Chemogenomics knowledgebased polypharmacology analyses of drug abuse related G-protein coupled receptors and their ligands

Drug abuse (DA) and addiction is a complex illness, broadly viewed as a neurobiological impairment with genetic and environmental factors that influence its development and manifestation. Abused substances can disrupt the activity of neurons by interacting with many proteins, particularly G-protein coupled receptors (GPCRs). A few medicines that target the central nervous system (CNS) can also modulate DA related proteins, such as GPCRs, which can act in conjunction with the controlled psychoactive substance(s) and increase side effects. To fully explore the molecular interaction networks that underlie DA and to effectively modulate the GPCRs in these networks with small molecules for DA treatment, we built a drug-abuse domain specific chemogenomics knowledgebase (DA-KB) to centralize the reported chemogenomics research information related to DA and CNS disorders in an effort to benefit researchers across a broad range of disciplines. We then focus on the analysis of GPCRs as many of them are closely related with DA. Their distribution in human tissues was also analyzed for the study of side effects caused by abused drugs. We further implement our computational algorithms/tools to explore DA targets, DA mechanisms and pathways involved in polydrug addiction and to explore polypharmacological effects of the GPCR ligands. Finally, the polypharmacology effects of GPCRs-targeted medicines for DA treatment were investigated and such effects can be exploited for the development of drugs with polypharmacophore for DA intervention. The chemogenomics database and the analysis tools will help us better understand the mechanism of drugs abuse and facilitate to design new medications for system pharmacotherapy of DA. © 2014 Xie, Wang, Liu, Ouyang, Fang and Su

Shallow optically active structural defect in wurtzite GaN epilayers grown on stepped 4H-SiC substrates

Shallow optically active structural defect in wurtzite GaN epilayers grown on stepped 4H-SiC substrates was investigated. The GaN epilayers grown with plasma-assisted molecular-beam epitaxy were optically characterized by photoluminescence and excitation spectra. Results showed that the localized states which were induced by the structural defect located about 100 meV above the maximum valence band of GaN.published_or_final_versio

Association of tumor necrosis factor genetic polymorphism with chronic atrophic gastritis and gastric adenocarcinoma in Chinese Han population.

0.05). However, TNF-beta Ncol*1/2 and d2/d6 genotypes did not relate to age, gender, grade of differentiation and clinicopathologic stage in patients with gastric adenocarcinoma. The frequency of TNFa6b5c1 haplotype homozygote was significantly lower in patients with gastric adenocarcinoma than in healthy controls (1.79% vs 15.85%, P=0.006). CONCLUSION: TNFa10 allele may be a risk factor for chronic atrophic gastritis. TNF-beta Ncol*1/2 and d2/d6 genotypes are associated with the susceptibility to gastric adenocarcinoma, whereas TNFa6b5c1 haplotype homozygote may contribute to the resistance against gastric adenocarcinoma

Current transport property of n-GaN/n-6H-SiC heterojunction: Influence of interface states

Heterostructures of n-GaNn-6H-SiC grown by hydride vapor phase epitaxy (HVPE) and molecular-beam epitaxy (MBE) are characterized with the current-voltage (I-V), capacitance-voltage (C-V), and deep level transient spectroscopy (DLTS) techniques. Using different contact configurations, the I-V results reveal a rectifying barrier in the n-GaNn-6H-SiC heterostructures. When GaN is negatively biased, the current is exponentially proportional to the applied voltage with the built-in barrier being 0.4-1.1 eV for the HVPE samples and 0.5 eV for the MBE sample. DLTS measurements reveal intense band-like deep level states in the interfacial region of the heterostructure, and the Fermi-level pinning by these deep level defects is invoked to account for the interfacial rectifying barrier of the heterostructures. © 2005 American Institute of Physics.published_or_final_versio

Direct observation of a Ga adlayer on a GaN(0001) surface by LEED Patterson inversion

A low-energy electron diffraction (LEED) Patterson function (PF) with multiple incident angles is used to obtain three-dimensional interatomic information of hexagonal GaN(0001) grown on a 6H-SiC(0001)-√3 x √3 surface. A Ga-Ga atomic pair between the Ga adlayer and the terminating Ga layer is observed in the LEED PF. This provides direct experimental evidence to support the structural model proposed by first-principles calculations. The LEED PF also shows that the GaN film has a hexagonal structure and the surface has single-bilayer steps.published_or_final_versio

Modeling skin sensitization potential of mechanistically hard-to-be-classified aniline and phenol compounds with quantum mechanistic properties

Background: Advanced structure-activity relationship (SAR) modeling can be used as an alternative tool for identification of skin sensitizers and in improvement of the medical diagnosis and more effective practical measures to reduce the causative chemical exposures. It can also circumvent ethical concern of using animals in toxicological tests, and reduce time and cost. Compounds with aniline or phenol moieties represent two large classes of frequently skin sensitizing chemicals but exhibiting very variable, and difficult to predict, potency. The mechanisms of action are not well-understood. Methods: A group of mechanistically hard-to-be-classified aniline and phenol chemicals were collected. An in silico model was established by statistical analysis of quantum descriptors for the determination of the relationship between their chemical structures and skin sensitization potential. The sensitization mechanisms were investigated based on the features of the established model. Then the model was utilized to analyze a subset of FDA approved drugs containing aniline and/or phenol groups for prediction of their skin sensitization potential. Results and discussion: A linear discriminant model using the energy of the highest occupied molecular orbital (εHOMO) as the descriptor yielded high prediction accuracy. The contribution of εHOMO as a major determinant may suggest that autoxidation or free radical binding could be involved. The model was further applied to predict allergic potential of a subset of FDA approved drugs containing aniline and/or phenol moiety. The predictions imply that similar mechanisms (autoxidation or free radical binding) may also play a role in the skin sensitization caused by these drugs. Conclusions: An accurate and simple quantum mechanistic model has been developed to predict the skin sensitization potential of mechanistically hard-to-be-classified aniline and phenol chemicals. The model could be useful for the skin sensitization potential predictions of a subset of FDA approved drugs

Preparation and analysis of a new bioorganic metallic material

Biofouling on metal surfaces is one of the main reasons for increased ship drag. Many methods have already been used to reduce or remove it with moderate success. In this study, a synthetic peptide has been utilized to react with 304 stainless steel aiming to generate a bioorganic stainless steel using a facile technique. After the reaction, white matter was found on the surface of the treated stainless steel via SEM, whilst the nontreated stainless steel had none. Elemental analysis confirmed that excessive N existed on the surface of the treated samples using an integrated SEM-EDS instrument, implying the presence of peptides binding on the surface of the bioorganic stainless steel. The FTIR spectra showed amide A and II peaks on the surface of the bioorganic stainless steel suggesting that either the peptides grafted onto the steel surface or the polypeptide composition accumulated on the steel samples. XPS analysis of the treated steel demonstrated that there was nitrogen bonding on the surface and it was a chemical bond via a previously unreported chemical interaction. The treated steel has a markedly increased contact angle (water contact angle of 65.7 ± 4.7° for nontreated steel in comparison to treated, 96.4 ± 2.1°), which supported the observation of the wettability change of the surface, i.e. the decrease of the surface energy value after peptide treatment. The changes of the surface parameters (such as, Sa, Sq, Ssk and Sku) of the treated steel by surface analysis were observed

In situ revelation of a zinc-blende InN wetting layer during Stranski-Krastanov growth on GaN(0001) by molecular-beam epitaxy

Indium nitride (InN) exists in two different structural phases, the equilibrium wurtzite (w) and the metastable zinc-blende (zb) phases. It is of scientific interest and practical relevance to examine the crystal structure of the epifilms during growth. In this paper, we use Patterson function inversion of low-energy electron diffraction I-V curves to reveal the preferential formation of zinc-blende InN wetting layer during the Stranski-Krastanov growth on GaN(0001). For three-dimensional islands nucleated afterwards on top of the wetting layer and for thick InN films, the equilibrium wurtzite structure is observed instead. This in situ revelation of the InN lattice structure is confirmed by ex situ transmission electron microscopy studies. Finally, the formation of zb-InN layer on w-GaN is explained in terms of the strain in the system. © 2005 The American Physical Society.published_or_final_versio

Molecular-beam Epitaxy of Monolayer MoSe2: Growth Characteristics and Domain Boundary Formation

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