Revisit of the Cardiac Inward Rectifier Potassium Current IK1

Inward rectifier potassium currents are present in different types of cells. In the heart, the inward rectifier potassium current IK1 plays a crucial role in maintaining cardiac resting membrane potential and excitability. It is generally believed that the strong inward rectification of cardiac IK1 channels makes it conduct substantial current near the resting potential but carry little or no current at depolarized potentials. However, recent studies in native cardiac myocytes and HEK 293 cell line stably expressing human Kir2.1 gene have demonstrated that a significant transient outward current carried by IK1 channels is activated by the upstroke of action potential. This review will revisit cardiac IK1 channels, especially the previously-ignored transient outward component of IK1 carried by Kir2.1 channels.published_or_final_versio

A study of various oxide/silicon interfaces by Ar + backsurface bombardment

A low-energy (550 eV) argon beam is used to bombard the backsurfaces of 6 kinds of metal–oxide–semiconductor capacitors, and the resulting effects on their interface characteristics are then investigated. The gate oxide of these capacitors includes thermal oxide, trichloroethyene (TCE) oxide, NH3-nitrided oxide, reoxidized-nitrided oxide, rapid-thermal-nitrided oxide, and N2O-nitrided oxide. Measurements show that for bombardment times up to 45 min the interface-state density of all the devices, in general, decreases with increasing bombardment time/dose, and the midgap energy at the silicon surface tends to rise. Moreover, the bombardment is more effective in reducing acceptor-type than donor-type interface states. On the other hand, the change of fixed-charge density is more complex. For TCE, N2O-nitrided and reoxidized-nitrided oxides, fixed-charge density decreases initially with increasing bombardment time, but then increases, while the trend is reversed for the other gate oxides. A model with stress compensation and weak bond breaking is suggested to explain the results. ©1999 American Institute of Physics.published_or_final_versio

Effects of chemical composition on humidity sensitivity of Al/BaTiO3/Si structure

Argon-ion-beam sputtering technique has been applied to deposit barium titanate (BaTiO3) films on silicon wafers at room temperature under vacuum, and then Al/BaTiO3/Si structures were fabricated. Results show that the current and capacitance of these devices are sensitive to the change of relative humidity at room temperature, and saturation absorption (response) time as well as humidity sensitivity of the devices depend on the chemical composition of the BaTiO3 films. For higher annealing temperature and longer annealing time, the oxygen composition increases while fixed charge density decreases. These changes result in lower humidity sensitivity and longer response time.© 1995 American Institute of Physics.published_or_final_versio

Influence of backsurface argon bombardment on SiO2-Si interface characteristics

A low-energy (550 eV) argon-ion beam was used to directly bombard the backsurface of polysilicon-gate metal-oxide-semiconductor (MOS) capacitors after the completion of all conventional processing steps. The interface characteristics of the MOS capacitors were investigated. The results show that, as the bombardment dose increases, the active dopant concentration near the oxide-semiconductor interface gets higher; maximum midgap energy increases; and interface-state density becomes lower. This simple technique is compatible with existing integrated-circuit processing, and can easily improve the interface characteristics, and therefore the electrical characteristics of MOS devices. © 1996 American Institute of Physics.published_or_final_versio

ChIP-Array: Combinatory analysis of ChIP-seq/chip and microarray gene expression data to discover direct/indirect targets of a transcription factor

Chromatin immunoprecipitation (ChIP) coupled with high-throughput techniques (ChIP-X), such as next generation sequencing (ChIP-Seq) and microarray (ChIP-chip), has been successfully used to map active transcription factor binding sites (TFBS) of a transcription factor (TF). The targeted genes can be activated or suppressed by the TF, or are unresponsive to the TF. Microarray technology has been used to measure the actual expression changes of thousands of genes under the perturbation of a TF, but is unable to determine if the affected genes are direct or indirect targets of the TF. Furthermore, both ChIP-X and microarray methods produce a large number of false positives. Combining microarray expression profiling and ChIP-X data allows more effective TFBS analysis for studying the function of a TF. However, current web servers only provide tools to analyze either ChIP-X or expression data, but not both. Here, we present ChIP-Array, a web server that integrates ChIP-X and expression data from human, mouse, yeast, fruit fly and Arabidopsis. This server will assist biologists to detect direct and indirect target genes regulated by a TF of interest and to aid in the functional characterization of the TF. ChIP-Array is available at http://jjwanglab.hku.hk/ChIP-Array, with free access to academic users. © 2011 The Author(s).published_or_final_versio

Overexpression of ubiquitin specific peptidase 14 predicts unfavorable prognosis in esophageal squamous cell carcinoma

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Regulation of human cardiac KCNQ1/KCNE1 channel by epidermal growth factor receptor kinase

The aim of the present study was to investigate whether/how the recombinant human cardiac I Ks could be regulated by epidermal growth factor receptor kinase in HEK 293 cells stably expressing hKCNQ1/hKCNE1 genes using the approaches of perforated patch clamp technique, immunoprecipitation and Western blot analysis. It was found that the broad spectrum isoflavone tyrosine kinase inhibitor genistein and the selective epidermal growth factor receptor kinase inhibitor tyrphostin AG556 suppressed the recombinant I Ks, and their inhibition was countered by the protein tyrosine phosphatase inhibitor orthovanadate. The Src-family kinase inhibitor PP2 reduced the current, but the effect was not antagonized by orthovanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hKCNQ1 protein was decreased by genistein or AG556, but not by PP2. These results provide the novel information that epidermal growth factor receptor kinase, but not Src-family kinases, regulates the recombinant cardiac I Ks stably expressed in HEK 293 cells via phosphorylating KCNQ1 protein of the channel. © 2009 Elsevier B.V. All rights reserved.postprin

Exploring the genome-wide roles of transcription factors and their complexes in chromosome interaction

Session - Bioinformatics and Genomic TechnologyThe tight regulation of genes in different cells is governed by temporal and spatial biological signals. It is very important to pinpoint the pattern of transcription factors (TFs) and their complexes in looping interactions and to detect TF complexes as well as the underlying cis-regulatory modules (CRMs) in different human cell types. Existing studies on analysis of TFs and their complexes were only performed at one dimension and not at genome-wide scale. Recently, the unbiased chromosome conformation capture, Hi-C, can detect the genome-wide chromatin interactions, but has restrictions on its resolution due to the variable cell-to-cell chromosome structures and inadequate sequencing depth. In this study, we provide a comprehensive analysis on TFs regulatory pattern within chromosome looping by combining Hi-C and ENCODE ChIP-Seq data from three human cell types (GM12878, H1-hESC and K562). We first devised a strategy to map ChIP-Seq peaks of each TF to a normalized 10kb Hi-C contact matrix and construct an interaction matrix for each participant TF. We observed tight correlation for TFs participant activities in high resolution chromosome looping between biological replicates, which indicate the TF activities is more stable than local DNA interactions. To check the enrichment of different chromatin marks and genomic features in the interaction region of each participant TF, we performed enrichment test on ...published_or_final_versio

Human ether-à-go-go gene potassium channels are regulated by EGFR tyrosine kinase

Human ether á-go-go gene potassium channels (hEAG1 or Kv10.1) are expressed in brain and various human cancers and play a role in neuronal excitement and tumor progression. However, the functional regulation of hEAG channels by signal transduction is not fully understood. The present study was therefore designed to investigate whether hEAG1 channels are regulated by protein tyrosine kinases (PTKs) in HEK 293 cells stably expressing hEAG1 gene using whole-cell patch voltage-clamp, immunoprecipitation, Western blot, and mutagenesis approaches. We found that the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556 (10μM), but not the platelet growth factor receptor (PDGFR) kinase inhibitor AG1295 (10μM) or the Src-family inhibitor PP2 (10μM), can inhibit hEAG1 current, and the inhibitory effect can be reversed by the protein tyrosine phosphatase (PTP) inhibitor orthovanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hEAG1 channels was reduced by AG556, and the reduction was significantly countered by orthovanadate. The hEAG1 mutants Y90A, Y344A and Y485A, but not Y376A and Y479A, exhibited reduced response to AG556. Interestingly, the inhibition effect of AG556 was lost in triple mutant hEAG1 channels at Y90, Y344, and Y485 with alanine. These results demonstrate for the first time that hEAG1 channel activity is regulated by EGFR kinase at the tyrosine residues Tyr 90, Try 344, and Try 485. This effect is likely involved in regulating neuronal activity and/or tumor growth. © 2011 Elsevier B.V.postprin

PLLA-PEG-TCH-labeled bioactive molecule nanofibers for tissue engineering

By mimicking the native extracellular matrix, electrospun nanofibrous scaffolds (ENSs) can provide both chemical and physical cues to modulate cell adherence and differentiation and to promote tissue regeneration while retaining bioresorbable and biocompatible properties. In this study, ENSs were developed to deliver multiple biomolecules by loading them into the core-sheath structure and/or by conjugating them to the nanofiber surfaces. In this work, poly(L-lactide)-poly(ethylene glycol)-NH2 and poly(L-lactide) were emulsion electrospun into nanofibers with a core-sheath structure. A model drug, tetracycline hydrochloride, was loaded within the nanofibers. Amino and carboxyl reactive groups were then activated on the fiber surfaces using saturated water vapor exposure and base hydrolysis, respectively. These reactive groups allowed the surface of the ENS to be functionalized with two other bioactive molecules, fluorescein isothiocyanate- and rhodamine-labeled bovine serum albumins, which were used as model proteins. The ENSs were shown to retain their antimicrobial capacity after two functionalization reactions, indicating that multifunctional nanofibers can potentially be developed into functional wound dressings or periodontal membranes or used in more complicated tissue systems where multiple growth factors and anti-infection precautions are critical for the successful implantation and regeneration of tissues