Backbone and side-chain 1H, 13C and 15N assignments of the ubiquitin-associated domain of human X-linked inhibitor of apoptosis protein

X-linked inhibitor of apoptosis protein (XIAP), a leading member of the family of inhibitor of apoptosis (IAP) proteins, is considered as the most potent and versatile inhibitor of caspases and apoptosis. It has been reported that XIAP is frequently overexpressed in cancer and its expression level is implicated in contributing to tumorigenesis, disease progression, chemoresistance and poor patient-survival. Therefore, XIAP is one of the leading targets in drug development for cancer therapy. Recently, based on bioinformatics study, a previously unrecognized but evolutionarily conserved ubiquitin-associated (UBA) domain in IAPs was identified. The UBA domain is found to be essential for the oncogenic potential of IAP, to maintain endothelial cell survival and to protect cells from TNF-α-induced apoptosis. Moreover, the UBA domain is required for XIAP to activate NF-κB. In the present study, we report the near complete resonance assignments of the UBA domain-containing region of human XIAP protein. Secondary structure prediction based on chemical shift index (CSI) analysis reveals that the protein is predominately α-helical, which is consistent with the structures of known UBA proteins

Interaction between Hydrogenase Maturation Factors HypA and HypB Is Required for [NiFe]-Hydrogenase Maturation

The active site of [NiFe]-hydrogenase contains nickel and iron coordinated by cysteine residues, cyanide and carbon monoxide. Metal chaperone proteins HypA and HypB are required for the nickel insertion step of [NiFe]-hydrogenase maturation. How HypA and HypB work together to deliver nickel to the catalytic core remains elusive. Here we demonstrated that HypA and HypB from Archaeoglobus fulgidus form 1∶1 heterodimer in solution and HypA does not interact with HypB dimer preloaded with GMPPNP and Ni. Based on the crystal structure of A. fulgidus HypB, mutants were designed to map the HypA binding site on HypB. Our results showed that two conserved residues, Tyr-4 and Leu-6, of A. fulgidus HypB are required for the interaction with HypA. Consistent with this observation, we demonstrated that the corresponding residues, Leu-78 and Val-80, located at the N-terminus of the GTPase domain of Escherichia coli HypB were required for HypA/HypB interaction. We further showed that L78A and V80A mutants of HypB failed to reactivate hydrogenase in an E. coli ΔhypB strain. Our results suggest that the formation of the HypA/HypB complex is essential to the maturation process of hydrogenase. The HypA binding site is in proximity to the metal binding site of HypB, suggesting that the HypA/HypB interaction may facilitate nickel transfer between the two proteins

Structural Basis for GTP-Dependent Dimerization of Hydrogenase Maturation Factor HypB

Maturation of [NiFe]-hydrogenase requires the insertion of iron, cyanide and carbon monoxide, followed by nickel, to the catalytic core of the enzyme. Hydrogenase maturation factor HypB is a metal-binding GTPase that is essential for the nickel delivery to the hydrogenase. Here we report the crystal structure of Archeoglobus fulgidus HypB (AfHypB) in apo-form. We showed that AfHypB recognizes guanine nucleotide using Asp-194 on the G5 loop despite having a non-canonical NKxA G4-motif. Structural comparison with the GTPγS-bound Methanocaldococcus jannaschii HypB identifies conformational changes in the switch I region, which bring an invariant Asp-72 to form an intermolecular salt-bridge with another invariant residue Lys-148 upon GTP binding. Substitution of K148A abolished GTP-dependent dimerization of AfHypB, but had no significant effect on the guanine nucleotide binding and on the intrinsic GTPase activity. In vivo complementation study in Escherichia coli showed that the invariant lysine residue is required for in vivo maturation of hydrogenase. Taken together, our results suggest that GTP-dependent dimerization of HypB is essential for hydrogenase maturation. It is likely that a nickel ion is loaded to an extra metal binding site at the dimeric interface of GTP-bound HypB and transferred to the hydrogenase upon GTP hydrolysis

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions

Collapse risk and residual drift performance of steel buildings using post-tensioned MRFs and viscous dampers in near-fault regions

The potential of post-tensioned self-centering moment-resisting frames (SC-MRFs) and viscous dampers to reduce the collapse risk and improve the residual drift performance of steel buildings in near-fault regions is evaluated. For this purpose, a prototype steel building is designed using different seismic-resistant frames, i.e.: moment-resisting frames (MRFs); MRFs with viscous dampers; SC-MRFs; and SC-MRFs with viscous dampers. The frames are modeled in OpenSees where material and geometrical nonlinearities are taken into account as well as stiffness and strength deterioration. A database of 91 near-fault, pulse-like ground motions with varying pulse periods is used to conduct incremental dynamic analysis (IDA), in which each ground motion is scaled until collapse occurs. The probability of collapse and the probability of exceeding different residual story drift threshold values are calculated as a function of the ground motion intensity and the period of the velocity pulse. The results of IDA are then combined with probabilistic seismic hazard analysis models that account for near-fault directivity to assess and compare the collapse risk and the residual drift performance of the frames. The paper highlights the benefit of combining the post-tensioning and supplemental viscous damping technologies in the near-source. In particular, the SC-MRF with viscous dampers is found to achieve significant reductions in collapse risk and probability of exceedance of residual story drift threshold values compared to the MRF. © 2016 Springer Science+Business Media Dordrech

Experiences and insights from the collection of a novel multimedia EEG dataset

There is a growing interest in utilising novel signal sources such as EEG (Electroencephalography) in multimedia research. When using such signals, subtle limitations are often not readily apparent without significant domain expertise. Multimedia research outputs incorporating EEG signals can fail to be replicated when only minor modifications have been made to an experiment or seemingly unimportant (or unstated) details are changed. This can lead to overoptimistic or overpessimistic viewpoints on the potential real-world utility of these signals in multimedia research activities. This paper describes an EEG/MM dataset and presents a summary of distilled experiences and knowledge gained during the preparation (and utilisiation) of the dataset that supported a collaborative neural-image labelling benchmarking task. The goal of this task was to collaboratively identify machine learning approaches that would support the use of EEG signals in areas such as image labelling and multimedia modeling or retrieval. The contributions of this paper can be listed thus; a template experimental paradigm is proposed (along with datasets and a baseline system) upon which researchers can explore multimedia image labelling using a brain-computer interface, learnings regarding commonly encountered issues (and useful signals) when conducting research that utilises EEG in multimedia contexts are provided, and finally insights are shared on how an EEG dataset was used to support a collaborative neural-image labelling benchmarking task and the valuable experiences gained

Bananas as an Energy Source during Exercise: A Metabolomics Approach

This study compared the acute effect of ingesting bananas (BAN) versus a 6% carbohydrate drink (CHO) on 75-km cycling performance and post-exercise inflammation, oxidative stress, and innate immune function using traditional and metabolomics-based profiling. Trained cyclists (N = 14) completed two 75-km cycling time trials (randomized, crossover) while ingesting BAN or CHO (0.2 g/kg carbohydrate every 15 min). Pre-, post-, and 1-h-post-exercise blood samples were analyzed for glucose, granulocyte (GR) and monocyte (MO) phagocytosis (PHAG) and oxidative burst activity, nine cytokines, F2-isoprostanes, ferric reducing ability of plasma (FRAP), and metabolic profiles using gas chromatography-mass spectrometry. Blood glucose levels and performance did not differ between BAN and CHO (2.41±0.22, 2.36±0.19 h, P = 0.258). F2-isoprostanes, FRAP, IL-10, IL-2, IL-6, IL-8, TNFα, GR-PHAG, and MO-PHAG increased with exercise, with no trial differences except for higher levels during BAN for IL-10, IL-8, and FRAP (interaction effects, P = 0.003, 0.004, and 0.012). Of 103 metabolites detected, 56 had exercise time effects, and only one (dopamine) had a pattern of change that differed between BAN and CHO. Plots from the PLS-DA model visualized a distinct separation in global metabolic scores between time points [R2Y(cum) = 0.869, Q2(cum) = 0.766]. Of the top 15 metabolites, five were related to liver glutathione production, eight to carbohydrate, lipid, and amino acid metabolism, and two were tricarboxylic acid cycle intermediates. BAN and CHO ingestion during 75-km cycling resulted in similar performance, blood glucose, inflammation, oxidative stress, and innate immune levels. Aside from higher dopamine in BAN, shifts in metabolites following BAN and CHO 75-km cycling time trials indicated a similar pattern of heightened production of glutathione and utilization of fuel substrates in several pathways

Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype

INTRODUCTION: Esmirtazapine is evaluated as a novel drug for treatment of insomnia. PURPOSE: The present study was designed to assess residual effects of single and repeated doses of esmirtazapine 1.5 and 4.5 mg on actual driving in 32 healthy volunteers in a double-blind, placebo-controlled study. Treatment with single doses of zopiclone 7.5 mg was included as active control. METHODS: Treatments were administered in the evening. Driving performance was assessed in the morning, 11 h after drug intake, in a standardized on-the-road highway driving test. The primary study parameter was standard deviation of lateral position (SDLP), a measure of "weaving". All subjects were subjected to CYP2D6 phenotyping in order to distinguish poor metabolizers from extensive metabolizers of esmirtazapine. RESULTS: Overall, esmirtazapine 1.5 mg did not produce any clinically relevant change in SDLP after single and repeated dosing. Driving impairment, i.e., a rise in SDLP, did occur after a single-dose administration of esmirtazapine 4.5 mg but was resolved after repeated doses. Acute driving impairment was more pronounced after both doses of esmirtazapine in a select group of poor metabolizers (N = 7). A single-dose zopiclone 7.5 mg also increased SDLP as expected. CONCLUSION: It is concluded that single and repeated doses of 1.5 mg esmirtazapine are generally not associated with residual impairment. Single-dose administration of 4.5 mg esmirtazapine was associated with residual impairment that generally resolved after repeated administration. Exploratory analysis in a small group of poor CYP 2D6 metabolizers suggested that these subjects are more sensitive to the impairing effects of esmirtazapine on car driving

Advances and Prospect of Nanotechnology in Stem Cells

In recent years, stem cell nanotechnology has emerged as a new exciting field. Theoretical and experimental studies of interaction between nanomaterials or nanostructures and stem cells have made great advances. The importance of nanomaterials, nanostructures, and nanotechnology to the fundamental developments in stem cells-based therapies for injuries and degenerative diseases has been recognized. In particular, the effects of structure and properties of nanomaterials on the proliferation and differentiation of stem cells have become a new interdisciplinary frontier in regeneration medicine and material science. Here we review some of the main advances in this field over the past few years, explore the application prospects, and discuss the issues, approaches and challenges, with the aim of improving application of nanotechnology in the stem cells research and development