bluuebunny/crossref_metadata_2025 huggingface dataset:
Control ofBorrelia burgdorferi-Specific CD4+-T-Cell Effector Function by Interleukin-12- and T-Cell Receptor-Induced p38 Mitogen-Activated Protein Kinase Activity
Authors: Hedrick Michael N. , Olson Chris M. , Conze Dietrich B. , Bates Tonya C. , Rincón Mercedes , Anguita Juan
Published: September 2006

Infection withBorrelia burgdorferi, the causative agent of Lyme disease, results in a Th1 response and proinflammatory cytokine production. Mice deficient for MKK3, an upstream activator of p38 mitogen-activated protein (MAP) kinase, develop a lower Th1 response and exhibit an impaired ability to produce proinflammatory cytokines upon infection with the spirochete. We investigated the contribution of p38 MAP kinase activity in gamma interferon (IFN-γ) production in CD4+T cells in response to specific antigen through T-cell receptor (TCR)- and interleukin-12 (IL-12)-mediated signals. The specific inhibition of p38 MAP kinase in T cells and the administration of a pharmacological inhibitor of the kinase during the course of infection with the spirochete resulted in reduced levels of IFN-γ in the sera of infected mice. Our results also demonstrate that although p38 MAP kinase activity is not required for the differentiation ofB. burgdorferi-specific CD4+T cells, the production of IFN-γ by Th1 effector cells is regulated by the kinase. Both TCR engagement and IL-12 induced the production of the Th1 cytokine through the activation of the p38 MAP kinase pathway. Thus, the inhibition of this pathway in vitro resulted in decreased levels of IFN-γ during restimulation ofB. burgdorferi-specific T cells in response to anti-CD3 and IL-12 stimulation. These results clarify the specific contribution of the p38 MAP kinase in the overall immune response to the spirochete and its role in the effector function ofB. burgdorferi-specific T cells.
Trichomonas vaginalisLipophosphoglycan Triggers a Selective Upregulation of Cytokines by Human Female Reproductive Tract Epithelial Cells
Authors: Fichorova Raina N. , Trifonova Radiana T. , Gilbert Robert O. , Costello Catherine E. , Hayes Gary R. , Lucas John J. , Singh Bibhuti N.
Published: September 2006

Trichomonas vaginalisis one of the most common nonviral sexually transmitted human infections and, worldwide, has been linked to increased incidence of human immunodeficiency virus type 1 transmission, preterm delivery, low birth weight, cervical cancer, and vaginitis. The molecular pathways that are important in initiating host inflammatory and immune responses toT. vaginalisare poorly understood. Here we report interactions of human cervicovaginal epithelial cells with the most abundant cell surface glycoconjugate of the parasite, theT. vaginalislipophosphoglycan (LPG). Purified LPG mediated the adhesion of parasites to human vaginal epithelial cells in a dose-dependent manner. Furthermore,T. vaginalisLPG (but not LPG fromTritrichomonas foetus, the causative agent of bovine trichomoniasis) induced a selective upregulation of chemotactic cytokines by human endocervical, ectocervical, and vaginal epithelial cells, which do not express Toll-like receptor 4/MD2. TheT. vaginalisLPG triggered interleukin 8 (IL-8), which promotes the adhesion and transmigration of neutrophils across the endothelium, and macrophage inflammatory protein 3α, which is a chemoattractant for immune cells and is essential for dendritic cell maturation. These effects were dose dependent and sustained in the absence of cytotoxicity and IL-1β release and utilized, at least in part, a signaling pathway independent from the Toll-like/IL-1 receptor adaptor protein MyD88.
The Transcriptional Regulator RovS Controls the Attachment of
Streptococcus agalactiae
to Human Epithelial Cells and the Expression of Virulence Genes
Authors: Samen Ulrike M. , Eikmanns Bernhard J. , Reinscheid Dieter J.
Published: September 2006

Streptococcus agalactiae
is part of the normal flora of the human gastrointestinal tract and also the leading cause of bacterial infections in human newborns and immunocompromised adults. The colonization and infection of different regions within the human host require a regulatory network in
S. agalactiae
that senses environmental stimuli and controls the formation of specific virulence factors. In the present study, we characterized an Rgg-like transcriptional regulator, designated RovS (
r
egulator
o
f
v
irulence in
Streptococcus agalactiae
). Deletion of the
rovS
gene in the genome of
S. agalactiae
resulted in strain 6313 Δ
rovS
, which exhibited an increased attachment to immobilized fibrinogen and a significant increase in adherence to the eukaryotic lung epithelial cell line A549. Quantification of expression levels of known and putative
S. agalactiae
virulence genes by real-time PCR revealed that RovS influences the expression of
fbsA
, gbs0230,
sodA
,
rogB
, and the
cyl
operon. The altered gene expression in mutant 6313 Δ
rovS
was restored by plasmid-mediated expression of
rovS
, confirming the RovS deficiency as the cause for the observed changes in virulence gene expression in
S. agalactiae
. DNA electrophoretic mobility shift assays showed that RovS specifically binds to the promoter regions of
fbsA
, gbs0230,
sodA
, and the
cyl
operon, indicating that RovS directly regulates their expression. Deletion and mutation studies in the promoter region of
fbsA
, encoding the main fibrinogen receptor in
S. agalactiae
, identified a RovS DNA motif. Similar motifs were also found in the promoter regions of gbs0230,
sodA
, and the
cyl
operon, and alignments allowed us to propose a consensus sequence for the DNA-binding site of RovS.
Acute Systemic Immune Activation following Conjunctival Exposure to Staphylococcal Enterotoxin B
Authors: Rajagopalan Govindarajan , Smart Michele K. , Patel Robin , David Chella S.
Published: September 2006

Conjunctival exposure to the
Staphylococcus aureus
superantigen staphylococcal enterotoxin B (SEB) may occur accidentally, as a result of bioterrorism, or during colonization or infection of the external eye. Using human leukocyte antigen class II transgenic mice, we show for the first time that conjunctival exposure to SEB can cause robust systemic immune activation.
Prophylaxis and Therapy of Inhalational Anthrax by a Novel Monoclonal Antibody to Protective Antigen That Mimics Vaccine-Induced Immunity
Authors: Vitale Laura , Blanset Diann , Lowy Israel , O'Neill Thomas , Goldstein Joel , Little Stephen F. , Andrews Gerard P. , Dorough Gary , Taylor Ronald K. , Keler Tibor
Published: September 2006

The neutralizing antibody response to the protective antigen (PA) component of anthrax toxin elicited by approved anthrax vaccines is an accepted correlate for vaccine-mediated protection against anthrax. We reasoned that a human anti-PA monoclonal antibody (MAb) selected on the basis of superior toxin neutralization activity might provide potent protection against anthrax. The fully human MAb (also referred to as MDX-1303 or Valortim) was chosen from a large panel of anti-PA human MAbs generated using transgenic mice immunized with recombinant PA solely on the basis of in vitro anthrax toxin neutralization. This MAb was effective in prophylactic and postsymptomatic treatment of rabbits exposed to aerosolized anthrax spores, and a single intramuscular injection of 1 mg/kg of body weight fully protected cynomolgus monkeys challenged with aerosolized anthrax spores. Importantly, MAb 1303 defines a novel neutralizing epitope that requires Fc receptor engagement for maximal activity. F(ab′)2 fragments of MAb 1303, which retain equivalent affinity for PA, are 10- to 100-fold less potent in neutralizing anthrax toxin in vitro. Addition of Fc receptor-blocking antibodies also greatly reduced the activity of MAb 1303. Moreover, we found that the neutralizing activity of mouse, rabbit, and human antisera elicited by PA vaccines was effectively abrogated by blocking Fc receptors. Selection of an anti-PA MAb by using a functional assay that is a surrogate for protection has resulted in the identification of a fully human MAb with potent activity in vivo and uncovered a previously unrecognized mechanism of antibody-mediated toxin neutralization that is important for currently used anthrax vaccines.
Genome-Wide Expression Analysis of
Burkholderia pseudomallei
Infection ina Hamster Model of Acute Melioidosis
Authors: Tuanyok Apichai , Tom Marina , Dunbar John , Woods Donald E.
Published: September 2006

Burkholderia pseudomallei
is the causative agent of melioidosis and represents
a potential bioterrorism threat. In the current studies we have examined gene expression in
B. pseudomallei
in an animal model of acute melioidosis using whole-genome microarrays. Gene expression
profiles were generated by comparing transcriptional levels of
B. pseudomallei
-expressed genes in infected hamster organs including liver, lung, and spleen following intraperitoneal and intranasal routes
of infection to those from bacteria grown in vitro. Differentially expressed genes were similar in infected livers irrespective of the route of infection. Reduced expression of a number of housekeeping genes suggested a lower bacterial growth rate during infection. Energy production during growth in vivo involved specific biochemical pathways such as isomerization of 3-phosphoglycerate, catabolism of
d
-glucosamine and inositol, and biosynthesis of particular amino acids. In addition, the induction of genes known to be involved in oxidative phosphorylation including ubiquinol oxidase, ferredoxin oxidoreductase, and formate dehydrogenase enzymes suggested the use of alternative pathways for energy production, while the expression of genes coding for ATP-synthase and NADH-dehydrogenase enzymes was reduced. Our studies have identified differentially expressed genes which include potential virulence genes such as those for a putative phospholipase C and a putative two-component regulatory system, and they have also provided a better understanding of bacterial metabolism in response to the host environment during acute melioidosis.
Porphyromonas gingivalisFimbriae Proactively Modulate β2Integrin Adhesive Activity and Promote Binding to and Internalization by Macrophages
Authors: Hajishengallis George , Wang Min , Harokopakis Evlambia , Triantafilou Martha , Triantafilou Kathy
Published: September 2006

In monocytes, the fimbriae of the oral pathogenPorphyromonas gingivalisactivate cross talk signaling from Toll-like receptor 2 (TLR2) to the β2integrin CD11b/CD18, leading to the induction of the high-affinity state of the latter receptor. CD14 plays an important role in this “inside-out” proadhesive pathway by binding fimbriae and facilitating the activation of TLR2 and phosphatidylinositol 3-kinase signaling. In its high-affinity state, CD11b/CD18 mediates monocyte adhesion to endothelial cells and transmigration to sites of infection. We have now shown thatP. gingivalisfimbriae function as both an activator and a ligand of CD11b/CD18; thus, fimbriae proactively promote their own binding to monocytes. Indeed, treatments that interfered with fimbria-induced activation of CD11b/CD18 (i.e., blockade of CD14, TLR2, or phosphatidylinositol 3-kinase signaling) also suppressed the cell binding activity of fimbriae, which was largely inducible and CD11b/CD18 dependent. Development of a recombinant inside-out signaling system in Chinese hamster ovary cells confirmed the ability of fimbriae to activate CD14/TLR2 signaling and induce their own CD11b/CD18-dependent binding. Induction of this proadhesive pathway byP. gingivalisfimbriae appeared to take place in lipid rafts. Indeed, methyl-β-cyclodextrin, a cholesterol-sequestering agent that disrupts lipid raft organization, was found to inhibit the fimbria-induced assembly of CD14/TLR2 signaling complexes and the activation of the high-affinity state of CD11b/CD18. Experiments using macrophages from mice deficient in various pattern recognition receptors indicated that the receptors involved in the inside-out proadhesive pathway (CD14, TLR2, and CD11b/CD18) are important for mediatingP. gingivalisinternalization within macrophages. It therefore appears thatP. gingivalisproactively modulates β2integrin adhesive activity for intracellular uptake.
Effects of ConcomitantSchistosoma haematobiumInfection on the Serum Cytokine Levels Elicited by AcutePlasmodium falciparumMalaria Infection in Malian Children
Authors: Lyke Kirsten E. , Dabo Abdoulaye , Sangare Lansana , Arama Charles , Daou Modibo , Diarra Issa , Plowe Christopher V. , Doumbo Ogobara K. , Sztein Marcelo B.
Published: September 2006

Polyparasitism is common in the developing world, and interactions that alter disease severity may occur. We previously demonstrated that infection withSchistosoma hematobiumwas associated with protection againstPlasmodium falciparuminfection in children who were 4 to 8 years old. In this study, we determined whether underlying helminth infections affected the cytokine responses to acute falciparum malaria. A total of 338 schistosomiasis-positive [Sch(+)] children who were 4 to 14 years old were matched by age, residence, and sex with 338 schistosomiasis-negative [Sch(−)] children and monitored for a malaria transmission season (25 weeks). Serologic cytokine levels were measured at the time of the first clinical malaria episode and in children who did not contract malaria. Elevated background levels of interleukin-6 (IL-6) (37.1 pg/ml versus 10.9 pg/ml [P= 0.04]), IL-4 (27.7 pg/ml versus 6.9 pg/ml [P= 0.02]), IL-10 (18.2 pg/ml versus 7.2 pg/ml [P< 0.001]), and gamma interferon (18.2 pg/ml versus 4.7 pg/ml [P= 0.006]) were noted in Sch(+) children compared to Sch(−) children without malaria. IL-6 and IL-10 levels were elevated in association with acute malaria, but the levels appeared to be blunted in Sch(+) children compared to Sch(−) children who were 4 to 8 years old (for IL-6, 96.2 pg/ml versus 137.2 pg/ml [P= 0.08]; for IL-10, 195.9 pg/ml versus 282.2 pg/ml [P= 0.06]). The level of IL-10 was similarly lower in Sch(+) children than in Sch(−) children who were 9 to 14 years old (91.2 pg/ml versus 141.2 pg/ml [P= 0.03]). IL-4 levels were inversely correlated with the time until the first malaria infection in both the Sch(+) children (P< 0.001) and the Sch(−) children (P< 0.001) who were 4 to 8 years old. We postulate that the Th2-enriched environment induced by schistosomiasis protects against malaria and alters the cytokine milieu during an actual infection.
Fatty Acids fromPlasmodium falciparumDown-Regulate the Toxic Activity of Malaria Glycosylphosphatidylinositols
Authors: Debierre-Grockiego Françoise , Schofield Louis , Azzouz Nahid , Schmidt Jörg , Santos de Macedo Cristiana , Ferguson Michael A. J. , Schwarz Ralph T.
Published: September 2006

Plasmodium falciparummalaria kills roughly 2.5 million people, mainly children, annually. Much of this mortality is thought to arise from the actions of a malarial toxin. This toxin, identified as glycosylphosphatidylinositol (GPI), is a major pathogenicity determinant in malaria. A malarial molecule, Pfj, labeled by [3H]glucosamine like the GPIs, was identified as a non-GPI molecule. Here we show that Pfj is able to down-regulate tumor necrosis factor alpha (TNF-α) production induced by the GPI ofP. falciparum. Mass spectrometry analysis showed that Pfj was not a single molecule but represented a number of molecules. Separation methods, such as cation-exchange chromatography and thin-layer chromatography, were used to isolate and identify the following four main fatty acids responsible for the inhibitory effect on TNF-α production: myristic, pentadecanoic, palmitic, and palmitoleic acids. This regulatory effect on cytokine production suggests that there is balanced bioactivity for the different categories of malarial lipids.
Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice
Authors: Galioto Ann Marie , Hess Jessica A. , Nolan Thomas J. , Schad Gerhard A. , Lee James J. , Abraham David
Published: September 2006

The goal of this study was to determine the roles of eosinophils and neutrophils in innate and adaptive protective immunity to larvalStrongyloides stercoralisin mice. The experimental approach used was to treat mice with an anti-CCR3 monoclonal antibody to eliminate eosinophils or to use CXCR2−/−mice, which have a severe neutrophil recruitment defect, and then determine the effect of the reduction or elimination of the particular cell type on larval killing. It was determined that eosinophils killed theS. stercoralislarvae in naïve mice, whereas these cells were not required for the accelerated killing of larvae in immunized mice. Experiments using CXCR2−/−mice demonstrated that the reduction in recruitment of neutrophils resulted in significantly reduced innate and adaptive protective immunity. Protective antibody developed in the immunized CXCR2−/−mice, thereby demonstrating that neutrophils were not required for the induction of the adaptive protective immune response. Moreover, transfer of neutrophil-enriched cell populations recovered from either wild-type or CXCR2−/−mice into diffusion chambers containing larvae demonstrated that larval killing occurred with both cell populations when the diffusion chambers were implanted in immunized wild-type mice. Thus, the defect in the CXCR2−/−mice was a defect in the recruitment of the neutrophils and not a defect in the ability of these cells to kill larvae. This study therefore demonstrated that both eosinophils and neutrophils are required in the protective innate immune response, whereas only neutrophils are necessary for the protective adaptive immune response to larvalS. stercoralisin mice.
Topological phase transitions in frustrated magnets
Authors: Southern B W , Peles A
Published: September 2006

The role of topological excitations in frustrated Heisenberg antiferromagnets between two and three spatial dimensions is considered. In particular, the antiferromagnetic Heisenberg model on a stacked triangular geometry with a finite number of layers is studied using Monte Carlo methods. A phase transition that is purely topological in nature occurs at a finite temperature for all film thicknesses. The results indicate that topological excitations are important for a complete understanding of the critical properties of the model between two and three dimensions. PACS Nos.: 75.10.Hk, 75.40.Cx, 75.40.Mg
The epistemic view of quantum states and the ether
Authors: Marchildon L
Published: September 2006

The idea that the wave function represents information, or knowledge, rather than the state of a microscopic object has been held to solve foundational problems of quantum mechanics. Realist interpretation schemes, like Bohmian trajectories, have been compared to the ether in prerelativistic theories. I argue that the comparison is inadequate, and that the epistemic view of quantum states begs the question of interpretation.PACS Nos.: 03.65.Ta, 03.50.De, 03.30.+p
Deterministic entanglement of assistance in quantum networks
Authors: Sanders B C , Gour G , Meyer D A
Published: September 2006

We present a powerful theorem for tripartite remote entanglement distribution protocols, which provides an operational interpretation of concurrence as a type of entanglement capacity, and we establish that concurrence of assistance, which we show is an entanglement monotone, identifies capabilities of and limitations to producing pure bipartite entangled states from pure tripartite entangled states. In addition, we show that, if concurrence of assistance for the pure tripartite state is at least as large as the concurrence of the desired pure bipartite state, then the former may be transformed to the latter via local operations and classical communication, and we calculate the maximum probability for this transformation when this condition is not met.PACS Nos.: 03.67.Mn, 03.67.Hk, 03.65.Ud
Anomalous magnetic moments of free and bound leptons
Authors: Czarnecki A , Jentschura U D , Pachucki K , Yerokhin V A
Published: September 2006

We review the theoretical knowledge of anomalous magnetic moments of free electrons and muons, and of electrons bound in hydrogenlike ions. We discuss applications of these observations in the determination of fundamental physical constants, the fine structure constant, the electron mass, and in searches for new interactions.PACS Nos.: 14.60.z, 13.40.Em, 32.10.Dk
Lorentz-like formulation of Galilean field theories
Authors: Montigny M de , Khanna F C , Santos E S
Published: September 2006

We review recent articles in which we have constructed nonrelativistic Lagrangian field models by enforcing Galilean covariance on a (4,1) Minkowski manifold and by reducing onto the (3,1) Newtonian space-time. This formalism provides an elegant construction of nonrelativistic Lagrangians, for example, those that describe the electric and magnetic limits of Galilean electromagnetism. We discuss the quantization of scalar and Fermi fields. Scattering amplitudes and cross sections are computed for the Coulomb interaction, as well as electron–electron and electron–positron scattering.PACS Nos.: 03.70.+k, 03.65.Nk, 11.10.Kk, 11.10.Cp
Possible fates for the accelerating Universe
Authors: Faraoni V
Published: September 2006

The accelerating Universe may end in eternal de Sitter expansion, in a Big Rip, or in super-exponential expansion. We discuss a gauge-independent stability analysis of de Sitter space in scalartensor and in modified gravity, the late-time dynamics of a phantom Universe with general potential, and the recent proposal of evading the Big Rip through wormhole tunneling.PACS Nos.: 98.80.k, 04.50.+h, 04.20.q
The pion form factor from twisted-mass lattice quantum chromodynamics
Authors: Abdel-Rehim A M , Lewis R
Published: September 2006

The pion form factor offers insight into the transition from perturbative to nonperturbative quantum chromodynamics (QCD), and is of current experimental interest. Twisted-mass lattice QCD is a method for eliminating unphysical zero modes from Wilson lattice simulations; it also allows for removal of the leading lattice spacing artifacts through a momentum-averaging prescription. In our study of the pion form factor, we performed the first explicit computation with momentum averaging in twisted-mass lattice QCD, and the first use of the GMRES-DR algorithm for twisted fermion matrix inversion.PACS No.: 12.38.Gc
Universality of highly damped quasinormal modes for single horizon black holes
Authors: Daghigh R G , Kunstatter G
Published: September 2006

It has been suggested that the highly damped quasinormal modes of black holes provide information about the microscopic quantum gravitational states underlying black-hole entropy. This interpretation requires the form of the highly damped quasinormal mode frequency to be universally of the form: [Formula: see text] = ln(l)kTBH, where l is an integer, and TBH is the black-hole temperature. We summarize the results of an analysis of the highly damped quasinormal modes for a large class of static single horizon, asymptotically flat black holes.PACS Nos.: 04.60.–m, 04.70.–s, 04.70.Dy, 04.70.Bw, 92.60.Dj
Superheavy dark matter and ultrahigh-energy cosmic rays
Authors: Dick R , Hopp K M , Wunderle K E
Published: September 2006

The phase of inflationary expansion in the early Universe produces superheavy relics in a mass window between 1012 and 1014 GeV. Decay or annihilation of these superheavy relics an explain the observed ultrahigh-energy cosmic rays beyond the Greisen–Zatsepin–Kuzmin cutoff. We emphasize that the pattern of cosmic-ray arrival directions seen by the Pierre Auger observatory will decide between the different proposals for the origin of ultrahigh-energy cosmic rays.PACS Nos.: 98.70.Sa, 98.70.–f, 95.35.+d, 14.80.–j
A study of the gravitational wave pulsar signal with orbital and spindown effects
Authors: Valluri S R , Rao K M , Wiegert P , Chishtie F A
Published: September 2006

In this work, we present an analytic and a preliminary numerical analysis of the gravitational wave signal from a pulsar that includes simple spindown effects. We estimate the phase corrections to a monochromatic source signal due to rotational and elliptical orbital motion of the Earth, and perturbations due to Jupiter and the Moon. We briefly discuss the Fourier transform of such a signal, expressed in terms of well-known special functions, and its applications. PACKS Nos.: 04.30.-w
Fast-ion-beam laser-induced-fluorescence measurements of spontaneous-emission branching ratios and oscillator strengths in Sm II
Authors: Rehse S J , Li R , Scholl T J , Sharikova A , Chatelain R , Holt R A , Rosner S D
Published: September 2006

We measured the spontaneous-emission branching ratios of 69 levels in Sm II selectively populated via single-frequency laser excitation of a 10 keV ion beam. The levels studied had term energies up to 29 600 cm–1, and decay branches with spontaneous emission in the range 250–850 nm were detected. The experimental accuracy was in the range of 10%. We used these branching ratios along with our previously determined radiative lifetimes to infer transition probabilities and oscillator strengths for 608 transitions in the wavelength range 363–771 nm, which are useful for stellar abundance determinations.PACS Nos.: 32.70.Cs, 95.30.Ky
SPLINE APPROXIMATIONS ON MANIFOLDS
Authors: DEMYANOVICH YU. K.
Published: September 2006

A method of construction of the local approximations in the case of functions defined on n-dimensional (n ≥ 1) smooth manifold with boundary is proposed. In particular, spline and finite-element methods on manifold are discussed. Nondegenerate simplicial subdivision of the manifold is introduced and a simple method for evaluations of approach is examined (the evaluations are optimal as to N-width of corresponding compact set).
ASYMPTOTIC FORMULAS FOR THE FRAME COEFFICIENTS GENERATED BY LAGUERRE AND HERMITE TYPE POLYNOMIALS
Authors: KHABIBOULLINE R. , PRESTIN J.
Published: September 2006

Polynomial frames based on orthogonal decompositions with respect to weights of Laguerre and Hermite type are considered. Asymptotic formulas for the coefficients from expansions on such frames are presented. The ability to detect singularities of all order is studied in detail.
ON THE ERRORS OF MULTIDIMENSIONAL MRA BASED ON NON-SEPARABLE SCALING FUNCTIONS
Authors: BACCHELLI BARBARA , BOZZINI MIRA , ROSSINI MILVIA
Published: September 2006

In this paper, we deal with two different problems. First, we provide the convergence rates of multiresolution approximations, with respect to the supremum norm, for the class of elliptic splines defined in Ref. 10, and in particular for polyharmonic splines. Secondly, we consider the problem of recovering a function from a sample of noisy data. To this end, we define a linear and smooth estimator obtained from a multiresolution process based on polyharmonic splines. We discuss its asymptotic properties and we prove that it converges to the unknown function almost surely.
CHARACTERIZATION OF IMAGE SPACE OF A WAVELET TRANSFORM
Authors: DENG CAIXIA , QU YULING , GU LIJUAN
Published: September 2006

In this paper, Journe wavelet function is introduced as a wavelet generating function. The expression of reproducing kernel function for the image space of this wavelet transform is obtained based on the fact that the image space of the wavelet transform is a reproducing kernel Hilbert space. Then the isometric identity of Journe wavelet transform is obtained. The connections between the image space of the wavelet transform and the image space of the known reproducing kernel space are established by the theories of reproducing kernel. The properties and the structures of the image space of the wavelet transform can be characterized by the properties and the structures of the image space of the known reproducing kernel space. Using the ideas of reproducing kernel, we consider there are relations between the wavelet transform and the sampling theorem. Meanwhile, the approximations in sampling theorems is shown and the truncation error is given. This provides a theoretical basis for us to study the image space of the general wavelet transform and broadens the scope of application of theories of the reproducing kernel space.
ENTREPRENEURSHIP IN THE RAINBOW NATION: EFFECT OF CULTURAL VALUES AND ESE ON INTENTIONS
Authors: URBAN BORIS
Published: September 2006

Because of South Africa's multicultural society, different cultural values were hypothesized to influence proclivity toward entrepreneurship across ethnic groups. Building on previous research conducted on ethnicity and entrepreneurship, selected findings were investigated to formulate hypotheses and contextualize the study. By adapting entrepreneurial intentions to reflect entrepreneurial self-efficacy (ESE) as a separate measure of feasibility to start a business, principal component analysis was conducted to verify the construct validity of the measures and internal consistency was established. The latest VSM 94 was used to capture the five dimensions of culture. ANOVA and Duncan's multiple tests indicated some significant differences across ethnic groups, while correlation and multiple regression analysis demonstrated that it was the ESE beliefs rather than cultural values that influence intentions.
ENTREPRENEURIAL DISCOVERY BY THE WORKING POOR
Authors: FIET JAMES O. , NIXON ROBERT D. , GUPTA MAHESH , PATEL PANKAJ C.
Published: September 2006

We test the proposition that it is possible to train the economically vulnerable, working poor of inner cities to make entrepreneurial discoveries. We demonstrate the effective use of a model of constrained, systematic search. We employ an experimental design with a control group using the alertness approach recommended by received theory and a treatment group using systematic search. Our results indicate the systematic search approach works 25 times better among a sample of the working poor. In addition, we operationalize systematic search training protocols and implementation. We conclude by discussing special challenges inherent in training the economically disadvantaged and suggest that the lack of trust of those from outside the local community necessitates the building of bridges to targeted residents. Bridge-building, as an integral part of public policy utilizing large-scale training, might be accomplished through reliance on established community relationships.
Cardiac Resynchronization Treatment of Heart Failure
Authors: Hasan Ayesha , Abraham William T.
Published: September 2006

Cardiac resynchronization therapy (CRT) is well established as a treatment for patients with moderate to severe heart failure on optimal medical therapy. Early studies demonstrated improved functional capacity and evidence of reverse remodeling; more recently, CRT has been associated with a survival benefit in advanced heart failure both with and without a defibrillator. We review the eight landmark trials in CRT. To date, criteria have focused on electrical delay, but echocardiographic parameters emphasize the importance of mechanical delay or ventricular dyssynchrony. With the exponential rise in implants, new issues have emerged, such as optimal device programming, identifying appropriate candidates, and accounting for cases without clinical benefit from CRT.
Cancer Stem Cells: At the Headwaters of Tumor Development
Authors: Ward Ryan J. , Dirks Peter B.
Published: September 2006

According to the cancer stem cell hypothesis, only a subpopulation of cells within a cancer has the capacity to sustain tumor growth. This subpopulation of cells is made up of cancer stem cells, which are defined simply as the population of cells within a tumor that can self-renew, differentiate, and regenerate a phenocopy of the cancer when injected in vivo. Cancer stem cells have now been prospectively isolated from human cancers of the blood, breast, and brain, and putative cancer stem cells have been identified from human skin, bone, and prostate tumors and from multiple established mammalian cancer cell lines. Furthermore, researchers are actively seeking cancer stem cells in every human cancer type. We present the current scientific evidence supporting the cancer stem cell hypothesis and discuss the experimental and therapeutic implications of the discovery of human cancer stem cells.
Regulation of Intestinal Cholesterol Absorption
Authors: Wang David Q.-H.
Published: September 2006

The identification of defective structures in the ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 in patients with sitosterolemia suggests that these two proteins are an apical sterol export pump promoting active efflux of cholesterol and plant sterols from enterocytes back into the intestinal lumen for excretion. The newly identified Niemann-Pick C1–like 1 (NPC1L1) protein is also expressed at the apical membrane of enterocytes and plays a crucial role in the ezetimibe-sensitive cholesterol absorption pathway. These findings indicate that cholesterol absorption is a multistep process that is regulated by multiple genes at the enterocyte level and that the efficiency of cholesterol absorption may be determined by the net effect between influx and efflux of intraluminal cholesterol molecules crossing the brush border membrane of the enterocyte. Combination therapy using cholesterol absorption (NPC1L1) inhibitor (ezetimibe) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) provides a powerful novel strategy for the prevention and treatment of hypercholesterolemia.
Endothelin-1 decreases CD36 protein expression in vascular smooth muscle cells
Authors: Kwok Ching Fai , Juan Chi-Chang , Ho Low-Tone
Published: September 2006

Recent studies have shown that CD36 plays important roles as a major scavenger receptor for oxidized low-density lipoproteins and as a crucial transporter for long-chain fatty acids. CD36 deficiency might be associated with insulin resistance and abnormal dynamics of long-chain fatty acids. Endothelin-1 (ET-1), which is synthesized and secreted by vascular endothelial cells, is the most potent endogenous vasoconstrictor known and also stimulates the proliferation of vascular smooth muscle cells (VSMCs) and thus is believed to play an important role in the development of various circulatory disorders, including hypertension and atherosclerosis. The aim of the present study was to investigate the regulatory effect of ET-1 on CD36 expression in cultured VSMCs. VSMCs were treated for different times (0–24 h) with a fixed concentration (100 nM) of ET-1 or with different concentrations (0–100 nM) for a fixed time (24 h); then CD36 expression was determined using Western blots. CD36 expression was significantly decreased by ET in a time- and dose-dependent manner. This inhibitory effect was prevented by the ETAreceptor antagonist BQ-610 (10 μM) but not the ETBreceptor antagonist BQ-788 (10 μM). To further explore the underlying mechanisms of ET-1 action, we examined the involvement of the tyrosine kinase-mediated and MAPK-mediated pathways. The inhibitory effect of ET-1 on CD36 protein expression was blocked by inhibition of tyrosine kinase activation by use of genistein (100 μM) and by the ERK inhibitor PD-98059 (75 μM) but not by the p38 MAPK inhibitor SB-203580 (20 μM). In conclusion, we have demonstrated that ET-1, acting via the ETAreceptor, suppresses CD36 protein expression in VSMCs by activation of the tyrosine kinase and ERK pathways.
Exercise and CaMK activation both increase the binding of MEF2A to theGlut4promoter in skeletal muscle in vivo
Authors: Smith James A. H. , Collins Malcolm , Grobler Liesl A. , Magee Carrie J. , Ojuka Edward O.
Published: September 2006

In vitro binding assays have indicated that the exercise-induced increase in muscle GLUT4 is preceded by increased binding of myocyte enhancer factor 2A (MEF2A) to its cis-element on the Glut4 promoter. Because in vivo binding conditions are often not adequately recreated in vitro, we measured the amount of MEF2A that was bound to the Glut4 promoter in rat triceps after an acute swimming exercise in vivo, using chromatin immunoprecipitation (ChIP) assays. Bound MEF2A was undetectable in nonexercised controls or at 24 h postexercise but was significantly elevated ∼6 h postexercise. Interestingly, the increase in bound MEF2A was preceded by an increase in autonomous activity of calcium/calmodulin-dependent protein kinase (CaMK) II in the same muscle. To determine if CaMK signaling mediates MEF2A/DNA associations in vivo, we performed ChIP assays on C2C12myotubes expressing constitutively active (CA) or dominant negative (DN) CaMK IV proteins. We found that ∼75% more MEF2A was bound to the Glut4 promoter in CA compared with DN CaMK IV-expressing cells. GLUT4 protein increased ∼70% 24 h after exercise but was unchanged by overexpression of CA CaMK IV in myotubes. These results confirm that exercise increases the binding of MEF2A to the Glut4 promoter in vivo and provides evidence that CaMK signaling is involved in this interaction.
Regulation of HOXA10 expression by phytoestrogens
Authors: Akbas G. Eda , Fei Xiaolan , Taylor Hugh S.
Published: September 2006

HOXA10 is necessary for normal development of the Müllerian duct, and continued adult expression in the uterus is necessary for female fertility. HOXA10 expression is altered by diethylstilbestrol, leading to uterine anomalies. Other endocrine disruptors may potentially lead to reproductive anomalies or dysfunction by altering HOXA10 expression. Here we investigated the effect of isoflavones on HOXA10 expression after in utero or adult exposure in the mouse. Genistein, but not diadzein, regulated HOXA10 mRNA and protein expression in the adult mouse uterus. In contrast, in utero genistein or diadzein exposure had no lasting effect on HOXA10 expression in the exposed offspring. Reporter gene expression driven by the HOXA10 estrogen response element was increased in a dose-responsive manner by genistein, but not daidzein. Neither estrogen receptor-α nor estrogen receptor-β binding to the HOXA10 estrogen response element was affected by genistein or daidzein. In utero exposure to isoflavones is unlikely to result in HOXA10-mediated developmental anomalies. Adult genistein exposure alters uterine HOXA10 expression, a potential mechanism by which this agent affects fertility.
Regulation of IGF-I receptor signaling in diabetic cardiac muscle: dysregulation of cytosolic and mitochondria HSP60
Authors: Lai Hui-Chin , Liu Tsun-Jui , Ting Chih-Tai , Yang Jia-Ying , Huang Lan , Wallace Douglas , Kaiser Peter , Wang Ping H.
Published: September 2006

Insulin deficiency downregulates HSP60 and IGF-I receptor signaling and disrupts intracellular signaling homeostasis in diabetic cardiac muscle. Our previous studies had shown that IGF-I receptor signaling can be modulated by the abundance of HSP60. Since HSP60 localizes to the cytoplasmic compartment and mitochondria, this study was carried out to determine the distribution of cytosolic and mitochondria HSP60 in diabetic myocardium and to explore whether cytosolic HSP60 can modulate IGF-I receptor signaling in cardiac muscle cells. In streptozotocin-induced diabetes, both the cytosolic and mitochondrial fractions of HSP60 were decreased in the myocardium. Incubating primary cardiomyocytes with insulin leads to increased abundance of HSP60 in the cytosolic and mitochondria compartments. To determine whether cytosolic HSP60 can modulate IGF-I receptor signaling, we used rhodamine 6G to deplete functional mitochondria in cardiomyocytes. In the mitochondria-depleted cells, overexpression of HSP60 with adenoviral vector increased the abundance of IGF-I receptor, enhanced IGF-I-activated receptor phosphorylation, and augmented IGF-I activation of Akt and ERK. Thus overexpressing HSP60 in the cytosolic compartment enhanced IGF-I receptor signaling through upregulation of IGF-I receptor protein. However, IGF-I receptor signaling was significantly reduced in the mitochondria-depleted cells, which suggested that maintaining normal IGF-I receptor signaling in cardiomyocytes required functioning mitochondria. The effect of cytosolic HSP60 involved suppression of ubiquitin conjugation to IGF-I receptor in cardiomyocytes. These data suggest two different mechanisms that can regulate IGF-I signaling, one via cytosolic HSP60 suppression of IGF-I receptor ubiquitination and the other via mitochondria modulation. These findings provide new insight into the regulation of IGF-I signaling in diabetic cardiomyopathy.
Parathyroid hormone-dependent endocytosis of renal type IIc Na-Picotransporter
Authors: Segawa Hiroko , Yamanaka Setsuko , Onitsuka Akemi , Tomoe Yuka , Kuwahata Masashi , Ito Mikiko , Taketani Yutaka , Miyamoto Ken-ichi
Published: September 2006

Hereditary hypophosphatemic rickets with hypercalciuria results from mutations of the renal type IIc Na-Picotransporter gene, suggesting that the type IIc transporter plays a prominent role in renal phosphate handling. The goal of the present study was to investigate the regulation of the type IIc Na-Picotransporter by parathyroid hormone (PTH). Type IIc Na-Picotransporter levels were markedly increased in thyroparathyroidectomized (TPTX) rats. Four hours after administration of PTH, type IIc transporter protein levels were markedly decreased in the apical membrane fraction but recovered to baseline levels at 24 h. Immunohistochemical analyses demonstrated the presence of the type IIc transporter in the apical membrane and subapical compartments in the proximal tubular cells in TPTX animals. After administration of PTH, the intensity of immunoreactive signals in apical and subapical type IIc transporter decreased in the renal proximal tubular cells in TPTX rats. Colchicine completely blocked the internalization of the type IIc transporter. In addition, leupeptin prevented the PTH-mediated degradation of the type IIa transporter in lysosomes but had no effect on PTH-mediated degradation of the lysosomal type IIc transporter. In PTH-treated TPTX rats, the internalization of the type IIc transporter occurred after administration of PTH(1–34) (PKA and PKC activator) or PTH(3–34) (PKC activator). Thus the present study demonstrated that PTH is a major hormonal regulator of the type IIc Na-Picotransporter in renal proximal tubules.
Uric acid inhibits renal proximal tubule cell proliferation via at least two signaling pathways involving PKC, MAPK, cPLA2, and NF-κB
Authors: Han Ho Jae , Lim Min Jin , Lee Yun Jung , Lee Jang Hern , Yang Il Suk , Taub Mary
Published: September 2006

The accumulation of uric acid, an end-product of purine metabolism, is responsible for the many deleterious effects observed in gouty arthritis, including renal injury. Here, we present evidence that under conditions of hyperuricemia (>10−4M uric acid) [3H]thymidine incorporation into primary renal proximal tubule cells (PTCs) is inhibited, and we delineate the signaling pathways involved. Elevated uric acid was observed to stimulate MAPK phosphorylation. The uric acid induced p38 MAPK phosphorylation was also blocked by H-7 (a PKC inhibitor), indicating that p38 MAPK was a downstream target of PKC. Evidence that cytoplasmic phospholipase A2(cPLA2) was involved further downstream included 1) the stimulatory effect of uric acid on [3H]-labeled arachidonic acid (AA) release; 2) the stimulation of AA release in response to uric acid was blocked by the PKC inhibitor H-7 as well as by the p38 MAPK inhibitor SB 203580; and 3) the uric acid-induced inhibition of [3H]thymidine incorporation was prevented by SB 203580, as well as by the cPLA2inhibitor arachidonyl trifluoromethyl ketone, and mepacrine (another PLA2inhibitor). Evidence of a uric acid-induced activation of NF-κB as well as PLA2was obtained. Moreover the uric acid-induced inhibition of [3H]thymidine incorporation was also blocked by two NF-κB inhibitors, pyrrolidine dithiocarbamate and SN 50. However, SN 50 did not block the uric acid induced [3H]AA release. Thus the inhibition of [3H]thymidine incorporation caused by uric acid can be explained by two distinct mechanisms, the activation of NF-κB as well as the activation of PLA2.
Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma
Authors: Varona Adolfo , Blanco Lorena , López José I. , Gil Javier , Agirregoitia Ekaitz , Irazusta Jon , Larrinaga Gorka
Published: September 2006

Peptides play important roles in cell regulation and signaling in many tissues and are regulated by peptidases, most of which are highly expressed in the kidney. Several peptide convertases have a function in different tumor stages, and some have been clearly characterized as diagnostic and prognostic markers for solid tumors, including renal cancer; however, little is known about their in vivo role in kidney tumors. The present study compares the activity of a range of peptidases in human tumor samples and nontumor tissue obtained from clear cell renal cell carcinoma (CCRCC) patients. To cover the complete spectrum and subcellular distribution of peptide-converting activity, acid, neutral, basic, and omega activities were selected. CCRCC displays a selective and restricted pattern of peptidase activities. Puromycin-sensitive aminopeptidase activity in the tumor increases [tumor (t) = 10,775 vs. nontumor (n) = 7,635 units of peptidase (UP)/mg protein; P < 0.05], whereas aminopeptidase N decreases (t = 6,664 vs. n = 33,381 UP/mg protein; P < 0.001). Aminopeptidase B activity of the particulate fraction in tumors decreases (t = 2,399 vs. n = 13,536 UP/mg protein; P < 0.001) compared with nontumor tissues, and aspartyl-aminopeptidase activity decreases significantly in CCRCC (t = 137 vs. n = 223 UP/mg protein; P < 0.05). Soluble and particulate pyroglutamyl peptidase I activities, aminopeptidase A activity, and soluble aminopeptidase B activity do not vary in renal cancer. The relative expression for the aforementioned peptidases, assayed using quantitative RT-PCR, increases in CCRCC for aminopeptidases B (1.5-fold) and A (19-fold), aspartyl-aminopeptidase (3.9-fold), puromycin-sensitive aminopeptidase (2.5-fold), and pyroglutamyl peptidase I (7.6-fold). Only aminopeptidase N expression decreases in tumors (1.3-fold). This peptidase activity profile in the neoplastic kidney suggests a specific role for the studied convertases and the possible involvement of an intracrine renin-angiotensin system in the pathogenesis of CCRCC.
Acute Injury to Superficial Cortex Leads to a Decrease in Synaptic Inhibition and Increase in Excitation in Neocortical Layer V Pyramidal Cells
Authors: Yang Lie , Benardo Larry S. , Valsamis Helen , Ling Douglas S. F.
Published: September 2006

Injury to the superficial layers of cerebral cortex produces alterations in the synaptic responses of local circuits that promote the development of seizures. To further delineate the specific changes in synaptic strength that are induced by this type of cortical injury, whole cell voltage-clamp recordings were used to examine evoked and spontaneous synaptic events from layer V pyramidal cells in coronal slices prepared from surgically traumatized rat neocortices in which the superficial third of the cortex (layers I, II, and part of III) was removed. Slices from intact neocortices were used as controls. Examinations of fast inhibitory postsynaptic currents (IPSCs) indicated that traumatized slices were disinhibited, exhibiting evoked IPSCs (eIPSCs) with lower peak amplitudes. Measurements of spontaneous IPSCs (sIPSCs) revealed no difference in the mean amplitudes of sIPSCs recorded in traumatized versus control slices. However, the mean sIPSC frequency was lower in traumatized slices, indicative of a decrease in GABA release at these inhibitory synapses. Traumatized slices also displayed an increase in synaptic excitation, exhibiting spontaneous EPSCs (sESPCs) with larger peak amplitudes and higher frequencies. Peak-scaled nonstationary fluctuation analysis of sEPSCs and sIPSCs was used to obtain estimates of the unit conductance and number of functional receptor channels. EPSC and IPSC channel numbers and IPSC unit conductance did not differ between traumatized and intact slices. However, the mean unit conductance of EPSCs was higher (+25%) in traumatized slices. These findings suggest that acute injury to the superficial neocortical layers results in a disinhibition of cortical circuits that stems from a decline in GABA release likely due to the loss of superficial inhibitory interneurons and an enhancement of synaptic excitation consequent to an increase in the AMPA receptor unit conductance.