bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotypic Diversity of Coagulase-Negative Staphylococci Causing Endocarditis: a Global Perspective
Authors: Petti Cathy A. , Simmon Keith E. , Miro Jose M. , Hoen Bruno , Marco Francesc , Chu Vivian H. , Athan Eugene , Bukovski Suzana , Bouza Emilio , Bradley Suzanne , Fowler Vance G. , Giannitsioti Efthymia , Gordon David , Reinbott Porl , Korman Tony , Lang Selwyn , Garcia-de-la-Maria Cristina , Raglio Annibale , Morris Arthur J. , Plesiat Patrick , Ryan Suzanne , Doco-Lecompte Thanh , Tripodi Francesca , Utili Riccardo , Wray Dannah , Federspiel J. Jeffrey , Boisson K. , Reller L. Barth , Murdoch David R. , Woods Christopher W.
Published: March 2008

Coagulase-negative staphylococci (CNS) are important causes of infective endocarditis (IE), but their microbiological profiles are poorly described. We performed DNA target sequencing and susceptibility testing for 91 patients with definite CNS IE who were identified from the International Collaboration on Endocarditis—Microbiology, a large, multicenter, multinational consortium. A hierarchy of gene sequences demonstrated great genetic diversity within CNS from patients with definite endocarditis that represented diverse geographic regions. In particular,
rpoB
sequence data demonstrated unique genetic signatures with the potential to serve as an important tool for global surveillance.
Molecular Characterization ofBartonella vinsoniisubsp.berkhoffiiGenotype III
Authors: Cadenas Maria B. , Bradley Julie , Maggi Ricardo G. , Takara Matt , Hegarty Barbara C. , Breitschwerdt Edward B.
Published: March 2008

The molecular characterization of aBartonella vinsoniisubsp.berkhoffiigenotype III strain (NCSU strain 06-CO1) isolated from the blood of a military working dog diagnosed with endocarditis is reported in this study. Several genes were amplified and sequenced for comparative sequence similarity with other strains.
A Fusion Inhibitor Prevents Spread of Immunodeficiency Viruses, but Not Activation of Virus-Specific T Cells, by Dendritic Cells
Authors: Frank I. , Stössel H. , Gettie A. , Turville S. G. , Bess J. W. , Lifson J. D. , Sivin I. , Romani N. , Robbiani M.
Published: March 2008

Dendritic cells (DCs) play a key role in innate immune responses, and their interactions with T cells are critical for the induction of adaptive immunity. However, immunodeficiency viruses are efficiently captured by DCs and can be transmitted to and amplified in CD4+T cells, with potentially deleterious effects on the induction of immune responses. In DC-T-cell cocultures, contact with CD4+, not CD8+, T cells preferentially facilitated virus movement to and release at immature and mature DC-T-cell contact sites. This occurred within 5 min of DC-T-cell contact. While the fusion inhibitor T-1249 did not prevent virus capture by DCs or the release of viruses at the DC-T-cell contact points, it readily blocked virus transfer to and amplification in CD4+T cells. Higher doses of T-1249 were needed to block the more robust replication driven by mature DCs. Virus accumulated in DCs within T-1249-treated cocultures but these DCs were actually less infectious than DCs isolated from untreated cocultures. Importantly, T-1249 did not interfere with the stimulation of virus-specific CD4+and CD8+T-cell responses when present during virus-loading of DCs or for the time of the DC-T-cell coculture. These results provide clues to identifying strategies to prevent DC-driven virus amplification in CD4+T cells while maintaining virus-specific immunity, an objective critical in the development of microbicides and therapeutic vaccines.
MicroRNA-155 Is an Epstein-Barr Virus-Induced Gene That Modulates Epstein-Barr Virus-Regulated Gene Expression Pathways
Authors: Yin Qinyan , McBride Jane , Fewell Claire , Lacey Michelle , Wang Xia , Lin Zhen , Cameron Jennifer , Flemington Erik K.
Published: March 2008

The cellular microRNA miR-155 has been shown to be involved in lymphocyte activation and is expressed in Epstein-Barr virus (EBV)-infected cells displaying type III latency gene expression but not type I latency gene expression. We show here that the elevated levels of miR-155 in type III latency cells is due to EBV gene expression and not epigenetic differences in cell lines tested, and we show that expression in EBV-infected cells requires a conserved AP-1 element in the miR-155 promoter. Gene expression analysis was carried out in a type I latency cell line transduced with an miR-155-expressing retrovirus. This analysis identified both miR-155-suppressed and -induced cellular mRNAs and suggested that in addition to direct targeting of 3′ untranslated regions (UTRs), miR-155 alters gene expression in part through the alteration of signal transduction pathways. 3′ UTR reporter analysis of predicted miR-155 target genes identified the transcriptional regulatory genes encoding BACH1, ZIC3, HIVEP2, CEBPB, ZNF652, ARID2, and SMAD5 as miR-155 targets. Western blot analysis of the most highly suppressed of these, BACH1, showed lower expression in cells transduced with a miR-155 retrovirus. Inspection of the promoters from genes regulated in EBV-infected cells and in cells infected with an miR-155 retrovirus identified potential binding sequences for BACH1 and ZIC3. Together, these experiments suggest that the induction of miR-155 by EBV contributes to EBV-mediated signaling in part through the modulation of transcriptional regulatory factors.
Arrangement of L2 within the Papillomavirus Capsid
Authors: Buck Christopher B. , Cheng Naiqian , Thompson Cynthia D. , Lowy Douglas R. , Steven Alasdair C. , Schiller John T. , Trus Benes L.
Published: March 2008

Papillomaviruses are a family of nonenveloped DNA tumor viruses. Some sexually transmitted human papillomavirus (HPV) types, including HPV type 16 (HPV16), cause cancer of the uterine cervix. Papillomaviruses encode two capsid proteins, L1 and L2. The major capsid protein, L1, can assemble spontaneously into a 72-pentamer icosahedral structure that closely resembles native virions. Although the minor capsid protein, L2, is not required for capsid formation, it is thought to participate in encapsidation of the viral genome and plays a number of essential roles in the viral infectious entry pathway. The abundance of L2 and its arrangement within the virion remain unclear. To address these questions, we developed methods for serial propagation of infectious HPV16 capsids (pseudoviruses) in cultured human cell lines. Biochemical analysis of capsid preparations produced using various methods showed that up to 72 molecules of L2 can be incorporated per capsid. Cryoelectron microscopy and image reconstruction analysis of purified capsids revealed an icosahedrally ordered L2-specific density beneath the axial lumen of each L1 capsomer. The relatively close proximity of these L2 density buttons to one another raised the possibility of homotypic L2 interactions within assembled virions. The concept that the N and C termini of neighboring L2 molecules can be closely apposed within the capsid was supported using bimolecular fluorescence complementation or “split GFP” technology. This structural information should facilitate investigation of L2 function during the assembly and entry phases of the papillomavirus life cycle.
Increased Loss of CCR5+CD45RA−CD4+T Cells in CD8+Lymphocyte-Depleted Simian Immunodeficiency Virus-Infected Rhesus Monkeys
Authors: Veazey Ronald S. , Acierno Paula M. , McEvers Kimberly J. , Baumeister Susanne H. C. , Foster Gabriel J. , Rett Melisa D. , Newberg Michael H. , Kuroda Marcelo J. , Williams Kenneth , Kim Eun-Young , Wolinsky Steven M. , Rieber E. Peter , Piatak Michael , Lifson Jeffrey D. , Montefiori David C. , Brown Charles R. , Hirsch Vanessa M. , Schmitz Jörn E.
Published: March 2008

Previously we have shown that CD8+T cells are critical for containment of simian immunodeficiency virus (SIV) viremia and that rapid and profound depletion of CD4+T cells occurs in the intestinal tract of acutely infected macaques. To determine the impact of SIV-specific CD8+T-cell responses on the magnitude of the CD4+T-cell depletion, we investigated the effect of CD8+lymphocyte depletion during primary SIV infection on CD4+T-cell subsets and function in peripheral blood, lymph nodes, and intestinal tissues. In peripheral blood, CD8+lymphocyte-depletion changed the dynamics of CD4+T-cell loss, resulting in a more pronounced loss 2 weeks after infection, followed by a temporal rebound approximately 2 months after infection, when absolute numbers of CD4+T cells were restored to baseline levels. These CD4+T cells showed a markedly skewed phenotype, however, as there were decreased levels of memory cells in CD8+lymphocyte-depleted macaques compared to controls. In intestinal tissues and lymph nodes, we observed a significantly higher loss of CCR5+CD45RA−CD4+T cells in CD8+lymphocyte-depleted macaques than in controls, suggesting that these SIV-targeted CD4+T cells were eliminated more efficiently in CD8+lymphocyte-depleted animals. Also, CD8+lymphocyte depletion significantly affected the ability to generate SIV Gag-specific CD4+T-cell responses and neutralizing antibodies. These results reemphasize that SIV-specific CD8+T-cell responses are absolutely critical to initiate at least partial control of SIV infection.
Swallow syncope: reflex or reflux?
Authors: Bajwa S , Stewart J A D , Treadwell S , Lakhani D R
Published: March 2008

A 51-year-old man presented with symptoms of syncope on consuming solid foods. He had a 5 year history of intermittent symptoms on eating only solids and his cardiovascular investigations revealed bradycardia during food ingestion. He was treated by insertion of a pacemaker with cessation of his syncopal symptoms.
Massive cardiac invasion by amelanotic melanoma with obstructive clinical features
Authors: Dubrey S , Grocott-Mason R , Mittal T , Burke M
Published: March 2008

Reports of malignant melanoma involving the heart usually describe metastatic spread of pigmented (melanotic) forms of this tumour. We describe, and illustrate, a patient presenting with features related to cardiac tamponade and intracardiac obstruction. Transthoracic echocardiography initially showed a large mass within the right ventricular outflow tract. The full extent of infiltration of this tumour was demonstrated by computed tomography scanning and the specific tumour type by immunohistochemical staining procedures. The case is unusual in relation to the extreme size of this amelanotic melanoma at presentation and the fact that it appears to be a solitary metastasis.
ECONOMIC GROWTH AND THE EHRENFEST FLEAS: THE CONVERGENCE AMONG COUNTRIES
Authors: DI GENNARO LUCA , GARIBALDI UBALDO
Published: March 2008

The aim of this work is to predict the economic convergence among countries by using a generalization of Ehrenfest's urn. In particular this work shows that the Ehrenfest model captures the convergence among countries. A empirical analysis is presented on the European Union countries, the G7 countries and the emerging countries.
BARRIER CROSSING PROCESS DRIVEN BY TWO DICHOTOMOUS NOISES
Authors: DYBIEC BARTŁOMIEJ
Published: March 2008

We study the motion of an overdamped Brownian particle in a linear potential between reflecting and absorbing boundaries. The moving particle experiences the combined action of random and deterministic forces. In the model, the well-known and celebrated phenomenon of resonant activation is visible. The presence of two dichotomous noises modulates the shape of the potential barrier and changes the force acting on the particle leading to further acceleration of the escape kinetics in comparison to the situation where only one dichotomous process is present. In the case of very small or very large correlation times of dichotomous noises, we can observe asymptotic behavior of the system in which effectively one of the dichotomous noises is eliminated.
Regulation and Functions of Blimp-1 in T and B Lymphocytes
Authors: Martins Gislâine , Calame Kathryn
Published: March 2008

B lymphocyte–induced maturation protein-1 (Blimp-1), discovered 16 years ago as a transcriptional repressor of the IFNβ promoter, plays fundamentally important roles in many cell lineages and in early development. This review focuses on Blimp-1 in lymphocytes. In the B cell lineage, Blimp-1 is required for development of immunoglobulin-secreting cells and for maintenance of long-lived plasma cells (LLPCs). Direct targets of Blimp-1 and the transcriptional cascades Blimp-1 initiates to trigger plasmacytic differentiation are described. Blimp-1 also affects the homeostasis and function of CD4+, CD8+, and regulatory CD4+T cells, and Blimp-1 levels are highest in antigen-experienced T cells. Blimp-1 attenuates T cell proliferation and survival and modulates differentiation. Roles for Blimp-1 in Th1/Th2 specification, regulatory T cell function, and CD8 differentiation and function are under investigation. Signals that induce Blimp-1 in B cells include Toll-like receptor ligands and cytokines; in T cells, T cell receptors and cytokines induce Blimp-1. In spite of some commonalities, different targets and regulators of Blimp-1 in B and T cells suggest intriguing evolutionary divergence of this regulatory machinery.
Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein O-GlcNAc and increased mitochondrial Bcl-2
Authors: Champattanachai Voraratt , Marchase Richard B. , Chatham John C.
Published: March 2008

We have previously reported that glucosamine protected neonatal rat ventricular myocytes against ischemia-reperfusion (I/R) injury, and this was associated with an increase in protein O-linked- N-acetylglucosamine ( O-GlcNAc) levels. However, the protective effect of glucosamine could be mediated via pathways other that O-GlcNAc formation; thus the initial goal of the present study was to determine whether increasing O-GlcNAc transferase (OGT) expression, which catalyzes the formation of O-GlcNAc, had a protective effect similar to that of glucosamine. To better understand the potential mechanism underlying O-GlcNAc-mediated cytoprotection, we examined whether increased O-GlcNAc levels altered the expression and translocation of members of the Bcl-2 protein family. Both glucosamine (5 mM) and OGT overexpression increased basal and I/R-induced O-GlcNAc levels, significantly decreased cellular injury, and attenuated loss of cytochrome c. Both interventions also attenuated the loss of mitochondrial membrane potential induced by H2O2 and were also associated with an increase in mitochondrial Bcl-2 levels but had no effect on Bad or Bax levels. Compared with glucosamine and OGT overexpression, NButGT (100 μM), an inhibitor of O-GlcNAcase, was less protective against I/R and H2O2 and did not affect Bcl-2 expression, despite a 5- to 10-fold greater increase in overall O-GlcNAc levels. Decreased OGT expression resulted in lower basal O-GlcNAc levels, prevented the I/R-induced increase in O-GlcNAc and mitochondrial Bcl-2, and increased cellular injury. These results demonstrate that the protective effects of glucosamine are mediated via increased formation of O-GlcNAc and suggest that this is due, in part, to enhanced mitochondrial Bcl-2 translocation.
NFATc3 is required for intermittent hypoxia-induced hypertension
Authors: de Frutos Sergio , Duling Laura , Alò Dominique , Berry Tammy , Jackson-Weaver Olan , Walker Mary , Kanagy Nancy , González Bosc Laura
Published: March 2008

Sleep apnea, defined as intermittent respiratory arrest during sleep, is associated with increased incidence of hypertension and peripheral vascular disease. Exposure of rodents to brief periods of intermittent hypercarbia/hypoxia (H-IH) during sleep mimics the cyclical hypoxia-normoxia of sleep apnea. Endothelin-1, an upstream activator of nuclear factor of activated T cells (NFAT), is increased during H-IH. Therefore, we hypothesized that NFATc3 is activated by H-IH and is required for H-IH-induced hypertension. Consistent with this hypothesis, we found that H-IH (20 brief exposures per hour to 5% O2-5% CO2for 7 h/day) induces systemic hypertension in mice [mean arterial pressure (MAP) = 97 ± 2 vs. 124 ± 2 mmHg, P < 0.05, n = 5] and increases NFATc3 transcriptional activity in aorta and mesenteric arteries. Cyclosporin A, an NFAT inhibitor, and genetic ablation of NFATc3 [NFATc3 knockout (KO)] prevented NFAT activation. More importantly, H-IH-induced hypertension was attenuated in cyclosporin A-treated mice and prevented in NFATc3 KO mice. MAP was significantly elevated in wild-type mice (Δ = 23.5 ± 6.1 mmHg), but not in KO mice (Δ = −3.9 ± 5.7). These results indicate that H-IH-induced increases in MAP require NFATc3 and that NFATc3 may contribute to the vascular changes associated with H-IH-induced hypertension.
Differential effects of phospholamban and Ca2+/calmodulin-dependent kinase II on [Ca2+]itransients in cardiac myocytes at physiological stimulation frequencies
Authors: Werdich Andreas A. , Lima Eduardo A. , Dzhura Igor , Singh Madhu V. , Li Jingdong , Anderson Mark E. , Baudenbacher Franz J.
Published: March 2008

In cardiac myocytes, the activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) is hypothesized to regulate Ca2+release from and Ca2+uptake into the sarcoplasmic reticulum via the phosphorylation of the ryanodine receptor 2 and phospholamban (PLN), respectively. We tested the role of CaMKII and PLN on the frequency adaptation of cytosolic Ca2+concentration ([Ca2+]i) transients in nearly 500 isolated cardiac myocytes from transgenic mice chronically expressing a specific CaMKII inhibitor, interbred into wild-type or PLN null backgrounds under physiologically relevant pacing conditions (frequencies from 0.2 to 10 Hz and at 37°C). When compared with that of mice lacking PLN only, the combined chronic CaMKII inhibition and PLN ablation decreased the maximum Ca2+release rate by more than 50% at 10 Hz. Although PLN ablation increased the rate of Ca2+uptake at all frequencies, its combination with CaMKII inhibition did not prevent a frequency-dependent reduction of the amplitude and the duration of the [Ca2+]itransient. High stimulation frequencies in the physiological range diminished the effects of PLN ablation on the decay time constant and on the maximum decay rate of the [Ca2+]itransient, indicating that the PLN-mediated feedback on [Ca2+]iremoval is limited by high stimulation frequencies. Taken together, our results suggest that in isolated mouse ventricular cardiac myocytes, the combined chronic CaMKII inhibition and PLN ablation slowed Ca2+release at physiological frequencies: the frequency-dependent decay of the amplitude and shortening of the [Ca2+]itransient occurs independent of chronic CaMKII inhibition and PLN ablation, and the PLN-mediated regulation of Ca2+uptake is diminished at higher stimulation frequencies within the physiological range.
Modest maternal caffeine exposure affects developing embryonic cardiovascular function and growth
Authors: Momoi Nobuo , Tinney Joseph P. , Liu Li J. , Elshershari Huda , Hoffmann Paul J. , Ralphe John C. , Keller Bradley B. , Tobita Kimimasa
Published: March 2008

Caffeine consumption during pregnancy is reported to increase the risk of in utero growth restriction and spontaneous abortion. In the present study, we tested the hypothesis that modest maternal caffeine exposure affects in utero developing embryonic cardiovascular (CV) function and growth without altering maternal hemodynamics. Caffeine (10 mg·kg−1·day−1subcutaneous) was administered daily to pregnant CD-1 mice from embryonic days (EDs) 9.5 to 18.5 of a 21-day gestation. We assessed maternal and embryonic CV function at baseline and at peak maternal serum caffeine concentration using high-resolution echocardiography on EDs 9.5, 11.5, 13.5, and 18.5. Maternal caffeine exposure did not influence maternal body weight gain, maternal CV function, or embryo resorption. However, crown-rump length and body weight were reduced in maternal caffeine treated embryos by ED 18.5 ( P < 0.05). At peak maternal serum caffeine concentration, embryonic carotid artery, dorsal aorta, and umbilical artery flows transiently decreased from baseline at ED 11.5 ( P < 0.05). By ED 13.5, embryonic aortic and umbilical artery flows were insensitive to the peak maternal caffeine concentration; however, the carotid artery flow remained affected. By ED 18.5, baseline embryonic carotid artery flow increased and descending aortic flow decreased versus non-caffeine-exposed embryos. Maternal treatment with the adenosine A2Areceptor inhibitor reproduced the embryonic hemodynamic effects of maternal caffeine exposure. Adenosine A2Areceptor gene expression levels of ED 11.5 embryo and ED 18.5 uterus were decreased. Results suggest that modest maternal caffeine exposure has adverse effects on developing embryonic CV function and growth, possibly mediated via adenosine A2Areceptor blockade.
Surfactant protein D is expressed and modulates inflammatory responses in human coronary artery smooth muscle cells
Authors: Snyder Gary D. , Oberley-Deegan Rebecca E. , Goss Kelli L. , Romig-Martin Sara A. , Stoll Lynn L. , Snyder Jeanne M. , Weintraub Neal L.
Published: March 2008

Surfactant protein D (SP-D) is a constituent of the innate immune system that plays a role in the host defense against lung pathogens and in modulating inflammatory responses. While SP-D has been detected in extrapulmonary tissues, little is known about its expression and function in the vasculature. Immunostaining of human coronary artery tissue sections demonstrated immunoreactive SP-D protein in smooth muscle cells (SMCs) and endothelial cells. SP-D was also detected in isolated human coronary artery SMCs (HCASMCs) by PCR and immunoblot analysis. Treatment of HCASMCs with endotoxin (LPS) stimulated the release of IL-8, a proinflammatory cytokine. This release was inhibited >70% by recombinant SP-D. Overexpression of SP-D by adenoviral-mediated gene transfer in HCASMCs inhibited both LPS- and TNF-α-induced IL-8 release. Overexpression of SP-D also enhanced uptake of Chlamydia pneumoniae elementary bodies into HCASMCs while attenuating IL-8 production induced by bacterial exposure. Both LPS and TNF-α increased SP-D mRNA levels by five- to eightfold in HCASMCs, suggesting that inflammatory mediators upregulate the expression of SP-D. In conclusion, SP-D is expressed in human coronary arteries and functions as an anti-inflammatory protein in HCASMCs. SP-D may also participate in the host defense against pathogens that invade the vascular wall.
Prolonged heterologous β2-adrenoceptor desensitization promotes proasthmatic airway smooth muscle function via PKA/ERK1/2-mediated phosphodiesterase-4 induction
Authors: Hu Aihua , Nino Gustavo , Grunstein Judith S. , Fatma Sumbul , Grunstein Michael M.
Published: March 2008

β2-Adrenergic receptor (β2AR) agonists acutely relieve bronchoconstriction via cAMP-mediated relaxation of airway smooth muscle (ASM). Airway constrictor responsiveness may be significantly heightened, however, following protracted exposure to these agents, presumably reflecting the effects of β2AR desensitization in ASM accompanying prolonged cAMP signaling. Because cAMP phosphodiesterase (PDE) activity can significantly modulate ASM contractility, we investigated the mechanism regulating PDE expression and its potential role in mediating changes in agonist-induced constrictor and relaxation responsiveness in ASM following its heterologous β2AR desensitization by prolonged exposure to cAMP-elevating agents. Isolated rabbit ASM tissues and cultured human ASM cells treated for 24 h with the receptor- or nonreceptor-coupled cAMP-stimulating agent, prostaglandin E2(PGE2) or forskolin, respectively, exhibited constrictor hyperresponsiveness to acetylcholine and impaired β2AR-mediated relaxation and cAMP accumulation. These proasthmatic-like changes in ASM function were associated with upregulated PDE4 activity, reflective of increased transcription of the PDE4D5 isoform, and were prevented by pretreatment of the ASM with a PDE4 inhibitor. Extended studies using gene silencing and pharmacological approaches to inhibit specific intracellular signaling molecules demonstrated that the mechanism underlying PGE2-induced transcriptional upregulation of PDE4D5 involves PKA-dependent activation of Giprotein signaling via the βγ-subunits, the latter eliciting downstream activation of ERK1/2 and its consequent induction of PDE4D5 transcription. Collectively, these findings identify that β2AR desensitization in ASM following prolonged exposure to cAMP-elevating agents is associated with proasthmatic-like changes in ASM responsiveness that are mediated by upregulated PDE4 expression induced by activated cross talk between the PKA and ERK1/2 signaling pathways.
The ΔF508-CFTR mutation results in increased biofilm formation byPseudomonas aeruginosaby increasing iron availability
Authors: Moreau-Marquis Sophie , Bomberger Jennifer M. , Anderson Gregory G. , Swiatecka-Urban Agnieszka , Ye Siying , O'Toole George A. , Stanton Bruce A.
Published: March 2008

Enhanced antibiotic resistance of Pseudomonas aeruginosa in the cystic fibrosis (CF) lung is thought to be due to the formation of biofilms. However, there is no information on the antibiotic resistance of P. aeruginosa biofilms grown on human airway epithelial cells or on the effects of airway cells on biofilm formation by P. aeruginosa. Thus we developed a coculture model and report that airway cells increase the resistance of P. aeruginosa to tobramycin (Tb) by >25-fold compared with P. aeruginosa grown on abiotic surfaces. Therefore, the concentration of Tb required to kill P. aeruginosa biofilms on airway cells is 10-fold higher than the concentration achievable in the lungs of CF patients. In addition, CF airway cells expressing ΔF508-CFTR significantly enhanced P. aeruginosa biofilm formation, and ΔF508 rescue with wild-type CFTR reduced biofilm formation. Iron (Fe) content of the airway in CF is elevated, and Fe is known to enhance P. aeruginosa growth. Thus we investigated whether enhanced biofilm formation on ΔF508-CFTR cells was due to increased Fe release by airway cells. We found that airway cells expressing ΔF508-CFTR released more Fe than cells rescued with WT-CFTR. Moreover, Fe chelation reduced biofilm formation on airway cells, whereas Fe supplementation enhanced biofilm formation on airway cells expressing WT-CFTR. These data demonstrate that human airway epithelial cells promote the formation of P. aeruginosa biofilms with a dramatically increased antibiotic resistance. The ΔF508-CFTR mutation enhances biofilm formation, in part, by increasing Fe release into the apical medium.
Elevation of body temperature is an essential factor for exercise-increased extracellular heat shock protein 72 level in rat plasma
Authors: Ogura Yuji , Naito Hisashi , Akin Senay , Ichinoseki-Sekine Noriko , Kurosaka Mitsutoshi , Kakigi Ryo , Sugiura Takao , Powers Scott K. , Katamoto Shizuo , Demirel Haydar A.
Published: March 2008

This study examined whether the exercise-increased extracellular heat shock protein 72 (eHsp72) levels in rats was associated with body temperature elevation during exercise. In all, 26 female Sprague-Dawley rats (3 mo old) were assigned randomly to control (CON; n = 8), exercise under warm temperature (WEx; n = 9), or exercise under cold temperature (CEx; n = 9). The WEx and CEx were trained at 25°C or 4°C, respectively, for nine days using a treadmill. Before and immediately after the final exercise bout, the colonic temperatures were measured as an index of body temperature. The animals were subsequently anesthetized, and blood samples were collected and centrifuged. Plasma samples were obtained to assess their eHsp72 levels. Only the colonic temperature in WEx was increased significantly ( P < 0.05) by exercise. The eHsp72 level in WEx was significantly higher ( P < 0.05) than that of either the CON or CEx. However, no significant difference was found between CON and CEx. Regression analyses revealed that the eHsp72 level increased as a function of the body temperature. In another experiment, the eHsp72 level of animals with body temperature that was passively elevated through similar kinetics to those of the exercise was studied. Results of this experiment showed that mere body temperature elevation was insufficient to induce eHsp72 responses. Collectively, our results suggest that body temperature elevation during exercise is important for induction of exercise-increased eHsp72. In addition, the possible role of body temperature elevation is displayed when the exercise stressor is combined with it.
Endoplasmic reticulum stress and unfolded protein response in renal pathophysiology: Janus faces
Authors: Kitamura Masanori
Published: March 2008

A number of pathophysiological insults lead to accumulation of unfolded proteins in the endoplasmic reticulum (ER) and cause ER stress. In response to accumulation of unfolded/misfolded proteins, cells adapt themselves to the stress condition via the unfolded protein response (UPR). For the cells, UPR is a double-edged sword. It triggers both prosurvival and proapoptotic signals. ER stress and UPR may, therefore, be involved in a diverse range of pathological situations. However, currently, information is limited regarding roles of ER stress and UPR in the renal pathophysiology. This review describes current knowledge on the relationship between ER stress and diseases and summarizes evidence for the link between ER stress/UPR and renal diseases.
Auditory Cortex Phase Locking to Amplitude-Modulated Cochlear Implant Pulse Trains
Authors: Middlebrooks John C.
Published: March 2008

Cochlear implant speech processors transmit temporal features of sound as amplitude modulation of constant-rate electrical pulse trains. This study evaluated the central representation of amplitude modulation in the form of phase-locked firing of neurons in the auditory cortex. Anesthetized pigmented guinea pigs were implanted with cochlear electrode arrays. Stimuli were 254 pulse/s (pps) trains of biphasic electrical pulses, sinusoidally modulated with frequencies of 10–64 Hz and modulation depths of −40 to −5 dB re 100% (i.e., 1–56.2% modulation). Single- and multiunit activity was recorded from multi-site silicon-substrate probes. The maximum frequency for significant phase locking (limiting modulation frequency) was ≥60 Hz for 42% of recording sites, whereas phase locking to pulses of unmodulated pulse trains rarely exceeded 30 pps. The strength of phase locking to frequencies ≥40 Hz often varied nonmonotonically with modulation depth, commonly peaking at modulation depths around −15 to −10 dB. Cortical phase locking coded modulation frequency reliably, whereas a putative rate code for frequency was confounded by rate changes with modulation depth. Group delay computed from the slope of mean phase versus modulation frequency tended to increase with decreasing limiting modulation frequency. Neurons in cortical extragranular layers had lower limiting modulation frequencies than did neurons in thalamic afferent layers. Those observations suggest that the low-pass characteristic of cortical phase locking results from intracortical filtering mechanisms. The results show that cortical neurons can phase lock to modulated electrical pulse trains across the range of modulation frequencies and depths presented by cochlear implant speech processors.
Relative Roles of Different Mechanisms of Depression at the Mouse Endbulb of Held
Authors: Yang Hua , Xu-Friedman Matthew A.
Published: March 2008

Several mechanisms can underlie short-term synaptic depression, including vesicle depletion, receptor desensitization, and changes in presynaptic release probability. To determine which mechanisms affect depression under physiological conditions, we studied the synapse formed by auditory nerve fibers onto bushy cells in the anteroventral cochlear nucleus (the “endbulb of Held”) using voltage-clamp recordings of brain slices from P15–P21 mice near physiological temperatures. Depression of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) excitatory postsynaptic currents (EPSCs) showed two phases of recovery. The fast component of depression for the AMPA EPSC was eliminated by cyclothiazide and aniracetam, suggesting it results from desensitization. The fast component of depression for the NMDA EPSC was reduced by the low-affinity antagonist l-AP5, suggesting it results from saturation. The remaining depression in AMPA and NMDA components is identical and therefore presynaptic in origin. It is likely to result from presynaptic vesicle depletion. Recovery from depression after trains of activity was slowed by the application of EGTA-AM, suggesting that the endbulb has a residual-calcium-dependent form of recovery. We developed a model that incorporates depletion, desensitization, and calcium-dependent recovery. This model replicated experimental findings over a range of experimental conditions. The model further indicated that desensitization plays only a minor role during prolonged activity, in large part because presynaptic release is so depleted. Thus depletion appears to be the dominant mechanism of depression at the endbulb during normal activity. Furthermore, calcium-dependent recovery at the endbulb is critical to prevent complete rundown during high activity and to preserve the reliability of information transmission.
Directed and Motivated Attention during Processing of Natural Scenes
Authors: Ferrari Vera , Codispoti Maurizio , Cardinale Rossella , Bradley Margaret M.
Published: March 2008

Visual attention can be voluntarily oriented to detect target stimuli in order to facilitate goal-directed behaviors. Other visual stimuli capture attention because of motivational significance. The aim of the present study was to investigate the relationship between directed and motivated attention using event-related potentials. Affectively engaging pictures were presented either as target stimuli or as nontargets in a categorization task. Results indicated that both task relevance and emotional significance modulated the late positive potential (LPP) over centro-parietal sensors. Effects of directed and motivated attention on the LPP were additive, with the largest centro-parietal positivity found for emotional pictures that were targets of directed attention, and the least for neutral pictures that were nontargets. Taken together, the data provide new information regarding the relationship between motivated and directed attention, and suggest that the LPP reflects the operation of attentional neural circuits that are utilized by both top-down and bottom-up processes.
Cortical Dynamics of Anticipatory Mechanisms in Interception: A Neuromagnetic Study
Authors: Senot Patrice , Baillet Sylvain , Renault Bernard , Berthoz Alain
Published: March 2008

Humans demonstrate an amazing ability for intercepting and catching moving targets, most noticeably in fast-speed ball games. However, the few studies exploring the neural bases of interception in humans and the classical studies on visual motion processing and visuomotor interactions have reported rather long latencies of cortical activations that cannot explain the performances observed in most natural interceptive actions. The aim of our experiment was twofold: (1) describe the spatio-temporal unfolding of cortical activations involved in catching a moving target and (2) provide evidence that fast cortical responses can be elicited by a visuomotor task with high temporal constraints and decide if these responses are task or stimulus dependent. Neuromagnetic brain activity was recorded with whole-head coverage while subjects were asked to catch a free-falling ball or simply pay attention to the ball trajectory. A fast, likely stimulus-dependent, propagation of neural activity was observed along the dorsal visual pathway in both tasks. Evaluation of latencies of activations in the main cortical regions involved in the tasks revealed that this entire network of regions was activated within 40 msec. Moreover, comparison of experimental conditions revealed similar patterns of activation except in contralateral sensorimotor regions where common and catch-specific activations were differentiated.
Vladimir Bonačić: Computer-Generated Works Made within Zagreb's New Tendencies Network (1961–1973)
Authors: Fritz Darko
Published: March 2008

Scientist Vladimir Bonačić began his artistic career in 1968 under the auspices of the international New Tendencies movement (NT). From 1968 to 1971 Bonačić created a series of “dynamic objects”—interactive computer-generated light installations, five of which were set up in public spaces. The author shows the context of Bonačić's work within the Zagreb cultural environment dominated by the New Tendencies movement and network (1961–1973). The paper shows his theoretical and practical criticism of the use of randomness in computer-generated art and describes his working methods as combining the algebra of Galois fields and an anti-commercial approach with custom-made hardware. It seems that Bonačić's work fulfills and develops Matko Meštrović's proposition that “in order to enrich that which is human, art must start to penetrate the extra-poetic and the extra-human.”
Dissipation of Synoptic-Scale Flow by Small-Scale Turbulence
Authors: Ngan K. , Bartello P. , Straub D. N.
Published: March 2008

Although it is now accepted that imbalance in the atmosphere and ocean is generic, the feedback of the unbalanced motion on the balanced flow has not received much attention. In this work the parameterization problem is examined in the context of rotating stratified turbulence, that is, with a nonhydrostatic Boussinesq model. Using the normal modes as a first approximation to the balanced and unbalanced flow, the growth of ageostrophic perturbations to the quasigeostrophic flow and the associated feedback are studied. For weak stratification, there are analogies with the three-dimensionalization of decaying 2D turbulence: the growth rate of the ageostrophic perturbation follows a linear estimate, geostrophic energy is extracted from the base flow, and the associated damping on the geostrophic base flow (the “eddy viscosity”) is peaked at large horizontal scales. For strong stratification, the transfer spectra and eddy viscosities maintain this structure if there is synoptic-scale motion and the buoyancy scale is adequately resolved. This has been confirmed for global Rossby and Froude numbers of O(0.1). Implications for atmospheric and oceanic modeling are discussed.
Time Scale and Feedback of Zonal-Mean-Flow Variability
Authors: Son Seok-Woo , Lee Sukyoung , Feldstein Steven B. , Ten Hoeve John E.
Published: March 2008

The physical processes that determine the time scale of zonal-mean-flow variability are examined with an idealized numerical model that has a zonally symmetric lower boundary. In the part of the parameter space where the time-mean zonal flow is characterized by a single (double) jet, the dominant form of zonal-mean-flow variability is the zonal index (poleward propagation), and the time-mean potential vorticity gradient is found to be strong and sharp (weak and broad). The e-folding time scale of the zonal index is found to be close to 55 days, much longer than the observed 10-day time scale. The e-folding time scale of the poleward propagation is about 40 days. The long e-folding time scales for the zonal index are found to be consistent with an unrealistically strong and persistent eddy–zonal-mean-flow feedback. A calculation of the refractive index indicates that the background flow supports eddies that are trapped within midlatitudes, undergoing relatively little meridional propagation.

Additional model runs are performed with an idealized mountain to investigate whether zonal asymmetry can disrupt the eddy feedback. For single-jet states, the time scale is reduced to about 30 days if the mountain height is 4 km or less. The reduction in the time scale occurs because the stationary eddies excited by the mountain alter the background flow in a manner that leads to the replacement of zonal-index events by shorter-time-scale poleward propagation. With a 5-km mountain, the time scale reverts and increases to 105 days. This threshold behavior is again attributed to a sharpening of the background zonal jet, which arises from an extremely strong stationary wave momentum flux convergence. In contrast, for double-jet states, the time scale changes only slightly and the poleward propagation is maintained in all mountain runs.
Infrasound Emitted by Tornado-Like Vortices: Basic Theory and a Numerical Comparison to the Acoustic Radiation of a Single-Cell Thunderstorm
Authors: Schecter David A. , Nicholls Melville E. , Persing John , Bedard Alfred J. , Pielke Roger A.
Published: March 2008

This paper addresses the physics and numerical simulation of the adiabatic generation of infrasound by tornadoes. Classical analytical results regarding the production of infrasound by vortex Rossby waves and by corotating “suction vortices” are reviewed. Conditions are derived for which critical layers damp vortex Rossby waves that would otherwise grow and continually produce acoustic radiation. These conditions are similar to those that theoretically suppress gravity wave radiation from larger mesoscale cyclones, such as hurricanes. To gain perspective, the Regional Atmospheric Modeling System (RAMS) is used to simulate the infrasound that radiates from a single-cell thunderstorm in a shear-free environment. In this simulation, the dominant infrasound in the 0.1–10-Hz frequency band appears to radiate from the vicinity of the melting level, where diabatic processes involving hail are active. It is shown that the 3D Rossby waves of a tornado-like vortex (simulated with RAMS) can generate stronger infrasound if the maximum wind speed of the vortex exceeds a modest threshold. Technical issues regarding the numerical simulation of tornado infrasound are also addressed. Most importantly, it is shown that simulating tornado infrasound likely requires a spatial resolution that is an order of magnitude finer than the current practical limit (10-m grid spacing) for modeling thunderstorms.
Exploring the Possible Role of Small-Scale Terrain Drag on Stable Boundary Layers over Land
Authors: Steeneveld G. J. , Holtslag A. A. M. , Nappo C. J. , van de Wiel B. J. H. , Mahrt L.
Published: March 2008

This paper addresses the possible role of unresolved terrain drag, relative to the turbulent drag on the development of the stable atmospheric boundary layer over land. Adding a first-order estimate for terrain drag to the turbulent drag appears to provide drag that is similar to the enhanced turbulent drag obtained with the so-called long-tail mixing functions. These functions are currently used in many operational models for weather and climate, although they lack a clear physical basis. Consequently, a simple and practical quasi-empirical parameterization of terrain drag divergence for use in large-scale models is proposed and is tested in a column mode. As an outcome, the cross-isobaric mass flow (a measure for cyclone filling) with the new scheme, using realistic turbulent drag, appears to be equal to what is found with the unphysical long-tail scheme. At the same time, the new scheme produces a much more realistic less-deep boundary layer than is obtained by using the long-tail mixing function.
SAL—A Novel Quality Measure for the Verification of Quantitative Precipitation Forecasts
Authors: Wernli Heini , Paulat Marcus , Hagen Martin , Frei Christoph
Published: March 2008

A novel object-based quality measure, which contains three distinct components that consider aspects of the structure (S), amplitude (A), and location (L) of the precipitation field in a prespecified domain (e.g., a river catchment) is introduced for the verification of quantitative precipitation forecasts (QPF). This quality measure is referred to as SAL. The amplitude component A measures the relative deviation of the domain-averaged QPF from observations. Positive values of A indicate an overestimation of total precipitation; negative values indicate an underestimation. For the components S and L, coherent precipitation objects are separately identified in the forecast and observations; however, no matching is performed of the objects in the two datasets. The location component L combines information about the displacement of the predicted (compared to the observed) precipitation field’s center of mass and about the error in the weighted-average distance of the precipitation objects from the total field’s center of mass. The structure component S is constructed in such a way that positive values occur if precipitation objects are too large and/or too flat, and negative values if the objects are too small and/or too peaked. Perfect QPFs are characterized by zero values for all components of SAL. Examples with both synthetic precipitation fields and real data are shown to illustrate the concept and characteristics of SAL. SAL is applied to 4 yr of daily accumulated QPFs from a global and finer-scale regional model for a German river catchment, and the SAL diagram is introduced as a compact means of visualizing the results. SAL reveals meaningful information about the systematic differences in the performance of the two models. While the median of the S component is close to zero for the regional model, it is strongly positive for the coarser-scale global model. Consideration is given to the strengths and limitations of the novel quality measure and to possible future applications, in particular, for the verification of QPFs from convection-resolving weather prediction models on short time scales.
Factors Influencing Asian Indian Graduate Students' Attitudes Toward People With Disabilities
Authors: Parashar Divya , Chan Fong , Leierer Stephen
Published: March 2008

Asian Indians are one of the fastest-growing immigrant groups in the United States, yet little is known about their attitudes toward persons with disabilities and rehabilitation. The purpose of this study was to examine factors influencing Asian Indian students' attitudes toward people with disabilities, using a conjoint analysis design ( N = 90). The design used a conjoint measurement where the variables included disability type, gender, age, education, and employment status. The results indicate that disability type was most heavily involved in the decision-making process, that attitude and preference formation were significantly affected by characteristics other than disability type, and that students' previous contact with people with disabilities affected the relative importance of disability type and age in attitudes and preference formation. The findings of this study are similar to those of conjoint analysis studies of other Asian and American students. Implications for rehabilitation counseling practices with Asian Indian Americans are discussed.
Hope for an Uncertain Future
Authors: Johnson Karen A.
Published: March 2008

This article explores the documented degree of the destruction triggered by Hurricane Katrina, the impact on the Orleans Parish School District (OPSD), and the efforts that have been made to recover, rebuild, and reopen the public schools. Using a framework that examines historical inequalities and long-term neglect of OPSD schools pre-Katrina, the author assesses whether or not current attempts to rebuild a new school system for New Orleans's students is constrained by a heritage of racial inequality in Louisiana. The author contends that the manner in which the school recovery efforts are currently developing, with its emphasis on a market-based privatization ideology, does not engender hope for a new and improved system that will produce a socially just and equitable schooling experience for its predominately African American and poor students.
Confusion About the Transition to Socialism
Authors: Fitzgerald Frank T. , Petras James F.
Published: March 2008

These gentlemen think that when they have changed the names of things they have changed the things themselves.