Complementary Array Research Articles

Insights Into the Mechanisms Involved in Magnesium-Dependent Inhibition of Primary Tumor Growth

We have previously shown that a low Magnesium (Mg)-containing diet reversibly inhibits the growth of primary tumors that develop after the injection of Lewis lung carcinoma (LLC) cells in mice. Here we investigate some of the mechanisms responsible for the Mg-dependent regulation of tumor development by studying cell cycle regulation, tumor angiogenesis, and gene expression under Mg deficiency. The inhibition of LLC tumor growth in Mg-deficient mice is due to a direct effect of low Mg on LLC cell proliferation and to an impairment of the angiogenic switch. We also observed an increase of nitric oxide synthesis and oxidative DNA damage. Complementary DNA arrays reveal that Mg deficiency modulates tumor expression of genes involved in the control of cell cycle, stress response, proteolysis, and adhesion. Our results suggest that Mg has multiple and complex roles in tumor development.

Synergistic effect between EGF and TGF-β1 in inducing oncogenic properties of intestinal epithelial cells

Transforming growth factor (TGF)-beta1 has a biphasic effect on rat intestinal epithelial (RIE) cells. By itself, TGF-beta1 functions as a tumor suppressor by inhibiting the growth, migration and invasion of RIE cells. We show in this study that in conjunction with epidermal growth factor (EGF), TGF-beta1 helped to augment migration, invasion and anchorage-independent growth (AIG) compared to that by EGF alone. EGF plus TGF-beta1 induced a dramatic morphological change characteristic of epithelial-mesenchymal transition (EMT). The mechanism for this enhanced effect of TGF-beta1 and EGF on oncogenic properties was explored by analysis of EGF- and TGF-beta1-mediated signaling pathways and complementary DNA arrays. TGF-beta1 augmented EGF-mediated signaling of mitogen-activated protein kinase (MAPK) and AKT by enhancing and prolonging the activation of the former and prolonging the activation of the latter. Inhibition of MAPK, but not phosphoinositide-3 kinase (PI3K), abolished TGF-beta1 plus EGF-induced EMT and downregulation of E-cadherin at mRNA and protein levels. By contrast, cell migration and invasion were sensitive to inhibition of either MAPK or PI3 kinase. TGF-beta1 plus EGF-induced AIG was significantly more resistant to inhibition of PI3K and MAPK compared to that induced by EGF alone. EGF and TGF-beta1 synergistically induced the expression of a series of proteases including matrix metalloproteinase (MMP) 1 (collagenase), MMP3, MMP9, MMP10, MMP14 and cathepsin. Among them, the expression of MMP1, MMP3, MMP9 and MMP10 was MAPK dependent. Inhibition of the MMPs or cathepsin significantly blocked EGF plus TGF-beta1-induced invasion, but had no effect on colony formation. Phospholipase C (PLC) and Cox2 induced by EGF plus TGF-beta1 also played a significant role in invasion, whereas PLC was also important for colony formation. Our study reveals specific signaling functions and induction of genes differentially required for enhanced effect of EGF- and TGF-beta1-induced oncogenic properties, and helps to explain the tumor-promoting effect of TGF-beta1 in human cancer with elevated expression or activation of TGF-beta1 and receptor protein tyrosine kinases.

Impact of hepatic vein deprivation on liver regeneration and function after major hepatectomy

In extended liver resections, the preservation of vascular and biliary structures of the entire remnant liver is of paramount importance. The impact of venous outflow impairment and its consequences for liver regeneration and function are still a matter of debate. Rats (n = 75) were subjected to a 90% partial hepatectomy (PH), to a 70% liver resection with narrowing of the hepatic outflow of an additional 20% parenchyma (70%+ PH) or to an anatomic 70% PH. Postoperatively hepatocyte proliferation (Ki-67), liver function and survival were assessed. Gene expression analysis for markers of regeneration was determined by in-house complementary (DNA) arrays and quantitative real-time polymerase chain reaction (RT-PCR). Ninety percent PH led to a greater regenerative response as shown Ki-67 compared to animals with a 70%+PH (p < 0.05). However, liver function was equally impaired in both groups. Rats with 70% PH showed a greater proliferation index with less hepatic injury and better liver function. While mortality was 0% in the group of 70% PH, rats with 90% PH and 70+PH had a reduced survival of 75% (p < 0.05) Venous outflow obstruction leads to an impairment of liver regeneration and liver function. In cases with critically small liver remnants, restoration of an adequate venous outflow may be mandatory.

Identification of Protein Disulfide Isomerase as a Cardiomyocyte Survival Factor in Ischemic Cardiomyopathy

The aim of the study was to analyze the molecular mechanisms activated during postinfarction remodeling in human hearts. The molecular mechanisms of initial response to ischemic insult in the heart and the pathways involved in compensation and remodeling are still largely unknown. Up-regulation or down-regulation of gene expression in the human viable peri-infarct (vs. remote) myocardial region was investigated by complementary deoxyribonucleic acid array technology and confirmed at a single-gene/protein level with reverse transcriptase polymerase chain reaction and immunohistochemistry. An in vitro model of cardiomyocyte hypoxia in HL1 cells was used to validate anti-apoptotic effects of the candidate gene/protein and to assess the associated downstream cascade. Finally, a mouse model of myocardial infarction was used to test the in vivo effects of exogenous transfection with the candidate gene/protein. Protein disulfide isomerase (PDI), a member of the unfolded protein response, is 3-fold up-regulated in the viable peri-infarct myocardial region, and in a postmortem model, its expression is significantly inversely correlated with apoptotic rate and with presence of heart failure (HF) and biventricular dilatation. Induced PDI expression in HL1 cells conferred protection from hypoxia-induced apoptosis. Adenoviral-mediated PDI gene transfer to the mouse heart resulted in 2.5-fold smaller infarct size, significantly reduced cardiomyocyte apoptosis in the peri-infarct region, and smaller left ventricular end-diastolic diameter versus mice treated with a transgene-null adenoviral vector. These results suggest that PDI promotes survival after ischemic damage and that zinc-superoxide dismutase is one of the PDI molecular targets. Pharmacological modulation of this pathway might prove useful for future prevention and treatment of HF.

Golay complementary array pairs

Constructions and nonexistence conditions for multi-dimensional Golay complementary array pairs are reviewed. A construction for a d-dimensional Golay array pair from a (d + 1)-dimensional Golay array pair is given. This is used to explain and expand previously known constructive and nonexistence results in the binary case.

Hydrogen-bonding patterns in pyrimethamine tetrafluoroborate

The title compound [systematic name: 2,4-diamino-5-(4-chloro­phen­yl)-6-ethyl­pyrimdinium tetra­fluoro­borate], C12H14ClN4+·BF4−, is isomorphous with pyrimethamine perchlorate. The pyrimethamine (PMN) mol­ecule is protonated at one of the pyrimidine N atoms. The protonated N atom and 2-amino group of the PMN cation inter­act with the tetra­fluoro­borate anion through a pair of N—H⋯F hydrogen bonds [graph set R22(8)]. The inversion-related PMN cations are linked through a pair of N—H⋯N hydrogen bonds. In addition to the base pairing, the F atoms bridge the 2-amino and 4-amino groups on either side of the paired bases, resulting in a complementary DADA array.

Tight Control of Matrix Metalloproteinase-1 Activity in Human Skin¶

Chronic ultraviolet irradiation leads to photoaging in human skin, which is associated with degradation of connective tissue. This is partly due to the fibroblast collagenase (matrix metalloproteinase 1 [MMP-1]). Using complementary DNA array technique we demonstrate that after UV irradiation, MMP-1, MMP-3 and the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) are time-dependently induced on the messenger RNA level in dermal fibroblasts in vitro and in vivo in human buttock skin. This increase in gene expression is paralleled by an increase of latent and active MMP-1 protein after low-dose UV-A exposure in vitro. In vivo the concentration of latent MMP-1 in suction blister fluids peaks 24 h after irradiation with 2 minimal erythema doses of solar simulated radiation. However, only a small proportion of MMP-1 in vitro (5.5 ± 1.5%) and in vivo is active, whereas the majority of MMP-1 remains in its inactive proform. Interestingly, in suction blister fluid the concentration and duration of TIMP-1 expression exceeds that of MMP-1. Taken together, these data indicate that MMP-1 activity is tightly regulated transcriptionally and posttranscriptionally. Furthermore, the pronounced individual differences in all targets investigated provide a possible explanation for the different susceptibility of individuals to UV exposure and, thus, to the clinical features of photodamage.

Measuring global gene expression in polyploidy; a cautionary note from allohexaploid wheat

The number of global gene expression studies has increased significantly in recent years. It is assumed that the different techniques employed report similar levels of gene expression for each sequence type. While this may be true for many species, polyploids containing homoeologous and paralogous gene copies represent a unique situation. In this paper, we describe the comparison of the Affymetrix GeneChip Wheat Genome Array, an in-house custom-spotted complementary DNA array and quantitative reverse transcription-polymerase chain reaction (PCR) for the study of gene expression in hexaploid wheat. Analysis of the data generated from each platform revealed little concordance and suggested that global comparisons are not possible. Potential causes of these inter-platform discrepancies were investigated and revealed to be due to the inability of the platforms to discriminate between different but related transcripts. Our results also showed that the traditionally used array validation technique, quantitative reverse transcription PCR, differs in its discriminatory ability, resulting in the poor confirmation rates seen in previous polyploid studies. These findings have implications for gene expression studies in polyploid organisms and highlight the need for homoeologous- and paralogous-specific arrays when investigating polyploid gene expression.

Induction of Cerebral Ischemic Tolerance by Erythromycin Preconditioning Reprograms the Transcriptional Response to Ischemia and Suppresses Inflammation

A single dose of the macrolide antibiotic erythromycin can induce tolerance against cerebral ischemia in vivo (pharmacologic preconditioning). This study identified potential mechanisms of tolerance induction by assessing effects of erythromycin preconditioning on the cerebral transcriptional response to transient global cerebral ischemia. Preconditioned and nonpreconditioned rats were exposed to 15 min of global cerebral ischemia, and changes in cerebral gene expression were identified by complementary DNA expression array and quantified by real-time reverse-transcription polymerase chain reaction. Ischemia caused a widespread up-regulation of transcription in nonpreconditioned brains in this model. Tolerance induction by erythromycin preconditioning reversed this pattern and caused a net down-regulation of a majority of genes, effectively reprogramming the brain's response pattern to ischemia. The most striking change in transcriptional response found in preconditioned animals was an almost complete suppression of the otherwise profound induction of proinflammatory genes by global ischemia. In contrast, the same treatment had little effect on the expression of apoptosis-inducing genes after ischemia. These findings present a new molecular correlate for the induction of ischemic tolerance achieved by erythromycin preconditioning and will further the understanding of this clinically important new regimen of preemptive neuroprotection.

Large‐scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis

Despite many research efforts in recent decades, the major pathogenetic mechanisms of osteoarthritis (OA), including gene alterations occurring during OA cartilage degeneration, are poorly understood, and there is no disease-modifying treatment approach. The present study was therefore initiated in order to identify differentially expressed disease-related genes and potential therapeutic targets. This investigation consisted of a large gene expression profiling study performed based on 78 normal and disease samples, using a custom-made complementary DNA array covering >4,000 genes. Many differentially expressed genes were identified, including the expected up-regulation of anabolic and catabolic matrix genes. In particular, the down-regulation of important oxidative defense genes, i.e., the genes for superoxide dismutases 2 and 3 and glutathione peroxidase 3, was prominent. This indicates that continuous oxidative stress to the cells and the matrix is one major underlying pathogenetic mechanism in OA. Also, genes that are involved in the phenotypic stability of cells, a feature that is greatly reduced in OA cartilage, appeared to be suppressed. Our findings provide a reference data set on gene alterations in OA cartilage and, importantly, indicate major mechanisms underlying central cell biologic alterations that occur during the OA disease process. These results identify molecular targets that can be further investigated in the search for therapeutic interventions.

Defect reduction and efficiency improvement of near-ultraviolet emitters via laterally overgrown GaN on a GaN/patterned sapphire template

An approach to improve the defect density and internal quantum efficiency of near-ultraviolet emitters was proposed using a combination of epitaxial lateral overgrowth (ELOG) and patterned sapphire substrate (PSS) techniques. Especially, a complementary dot array pattern corresponding to the underlying PSS was used for the ELOG-SiO2 mask design. Based on the transmission-electron-microscopy and etch-pit-density results, the ELOG∕SiO2∕GaN∕PSS structure can reduce the defect density to a level of 105cm−2. The internal quantum efficiency of the InGaN-based ELOG-PSS light-emitting diode (LED) sample showed three times in magnitude as compared with that of the conventional GaN/sapphire one. Under a 20mA injection current, the output powers of ELOG-PSS, PSS, and conventional LED samples were measured to be 3.3, 2.9, and 2.5mW, respectively. The enhanced output power could be due to a combination of the reduction in dislocation density (by ELOG) and improved light extraction efficiency (by PSS). Unlike the previ...

Hydrogen-bonding patterns in pyrimethaminium 3-chlorobenzoate

In the crystal structure of the title compound, 2,4-diamino-5-(4-chloro­phen­yl)-6-ethyl­pyrimidin-1-ium 3-chloro­benzoate, C12H14ClN4+·C7H4ClO2−, the cation inter­acts with the carboxyl­ate group of the anion through a pair of N—H⋯O hydrogen bonds, forming a cyclic hydrogen-bonded motif [graph-set notation R22(8)]. This motif self-assembles through a complementary DDAA array of quadruple hydrogen bonds. The pyrimethamine cations are paired about inversion centers through N—H⋯N hydrogen bonds involving a pyrimidine N atom and the 4-amino group of the pyrimethamine cations. Concurrent with hydrogen bonding are Cl⋯Cl and sandwich stacking inter­actions.

Quantum efficiency overestimation and deterministic cross talk resulting from interpixel capacitance

Pixels in both hybridized and monolithic complementary metal-oxide semiconductor CMOS detector arrays may couple capaci- tively to their neighboring pixels. This interpixel capacitance can signifi- cantly distort the characterization of conversion efficiency and modula- tion transfer function MTF in CMOS devices. These effects have been largely unaccounted for in measurements to date. In this work, the ef- fects of this coupling are investigated. Compensation methods for these errors are described and applied to silicon P-I-N array measurements. The measurement of Poisson noise, traditionally done by finding the mean square difference in a pair of images, needs to be modified to include the mean square correlation of differences with neighboring pixels. © 2006 Society of Photo-Optical Instrumentation Engineers.

DNA chip replication for a personalized DNA chip

We report the replication technology of DNA chip using by sequence specific localization of nucleic acids via hybridization and electric transfer of the nucleic acids onto a new substrate without losing their array information. The denatured DNA fragments are first spotted and UV-cross-linked on a nylon membrane. The membrane is then immersed and hybridized in a DNA mixture solution that contains all complementary sequences of the nucleic acids to be hybridized with the DNA fragments on the membrane. The hybridized DNA fragments are transferred to another membrane at the denatured condition. After separating two membranes, the transferred membrane contains a complementary array of DNA fragments. This method can be used for the replication of the same copy of DNA chip repeatedly and moreover could be applied for a personalized DNA chip fabrication, where specific information of each spot of DNA chip is originated from the genetic information of a personal sample.

Expression profiling in primates reveals a rapid evolution of human transcription factors

Although it has been hypothesized for thirty years that many human adaptations are likely to be due to changes in gene regulation, almost nothing is known about the modes of natural selection acting on regulation in primates. Here we identify a set of genes for which expression is evolving under natural selection. We use a new multi-species complementary DNA array to compare steady-state messenger RNA levels in liver tissues within and between humans, chimpanzees, orangutans and rhesus macaques. Using estimates from a linear mixed model, we identify a set of genes for which expression levels have remained constant across the entire phylogeny (approximately 70 million years), and are therefore likely to be under stabilizing selection. Among the top candidates are five genes with expression levels that have previously been shown to be altered in liver carcinoma. We also find a number of genes with similar expression levels among non-human primates but significantly elevated or reduced expression in the human lineage, features that point to the action of directional selection. Among the gene set with a human-specific increase in expression, there is an excess of transcription factors; the same is not true for genes with increased expression in chimpanzee.

WITHDRAWN: Collective optical behavior in complementary wire arrays with Au nanoparticles

The publisher regrets that this article is an accidental duplication of an article that has already been published in MEE Volume 77/3-4 (2004) 277–284 of original article, doi: 10.1016/j.mee.2004.11.016 . The duplicate article has therefore been withdrawn.

Hydrogen-bonding patterns in trimethoprim picolinate and 2-amino-4,6-dimethylpyrimidinium picolinate hemihydrate

In the title compounds, namely 2,4-diamino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-1-ium pyridine-2-carboxylate, C14H19N4O3+.C6H4NO2-, (I), and 2-amino-4,6-dimethylpyrimidin-1-ium pyridine-2-carboxylate hemihydrate, C6H10N3+.C6H4NO2-.0.5H2O, (II), the trimethoprim and 2-amino-4,6-dimethylpyrimidin-1-ium cations are protonated at one of the pyrimidine N atoms. In (I), bifurcated hydrogen bonds are observed between a picolinate O atom, the protonated N atom and the 2-amino group; the graph-set designator is R2(1)(6). The pyrimidine moieties of the trimethoprim cations are centrosymmetrically paired through a pair of N-H...N hydrogen bonds. In addition to the base pairing, one of the picolinate O atoms bridges the 2- and 4-amino groups on either side of the paired bases, resulting in a complementary DADA array. In (II), the carboxylate group of the picolinate anion binds with the protonated pyrimidine N atom and the 2-amino group of the pyrimidine moiety through a pair of N-H...O hydrogen bonds, leading to the common ring motif R2(2)(8). The water molecule, which resides on a twofold rotation axis, bridges the carboxylate group of the picolinate anion via O-H...O hydrogen bonds.

The Changes in Angiogenic Gene Expression in Recurrent Multiple Chorioangiomas

Objectives: To assess the messenger ribonucleic acid expression in placental tissue of growth factors, cytokines, angiogenic and anti-angiogenic factors in one case of recurrent multiple chorioangiomas. Methods: Complementary deoxyribonucleic acid array analysis was performed on the affected placentae and on normal placentaes (controls) to compare messenger ribonucleic acid levels of 96 genes involved in angiogenesis. Results: Eleven genes presented more than two-fold alteration in expression levels: undetectable (angiopoietin 1, osteonectin, tyrosine kinase endothelial, neuropilin 1), decreased (transcription growth factor β receptor 3, tissue inhibitor of metalloproteinase type 2, EGF receptor, integrin-α V, tyrosine kinase vascular endothelial growth factor receptor 2), increased (angiopoietin 2, osteopontin). Conclusions: We illustrated the complexity of angiogenic disruption in recurrent multiple chorioangiomas leading to the difficulty to propose a single candidate gene to explain this pathology.

Edge-adaptive color interpolation for complementary color filter array

Complementary color filter array (CCFA) is widely used in consumer-level digital video cameras, since it not only has high sensitivity and good signal-to-noise ratio in low-light condition but also is compatible with the interlaced scanning used in broadcast systems. However, the full-color images obtained from CCFA suffer from the color artifacts such as false color and zipper effects. These artifacts can be removed with edge-adaptive color interpolation (ECI) approaches which are generally used in primary color filter array (PCFA). Unfortunately, the unique array pattern of CCFA makes it difficult that CCFA adopts ECI approaches. Therefore, to apply ECI approaches suitable for CCFA to color interpolation is one of the major issues to reconstruct the full-color images. In this paper, we propose a new ECI algorithm for CCFA. To estimate an edge direction precisely and enhance the quality of the reconstructed image, a function of spatial variances is used as a weight, and new color conversion matrices are presented for considering various edge directions. Experimental results indicate that the proposed algorithm outperforms the conventional method with respect to both objective and subjective criteria. © 2006 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 16, 92–102, 2006

Monitoring the stability of crosslinked protein crystals biotemplates: A feasibility study

Protein crystals, routinely prepared for the elucidation of protein 3D structures by X-ray crystallography, present an ordered and highly accurate 3D array of protein molecules. Inherent to the 3D arrangement of the protein molecules in the crystal is a complementary 3D array of voids made of interconnected cavities and exhibiting highly ordered porosity. The permeability of the porosity of chemically crosslinked enzyme protein crystals to low molecular weight solutes, was used for enzyme mediated organic synthesis and size exclusion chromatography. This permeability might be extended to explore new potential applications for protein crystals, for example, their use as bio-templates for the fabrication of novel, nano-structured composite materials. The quality of composites obtained from "filling" of the ordered voids in protein crystals and their potential applications will be strongly dependent upon an accurate preservation of the order in the original protein crystal 3D array during the "filling" process. Here we propose and demonstrate the feasibility of monitoring the changes in 3D order of the protein array by a step-by-step molecular level monitoring of a model system for hydrogel bio-templating by glutaraldehyde crosslinked lysozyme crystals. This monitoring is based on step-by-step comparative analysis of data obtained from (i) X-ray crystallography: resolution, unit cell dimensions and B-factor values and (ii) fluorescence decay kinetics of ultra-fast laser activated dye, impregnated within these crystals. Our results demonstrated feasibility of the proposed monitoring approach and confirmed that the stabilized protein crystal template retained its 3D structure throughout the process.