Detailed analysis of distorted retinal and its interaction with surrounding residues in the K intermediate of bacteriorhodopsin

The K intermediate of proton pumping bacteriorhodopsin is the first intermediate generated after isomerization of retinal to the 13-cis form. Although various structures have been reported for the K intermediate until now, these differ from each other, especially in terms of the conformation of the retinal chromophore and its interaction with surrounding residues. We report here an accurate X-ray crystallographic analysis of the K structure. The polyene chain of 13-cis retinal is observed to be S-shaped. The side chain of Lys216, which is covalently bound to retinal via the Schiff-base linkage, interacts with residues, Asp85 and Thr89. In addition, the Nζ-H of the protonated Schiff-base linkage interacts with a residue, Asp212 and a water molecule, W402. Based on quantum chemical calculations for this K structure, we examine the stabilizing factors of distorted conformation of retinal and propose a relaxation manner to the next L intermediate

Control of Dual-Output DC/DC Converters Using Duty Cycle and Frequency

As part of the integration process of the auxiliary power systems of electric vehicles, plug-in hybrid vehicles and fuel cell vehicles, this study proposes a method to control two different voltage types using two control factors of the rectangular alternating waveforms contained in DC/DC converters, namely the duty cycle and frequency. A prototype circuit consisting of an H-bridge inverter, a transformer, two series resonant filters and two diode bridge circuits was constructed. The H-bridge inverter was connected to the primary side of the transformer and the diode bridge rectifier circuit was connected to the secondary side in parallel. Series resonant filters were inserted between one of the diode bridge circuits and the transformer. Thereafter, the proposed control method was applied to the transformer voltage of the prototype circuit. Although the circuit operation became complex owing to the circulating current flowing between the ground (GND) of the two output circuits, it exhibited ideal static and dynamic characteristics, thereby confirming the possibility of controlling two voltages with the duty cycle and frequency control factors. The results of the efficiency evaluation and loss analysis demonstrated a minimum efficiency of 68.3% and a maximum efficiency of 88.9%. As the output power of the circuit containing the resonant filters increased, the current peak value increased and the circuit became less efficient. Document type: Articl

Normal Values of Diffusion Tensor Magnetic Resonance Imaging Parameters in the Cervical Spinal Cord

Study DesignProspective study.PurposeWe evaluated the usefulness of diffusion tensor imaging (DTI) in diagnosing patients with cervical myelopathy by determining the accuracy of normal DTI parameter values.Overview of LiteratureDTI can visualize white matter tracts in vivo and quantify anisotropy. DTI is known to be more sensitive than conventional magnetic resonance imaging (MRI) in detecting subtle pathological changes of the spinal cord.MethodsA total of 31 normal subjects (13 men and 18 women; age, 23-87 years; mean age, 46.0 years) were included in this study. The patients had no symptoms of myelopathy or radiculopathy. A Philips Achieva 3-Tesla MRI with SE-type Single Shot EPI was used to obtain diffusion tensor images. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured as DTI parameters on axial sections of several cervical levels. Subjects were divided into two groups: >40 years (n=16) and ≤40 years (n=15). A paired t-test was used to compare significant differences between the groups. ADC and FA values were most stable on axial sections.ResultsFor all subjects, mean ADC and FA values were 1.06±0.09×10-3 mm2/sec and 0.68±0.05, respectively. ADC was significantly higher in subjects >40 years of age than in those ≤40 years. There was no significant difference in FA values between the two groups. The mean ADC value was significantly higher in normal subjects >40 years of age than in those ≤40 years.ConclusionsIt is important to consider age when evaluating cervical myelopathy by DTI

Honeycomb-Layered Oxides With Silver Atom Bilayers and Emergence of Non-Abelian SU(2) Interactions

Honeycomb-layered oxides with monovalent or divalent, monolayered cationic lattices generally exhibit myriad crystalline features encompassing rich electrochemistry, geometries, and disorders, which particularly places them as attractive material candidates for next-generation energy storage applications. Herein, global honeycomb-layered oxide compositions, Ag2M2TeO6 ((Formula presented.).) exhibiting (Formula presented.) atom bilayers with sub-valent states within Ag-rich crystalline domains of Ag6M2TeO6 and (Formula presented.) -deficient domains of (Formula presented.) ((Formula presented.)). The (Formula presented.) -rich material characterized by aberration-corrected transmission electron microscopy reveals local atomic structural disorders characterized by aperiodic stacking and incoherency in the bilayer arrangement of (Formula presented.) atoms. Meanwhile, the global material not only displays high ionic conductivity but also manifests oxygen-hole electrochemistry during silver-ion extraction. Within the (Formula presented.) -rich domains, the bilayered structure, argentophilic interactions therein and the expected (Formula presented.) sub-valent states ((Formula presented.), etc.) are theoretically understood via spontaneous symmetry breaking of SU(2) 7 U(1) gauge symmetry interactions amongst 3 degenerate mass-less chiral fermion states, justified by electron occupancy of silver (Formula presented.) and 5s orbitals on a bifurcated honeycomb lattice. This implies that bilayered frameworks have research applications that go beyond the confines of energy storage

Consolidating metabolite identifiers to enable contextual and multi-platform metabolomics data analysis

<p>Abstract</p> <p>Background</p> <p>Analysis of data from high-throughput experiments depends on the availability of well-structured data that describe the assayed biomolecules. Procedures for obtaining and organizing such meta-data on genes, transcripts and proteins have been streamlined in many data analysis packages, but are still lacking for metabolites. Chemical identifiers are notoriously incoherent, encompassing a wide range of different referencing schemes with varying scope and coverage. Online chemical databases use multiple types of identifiers in parallel but lack a common primary key for reliable database consolidation. Connecting identifiers of analytes found in experimental data with the identifiers of their parent metabolites in public databases can therefore be very laborious.</p> <p>Results</p> <p>Here we present a strategy and a software tool for integrating metabolite identifiers from local reference libraries and public databases that do not depend on a single common primary identifier. The program constructs groups of interconnected identifiers of analytes and metabolites to obtain a local metabolite-centric SQLite database. The created database can be used to map in-house identifiers and synonyms to external resources such as the KEGG database. New identifiers can be imported and directly integrated with existing data. Queries can be performed in a flexible way, both from the command line and from the statistical programming environment R, to obtain data set tailored identifier mappings.</p> <p>Conclusions</p> <p>Efficient cross-referencing of metabolite identifiers is a key technology for metabolomics data analysis. We provide a practical and flexible solution to this task and an open-source program, the metabolite masking tool (MetMask), available at <url>http://metmask.sourceforge.net</url>, that implements our ideas.</p

Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells.

Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells

Assessment of Metabolome Annotation Quality: A Method for Evaluating the False Discovery Rate of Elemental Composition Searches

BACKGROUND: In metabolomics researches using mass spectrometry (MS), systematic searching of high-resolution mass data against compound databases is often the first step of metabolite annotation to determine elemental compositions possessing similar theoretical mass numbers. However, incorrect hits derived from errors in mass analyses will be included in the results of elemental composition searches. To assess the quality of peak annotation information, a novel methodology for false discovery rates (FDR) evaluation is presented in this study. Based on the FDR analyses, several aspects of an elemental composition search, including setting a threshold, estimating FDR, and the types of elemental composition databases most reliable for searching are discussed. METHODOLOGY/PRINCIPAL FINDINGS: The FDR can be determined from one measured value (i.e., the hit rate for search queries) and four parameters determined by Monte Carlo simulation. The results indicate that relatively high FDR values (30-50%) were obtained when searching time-of-flight (TOF)/MS data using the KNApSAcK and KEGG databases. In addition, searches against large all-in-one databases (e.g., PubChem) always produced unacceptable results (FDR >70%). The estimated FDRs suggest that the quality of search results can be improved not only by performing more accurate mass analysis but also by modifying the properties of the compound database. A theoretical analysis indicates that FDR could be improved by using compound database with smaller but higher completeness entries. CONCLUSIONS/SIGNIFICANCE: High accuracy mass analysis, such as Fourier transform (FT)-MS, is needed for reliable annotation (FDR <10%). In addition, a small, customized compound database is preferable for high-quality annotation of metabolome data