Bilateral Proximal Tibial Sleeve Fractures in a Child: A Case Report

Introduction: A sleeve fracture classically describes an avulsion of cartilage or periosteum with or without osseous fragments and usually occurs at the inferior margin of the patella. Tibial tubercle sleeve fractures in the skeletally immature are extremely rare. Case Presentation: In this report the authors describe a 12-year-old boy with no systemic disease and no steroid use who sustained bilateral proximal tibial sleeve fractures whilst playing football. Both ruptures were associated with rupture of the medial patellofemoral ligament and tear of the medial retinaculum. Treatment was performed with primary end-to-end repair, reinforcement with bone anchors and cerclage wires with an excellent outcome. Conclusions: We feel this rare, currently unclassified variant of a tibial tubercle avulsion fracture should be recognised and consideration taken to adding it to existing classification systems

Combined high-pressure and multiquantum NMR and molecular simulation propose a role for N-terminal salt bridges in amyloid-beta

Salts, Aggregation, Molecular structure, Cell and molecular biology, Post-translational modificatio

Frame-Recurrent Video Super-Resolution

Recent advances in video super-resolution have shown that convolutional neural networks combined with motion compensation are able to merge information from multiple low-resolution (LR) frames to generate high-quality images. Current state-of-the-art methods process a batch of LR frames to generate a single high-resolution (HR) frame and run this scheme in a sliding window fashion over the entire video, effectively treating the problem as a large number of separate multi-frame super-resolution tasks. This approach has two main weaknesses: 1) Each input frame is processed and warped multiple times, increasing the computational cost, and 2) each output frame is estimated independently conditioned on the input frames, limiting the system's ability to produce temporally consistent results. In this work, we propose an end-to-end trainable frame-recurrent video super-resolution framework that uses the previously inferred HR estimate to super-resolve the subsequent frame. This naturally encourages temporally consistent results and reduces the computational cost by warping only one image in each step. Furthermore, due to its recurrent nature, the proposed method has the ability to assimilate a large number of previous frames without increased computational demands. Extensive evaluations and comparisons with previous methods validate the strengths of our approach and demonstrate that the proposed framework is able to significantly outperform the current state of the art.Comment: Accepted at CVPR 201

Probing the accuracy of explicit solvent constant pH molecular dynamics simulations for peptides

Protonation states of titratable amino acids play a key role in many biomolecular processes. Knowledge of protonatable residue charges at a given pH is essential for a correct understanding of protein catalysis, inter- and intramolecular interactions, substrate binding, and protein dynamics for instance. However, acquiring experimental values for individual amino acid protonation states of complex systems is not straightforward; therefore, several in silico approaches have been developed to tackle this issue. In this work, we assess the accuracy of our previously developed constant pH MD approach by comparing our theoretically obtained pKa values for titratable residues with experimental values from an equivalent NMR study. We selected a set of four pentapeptides, of adequately small size to ensure comprehensive sampling, but concurrently, due to their charge composition, posing a challenge for protonation state calculation. The comparison of the pKa values shows good agreement of the experimental and the theoretical approach with a largest difference of 0.25 pKa units. Further, the corresponding titration curves are in fair agreement, although the shift of the Hill coefficient from a value of 1 was not always reproduced in simulations. The phase space overlap in Cartesian space between trajectories generated in constant pH and standard MD simulations is fair and suggests that our constant pH MD approach reasonably well preserves the dynamics of the system, allowing dynamic protonation MD simulations without introducing structural artifacts

Structure and absolute configuration of phenanthro-perylene quinone pigments from the deep-sea crinoid Hypalocrinus naresianus

Two new water-soluble phenanthroperylene quinones, gymnochrome H (2) and monosulfated gymnochrome A (3), as well as the known compounds gymnochrome A (4) and monosulfated gymnochrome D (5) were isolated from the deep-sea crinoid Hypalocrinus naresianus, which had been collected in the deep sea of Japan. The structures of the compounds were elucidated by spectroscopic analysis including HRMS, 1D 1H and 13C NMR, and 2D NMR. The absolute configuration was determined by ECD spectroscopy, analysis of J-couplings and ROE contacts, and DFT calculations. The configuration of the axial chirality of all isolated phenanthroperylene quinones (2–5) was determined to be (P). For gymnochrome H (2) and monosulfated gymnochrome A (3), a (2′S,2″R) configuration was determined, whereas for monosulfated gymnochrome D (5) a (2′R,2″R), configuration was determined. Acetylated quinones are unusual among natural products from an echinoderm and gymnochrome H (2) together with the recently reported gymnochrome G (1) represent the first isolated acetylated phenanthroperylene quinones

Pox proteomics: mass spectrometry analysis and identification of Vaccinia virion proteins

BACKGROUND: Although many vaccinia virus proteins have been identified and studied in detail, only a few studies have attempted a comprehensive survey of the protein composition of the vaccinia virion. These projects have identified the major proteins of the vaccinia virion, but little has been accomplished to identify the unknown or less abundant proteins. Obtaining a detailed knowledge of the viral proteome of vaccinia virus will be important for advancing our understanding of orthopoxvirus biology, and should facilitate the development of effective antiviral drugs and formulation of vaccines. RESULTS: In order to accomplish this task, purified vaccinia virions were fractionated into a soluble protein enriched fraction (membrane proteins and lateral bodies) and an insoluble protein enriched fraction (virion cores). Each of these fractions was subjected to further fractionation by either sodium dodecyl sulfate-polyacrylamide gel electophoresis, or by reverse phase high performance liquid chromatography. The soluble and insoluble fractions were also analyzed directly with no further separation. The samples were prepared for mass spectrometry analysis by digestion with trypsin. Tryptic digests were analyzed by using either a matrix assisted laser desorption ionization time of flight tandem mass spectrometer, a quadrupole ion trap mass spectrometer, or a quadrupole-time of flight mass spectrometer (the latter two instruments were equipped with electrospray ionization sources). Proteins were identified by searching uninterpreted tandem mass spectra against a vaccinia virus protein database created by our lab and a non-redundant protein database. CONCLUSION: Sixty three vaccinia proteins were identified in the virion particle. The total number of peptides found for each protein ranged from 1 to 62, and the sequence coverage of the proteins ranged from 8.2% to 94.9%. Interestingly, two vaccinia open reading frames were confirmed as being expressed as novel proteins: E6R and L3L

Antidepressants for cognitive impairment in schizophrenia - A systematic review and meta-analysis

Background: Cognitive impairment in schizophrenia is disabling, but current treatment options remain limited. Objective: To meta-analyze the efficacy and safety of adjunctive antidepressants for cognitive impairment in schizophrenia. Data sources and study selection: PubMed, MEDLINE, PsycINFO, and Cochrane Library databases were searched until 12/2013 for randomized controlled trials comparing antidepressant augmentation of antipsychotics with placebo regarding effects on cognitive functioning in schizophrenia. Data extraction: Two authors independently extracted data. Standardized mean differences (SMDs) were calculated for continuous outcomes and risk ratios for categorical outcomes. SMDs of individual cognitive tests were pooled on a study level within domains (primary outcome) and across domains. When results were heterogeneous, random instead of fixed effects models were used. Results: We meta-analyzed 11 studies (duration=8.7 +/- 3.7 weeks) including 568 patients (mean age=39.5 +/- 6.9 years, males=67.2%, illness duration=12.5 +/- 8.0 years). Antidepressants included mirtazapine (4 studies; n=126), citalopram (2 studies; n=231), fluvoxamine (1 study; n=47), duloxetine (1 study; n=40), mianserin (1 study; n=30), bupropion (1 study; n=61), and reboxetine (1 study; n=33). Statistically significant, but clinically negligible, advantages were found for pooled antidepressants compared to placebo in executive function (Hedges\u27 g=0.17, p=0.02) and a composite cognition score (Hedges\u27 g=0.095, p=0.012). Depression improved with serotonergic antidepressants (p=0.0009) and selective serotonin reuptake inhibitors (p=0.009), but not with pooled antidepressants (p=0.39). Sedation was more common with pooled antidepressants (p=0.04). Conclusion: Adjunctive antidepressants do not demonstrate clinically significant effects on cognition in schizophrenia patients, however, larger studies, preferably in euthymic schizophrenia patients and using full neurocognitive batteries, are needed to confirm this finding. (C) 2014 Elsevier B. V. All rights reserved

Cu2+-induced self-assembly and amyloid formation of a cyclic d,l-α-peptide: Structure and function

In a wide spectrum of neurodegenerative diseases, self-assembly of pathogenic proteins to cytotoxic intermediates is accelerated by the presence of metal ions such as Cu2+. Only low concentrations of these early transient oligomeric intermediates are present in a mixture of species during fibril formation, and hence information on the extent of structuring of these oligomers is still largely unknown. Here, we investigate dimers as the first intermediates in the Cu2+-driven aggregation of a cyclic D,L-alpha-peptide architecture. The unique structural and functional properties of this model system recapitulate the self-assembling properties of amyloidogenic proteins including beta-sheet conformation and cross-interaction with pathogenic amyloids. We show that a histidine-rich cyclic D,L-alpha-octapeptide binds Cu2+ with high affinity and selectivity to generate amyloid-like cross-beta-sheet structures. By taking advantage of backbone amide methylation to arrest the self-assembly at the dimeric stage, we obtain structural information and characterize the degree of local order for the dimer. We found that, while catalytic amounts of Cu2+ promote aggregation of the peptide to fibrillar structures, higher concentrations dose-dependently reduce fibrillization and lead to formation of spherical particles, showing self-assembly to different polymorphs. For the initial self-assembly step to the dimers, we found that Cu2+ is coordinated on average by two histidines, similar to self-assembled peptides, indicating that a similar binding interface is perpetuated during Cu2+-driven oligomerization. The dimer itself is found in heterogeneous conformations that undergo dynamic exchange, leading to the formation of different polymorphs at the initial stage of the aggregation process

Enhanced antiviral function of magnesium chloride-modified Heparin on a broad spectrum of viruses

Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium. To broadly explore this discovery, we tested the antiviral function of modified heparin against herpes simplex virus type 1 (HSV-1) and found that the replication of HSV-1 was even further decreased compared to aciclovir. Moreover, we investigated the antiviral effect against the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and measured a 55-fold decreased viral load in the supernatant of infected cells associated with a 38-fold decrease in virus growth. The advantage of our modified heparin is an increased antiviral effect compared to regular heparin