bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and characterization of a new carbonic anhydrase in the marine diatom Phaeodactylum tricornutum
Authors: Harada Hisashi , Matsuda Yusuke
Published: September 2005

A cDNA encoding a new isoenzyme of β-type carbonic anhydrase (CA; EC 4.2.1.1) in the marine diatom Phaeodactylum tricornutum Bohlin has been cloned. The cDNA contained an open reading frame of 819 bp, which encodes a polypeptide of 273 amino acids. This gene, which is designated as ptca2, was found to be highly homologous (83% at the nucleotide level) to the previously isolated intracellular β-CA gene from Phaeodactylum tricornutum (ptca1). Comparison of the deduced amino acid sequence of ptca2 with β-CAs from other sources demonstrated that PtCA2 possesses the completely conserved zinc coordination residues of β-CA. The N-terminus 19 amino acid sequence of PtCA2 was predicted to be an endoplasmic reticulum-targeting signal, suggesting localization of the protein in an organelle or in the periplasmic space. Quantitative analysis of mRNA accumulation of ptca2 using real-time polymerase chain reaction revealed a significant level of mRNA accumulation even under 5% CO2 and a 3.5-fold increase in accumulation upon acclimation of the diatom to air. This indicates that ptca2 belongs to a constitutive class of enzyme that responds only weakly to the ambient CO2 concentration. The sequences of both ptca1 and ptca2 were shown to be grouped into a phylogeny that is composed of mixture of sequences from the eucarya and procarya domains, including sequences from the red alga Porphyridium purpureum, the green alga Coccomyxa, the red mold Neurospora crassa, and the yeast Saccharomyces cerevisiae.Key words: carbonic anhydrase, marine diatom, inorganic carbon concentrating mechanism (CCM), Phaeodactylum tricornutum.
CO2-concentrating mechanisms in aquatic photosynthetic microorganisms
Authors: Espie George S , Colman Brian
Published: September 2005

The articles in this issue of the Canadian Journal of Botany arose from presentations given at The Fifth International Symposium on Inorganic Carbon Utilization by Aquatic Photosynthetic Organisms held from 24 to 28 August 2004 at Saint-Sauveur, Quebec, Canada. They represent the current state of our understanding of CO2-concentrating mechanisms in these organisms and highlight recent molecular, physiological, and ecological advances made in this field of study. The influence of CO2-concentrating mechanisms on global carbon sequestration, species diversity, and population dynamics are also explored.Key words: algae, CO2-concentrating mechanisms, cyanobacteria, photosynthesis.
A mannanase, ManA, of the polycentric anaerobic fungusOrpinomycessp. strain PC-2 has carbohydrate binding and docking modules
Authors: Ximenes Eduardo A , Chen Huizhong , Kataeva Irina A , Cotta Michael A , Felix Carlos R , Ljungdahl Lars G , Li Xin-Liang
Published: September 2005

The anaerobic fungus Orpinomyces sp. strain PC-2 produces a broad spectrum of glycoside hydrolases, most of which are components of a high molecular mass cellulosomal complex. Here we report about a cDNA (manA) having 1924 bp isolated from the fungus and found to encode a polypeptide of 579 amino acid residues. Analysis of the deduced sequence revealed that it had a mannanase catalytic module, a family 1 carbohydrate-binding module, and a noncatalytic docking module. The catalytic module was homologous to aerobic fungal mannanases belonging to family 5 glycoside hydrolases, but unrelated to the previously isolated mannanases (family 26) of the anaerobic fungus Piromyces. No mannanase activity could be detected in Escherichia coli harboring a manA-containing plasmid. The manA was expressed in Saccharomyces cerevisiae and ManA was secreted into the culture medium in multiple forms. The purified extracellular heterologous mannanase hydrolyzed several types of mannan but lacked activity against cellulose, chitin, or β-glucan. The enzyme had high specific activity toward locust bean mannan and an extremely broad pH profile. It was stable for several hours at 50 °C, but was rapidly inactivated at 60 °C. The carbohydrate-binding module of the Man A produced separately in E. coli bound preferably to insoluble lignocellulosic substrates, suggesting that it might play an important role in the complex enzyme system of the fungus for lignocellulose degradation.Key words: Orpinomyces, anaerobic fungi, mannanase, cellulose-binding module, cellulosome.
Stress-dependent regulation of a monothiol glutaredoxin gene fromSchizosaccharomyces pombe
Authors: Kim Hong-Gyum , Kim Byung-Chul , Park Eun-Hee , Lim Chang-Jin
Published: September 2005

Glutaredoxin (Grx) is a small, heat-stable protein acting as a multi-functional glutathione-dependent disulfide oxidoreductase. In this work, a gene encoding the monothiol glutaredoxin Grx4 was cloned from the genomic DNA of the fission yeast Schizosaccharomyces pombe. The determined DNA sequence carries 1706 bp, which is able to encode the putative 244 amino acid sequence of Grx with 27 099 Da. It does not contain an intron, and the sequence CGFS is found in the active site. Grx activity was increased 1.46-fold in S. pombe cells harboring the cloned Grx4 gene, indicating that the Grx4 gene is in vivo functioning. Although aluminum, cadmium, and hydrogen peroxide marginally enhanced the synthesis of β-galactosidase from the Grx4-lacZ fusion gene, NO-generating sodium nitroprusside (0.5 mmol/L and 1.0 mmol/L) and potassium chloride (0.2 mol/L and 0.5 mol/L) significantly enhanced it. The Grx4 mRNA level was also enhanced after the treatment with sodium nitroprusside and potassium chloride. The synthesis of β-galactosidase from the Grx4-lacZ gene was increased by fermentable carbon sources, such as glucose (lower than 2%) and sucrose, but not by nonfermentable carbon sources such as acetate and ethanol. The basal expression of the S. pombe Grx4 gene did not depend on the presence of Pap1. These results imply that the S. pombe monothiol Grx4 gene is genuinely functional and regulated by a variety of stresses.Key words: monothiol glutaredoxin, Pap1, regulation, Schizosaccharomyces pombe, stress response.
Diagnosis of Helicobacter pylori infection and determination of clarithromycin resistance by fluorescence in situ hybridization from formalin-fixed, paraffin-embedded gastric biopsy specimens
Authors: Can Fusun , Yilmaz Zerrin , Demirbilek Muge , Bilezikci Banu , Kunefeci Ganiye , Atac Fatma Belgin , Selcuk Haldun , Arslan Hande , Boyacioglu Sedat , Sahin Feride Iffet
Published: September 2005

A reliable diagnostic test for Helicobacter pylori is important in clinical practice and research. The ideal diagnostic test for H. pylori should be sensitive, specific, and cost-effective. Helicobacter pylori resistance to clarithromycin is a common reason for failure of eradication therapy. The aim of this study was to evaluate the fluorescent in situ hybridization (FISH) method to detect H. pylori and determine clarithromycin resistance in formalin-fixed, paraffin-embedded gastric biopsy specimens. One hundred seventeen gastric biopsy specimens from patients with dyspepsia were examined for the presence of H. pylori by conventional culture, FISH, and histopathological methods. A set of fluorescent-labeled oligonucleotide probes binding to either H. pylori 16S rRNA or 23S rRNA sequences were used for FISH analysis. Phenotypic antibiotic susceptibilities of the isolates were tested using the Epsilometer test method (E test). Helicobacter pylori was detected in 70 of 117 biopsy specimens by histopathological examination and FISH, whereas it was detected in 47 specimens by culturing. Histopathology and FISH techniques failed to identify H. pylori in 1 biopsy sample isolated by culture. Clarithromycin resistance was found in 11 of 46 H. pylori isolates using the E test method. All of the phenotypic resistance measurements of isolates were correlated with genotypic clarithromycin resistance. Eleven clarithromycin-resistant strains were identified by FISH. The diagnosis of H. pylori infection and the determination of clarithromycin resistance in formalin-fixed, paraffin-embedded specimens using FISH is promising because it provides a rapid, reliable, and culture-independent diagnosis.Key words: Helicobacter pylori, clarithromycin resistance, FISH.
Virulence deficiency caused by a transposon insertion in the purH gene of Xanthomonas oryzae pv. oryzae
Authors: Chatterjee Subhadeep , Sonti Ramesh V
Published: September 2005

Xanthomonas oryzae pv. oryzae causes bacterial leaf blight, a serious disease of rice. We have identified a Tn5-induced virulence-deficient mutant (BXO1704) of X. oryzae pv. oryzae. The BXO1704 mutant exhibited growth deficiency in minimal medium but was proficient in inducing a hypersensitive response in a non-host tomato plant. Sequence analysis of the chromosomal DNA flanking the Tn5 insertion indicated that the Tn5 insertion is in the purH gene, which is highly homologous to purH genes of other closely related plant pathogenic bacteria Xanthomonas axonopodis pv. citri and Xanthomonas campestris pv. campestris. Purine supplementation reversed the growth deficiency of BXO1704 in minimal medium. These results suggest that the virulence deficiency of BXO1704 may be due to the inability to use sufficient purine in the host.Key words: auxotroph, plant pathogen, resistance.
EXACT SOLITON SOLUTIONS FOR THE HIGHER-ORDER NONLINEAR SCHRÖDINGER EQUATION
Authors: LI BIAO
Published: September 2005

Based on the complex envelope ansatz method, the projective Riccati equation method and q-deformed hyperbolic functions, a method is developed for constructing a series of exact analytical solutions for higher-order nonlinear Schrödinger (HNLS) equation, which describes propagation of femtosecond light pulse in optical fiber under certain parametric conditions. With the help of symbolic computation, six families of new solitary wave solutions are obtained. The solitary wave solutions obtained by Li et al.18are special cases of our solutions. The novel soliton solutions can describe W-shaped, bright and dark soliton properties in the same expression and their amplitude may approach nonzero when the time variable approaches infinity. Furthermore, the soliton propagation and solitons interaction scenario are discussed and simulated by computer.
AN EVOLUTIONARY MODEL BASED ON BIT-STRING WITH INTELLIGENCE
Authors: HE MINGFENG , PAN QIUHUI , YU BINGLIN
Published: September 2005

An evolutionary model based on bit-strings with intelligence is set up in this paper. In this model, gene is divided into two parts which relative to health and intelligence. The accumulated intelligence influences the survival process by the effect of food and space restrictions. We modify the Verhulst factor to study this effect. Both asexual and sexual model are discussed in this paper. The results show that after many time steps, stability is reached and the population self-organizes, just like the standard Penna model. The intelligence made the equilibrium to be reached larger both in asexual model and sexual model. Compared with asexual model the population size fluctuates more strongly in the sexual model.
RAMAN SCATTERING STUDIES ON THE STRUCTURAL PROPERTIES OF PULSED LASER DEPOSITED AMORPHOUS CARBON NITRIDE THIN FILMS
Authors: RUSOP M. , SOGA T. , JIMBO T.
Published: September 2005

Raman scattering analysis revealed that the structure of carbon films prepared by pulsed laser deposition (PLD) at room temperature is predominantly amorphous and the structure of amorphous carbon nitride ( a-CN x) thin films can be changed with varying substrate temperatures (ST) from 20°C to 500°C. The deposited a-CN x films are composed of C – N , C ≡ N and C – O bonded materials and the C – N and C ≡ N bonds are increased with ST. We have found that no other obvious peaks can be distinguished in the range 900–2300 cm-1 in which several peaks always appear in a-CN x films. The spectra were deconvoluted into Raman D and G peaks and the structural parameters are determined. The upward shifts of the Raman G peak towards 1592 cm-1 shows the evidence of a progressive formation of crystallites in a-CN x films upon increase of ST. While the upward shifts of the Raman D peak towards 1397 cm-1 have been related to the decrease of bond-angle disorder and sp3 tetrahedral bonding in its structure. Raman FWHM and I D /I G also indicate that N incorporation with increase of ST caused an increase in the number and/or size of graphitic domains in the a-CN x films.
THREE-WAVE SOLITON EXCITATIONS IN A DISK-SHAPED BOSE–EINSTEIN CONDENSATE
Authors: SUN CHUNLIU , XU YOUSHENG , CUI WEINA , HUANG GUOXIANG , SZEFTEL JACOB , HU BAMBI
Published: September 2005

A three-wave resonant interaction of collective modes and related soliton excitations in a disk-shaped Bose–Einstein condensate are investigated. The phase-matching conditions for the resonant interaction are satisfied by suitably choosing the wavevectors and the frequencies of the collective modes. A set of nonlinearly coupled envelope equations describing the spatio-temporal evolution of the three-wave resonant interaction are derived by using a method of multiple-scales, and some explicit (2+1)-dimensional three-wave soliton solutions are also presented and discussed.
CHAOS SYNCHRONIZATION IN THE MULTIFEEDBACK MACKEY–GLASS MODEL
Authors: SHAHVERDIEV E. M. , NURIEV R. A. , HASHIMOVA L. H. , HUSEYNOVA E. M. , HASHIMOV R. H.
Published: September 2005

We investigate synchronization between two unidirectionally linearly coupled chaotic multifeedback Mackey–Glass systems and find the existence and stability conditions for complete synchronization. Numerical simulations fully support the theory. We also present generalization of the approach to the wider class of nonlinear systems.
A COLLAPSING METHOD FOR THE EFFICIENT RECOVERY OF OPTIMAL EDGES IN PHYLOGENETIC TREES
Authors: HU MICHAEL , KEARNEY PAUL , BADGER JONATHAN
Published: September 2005

As the amount of sequencing efforts and genomic data volume continue to increase at an accelerated rate, phylogenetic analysis provides an evolutionary context for understanding and interpreting this growing set of complex data. We introduce a novel quartet based method for inferring molecular based phylogeny called hypercleaning* (HC*). The HC* method is based on the hypercleaning (HC) technique,2 which possesses an interesting property of recovering edges (of a phylogenetic tree) that are best supported by the witness quartet set. HC* extends HC in two regards: (i) whereas HC constrains the input quartet set to be unweighted (binary valued), HC* allows any positive valued quartet scores, enabling more informative quartets to be defined. (ii) HC* employs a novel collapsing technique which significantly speeds up the inference stage, making it empirically on par with quartet puzzling in terms of speed, while still guaranteeing optimal edge recovery as in HC. This paper is primarily aimed at presenting the algorithmic construction of HC*. We also report some preliminary studies on an implementation of HC* as a potentially powerful approximation scheme for maximum likelihood based inference.

Details of proofs can be found in report at: ().
SEQUENCE SIMILARITY SEARCH USING DISCRETE FOURIER AND WAVELET TRANSFORMATION TECHNIQUES
Authors: AGHILI S. ALIREZA , AGRAWAL DIVYAKANT , EL ABBADI AMR
Published: September 2005

In this paper, we study the problem of sequence similarity search. We incorporate vector transformations and apply DFT (Discrete Fourier Transformation) and DWT (Discrete Wavelet Transformation, Haar) dimensionality reduction techniques to reduce the search space/time of sequence similarity range queries. Our empirical results on a number of Prokaryote and Eukaryote DNA contig databases demonstrate up to 50-fold filtration ratio reduction of the search space and up to 13 times faster filtration. The proposed transformation techniques may easily be integrated as a pre-processing phase on top of current similarity search heuristics/techniques such as BLAST, PatternHunter, FastA and QUASAR to efficiently prune non-relevant sequences. We study the precision of applying dimensionality reduction techniques for faster and more efficient range query searches and discuss the imposed trade-offs.
VECTOR SPACE INDEXING FOR BIOSEQUENCE SIMILARITY SEARCHES
Authors: OZTURK OZGUR , FERHATOSMANOGLU HAKAN
Published: September 2005

We present a multi-dimensional indexing approach for fast sequence similarity search in DNA and protein databases. In particular, we propose effective transformations of subsequences into numerical vector domains and build efficient index structures on the transformed vectors. We then define distance functions in the transformed domain and examine properties of these functions. We experimentally compared their (a) approximation quality for k-Nearest Neighbor (k-NN) queries and both (b) pruning ability and (c) approximation quality for ε-range queries. Results for k-NN queries, which we present here, show that our proposed distances FD2 and WD2 (i.e. Frequency and Wavelet Distance functions for 2-grams) perform significantly better than the others. We then develop effective index structures, based on R-trees and scalar quantization, on top of transformed vectors and distance functions. Promising results from the experiments on real biosequence data sets are presented.
LONG-RANGE FLUCTUATIONS OF RANDOM POTENTIAL LANDSCAPE AS A MECHANISM OF 1/f NOISE IN HYDROGENATED AMORPHOUS SILICON
Authors: FINE BORIS V. , BAKKER JEROEN P. R. , DIJKHUIS JAAP I.
Published: September 2005

We describe a mechanism that links the long-range potential fluctuations induced by charged defects to the low-frequency resistance noise widely known as 1/fnoise. This mechanism is amenable to the first principles microscopic calculation of the noise spectrum, which includes the absolute noise intensity. We have performed such a calculation for the thin films of hydrogenated amorphous silicon ( a-Si:H ) under the condition that current flows perpendicular to the plane of the films, and have found a very good agreement between the theoretical noise intensity and the measured one. The mechanism described is quite general. It should be present in a broad class of systems containing poorly screened charged defects.
LOCAL ENERGY ESTIMATES FOR THE MAXWELL–LANDAU–LIFSHITZ SYSTEM AND APPLICATIONS
Authors: STARYNKÉVITCH JEAN
Published: September 2005

We study the Maxwell–Landau–Lifshitz system without exchange energy. First, we prove an [Formula: see text] estimate for the linear wave equation and apply this local energy estimate to obtain a bound on the curl of the electromagnetic field, uniformly in time and locally in space. Next, we prove strong convergence results, when the time t tends to ∞ or when the speed of light tends to ∞ (which corresponds to the quasi-stationary approximation). Finally, we establish a stability result with respect to the damping parameter of the Landau–Lifshitz equation.
LpASYMPTOTIC BEHAVIOR OF PERTURBED VISCOUS SHOCK PROFILES
Authors: RAOOFI MOHAMMADREZA
Published: September 2005

We investigate the Lpasymptotic behavior (1 ≤ p ≤ ∞) of a perturbation of a Lax or overcompressive type shock wave solution to a system of conservation law in one dimension. The system of the equations can be strictly parabolic, or partially parabolic (real viscosity case, e.g. compressible Navier–Stokes equations or equations of Magnetohydrodynamics). We use known pointwise Green function bounds for the linearized equation around the shock to show that the perturbation of such a solution can be decomposed into a part corresponding to shift in shock position or shape, a part which is the sum of diffusion waves, i.e. the solutions to a viscous Burger's equation, conserving the initial mass and convecting away from the shock profile in outgoing modes, and another part which is more rapidly decaying in any Lpnorm.
THE POINTWISE ESTIMATES OF SOLUTIONS TO THE ISENTROPIC NAVIER–STOKES EQUATIONS IN EVEN SPACE-DIMENSIONS
Authors: WANG WEIKE , YANG XIONGFENG
Published: September 2005

We study the dissipation of solutions for the isentropic Navier–Stokes equations in even space-dimensions. Based on the global existence of solutions and on the analysis of the Green function associated with the linearized system, the pointwise estimates of solution for the isentropic Navier–Stokes equations are established. It is observed here that in even dimensions the time-asymptotic behavior of the solutions follows from the weak Huygen's principle.
HYPERBOLIC DOMAINS OF DETERMINACY AND HAMILTON–JACOBI EQUATIONS
Authors: JOLY JEAN-LUC , MÉTIVIER GUY , RAUCH JEFFREY
Published: September 2005

If L(t, x, ∂t, ∂x) is a linear hyperbolic system of partial differential operators for which local uniqueness in the Cauchy problem at spacelike hypersurfaces is known, we find nearly optimal domains of determinacy of open sets Ω0⊂ {t = 0}. The frozen constant coefficient operators [Formula: see text] determine local convex propagation cones, [Formula: see text]. Influence curves are curves whose tangent always lies in these cones. We prove that the set of points Ω which cannot be reached by influence curves beginning in the exterior of Ω0is a domain of determinacy in the sense that solutions of Lu = 0 whose Cauchy data vanish in Ω0must vanish in Ω. We prove that Ω is swept out by continuous spacelike deformations of Ω0and is also the set described by maximal solutions of a natural Hamilton–Jacobi equation (HJE). The HJE provides a method for computing approximate domains and is also the bridge from the raylike description using influence curves to that depending on spacelike deformations. The deformations are obtained from level surfaces of mollified solutions of HJEs.
Tachycardia-induced myocardial ischemia and diastolic dysfunction potentiate secretion of ANP, not BNP, in hypertrophic cardiomyopathy
Authors: Kido Shinsuke , Hasebe Naoyuki , Ishii Yoshinao , Kikuchi Kenjiro
Published: September 2005

The aim of this study was to investigate what factor determines tachycardia-induced secretion of atrial and brain natriuretic peptides (ANP and BNP, respectively) in patients with hypertrophic cardiomyopathy (HCM). HCM patients with normal left ventricular (LV) systolic function and intact coronary artery ( n = 22) underwent rapid atrial pacing test. The cardiac secretion of ANP and BNP and the lactate extraction ratio (LER) were evaluated by using blood samples from the coronary sinus and aorta. LV end-diastolic pressure (LVEDP) and the time constant of LV relaxation of tau were measured by a catheter-tip transducer. These parameters were compared with normal controls ( n = 8). HCM patients were divided into obstructive (HOCM) and nonobstructive (HNCM) groups. The cardiac secretion of ANP was significantly increased by rapid pacing in HOCM from 384 ± 101 to 1,268 ± 334 pg/ml ( P < 0.05); however, it was not significant in control and HNCM groups. In contrast, the cardiac secretion of BNP was fairly constant and rather significantly decreased in HCM ( P < 0.01). The cardiac ANP secretion was significantly correlated with changes in LER ( r = −0.57, P < 0.01) and tau ( r = 0.73, P < 0.001) in HCM patients. Tachycardia potentiates the cardiac secretion of ANP, not BNP, in patients with HCM, particularly when it induces myocardial ischemia and LV diastolic dysfunction.
Oxidized phospholipids mediate occludin expression and phosphorylation in vascular endothelial cells
Authors: DeMaio Lucas , Rouhanizadeh Mahsa , Reddy Srinivasa , Sevanian Alex , Hwang Juliana , Hsiai Tzung K.
Published: September 2005

Oxidized l-α-1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine (OxPAPC), a component of minimally modified LDL, induces production of proinflammatory cytokines and development of atherosclerotic lesions. We tested the hypothesis that OxPAPC alters expression, phosphorylation, and localization of tight junction (TJ) proteins, particularly occludin, a transmembrane TJ protein. OxPAPC reduced total occludin protein and increased occludin phosphorylation dose dependently (10–50 μg/ml) and time dependently in bovine aortic endothelial cells. OxPAPC decreased occludin mRNA and reduced the immunoreactivity of zonula occludens-1 at the cell-cell contacts. Furthermore, OxPAPC increased the diffusive flux of 10-kDa dextran in a dose-dependent manner. O2−· production by bovine aortic endothelial cells increased nearly twofold after exposure to OxPAPC. Also, enzymatic generation of O2−· by xanthine oxidase-lumazine and H2O2by glucose oxidase-glucose increased occludin phosphorylation, implicating reactive oxygen species as modulators of the OxPAPC effects on occludin phosphorylation. Superoxide dismutase and/or catalase blocked the effects of OxPAPC on occludin protein content and phosphorylation, occludin mRNA, zonula occludens-1 immunoreactivity, and diffusive flux of 10-kDa dextran. These findings suggest that changes in TJ proteins are potential mechanisms by which OxPAPC compromises the barrier properties of the vascular endothelium. OxPAPC-induced disruption of TJs, which likely facilitates transmigration of LDL and inflammatory cells into the subendothelial layers, may be mediated by reactive oxygen species.
Cardioprotective effects of nitroparacetamol and paracetamol in acute phase of myocardial infarction in experimental rats
Authors: Zhu Yi Zhun , Chong Chew Lan , Chuah Shin Chet , Huang Shan Hong , Nai Huey Shan , Tong How Teng , Whiteman Matt , Moore Philip K.
Published: September 2005

We aimed to determine whether nitroparacetamol (NO-paracetamol) and paracetamol exhibit cardioprotective effects. Myocardial infarction (MI) was induced in rats, and drug treatment was started 1 wk before surgery. Mortality rate and infarct size at 2 days after MI were compared. Treatment groups included vehicle (saline), paracetamol (5 mg·kg−1·day−1) and NO-paracetamol (15 mg·kg−1·day−1). Mortality rates for vehicle ( n = 80), paracetamol ( n = 79), and NO-paracetamol ( n = 76) groups were 37.5%, 21.5%, and 26.3%, respectively. Infarct size for the vehicle group was 44.8% (±6.1%) of the left ventricle (LV). For the paracetamol and NO-paracetamol groups, infarct size was 31.3% (±5.6%) and 30.7% (±8.1%) of the LV, respectively. Both paracetamol- and NO-paracetamol-treated groups showed increased activities of catalase and SOD compared with the vehicle group. They could attenuate endothelial, inducible, and neuronal nitric oxide synthase and cyclooxygenase-1 and -2 gene expression after MI. The observation indicates the potential clinical significance of the cardioprotective effects of these drugs.
Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling
Authors: Baffert Fabienne , Le Tom , Sennino Barbara , Thurston Gavin , Kuo Calvin J. , Hu-Lowe Dana , McDonald Donald M.
Published: September 2005

The vasculature of the embryo requires vascular endothelial growth factor (VEGF) during development, but most adult blood vessels lose VEGF dependence. However, some capillaries in the respiratory tract and selected other organs of adult mice regress after VEGF inhibition. The present study sought to identify the sequence of events and the fate of endothelial cells, pericytes, and vascular basement membrane during capillary regression in mouse tracheas after VEGF signaling was blocked with a VEGF-receptor tyrosine kinase inhibitor AG-013736 or soluble receptor construct (VEGF Trap or soluble adenoviral VEGFR-1). Within 1 day, patency was lost and fibrin accumulated in some tracheal capillaries. Apoptotic endothelial cells marked by activated caspase-3 were present in capillaries without blood flow. VEGF inhibition was accompanied by a 19% decrease in tracheal capillaries over 7 days and 30% over 21 days. During this period, desmin/NG2-immunoreactive pericytes moved away from regressing capillaries onto surviving vessels. Empty sleeves of basement membrane, left behind by regressing endothelial cells, persisted for about 2 wk and served as a scaffold for vascular regrowth after treatment ended. The amount of regrowth was limited by the number of surviving basement membrane sleeves. These findings demonstrate that, after inhibition of VEGF signaling, some normal capillaries regress in a systematic sequence of events initiated by a cessation of blood flow and followed by apoptosis of endothelial cells, migration of pericytes away from regressing vessels, and formation of empty basement membrane sleeves that can facilitate capillary regrowth.
Axial nonuniformity of geometric and mechanical properties of mouse aorta is increased during postnatal growth
Authors: Huang Yi , Guo Xiaomei , Kassab Ghassan S.
Published: September 2005

The hemodynamic conditions of aorta are relatively uniform prenatally and become more heterogeneous postnatally. Our objective was to quantify the heterogeneity of geometry and mechanical properties during growth and development. To accomplish this objective, we obtained a systematic set of data on the geometry and mechanical properties along the length of mouse aorta during postnatal development. C57BL/6 mice of ages 1–33 days were studied. The ascending aorta was cannulated in situ and preconditioned with several cyclic changes in pressure. We investigated the axial variations of geometry (diameter and length) and mechanical properties (stress-stain relation, elastic modulus and compliance) of the mouse aorta from the aortic valve to the common iliac. Our results show that the arterial blood pressure of mice increased from ∼30 to 80 mmHg during the first 2 wk of life. The stretch ratio, diameter, wall (intima-media) thickness, and total lumen volume of mouse aorta increased with age. The aorta was transformed from a cylindrical tube at birth to a tapered structure during growth. Furthermore, we found the mechanical properties were fairly uniform along the length of the aorta at birth and become more nonuniform with age. We conclude that the rapid change of blood pressure and blood flow after birth alter the geometric and mechanical properties differentially along the length of the aorta. Hence, the axial nonuniformity of the aorta increases as the organ becomes more specialized during growth and development.
Type III Secretion: More Systems Than You Think
Authors: Troisfontaines Paul , Cornelis Guy R.
Published: September 2005

The type III secretion (T3S) pathway allows bacteria to inject effector proteins into the cytosol of target animal or plant cells. T3S systems evolved into seven families that were distributed among Gram-negative bacteria by horizontal gene transfer. There are probably a few hundred effectors interfering with control and signaling in eukaryotic cells and offering a wealth of new tools to cell biologists.
Mitochondrial Ion Channels: Gatekeepers of Life and Death
Authors: O’Rourke Brian , Cortassa Sonia , Aon Miguel A.
Published: September 2005

Continuous generation of ATP by mitochondrial oxidative phosphorylation is essential to maintain function in mechanically active cells such as cardiomyocytes. Emerging evidence indicates that mitochondrial ion channels activated by reactive oxygen species can induce a mitochondrial “critical” state, which can scale to cause electrical and contractile dysfunction of the cardiac cell and, ultimately, the whole heart. Here we focus on how mitochondrial ion channels participate in life-and-death decisions of the cell and discuss the challenges ahead for translating recent findings into novel therapeutic applications.
Looking Chloride Channels Straight in the Eye: Bestrophins, Lipofuscinosis, and Retinal Degeneration
Authors: Hartzell Criss , Qu Zhiqiang , Putzier Ilva , Artinian Liana , Chien Li-Ting , Cui Yuanyuan
Published: September 2005

Recent evidence suggests that Cl−ion channels are important for retinal integrity. Bestrophin Cl−channel mutations in humans are genetically linked to a juvenile form of macular degeneration, and disruption of some ClC Cl−channels in mice leads to retinal degeneration. In both cases, accumulation of lipofuscin pigment is a key feature of the cellular degeneration. Because Cl−channels regulate the ionic environment inside organelles in the endosomal-lysosomal pathway, retinal degeneration may result from defects in lysosomal trafficking or function.
The Bone Marrow Vascular Niche: Home of HSC Differentiation and Mobilization
Authors: Kopp Hans-Georg , Avecilla Scott T. , Hooper Andrea T. , Rafii Shahin
Published: September 2005

The bone marrow vasuclar niche consists of a network of thin-walled and fenestrated sinusoidal vessels whose integrity is maintained and supported by surrounding hematopoietic cells. However, this dependence is highly reciprocal in that the bone marrow vasculature provides not only a conduit for mature hematopoietic cells to the peripheral circulation but also a site where hematopoietic progenitors, especially megakaryocytes, differentiate and set the stage for full reconstitution of hematopoiesis.
Reciprocal service department cost allocation and decision making
Authors: Lowenthal Franklin , Malek Massoud
Published: September 2005

In a manufacturing company, certain departments can be
characterized as production departments and others as service
departments. Examples of service departments are purchasing,
computing services, repair and maintenance, security, food
services, and so forth. The costs of such service departments must
be allocated to the production departments, which in turn will
allocate them to the product. It is known that one can view the
cost allocation problem as an absorbing Markov process, with the
production departments as the absorbing states and the service
departments as the transient states. Using Markov analysis, we
will show that this yields additional insight into the underlying
concept of reciprocal service department cost allocation by
proving that the “full service” department costs can be used to
determine the price that should be paid to an external supplier of
the same service currently supplied by the service department.
A new approach to multiple class pattern classification with random matrices
Authors: Wang Dong Q. , Zhang Mengjie
Published: September 2005

We describe a new approach to multiple class pattern
classification problems with noise and high dimensional feature
space. The approach uses a random matrix X which has a specified
distribution with mean M and covariance matrix rij(Σs+Σε) between any two columns of X.
When Σε is known, the maximum likelihood estimators
of the expectation M, correlation Γ, and covariance
Σs can be obtained. The patterns with high dimensional
features and noise are then classified by a modified discriminant
function according to the maximum likelihood estimation results.
This new method is compared with a multilayer feed forward neural
network approach on nine digit recognition tasks of increasing
difficulty. Both methods achieved good results for those
classification tasks, but the new approach was more effective and
more efficient than the neural network method for difficult
problems.
E6 and E7 Oncoproteins Induce Distinct Patterns of Chromosomal Aneuploidy in Skin Tumors from Transgenic Mice
Authors: Schaeffer Anthony J. , Nguyen Marie , Liem Amy , Lee Denis , Montagna Cristina , Lambert Paul F. , Ried Thomas , Difilippantonio Michael J.
Published: September 2005

Inactivation of the tumor suppressor genes p53 and Rb are two of the most common genetic alterations in cancer cells. We use a mouse model to dissect the consequences of compromising the function of either of these genes on the maintenance of genomic stability. Thirteen cell lines established from skin tumors of mice expressing either the E6 or E7 oncoprotein of the human papillomavirus (HPV) type 16 under control of the keratin 14 promoter were analyzed by comparative genomic hybridization, spectral karyotyping and fluorescence in situ hybridization, reverse transcription-PCR, and mutation analysis. Deducing from the wealth of molecular cytogenetic data available from human cancers, we hypothesized that the more benign tumors in mice expressing E7 would be distinct from the more aggressive lesions in E6 transgenic mice. Tumorigenesis in E6-expressing mice required specifically the selection and maintenance of cells with extra copies of chromosome 6. Aneuploidy of chromosome 6 was independent of activating mutations in H-ras on chromosome 7. Expression of either E6 or E7 resulted in centrosome aberrations, indicating that each viral oncoprotein interferes independently with the centrosome cycle. Although centrosome aberrations are consistent with development of aneuploidy, no direct correlation was evident between the degree of aneuploidy and the percentage of cells with aberrant centrosomes. Our results show that although aneuploidy and centrosome aberrations are present in tumor cells from mice expressing either E6 or E7, tumorigenesis via E6 requires copy number increases of mouse chromosome 6, which is partially orthologous to human chromosome 3q, a region gained in HPV-associated carcinomas.
Stromal Matrix Metalloproteinase-9 Regulates the Vascular Architecture in Neuroblastoma by Promoting Pericyte Recruitment
Authors: Chantrain Christophe F. , Shimada Hiroyuki , Jodele Sonata , Groshen Susan , Ye Wei , Shalinsky David R. , Werb Zena , Coussens Lisa M. , DeClerck Yves A.
Published: September 2005

Advanced stages of neuroblastoma show increased expression of matrix metalloproteinases MMP-2 and MMP-9 (Y. Sugiura et al., Cancer Res., 58: 2209–2216, 1998) that have been implicated in many steps of tumor progression, suggesting that they play a contributory role. Using pharmacological and genetic approaches, we have examined the role of these MMPs in progression of SK-N-BE (2).10 human neuroblastoma tumors orthotopically xenotransplanted into immunodeficient mice. Mice treated with Prinomastat, a synthetic inhibitor of MMPs, showed an inhibition of tumor cell proliferation in implanted tumors and a prolonged survival (50 versus 39 days in control group, P < 0.035). Treatment with Prinomastat did not affect formation of liver metastases (P = 0.52) but inhibited intravascular colonization by the tumor cells in the lung by 73.8% (P = 0.03) and angiogenesis in both primary tumors and experimental liver metastases. The primary tumors from Prinomastat-treated mice showed a 39.3% reduction in endothelial area detected by PECAM/CD31 staining in tumor sections (P < 0.001), primarily due to the presence of smaller vessels (P = 0.004). MMP-2 is expressed by neuroblastoma tumor cells and stromal cells, whereas MMP-9 is exclusively expressed by stromal cells, particularly vascular cells. To examine the contribution of MMP-9 to tumor angiogenesis, we generated RAG1/MMP-9 double-deficient mice. We observed a significant inhibition of angiogenesis in the immunodeficient RAG1/MMP-9 double-deficient mice orthotopically implanted with tumor cells (P = 0.043) or implanted s.c. with a mixture of tumor cells and Matrigel (P < 0.001). Using an FITC-labeled lectin, we demonstrated an inhibition in the architecture of the tumor vasculature in MMP-9-deficient mice, resulting in fewer and smaller blood vessels. These changes were associated with a 48% decrease in pericytes present along microvessels. Taken together, the data demonstrate that in neuroblastoma, stromally derived MMP-9 contributes to angiogenesis by promoting blood vessel morphogenesis and pericyte recruitment.
Expression of the Receptor Tyrosine Kinase Axl Promotes Ocular Melanoma Cell Survival
Authors: van Ginkel Paul R. , Gee Ricardo L. , Shearer Rebecca L. , Subramanian Lalita , Walker Teresa M. , Albert Daniel M. , Meisner Lorraine F. , Varnum Brian C. , Polans Arthur S.
Published: September 2005

Metastatic tumor cells originating from cancers of a variety of tissues such as breast, skin, and prostate may remain dormant for long periods of time. In the case of uveal melanoma, the principal malignancy of the eye, complete removal of the primary tumor by enucleation can nonetheless be followed by metastatic tumor growth in distant organs months, years, or even decades later. This suggests that tumor cells have already spread to secondary sites at the time of treatment and remain dormant as micrometastases. Identifying factors that govern long-lived survival of metastatic tumor cells is therefore key to decreasing mortality associated with this and other diseases. While investigating factors differentially expressed in melanoma cells and normal melanocytes, we identified the receptor tyrosine kinase Axl and found up-regulation of Axl in uveal melanomas and melanoma cell lines by RNase protection, Western analysis, and immunohistochemistry. Axl has been shown to mediate cell growth and survival through its ligand Gas6 in non-transformed cells. To test whether stimulation of Axl can enhance survival of uveal melanoma cells, we assessed the degree of mitogenesis and cell survival by bromodeoxyuridine incorporation and trypan blue exclusion, respectively, upon stimulation of Mel 290 uveal melanoma cells with Gas6 in vitro. We show that Gas6 mediates mitogenesis and cell survival in Mel 290 cells. We further demonstrate that these effects occur specifically through the Axl receptor by modulating the expression of Axl with an antisense construct. cDNA microarray analysis of 12,687 genes then revealed that Gas6 stimulation of Axl in Mel 290 cells results primarily in the down-regulation of Cyr61, a member of the CCN protein family involved in tumor progression. These data show that the Axl pathway mediates increased survival of uveal melanoma cells, potentially advantageous during cancer dormancy, and that Axl may function in part through regulation of Cyr61.
Interleukin-1β Regulates Angiopoietin-1 Expression in Human Endothelial Cells
Authors: Fan Fan , Stoeltzing Oliver , Liu Wenbiao , McCarty Marya F. , Jung Young D. , Reinmuth Niels , Ellis Lee M.
Published: September 2005

Angiopoietin (Ang)-1 is an important regulator of endothelial cell (EC) survival and stabilization. Ang-1 exerts its biological effects by binding to the EC-specific tyrosine kinase receptor Tie-2, and initiates intracellular signaling in ECs. However, regulatory mechanisms for endothelial Ang-1 expression have not been completely elucidated. In this study, we investigated the effects of angiogenic cytokines and growth factors on Ang-1 expression in human umbilical vein ECs (HUVECs). Northern blot analysis was performed after HUVECs were exposed to interleukin-1β (IL-1β), tumor necrosis factor-α, platelet-derived growth factor-BB, insulin-like growth factor-1, or vascular endothelial growth factor (VEGF). Both IL-1β and tumor necrosis factor-α caused marked down-regulation of Ang-1 mRNA levels at 4 h with a further decrease observed at 24 h. Using signaling inhibitors, we identified the P38 pathway as the pathway that mediates IL-1β down-regulation of Ang-1. Furthermore, treatment of cells with IL-1β indirectly (via down-regulation of Ang-1) led to a decrease in Tie-2 autophosphorylation levels in HUVECs. We previously demonstrated that IL-1β regulates VEGF expression in tumor cells. This observation was confirmed in ECs in the present study. Because pericytes play a role in regulating EC function, we also determined whether IL-1β would also down-regulate Ang-1 in human vascular smooth muscle cells. Similar to our findings in HUVECs, we found that IL-1β decreased Ang-1 expression in human vascular smooth muscle cells. Direct effects of IL-1β on angiogenesis were investigated by use of an in vivo Gelfoam angiogenesis assay in which IL-1β produced a significant increase in vessel counts (P = 0.0189). These results suggest that IL-1β indirectly regulates angiogenesis by modulating the expression of Ang-1. IL-1β may trigger a proangiogenic response by decreasing Ang-1 levels in ECs and pericytes and up-regulating VEGF in ECs and tumor cells.
Cyclophilin D, a Component of the Permeability Transition-Pore, Is an Apoptosis Repressor
Authors: Schubert Alexis , Grimm Stefan
Published: September 2005

The permeability transition (PT)-pore is an important proapoptotic protein complex in mitochondria. Although it is activated by many signals for apoptosis induction, the role of its various subunits in cell death induction has remained largely unknown. We found that of its components, only the voltage-dependent anion channel in the outer mitochondrial membrane and the adenine nucleotide translocator-1 (ANT-1), a PT-pore subunit of the inner membrane, are apoptosis inducers. We also report that ANT-1’s direct interactor, cyclophilin D, can specifically repress ANT-1-induced apoptosis. In addition, cotransfection experiments revealed that for a diverse range of apoptosis inducers, cyclophilin D shows the same repression profile as the compound bongkrekic acid, a specific inhibitor of the PT-pore. This activity seems to be independent of its chaperone activity, the only known function of cyclophilin D to date. Importantly, cyclophilin D is specifically up-regulated in human tumors of the breast, ovary, and uterus, suggesting that inhibition of the PT-pore via up-regulation of cyclophilin D plays a role in tumorigenesis.
Soluble Decoy Receptor 3 Induces Angiogenesis by Neutralization of TL1A, a Cytokine Belonging to Tumor Necrosis Factor Superfamily and Exhibiting Angiostatic Action
Authors: Yang Chia-Ron , Hsieh Shie-Liang , Teng Che-Ming , Ho Feng-Ming , Su Wen-Ling , Lin Wan-Wan
Published: September 2005

TL1A is a member of the tumor necrosis factor superfamily and plays an important role in regulating endothelial cell apoptosis. A previous study shows TL1A is able to interact with death receptor 3 and decoy receptor 3 (DcR3). Here, we demonstrate that DcR3 is able to induce angiogenesis in human umbilical vein endothelial cells (HUVECs). DcR3 promotes HUVEC proliferation and migration and up-regulates matrix metalloproteinase-2 mRNA expression and enzyme activity. Furthermore, DcR3 enhances EC differentiation into cord vascular-like structures in vitro, as well as neovascularization in vivo. The effects of DcR3 on HUVECs are also mimicked by anti-TL1A and antideath receptor 3 antibodies. In contrast, human aortic endothelial cells, which do not express TL1A, are not responsive to DcR3 treatment, including cell proliferation, migration, and angiogenic differentiation. These data demonstrate DcR3 might not only help tumor cells to escape immune surveillance but also induce angiogenesis by blocking TL1A action in endothelial cells. The pathological role of DcR3 in promoting cancer progress raises the possibility to target DcR3 for antiangiogenic therapy in the future.