bluuebunny/crossref_metadata_2025 huggingface dataset:
An orthogonality relation-based technique for post-processing finite element predictions of waves scattering in solid waveguides
Authors: Moreau L. , Castaings M. , Hosten B. , Predoi M. V.
Published: August 2006

In this paper we propose an efficient way to post-process output data predicted by Finite Element (FE) or Boundary Element (BE) codes, when the scattering of Lamb modes by defects in plate-like structures is considered. The use of a general orthogonality relation is compared to classical post-processing made with spatial FFT. To get the amplitudes of incident or scattered modes, this orthogonality relation requires the numerical prediction of the through-thickness displacements, and stress-fields distributions, on each side of the scatterer. The distance between the location where these fields are predicted and the scatterer can be very small, thus allowing huge reductions in the size of the mesh. Through two examples, this orthogonality relation is used to calculate the reflection and transmission coefficients of a pure Lamb mode incident on a notch-like defect, in either an elastic or a viscoelastic plate. Thanks to efficient absorbing regions, the FE meshed domains are reduced to the vicinity of the defects, thus allowing several advantages of the method to be demonstrated in comparison to some weaknesses of the classical post-processing based on spatial FFT.
Neural correlates of intelligibility in speech investigated with noise vocoded speech—A positron emission tomography study
Authors: Scott Sophie K. , Rosen Stuart , Lang Harriet , Wise Richard J. S.
Published: August 2006

Functional imaging studies of speech perception in the human brain have identified a key role for auditory association areas in the temporal lobes (bilateral superior temporal gyri and sulci) in the perceptual processing of the speech signal. This is extended to suggest some functional specialization within this bilateral system, with a particular role for the left anterior superior temporal sulcus (STS) in processing intelligible speech. In the current study, noise-vocoded speech was used to vary the intelligibility of speech parametrically. This replicated the finding of a selective response to intelligibility in speech in the left anterior superior temporal sulcus, in contrast to the posterior superior temporal sulcus, which showed a response profile insensitive to the degree of intelligibility. These results are related to theories of functional organization in the human auditory system, which have indicated that there are separate processing streams, with different functional roles, running anterior and posterior to primary auditory cortex. Specifically, it is suggested that an anterior stream processing intelligibility can be distinguished from a posterior stream associated with transient representations, important in spoken repetition and working memory.
Auralization study of optimum reverberation times for speech intelligibility for normal and hearing-impaired listeners in classrooms with diffuse sound fields
Authors: Yang Wonyoung , Hodgson Murray
Published: August 2006

Speech-intelligibility tests auralized in a virtual classroom were used to investigate the optimal reverberation times for verbal communication for normal-hearing and hearing-impaired adults. The idealized classroom had simple geometry, uniform surface absorption, and an approximately diffuse sound field. It contained a speech source, a listener at a receiver position, and a noise source located at one of two positions. The relative output levels of the speech and noise sources were varied, along with the surface absorption and the corresponding reverberation time. The binaural impulse responses of the speech and noise sources in each classroom configuration were convolved with Modified Rhyme Test (MRT) and babble-noise signals. The resulting signals were presented to normal-hearing and hearing-impaired adult subjects to identify the configurations that gave the highest speech intelligibilities for the two groups. For both subject groups, when the speech source was closer to the listener than the noise source, the optimal reverberation time was zero. When the noise source was closer to the listener than the speech source, the optimal reverberation time included both zero and nonzero values. The results generally support previous theoretical results.
Radiation forces exerted on arbitrarily located sphere by acoustic tweezer
Authors: Lee Jungwoo , Shung K. Kirk
Published: August 2006

In a previous paper acoustic radiation force on a lipid sphere in a 100-MHz focused Gaussian field was calculated to demonstrate the acoustic tweezer effect near the focus. The theoretical formulation was based on the situation where the sphere is centered along the beam axis. Given intensity distribution independent of the x axis, it was then approximated by a cylindrical model for the sake of simplicity. Only the axial forces were considered because no lateral forces exist due to an object’s symmetry. However, it was difficult to employ the same technique to the more general case when it is off the beam axis. To overcome the limitation, in this paper the previous model is modified to compute two additional lateral forces by carrying out the projection over arbitrary incident planes to restrict the integration limits. For different sizes of the sphere, the magnitudes of the net forces in three orthogonal directions are computed. The results show that the acoustic tweezer can be realized more easily in the lateral directions than in the axial directions. Differing from the axisymmetric case, the spheres of small sizes tend to be more strongly attracted than the larger ones in the lateral directions.
Programmed Transcription of the
var
Gene Family, but Not of
stevor
, in
Plasmodium falciparum
Gametocytes
Authors: Sharp Sarah , Lavstsen Thomas , Fivelman Quinton L. , Saeed Maha , McRobert Louisa , Templeton Thomas J. , Jensen Anja T. R. , Baker David A. , Theander Thor G. , Sutherland Colin J.
Published: August 2006

The
var
genes encode
Plasmodium falciparum
erythrocyte membrane protein 1 (PfEMP1) proteins, a set of highly diverse surface-expressed proteins that mediate adhesion of erythrocytes infected with asexual blood-stage parasites to host endothelium. Switching among expressed PfEMP1 variants in the course of a blood-stage infection is a key component of antigenic variation, and thus immune evasion, by the parasite. The majority of
var
loci are found in the subtelomeric regions of
P. falciparum
chromosomes associated with members of other multigene families, including
stevor
. Both PfEMP1 and STEVOR are expressed in gametocytes, the transmissible parasite stage, but the role of these proteins in the biology of sexual-stage parasites remains unknown. PfEMP1 may continue to mediate antigenic variation in gametocytes, which need to persist in the host for many days before reaching maturity. Using quantitative reverse transcription-PCR and Northern hybridization, we demonstrate that transcription of a defined subset of type C
var
loci occurs during gametocyte development in vitro. This transcriptional program occurs in gametocytes regardless of the
var
expression phenotype of their asexual progenitors and therefore is subject to regulatory processes distinct from those that manage antigenic variation in the asexual parasite. In contrast, the same
stevor
variants are transcribed in both gametocytes and their asexual progenitors. We also provide evidence that for both asexual parasites and gametocytes,
var
and
stevor
transcription patterns are not linked to each other.
The
vtc4
Gene Influences Polyphosphate Storage, Morphogenesis, and Virulence in the Maize Pathogen
Ustilago maydis
Authors: Boyce Kylie J. , Kretschmer Matthias , Kronstad James W.
Published: August 2006

The maize pathogen
Ustilago maydis
switches from budding to filamentous, dikaryotic growth in response to environmental signals including nutrient status, growth in the host, and the presence of mating pheromones. The filamentous dikaryon is capable of proliferating within host tissue to cause disease symptoms including tumors. The transition from yeast cells to hyphal filaments is regulated by a mitogen-activated protein kinase cascade and a cyclic-AMP-protein kinase A (PKA) pathway. Serial analysis of gene expression with PKA mutants identified orthologs of components of the PHO phosphate acquisition pathway as transcriptional targets of the PKA pathway, and these included genes for Pho84, an acid phosphatase, and the vacuolar transport chaperones Vtc1 and Vtc4. In
Saccharomyces cerevisiae
, Vtc4p is required during the fusion of inorganic-phosphate-containing vesicles to the vacuolar membrane and the consequent accumulation of phosphate stored as polyphosphate (polyP) in the vacuole. We found that deletion of
vtc4
in
U. maydis
also reduced polyP stored in vacuoles. Intriguingly, Δ
vtc4
mutants possessed a filamentous cellular morphology, in contrast to the budding, yeast-like growth of the wild-type parent. The Δ
vtc4
mutants also displayed decreased symptom development and reduced proliferation in planta. The interaction with PKA signaling was further investigated by the generation of Δ
vtc4 ubc1
double mutants. Deletion of
vtc4
completely suppressed the multiple-budded phenotype of a Δ
ubc1
mutant, indicating that polyP stores are essential for this PKA-induced trait. Overall, this study reveals a novel role for PKA-regulated polyP accumulation in the control of fungal morphogenesis and virulence.
Molecular Genetic Analysis of an
SNF2
/
brahma
-Related Gene in
Tetrahymena thermophila
Suggests Roles in Growth and Nuclear Development
Authors: Fillingham Jeffrey S. , Garg Jyoti , Tsao Nora , Vythilingum Nama , Nishikawa Takamitsu , Pearlman Ronald E.
Published: August 2006

We used a reverse genetic approach to identify three members of the
SNF2
superfamily of chromatin remodeling genes in the ciliated protozoan
Tetrahymena thermophila
in order to investigate possible functions of ATP-dependent chromatin remodeling factors in growth and nuclear development. Comparative sequence analysis of the gene product of the
Tetrahymena brahma-
related gene (Tt
BRG1
) indicates it is a member of the SNF2/BRM subgroup of the SNF2 superfamily. Northern analysis suggests that Tt
BRG1
has roles in growth and nuclear development in
Tetrahymena
. Indirect immunofluorescence analysis during nuclear development indicates that TtBrg1p localizes to both the parental and developing macronucleus of
Tetrahymena
during the time period corresponding to genome rearrangements. We generated germ line knockout heterokaryons for Tt
BRG1
and demonstrated that expression of the gene is required to complete nuclear development of
Tetrahymena
. In addition, the formation of distinct Pdd1p-containing structures is disturbed during the late stages of conjugation in Tt
BRG1
germ line knockout heterokaryons. We discuss these results in light of possible roles of SNF2-related proteins in growth and nuclear development of
Tetrahymena
.
Transcript Profiles of
Candida albicans
Cortical Actin Patch Mutants Reflect Their Cellular Defects: Contribution of the Hog1p and Mkc1p Signaling Pathways
Authors: Oberholzer Ursula , Nantel André , Berman Judith , Whiteway Malcolm
Published: August 2006

In
Candida albicans
, Myo5p and Sla2p are required for the polarized localization and function of cortical actin patches, for hyphal formation, and for endocytosis. Deletion of either the
MYO5
or the
SLA2
gene generated a common transcriptional response that involved changes in the transcript levels of cell wall protein- and membrane protein-encoding genes. However, these profiles were distinct from those observed for a mutant with specific deletions of the actin-organizing domains of Myo5p or for wild-type cells treated with cytochalasin A, both of which also generate defects in the organization of cortical actin patches. The profiles observed for the
myo5
Δ and
sla2
Δ mutants had similarities to those of wild-type cells subjected to an osmotic shock, and the defects in cortical patch function found with
myo5
Δ and
sla2
Δ mutants, but not cortical actin patch distribution per se, affected sensitivity to various stresses, including heat and osmotic shocks and cell wall damage. Secondary effects coupled with defective endocytosis, such as lack of polarized lipid rafts and associated protein Rvs167-GFP (where GFP is green fluorescent protein) and lack of polarized wall remodeling protein GFP-Gsc1, were also observed for the
myo5
Δ and
sla2
Δ mutants. The mitogen-activated protein kinases Hog1p and Mkc1p, which mediate signaling in response to osmotic stress and cell wall damage, do not play a major role in regulating the transcript level changes in the
myo5
Δ and
sla2
Δ mutants. Hog1p was not hyperphosphorylated in the
myo5
Δ and
sla2
Δ mutants, and the transcript levels of only a subset of genes affected in the
myo5
Δ mutant were dependent upon the presence of Hog1p and Mkc1p. However, it appears that Hog1p and Mkc1p play important roles in the
myo5
Δ mutant cells because double deletion of myosin I and either Hog1p or Mkc1p resulted in very-slow-growing cells.
Effects of exercise and nutritional counseling in women with polycystic ovary syndrome
Authors: Bruner Brenda , Chad Karen , Chizen Donna
Published: August 2006

This pilot study assessed the effects of exercise and nutritional counseling on hormonal, menstrual, and reproductive function in women with polycystic ovary syndrome (PCOS). Twelve females with a clinical, biochemical, and ultrasonographic diagnosis of PCOS were randomly assigned to endurance and resistance exercise plus nutritional counseling (EN) or nutritional counseling only (N) for a period of 12 weeks. Anthropometry, resting metabolic rate (RMR), selected hormones, and ovarian follicle population were measured pre and post-intervention. Following the 12 week intervention, greater decreases in sum of 2 skinfolds (p = 0.002) and a greater increase in estimated VO2 max (p = 0.017) occurred in the exercise group. Significant decreases in waist girth (p = 0.001) and insulin levels (p = 0.03) occurred in both groups. Hormonal changes were not statistically significant; however, a trend towards an improved hormonal profile, specifically sex-hormone binding globulin (EN, 39% increase; N, 8% increase) and lutenizing hormone : follicle-stimulating hormone (LH:FSH) (EN, 9% decrease; N, 27% decrease) occurred in the absence of weight loss. These findings suggest exercise and nutritional counseling may benefit the metabolic and reproductive abnormalities associated with PCOS.
Effets de la puberté sur la balance glucido-lipidique lors de l’exercice de l’enfant obèse
Authors: Zunquin Gautier , Theunynck Denis , Sesboüé Bruno , Arhan Pierre , Bouglé Dominique
Published: August 2006

Étudier l’effet de la puberté sur l’oxydation des substrats énergétiques lors d’un test d’effort aérobie chez des enfants obèses. Deux groupes d’adolescents obèses garçons (34 pré-pubères : indice de masse corporelle (IMC) = 25,94 ± 2,63; Z-score = 4,43 ± 1,83 et 26 post-pubères : IMC = 31,14 ± 4,88; Z-score = 5,264 ± 1,76) ont effectué un test d’intensité croissante sur cycloergomètre. Le premier palier du test est fixé à 30 W, puis l’incrémentation est de 20 W toutes les 3 min 30 s. La moyenne des mesures des gaz ventilatoires, effectuée lors des 30 dernières secondes de chaque palier, nous a permis de calculer les taux d’oxydation des glucides et des lipides en fonction de l’intensité de l’exercice. Les taux d’oxydation des lipides sont significativement supérieurs dans le groupe d’enfants post-pubères. Quand les niveaux d’oxydation sont rapportés à l’importance de la masse maigre (mg·min–1·kg–1 de masse maigre), les niveaux d’oxydations des lipides sont plus importants pour les enfants n’ayant pas effectué leur puberté. La puberté est responsable d’une diminution de la capacité de la masse maigre à utiliser les lipides pour un même niveau d’exercice.
Early effects of spinal cord transection on skeletal muscle properties
Authors: Kelley Melissa D. , Nim Satra , Rousseau Guy , Fowles Jonathon R. , Murphy René J.L.
Published: August 2006

Modulation of β-adrenergic receptor (β-AR) activity affects muscle mass and could have a role in the reduction of muscle mass observed following spinal cord transection (Tx). The aims of this study were to examine the early acute effects of Tx on muscle mass, total and myofibrillar protein concentrations, cytochrome c oxidase activity, and β-AR density of skeletal muscle, to ascertain if any change in muscle properties could be related to β-AR signalling events. Female Sprague–Dawley rats (n = 33; ~255 g) were randomly assigned to 4 experimental groups: control 4 d, control 8 d, Tx 4 d, and Tx 8 d. A complete Tx was performed surgically at the T10 cord level. Compared with controls, muscle mass and muscle – body mass ratios decreased significantly following Tx, with no significant change observed in total and myofibrillar protein concentrations. Spinal cord Tx also resulted in a significant decrease in plantaris cytochrome c oxidase activity by 24% at Tx 4 d and 28% at Tx 8 d (p < 0.05). β-AR density of the lateral gastrocnemius was unchanged; however, the β-AR density of the forelimb triceps brachii m. was found to increase after Tx. Our results suggest that changes in muscle mass and cytochrome c oxidase activity rapidly occur after Tx and do not appear to be related to changes in β-AR density.
Effect of differences in post-exercise lactate accumulation in athletes’ haemodynamics
Authors: Crisafulli Antonio , Tocco Filippo , Pittau Gianluigi , Lorrai Luigi , Porru Cristina , Salis Enrico , Pagliaro Pasquale , Melis Franco , Concu Alberto
Published: August 2006

To verify the relationship between exercise intensity and post-exercise haemodynamics, we studied haemodynamic and lactate responses during 10 min following 3 bicycle tests. Two tests were performed for 3 min at 70% and 130% of the workload corresponding to anaerobic threshold (70% Wat and 130% Wat tests), and 1 was performed until exhaustion at 150% of the maximum workload achieved during a previous incremental test (150% Wmax test). During the recovery period after the 150% Wmax test we observed the highest increases in blood lactate with respect to the baseline: at the 9th minute of recovery lactate concentration increased by +9.3 ± 2.7, +6.4 ± 3.1, and +1.1 ± 0.9 mmol·L–1 in the 150% Wmax (p > 0.05 with respect to the other protocol sessions), 130% Wat, and 70% Wat tests, respectively. We also observed greater reductions in cardiac pre-load and systemic vascular resistance in the 150% Wmax test than in the 130% Wat and 70% Wat tests. However, the cardiac output response successfully faced the increased vasodilatation occurring during 150% Wmax test so that changes in mean blood pressure were similar in the 3 test conditions. This study shows that exercises that yielded different lactate concentrations also led to greater vasodilatation. Nevertheless, mechanisms controlling the cardiovascular apparatus successfully prevented a drop in blood pressure in spite of the cardiovascular stress.
Application of the nuclear factor-κB inhibitor BAY 11-7085 for the treatment of endometriosis: an in vitro study
Authors: Nasu Kaei , Nishida Masakazu , Ueda Tami , Yuge Akitoshi , Takai Noriyuki , Narahara Hisashi
Published: August 2006

Most of the current medical treatments for endometriosis aim to downregulate estrogen activity. However, a high recurrence rate after medical treatment has been the most significant problem. BAY 11-7085, a soluble inhibitor of NK-κB activation, has been shown to inhibit cell proliferation and induce apoptosis of a variety of cells. To examine the potential application of BAY 11-7085 in the treatment of endometriosis, we investigated the effects of this agent on the cell proliferation and apoptosis of cultured ovarian endometriotic cyst stromal cells (ECSCs) by a modified methylthiazole tetrazolium assay, a 5-bromo-2′-deoxyuridine incorporation assay, and internucleosomal DNA fragmentation assays. The effect of BAY 11-7085 on the cell cycle of ECSCs was also determined by flow cytometry. The expression of apoptosis-related molecules was examined in ECSCs with Western blot analysis. BAY 11-7085 significantly inhibited the cell proliferation and DNA synthesis of ECSCs and induced apoptosis and the G0/G1 phase cell cycle arrest of these cells. Additionally, downregulation of the B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl-XLexpression with simultaneous activation of caspase-3, -8, and -9 was observed in ECSCs after treatment with BAY 11-7085. These results suggest that BAY 11-7085 induces apoptosis of ECSCs by suppressing antiapoptotic proteins, and that caspase-3-, -8-, and -9-mediated cascades are involved in this mechanism. Therefore, BAY 11-7085 could be used as a therapeutic agent for the treatment of endometriosis.
Contributions of working muscle to whole body lipid metabolism are altered by exercise intensity and training
Authors: Friedlander Anne L. , Jacobs Kevin A. , Fattor Jill A. , Horning Michael A. , Hagobian Todd A. , Bauer Timothy A. , Wolfel Eugene E. , Brooks George A.
Published: August 2006

To evaluate the contribution of working muscle to whole body lipid oxidation, we examined the effects of exercise intensity and endurance training (9 wk, 5 days/wk, 1 h, 75% V̇o2 peak) on whole body and leg free fatty acid (FFA) kinetics in eight male subjects (26 ± 1 yr, means ± SE). Two pretraining trials [45 and 65% V̇o2 max(45UT, 65UT)] and two posttraining trials [65% of pretraining V̇o2 peak(ABT), and 65% of posttraining V̇o2 peak(RLT)] were performed using [1-13C]palmitate infusion and femoral arteriovenous sampling. Training increased V̇o2 peakby 15% (45.2 ± 1.2 to 52.0 ± 1.8 ml·kg−1·min−1, P < 0.05). Muscle FFA fractional extraction was lower during exercise (EX) compared with rest regardless of workload or training status (≈20 vs. 48%, P < 0.05). Two-leg net FFA balance increased from net release at rest (≈−36 μmol/min) to net uptake during EX for 45UT (179 ± 75), ABT (236 ± 63), and RLT (136 ± 110) ( P < 0.05), but not 65UT (51 ± 127). Leg FFA tracer measured uptake was higher during EX than rest for all trials and greater during posttraining in RLT (716 ± 173 μmol/min) compared with pretraining (45UT 450 ± 80, 65UT 461 ± 72, P < 0.05). Leg muscle lipid oxidation increased with training in ABT (730 ± 163 μmol/min) vs. 65UT (187 ± 94, P < 0.05). Leg muscle lipid oxidation represented ∼62 and 30% of whole body lipid oxidation at lower and higher relative intensities, respectively. In summary, training can increase working muscle tracer measured FFA uptake and lipid oxidation for a given power output, but both before and after training the association between whole body and leg lipid metabolism is reduced as exercise intensity increases.
Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats
Authors: Hsieh Yih-Shou , Yang Shun-Fa , Kuo Dong-Yih
Published: August 2006

Although amphetamine (AMPH)-induced appetite suppression has been attributed to its inhibitory action on neuropeptide Y (NPY), an appetite neurotransmitter abundant in the brain, molecular mechanisms underlying this effect are not well known. This study examined the possible role of protein kinase A (PKA) and cAMP response element-binding protein (CREB) signaling in this anorectic effect, and the results showed that both PKA and CREB mRNA levels in hypothalamus were increased following AMPH treatment, which was relevant to a reduction of NPY mRNA level. To determine whether PKA or CREB was involved in the anorectic response, intracerebroventricular infusions of antisense oligonucleotide (or missense control) were performed 60 min before daily AMPH treatment in conscious rats, and results showed that either PKA or CREB knockdown could block AMPH-induced anorexia as well as restore NPY mRNA level, indicating the respective involvement of PKA and CREB signaling in the regulation of NPY gene expression. It is suggested that hypothalamic PKA and CREB signaling may involve the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression.
Focal adhesion kinase protein levels in gut epithelial motility
Authors: Basson Marc D. , Sanders Matthew A. , Gomez Ruben , Hatfield James , VanderHeide Richard , Thamilselvan Vijayalakshmi , Zhang Jianhu , Walsh Mary F.
Published: August 2006

Mucosal healing requires migration and proliferation. Most studies of focal adhesion kinase (FAK), a protein that regulates motility, proliferation, and apoptosis, have focused on rapid phosphorylation. We reported lower FAK protein levels in motile Caco-2 colon cancer cells and postulated that this reduction in FAK available for activation might impact cell migration and mucosal healing. Therefore, total and active FAK (FAK397) immunoreactivity was assessed at the migrating fronts of human Caco-2 and rat IEC-6 intestinal epithelial cells. Caco-2 and IEC-6 motility, quantitated as migration into linear or circular wounds, was examined following FAK protein inhibition by small interfering RNA (siRNA). FAK protein stability and mRNA expression were ascertained by cycloheximide decay, RT-PCR, and in situ hybridization in static and migrating Caco-2 cells. Cells at the migrating front of Caco-2 and IEC-6 monolayers exhibited lower immunostaining for both total and activated FAK than cells immediately behind the front. Western blot analysis also demonstrated diminished FAK protein levels in motile cells by ≥30% in both the differential density seeding and multiple scrape models. siRNA FAK protein inhibition enhanced motility in both the linear scrape (20% in Caco-2) and circular wound (16% in Caco-2 and 19% in IEC-6 cells) models. FAK protein degradation did not differ in motile and static Caco-2 cells and was unaffected by FAK397phosphorylation, but FAK mRNA was lower in migrating Caco-2 cells. Thus FAK protein abundance appears regulated at the mRNA level during gut epithelial cell motility and may influence epithelial cell migration coordinately with signals that modify FAK phosphorylation.
CD23-mediated transport of IgE/immune complexes across human intestinal epithelium: role of p38 MAPK
Authors: Tu Yahong , Perdue Mary H.
Published: August 2006

We previously reported that CD23/FcεRII (low-affinity IgE receptor) is expressed on human intestinal epithelial cells and is responsible for transepithelial transport of IgE. In this study, we compared the transport of IgE with that of immune complexes in both the apical-to-serosal and the serosal-to-apical directions across HT29 epithelial cell layers and examined the effects of two p38 MAPK inhibitors, SKF86002 and SB203580, on the expression and function of CD23. Our study showed that both p38 MAPK inhibitors at 10 μM significantly inhibited constitutive and IL-4-upregulated CD23 protein expression in epithelial cells. Both inhibitors, in a concentration-dependent manner, also significantly reduced IgE binding and uptake into cells. Transepithelial transport of IgE and immune complexes across the epithelial barrier were similarly inhibited. IL-4 upregulated the phosphorylation and activity of p38 MAPK and the phosphorylation of the downstream substrate MAPKAPK-2 (MK-2). The inhibitors exerted effects in the pathway post the p38 MAPK; SB203580 significantly inhibited the phosphorylation of MK-2. Our results indicate that CD23 expression in these human intestinal epithelial cells is mediated through the p38 MAPK pathway and that inhibition of p38 MAPK consequently interferes with the transport of IgE and immune complexes across the intestinal epithelial barrier.
Nutrient modulation of intestinal gas dynamics in healthy humans: dependence on caloric content and meal consistency
Authors: Gonlachanvit Sutep , Coleski Radoslav , Owyang Chung , Hasler William L.
Published: August 2006

The actions of nutrients on gut transit of liquids and solids have been extensively studied, but the effects of meal ingestion on intestinal gas flow are unexplored. We hypothesized that meals of varying caloric content and consistency modulate gas transit to different degrees. Nine healthy volunteers underwent jejunal perfusion of physiological gas mixtures at 12 ml·min−1·3 h, with ingestion of nothing (control), water (240 ml), 240-kcal liquid meals, and 240-kcal solid meals at the end of the second hour in separate studies. Gas was quantified from an intrarectal catheter. After an initial lag phase, gas evacuation approached steady state by the end of the fasting period. Solid and liquid caloric meals increased total gas volumes evacuated from 5–40 min after ingestion vs. control studies ( P < 0.05). These increases resulted from increased numbers of bolus gas evacuations ( P < 0.05), whereas bolus volumes, pressures, and flow rates were similar for all test conditions. Solid and liquid caloric meals elicited similar effects on bolus gas dynamic parameters, whereas water did not affect these measures vs. control (NS, not significant). Both caloric meals and the noncaloric liquid meal increased continuous gas flow, which represented <2% of total gas expulsion. In conclusion, caloric meals promote bolus gas transit in healthy humans, whereas noncaloric liquids have no effect. Solids stimulate early postprandial gas dynamics to the same extent as liquid meals of similar caloric content. Thus modulatory effects of meals on intestinal gas transit depend on their caloric content but not their consistency.
Intracellular signal transduction for migration and actin remodeling in vascular smooth muscle cells after sphingosylphosphorylcholine stimulation
Authors: Li Sheng , Tanaka Hideyuki , Wang Hong Hui , Yoshiyama Shinji , Kumagai Hiroyuki , Nakamura Akio , Brown Dawn L. , Thatcher Sean E. , Wright Gary L. , Kohama Kazuhiro
Published: August 2006

Molecular mechanisms underlying migration of vascular smooth muscle cells (VSMCs) toward sphingosylphosphorylcholine (SPC) were analyzed in light of the hypothesis that remodeling of the actin cytoskeleton should be involved. After SPC stimulation, mitogen-activated protein kinases (MAPKs), including p38 MAPK (p38) and p42/44 MAPK (p42/44), were found to be phosphorylated. Migration of cells toward SPC was reduced in the presence of SB-203580, an inhibitor of p38, but not PD-98059, an inhibitor of p42/44. Pertussis toxin (PTX), a Giprotein inhibitor, induced an inhibitory effect on p38 phosphorylation and VSMC migration. Myosin light chain (MLC) phosphorylation occurred after SPC stimulation with or without pretreatment with SB-203580 or PTX. The MLC kinase inhibitor ML-7 and the Rho kinase inhibitor Y-27632 inhibited MLC phosphorylation but only partially inhibited SPC-directed migration. Complete inhibition was achieved with the addition of SB-203580. After SPC stimulation, the actin cytoskeleton formed thick bundles of actin filaments around the periphery of cells, and the cells were surrounded by elongated filopodia, i.e., magunapodia. The peripheral actin bundles consisted of α- and β-actin, but magunapodia consisted exclusively of β-actin. Such a remodeling of actin was reversed by addition of SB-203580 and PTX, but not ML-7 or Y-27632. Taken together, our biochemical and morphological data confirmed the regulation of actin remodeling and suggest that VSMCs migrate toward SPC, not only by an MLC phosphorylation-dependent pathway, but also by an MLC phosphorylation-independent pathway.
Positive transcriptional regulatory element located within exon 1 of elastin gene
Authors: Pierce Richard A. , Moore Carla H. , Arikan Meltem Cevik
Published: August 2006

Elastin gene transcription is cell type specific and developmentally regulated, but the promoter often exhibits relatively weak activity in transient transfections of cells that express elastin at high levels. To search for positive-acting regulatory sequences, we isolated genomic clones spanning the mouse elastin gene and extensive 5′- and 3′-flanking regions. Restriction fragments of potential regulatory regions were ligated 5′ or 3′ relative to the active promoter to test for enhancer activity in transient transfections of fetal rat lung fibroblasts, which express elastin at high levels, and distal lung epithelial cells, which do not express detectable elastin. Fragments of intron 1 did not exhibit significant enhancer activity. Inclusion of the 84-bp exon 1 and adjacent 5′-untranslated region increased activity of the elastin promoter approximately sixfold compared with parental constructs. Transfections with constructs of varying promoter length showed that as little as 40 bp of the 5′ end of exon 1 confers enhanced activity in elastin-expressing rat lung fibroblasts, but these constructs had variable activity in lung epithelial cell lines. This region, localized between the transcription start site and extending into exon 1, binds Sp1 in nuclear extracts from elastin-expressing cells. These studies indicate a role for the 5′ end of the first exon of the elastin gene in regulating strong transcriptional activity in elastogenic cells.
Protoporphyrin IX generation from δ-aminolevulinic acid elicits pulmonary artery relaxation and soluble guanylate cyclase activation
Authors: Mingone Christopher J. , Gupte Sachin A. , Chow Joseph L. , Ahmad Mansoor , Abraham Nader G. , Wolin Michael S.
Published: August 2006

Protoporphyrin IX is an activator of soluble guanylate cyclase (sGC), but its role as an endogenous regulator of vascular function through cGMP has not been previously reported. In this study we examined whether the heme precursor δ-aminolevulinic acid (ALA) could regulate vascular force through promoting protoporphyrin IX-elicited activation of sGC. Exposure of endothelium-denuded bovine pulmonary arteries (BPA) in organoid culture to increasing concentrations of the heme precursor ALA caused a concentration-dependent increase in BPA epifluorescence, consistent with increased tissue protoporphyrin IX levels, associated with decreased force generation to increasing concentrations of serotonin. The force-depressing actions of 0.1 mM ALA were associated with increased cGMP-associated vasodilator-stimulated phosphoprotein (VASP) phosphorylation and increased sGC activity in homogenates of BPA cultured with ALA. Increasing iron availability with 0.1 mM FeSO4inhibited the decrease in contraction to serotonin and increase in sGC activity caused by ALA, associated with decreased protoporphyrin IX and increased heme. Chelating endogenous iron with 0.1 mM deferoxamine increased the detection of protoporphyrin IX and force depressing activity of 10 μM ALA. The inhibition of sGC activation with the heme oxidant 10 μM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) attenuated the force depressing actions of an NO donor without altering the actions of ALA. Thus control of endogenous formation of protoporphyrin IX from ALA by the availability of iron is potentially a novel physiological mechanism of controlling vascular function through regulating the activity of sGC.
Increased AQP2 targeting in primary cultured IMCD cells in response to angiotensin II through AT1receptor
Authors: Lee Yu-Jung , Song In-Kyung , Jang Kyung-Jin , Nielsen Jakob , Frøkiær Jørgen , Nielsen Søren , Kwon Tae-Hwan
Published: August 2006

Vasopressin and angiotensin II (ANG II) play a major role in renal water and Na+reabsorption. We previously demonstrated that ANG II AT1receptor blockade decreases dDAVP-induced water reabsorption and AQP2 levels in rats, suggesting cross talk between these two peptide hormones ( Am J Physiol Renal Physiol 288: F673–F684, 2005). To directly address this issue, primary cultured inner medullary collecting duct (IMCD) cells from male Sprague-Dawley rats were treated for 15 min with 1) vehicle, 2) ANG II, 3) ANG II + the AT1receptor blocker candesartan, 4) dDAVP, 5) ANG II + dDAVP, or 6) ANG II + dDAVP + candesartan. Immunofluorescence microscopy revealed that 10−8M ANG II or 10−11M dDAVP ( protocol 1) was associated with increased AQP2 labeling of the plasma membrane and decreased cytoplasmic labeling, respectively. cAMP levels increased significantly in response to 10−8M ANG II and were potentiated by cotreatment with 10−11M dDAVP. Consistent with this finding, immunoblotting revealed that this cotreatment significantly increased expression of phosphorylated AQP2. ANG II-induced AQP2 targeting was blocked by 10−5M candesartan. In protocol 2, treatment with a lower concentration of dDAVP (10−12M) or ANG II (10−9M) did not change subcellular AQP2 distribution, whereas 10−12M dDAVP + 10−9M ANG II enhanced AQP2 targeting. This effect was inhibited by cotreatment with 10−5M candesartan. ANG II-induced cAMP accumulation and AQP2 targeting were inhibited by inhibition of PKC activity. In conclusion, ANG II plays a role in the regulation of AQP2 targeting to the plasma membrane in IMCD cells through AT1receptor activation and potentiates the effect of dDAVP on AQP2 plasma membrane targeting.
Angiotensin metabolism in renal proximal tubules, urine, and serum of sheep: evidence for ACE2-dependent processing of angiotensin II
Authors: Shaltout Hossam A. , Westwood Brian M. , Averill David B. , Ferrario Carlos M. , Figueroa Jorge P. , Diz Debra I. , Rose James C. , Chappell Mark C.
Published: August 2006

Despite the evidence that angiotensin-converting enzyme (ACE)2 is a component of the renin-angiotensin system (RAS), the influence of ACE2 on angiotensin metabolism within the kidney is not well known, particularly in experimental models other than rats or mice. Therefore, we investigated the metabolism of the angiotensins in isolated proximal tubules, urine, and serum from sheep. Radiolabeled [125I]ANG I was hydrolyzed primarily to ANG II and ANG-(1–7) by ACE and neprilysin, respectively, in sheep proximal tubules. The ACE2 product ANG-(1–9) from ANG I was not detected in the absence or presence of ACE and neprilysin inhibition. In contrast, the proximal tubules contained robust ACE2 activity that converted ANG II to ANG-(1–7). Immunoblots utilizing an NH2terminal-directed ACE2 antibody revealed a single 120-kDa band in proximal tubule membranes. ANG-(1–7) was not a stable product in the tubule preparation and was rapidly hydrolyzed to ANG-(1–5) and ANG-(1–4) by ACE and neprilysin, respectively. Comparison of activities in the proximal tubules with nonsaturating concentrations of substrate revealed equivalent activities for ACE (ANG I to ANG II: 248 ± 17 fmol·mg−1·min−1) and ACE2 [ANG II to ANG-(1–7): 253 ± 11 fmol·mg−1·min−1], but lower neprilysin activity [ANG II to ANG-(1–4): 119 ± 24 fmol·mg−1·min−1; P < 0.05 vs. ACE or ACE2]. Urinary metabolism of ANG I and ANG II was similar to the proximal tubules; soluble ACE2 activity was also detectable in sheep serum. In conclusion, sheep tissues contain abundant ACE2 activity that converts ANG II to ANG-(1–7) but does not participate in the processing of ANG I into ANG-(1–9).
Decomposition of Surface EMG Signals
Authors: De Luca Carlo J. , Adam Alexander , Wotiz Robert , Gilmore L. Donald , Nawab S. Hamid
Published: August 2006

This report describes an early version of a technique for decomposing surface electromyographic (sEMG) signals into the constituent motor unit (MU) action potential trains. A surface sensor array is used to collect four channels of differentially amplified EMG signals. The decomposition is achieved by a set of algorithms that uses a specially developed knowledge-based Artificial Intelligence framework. In the automatic mode the accuracy ranges from 75 to 91%. An Interactive Editor is used to increase the accuracy to >97% in signal epochs of about 30-s duration. The accuracy was verified by comparing the firings of action potentials from the EMG signals detected simultaneously by the surface sensor array and by a needle sensor. We have decomposed up to six MU action potential trains from the sEMG signal detected from the orbicularis oculi, platysma, and tibialis anterior muscles. However, the yield is generally low, with typically ≤5 MUs per contraction. Both the accuracy and the yield should increase as the algorithms are developed further. With this technique it is possible to investigate the behavior of MUs in muscles that are not easily studied by needle sensors. We found that the inverse relationship between the recruitment threshold and the firing rate previously reported for muscles innervated by spinal nerves is also present in the orbicularis oculi and the platysma, which are innervated by cranial nerves. However, these two muscles were found to have greater and more widespread values of firing rates than those of large limb muscles.
Coherent Spontaneous Activity Identifies a Hippocampal-Parietal Memory Network
Authors: Vincent Justin L. , Snyder Abraham Z. , Fox Michael D. , Shannon Benjamin J. , Andrews Jessica R. , Raichle Marcus E. , Buckner Randy L.
Published: August 2006

Despite traditional theories emphasizing parietal contributions to spatial attention and sensory-motor integration, functional MRI (fMRI) experiments in normal subjects suggest that specific regions within parietal cortex may also participate in episodic memory. Here we examined correlations in spontaneous blood-oxygenation-level-dependent (BOLD) signal fluctuations in a resting state to identify the network associated with the hippocampal formation (HF) and determine whether parietal regions were elements of that network. In the absence of task, stimuli, or explicit mnemonic demands, robust correlations were observed between activity in the HF and several parietal regions (including precuneus, posterior cingulate, retrosplenial cortex, and bilateral inferior parietal lobule). These HF-correlated regions in parietal cortex were spatially distinct from those correlated with the motion-sensitive MT+ complex. Reanalysis of event-related fMRI studies of recognition memory showed that the regions spontaneously correlated with the HF (but not MT+) were also modulated during directed recollection. These regions showed greater activity to successfully recollected items as compared with other trial types. Together, these results associate specific regions of parietal cortex that are sensitive to successful recollection with the HF.
Continuous Tonic Spike Activity in Spider Warm Cells in the Absence of Sensory Input
Authors: Gingl E. , Tichy H.
Published: August 2006

The warm cells of the spider tarsal organ respond very sensitively to low-amplitude changes in temperature and discharge continuously as the rate of change in temperature reaches zero. To test whether the continuous tonic discharge remains without sensory input, we blocked the warm cell's receptive region by Epoxy glue. The activity continued in this situation, but its dependence on temperature changes was strongly reduced. We interpret this to mean that the warm cells exhibit specific intrinsic properties that underlie the generation of the tonic discharge. Experiments with electrical stimulation confirmed the observation that the warm cells persist in activity without an external drive. In warm cells with blocked receptive region, the response curves describing the relationship between the tonic discharge and the level of depolarization is the same for different temperatures. In warm cells with intact receptive region, the curves are shifted upward with rising temperature, as if the injected current is simply added to the receptor current. This indicates a modulating effect of the receptor current on the tonic discharge. Stimulation causes a change in the tonic discharge rate and thereby enables individual warm cells to signal the direction in addition to the magnitude of temperature changes.
Group Delay of Acoustic Emissions in the Ear
Authors: Ren Tianying , He Wenxuan , Scott Matthews , Nuttall Alfred L.
Published: August 2006

It is commonly accepted that the cochlea emits sound by a backward traveling wave along the cochlear partition. This belief is mainly based on an observation that the group delay of the otoacoustic emission measured in the ear canal is twice as long as the forward delay. In this study, the otoacoustic emission was measured in the gerbil under anesthesia not only in the ear canal but also at the stapes, eliminating measurement errors arising from unknown external- and middle-ear delays. The emission group delay measured at the stapes was compared with the group delay of basilar membrane vibration at the putative emission-generation site, the forward delay. The results show that the total intracochlear delay of the emission is equal to or smaller than the forward delay. For emissions with an f2/f1 ratio <1.2, the data indicate that the reverse propagation of the emission from its generation site to the stapes is much faster than a forward traveling wave to the f2 location. In addition, that the round-trip delays are smaller than the forward delay implies a basal shift of the emission generation site, likely explained by the basal shift of primary-tone response peaks with increasing intensity. However, for emissions with an f1 ≪ f2, the data cannot distinguish backward traveling waves from compression waves because of a very small f1 delay at the f2 site.
Impedance Modulation and Feedback Corrections in Tracking Targets of Variable Size and Frequency
Authors: Selen Luc P. J. , van Dieën Jaap H. , Beek Peter J.
Published: August 2006

Humans are able to adjust the accuracy of their movements to the demands posed by the task at hand. The variability in task execution caused by the inherent noisiness of the neuromuscular system can be tuned to task demands by both feedforward (e.g., impedance modulation) and feedback mechanisms. In this experiment, we studied both mechanisms, using mechanical perturbations to estimate stiffness and damping as indices of impedance modulation and submovement scaling as an index of feedback driven corrections. Eight subjects tracked three differently sized targets (0.0135, 0.0270, and 0.0405 rad) moving at three different frequencies (0.20, 0.25, and 0.33 Hz). Movement variability decreased with both decreasing target size and movement frequency, whereas stiffness and damping increased with decreasing target size, independent of movement frequency. These results are consistent with the theory that mechanical impedance acts as a filter of noisy neuromuscular signals but challenge stochastic theories of motor control that do not account for impedance modulation and only partially for feedback control. Submovements during unperturbed cycles were quantified in terms of their gain, i.e., the slope between their duration and amplitude in the speed profile. Submovement gain decreased with decreasing movement frequency and increasing target size. The results were interpreted to imply that submovement gain is related to observed tracking errors and that those tracking errors are expressed in units of target size. We conclude that impedance and submovement gain modulation contribute additively to tracking accuracy.