PDB-Ligand: a ligand database based on PDB for the automated and customized classification of ligand-binding structures

PDB-Ligand (http://www.idrtech.com/PDB-Ligand/) is a three-dimensional structure database of small molecular ligands that are bound to larger biomolecules deposited in the Protein Data Bank (PDB). It is also a database tool that allows one to browse, classify, superimpose and visualize these structures. As of May 2004, there are about 4870 types of small molecular ligands, experimentally determined as a complex with protein or DNA in the PDB. The proteins that a given ligand binds are often homologous and present the same binding structure to the ligand. However, there are also many instances wherein a given ligand binds to two or more unrelated proteins, or to the same or homologous protein in different binding environments. PDB-Ligand serves as an interactive structural analysis and clustering tool for all the ligand-binding structures in the PDB. PDB-Ligand also provides an easier way to obtain a number of different structure alignments of many related ligand-binding structures based on a simple and flexible ligand clustering method. PDB-Ligand will be a good resource for both a better interpretation of ligand-binding structures and the development of better scoring functions to be used in many drug discovery applications

Role of G{alpha}12 and G{alpha}13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

G{alpha}12 and G{alpha}13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by G{alpha}12 and G{alpha}13. A deficiency of G{alpha}12, but not of G{alpha}13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, G{alpha}12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by G{alpha}12 gene knockout. G{alpha}12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did G{alpha}13 deficiency. The absence of G{alpha}12, but not of G{alpha}13, increased protein kinase C {delta} (PKC {delta}) activation and the PKC {delta}-mediated serine phosphorylation of Nrf2. G{alpha}13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by G{alpha}12 deficiency, suggesting that relief from G{alpha}12 repression leads to the G{alpha}13-mediated activation of Nrf2. Constitutive activation of G{alpha}13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC {delta} activation, corroborating positive regulation by G{alpha}13. In summary, G{alpha}12 and G{alpha}13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas G{alpha}13 regulates Rho-PKC {delta}-mediated Nrf2 phosphorylation, which is negatively balanced by G{alpha}12

Staphylococcal enterotoxin sensitization in a community-based population : a potential role in adult-onset asthma

Background: Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations. Objective: We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations. Methods: The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age=60.2years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP. Results: Staphylococcal enterotoxin sensitization (0.35kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (61years), and inhalant allergen sensitization. Current asthma was mostly adult onset (18years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level. Conclusions and Clinical Relevance: Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis

Soil-Pile Interaction Analysis using FE-BE Coupling in Frequency Domain

In this study, a numerical method for soil-pile interaction problems in multi-layered half-plane is developed in frequency domain using FE-BE coupling technique. The soil-pile interaction system is divided into two parts, so-called near field and far field. In the near field, beam elements are used for modeling pile and plane-strain finite elements for surrounding soil media. Also, a superstructure is considered as a lumped mass on a pile. In the far field, layered soil media is modeled by boundary element formulation using the dynamic fundamental solution. Then, these two fields are assembled using FE-BE coupling technique. This coupled numerical method automatically satisfies the radiation conditions because the far field boundary element formulation can handle the radiation conditions in a half plane. Additionally, the difference of relative displacement at the interface between soil and pile is considered by applying interface spring elements. In order to verify the proposed method for soil-pile interaction system, the dynamic responses of a pile in a multi-layered half-plane are performed and the numerical results are compared with the measured values from experiments. It is shown that the developed method can be an efficient numerical tool to solve the dynamic response of a pile buried in a multi-layered half plane

Quantitative agreement of Dzyaloshinskii-Moriya interactions for domain-wall motion and spin-wave propagation

The magnetic exchange interaction is the one of the key factors governing the basic characteristics of magnetic systems. Unlike the symmetric nature of the Heisenberg exchange interaction, the interfacial Dzyaloshinskii-Moriya interaction (DMI) generates an antisymmetric exchange interaction which offers challenging opportunities in spintronics with intriguing antisymmetric phenomena. The role of the DMI, however, is still being debated, largely because distinct strengths of DMI have been measured for different magnetic objects, particularly chiral magnetic domain walls (DWs) and non-reciprocal spin waves (SWs). In this paper, we show that, after careful data analysis, both the DWs and SWs experience the same strength of DMI. This was confirmed by spin-torque efficiency measurement for the DWs, and Brillouin light scattering measurement for the SWs. This observation, therefore, indicates the unique role of the DMI on the magnetic DW and SW dynamics and also guarantees the compatibility of several DMI-measurement schemes recently proposed.Comment: 24 pages, 5 figure

Highly sensitive colorimetric detection of allergies based on an immunoassay using peroxidase-mimicking nanozymes

Nanomaterials that exhibit enzyme-like characteristics, which are called nanozymes, have recently attracted significant attention due to their potential to overcome the intrinsic limitations of natural enzymes, such as low stability and relatively high cost for preparation and purification. In this study, we report a highly efficient colorimetric allergy detection system based on an immunoassay utilizing the peroxidase- mimicking activity of hierarchically structured platinum nanoparticles (H-Pt NPs). The H-Pt NPs had a diameter of 30 nm, and were synthesized by a seed-mediated growth method, which led to a significant amount of peroxidase-like activity. This activity mainly occurs because of the high catalytic power of the Pt element, and the fact that the H-Pt NPs have a large surface area available for catalytic events. The H-Pt NPs were conjugated to an antibody for the detection of immunoglobulin E (IgE) in the analytes; IgE is a representative marker for the diagnosis of allergies. They were then successfully integrated into a conventionally used allergy diagnostic test, the ImmunoCAP diagnostic test, as a replacement for natural signaling enzymes. Using this strategy, total and specific IgE levels were detected within 5 min at room temperature, with high specificity and sensitivity. The practical utility of the immunoassay was also successfully verified by correctly determining the levels of both total and specific IgE in real human serum samples with high precision and reproducibility. The present H-Pt NP-based immunoassay system would serve as a platform for rapid, robust, and convenient analysis of IgE, and can be extended to the construction of diagnostic systems for a variety of clinically important target molecules.11Ysciescopu