusion surgery for cervical and/or high thoracic lesions using a polyaxial screw-rod system. PATIENTS AND METHODS: A total of 486 screws were implanted in 65 patients. RESULTS: Fixation of the screws was carried out over an average of 2.9 spinal segments. Upon evaluation by postoperative CT scans, twelve (2.5%) screws had suboptimal trajectories but two of these revealed radiculopathy in one patient and required screw repositioning. No vascular sequelae resulted. There has been no segmental motion in any of the cases to date. As for other complications, there was one case of dural tearing and two cases of lateral mass fractures. There were no infections or other wound healing problems or hardware failures. No patients had neurological deterioration after surgery. There were statistically significant improvements in the mean Neck Disability Index (NDI) scores and Visual Analogue Scale (VAS) scores in the preoperative and late postoperative follow-up evaluations. Although further studies are required to establish the long-term results of fusion rates and clinical outcomes. CONCLUSION: We cautiously suggest that the posterior polyaxial screw-rod system can be safely used as a primary or additional fusion method in this risky region. The successful and safe use of this method is dependent on a precise preoperative surgical plan and tactics for ensuring safe screw fixation.ope

Spinal Cord Tumors of the Thoracolumbar Junction Requiring Surgery: A Retrospective Review of Clinical Features and Surgical Outcome

PURPOSE: A retrospective review of medical records and imaging studies. To investigate characteristic clinical features and surgical outcomes of spinal cord tumors (SCTs) of the thoracolumbar junction (TLJ). The spinal cord transitions to the cauda equina in the TLJ. The TLJ contains the upper and lower motor neurons of the spinal cord and cauda equina. As a result, the clinical features of lesions in the TLJ vary, and these anatomical characteristics may affect surgical outcome. MATERIALS AND METHODS: Pathological diagnosis, clinical features, neurological signs, and surgical outcomes were investigated in 76 patients surgically treated at our institute for SCTs arising from T11 to L2. The patients were divided into epiconus (T11-12, n=18) and conus groups (L1-2, n=58). RESULTS: Patients in the epiconus group had hyperactive deep tendon reflexes (DTRs), while those in the conus group had hypoactive DTRs (p < 0.05). Nine patients were misdiagnosed with intervertebral disc diseases (IVDs) before correct diagnoses were made. It was impossible to definitively determine the exact cause of symptoms in four patients who had both SCTs and IVDs. CONCLUSION: Among SCTs of the TLJ, the epiconus group displayed upper motor neuron syndrome and the conus group displayed lower motor neuron syndrome. SCTs of the TLJ were frequently misdiagnosed as IVDs due to symptomatic similarities. SCTs of the TLJ should be included in differential diagnosis of back and leg pain, and it is highly recommended that routine lumbar magnetic resonance imaging include the TLJ.ope