bluuebunny/crossref_metadata_2025 huggingface dataset:
VIP and PACAP regulate localized Ca2+ transients via cAMP-dependent mechanism
Authors: Hagen Brian M. , Bayguinov Orline , Sanders Kenton M.
Published: March 2006

Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have been suggested as participants in enteric inhibitory neural regulation of gastrointestinal motility. These peptides cause a variety of postjunctional responses including membrane hyperpolarization and inhibition of contraction. Neuropeptides released from enteric motor neurons can elicit responses by direct stimulation of smooth muscle cells as opposed to other transmitters that rely on synapses between motor nerve terminals and interstitial cells of Cajal. Therefore, we studied the responses of murine colonic smooth muscle cells to VIP and PACAP(1–38) with confocal microscopy and patch-clamp technique. Localized Ca2+ transients (Ca2+ puffs) were observed in colonic myocytes, and these events coupled to spontaneous transient outward currents (STOCs). VIP and PACAP increased Ca2+ transients and STOC frequency and amplitude. Application of dibutyryl cAMP had similar effects. The adenylyl cyclase blocker MDL-12,330A alone did not affect spontaneous Ca2+ puffs and STOCs but prevented responses to VIP. Disruption of A-kinase-anchoring protein (AKAP) associations by application of AKAP St-Ht31 inhibitory peptide had effects similar to those of MDL-12,330A. Inhibition of ryanodine receptor channels did not block spontaneous Ca2+ puffs and STOCs but prevented the effects of dibutyryl cAMP. These findings suggest that regulation of Ca2+ transients (which couple to activation of STOCs) may contribute to the inhibitory effects of VIP and PACAP. Regulation of Ca2+ transients by VIP and PACAP occurs via adenylyl cyclase, increased synthesis of cAMP, and PKA-dependent regulation of ryanodine receptor channels.
Tumor necrosis factor inhibits growth hormone-mediated gene expression in hepatocytes
Authors: Ahmed Tamer , Yumet Gladys , Shumate Margaret , Lang Charles H. , Rotwein Peter , Cooney Robert N.
Published: March 2006

Growth hormone (GH) stimulates STAT5 phosphorylation by JAK2, which activates IGF-I and serine protease inhibitor 2.1 (Spi 2.1) transcription, whereas STAT5 dephosphorylation by protein tyrosine phosphatases (PTPs) terminates this signal. We hypothesized that the inhibitory effects of TNF on GH signaling and gene transcription were responsible for hepatic GH resistance. CWSV-1 hepatocytes were treated with TNF, pervanadate (a PTP inhibitor), or both, before GH stimulation. Total and tyrosine-phosphorylated JAK2, STAT5, ERK1/2, SHP-1 and SHP-2, IGF-I, and Spi 2.1 mRNA levels were measured. GH stimulated STAT5 and ERK1/2 phosphorylation, IGF-I, and Spi 2.1 mRNA expression. TNF attenuated JAK2/STAT5 and ERK1/2 phosphorylation and IGF-I and Spi 2.1 mRNA expression following GH stimulation. SHP-1 and SHP-2 protein levels were unaltered by TNF or GH, and the GH-induced increase in SHP-1 PTP activity was not further increased by TNF. In TNF-treated cells, pervanadate restored STAT5 and ERK1/2 phosphorylation to control levels following GH stimulation but did not restore IGF-I or Spi 2.1 mRNA induction. Cells transfected with a Spi 2.1 promoter-luciferase vector demonstrate a 50-fold induction in luciferase activity following GH stimulation or cotransfection with a constitutively active STAT5 vector. TNF prevented the induction of Spi 2.1 promoter activity by GH and the STAT5 construct. We conclude that TNF does not inhibit GH activity by inducing SHP-1 or -2 expression and that correction of GH signaling defects in TNF-treated cells by pervanadate does not restore GH-induced gene expression. The inhibitory effects of TNF on GH-mediated gene transcription appear independent of STAT5 activity and previously identified abnormalities in JAK2/STAT5 signaling.
Susceptibility to metanephric apoptosis in bradykinin B2 receptor null mice via the p53-Bax pathway
Authors: Fan Hao , Stefkova Jana , El-Dahr Samir S.
Published: March 2006

In response to gestational high salt intake, BdkrB2−/− embryos acquire an aberrant renal phenotype mimicking renal dysplasia in humans. Genetic analysis identified p53 as a mediator of the renal dysplasia in salt-stressed BdkrB2−/− mice, acting partly via repression of terminal epithelial differentiation genes. The present study tested the hypothesis that inactivation of BdkrB2 predisposes the salt-stressed embryo to p53-mediated metanephric apoptosis. Newborn BdkrB2−/− pups exhibited hyperphosphorylation of metanephric p53 on serine 20 (mouse serine 23), a modification known to increase p53 stability and apoptotic activity. As a result, there was widespread, ectopic expression of p53 in the BdkrB2−/− kidney. However, no differences were found in the apoptosis index or gene expression in BdkrB2−/− and +/+ kidneys, indicating that p53 stabilization as a result of BdkrB2 inactivation is not sufficient to induce metanephric apoptosis. On gestational salt stress, fulminant metanephric apoptosis and enhanced Bax gene expression occurred in BdkrB2−/− but not their +/− or +/+ littermates. Germline deletion of p53 from BdkrB2−/− mice prevented Bax activation and normalized the apoptosis index. Rescue of metanephric apoptosis in BdkrB2−/− mice was similarly achieved by Bax gene deletion. Aberrant apoptosis in salt-stressed BdkrB2−/− mice was triggered on embryonic day E15.5 and involved both ureteric bud (UB) and metanephric mesenchyme-derived nephron elements. Cultured E12.5 salt-stressed BdkrB2−/− metanephroi manifested stunted UB branching compared with +/− and +/+ littermates; the abnormal UB branching was corrected by p53 deletion. Our results suggest a model whereby a seemingly silent genetic mutation of BdkrB2 predisposes mice to renal dysplasia by creating a “preapoptotic” state through p53 activation.
Mice heterozygous for β-ENaC deletion have defective potassium excretion
Authors: Cao X. Renee , Shi P. Peter , Sigmund Rita D. , Husted Russell F. , Sigmund Curt D. , Williamson Roger A. , Stokes John B. , Yang Baoli
Published: March 2006

The present studies were designed to determine whether mice heterozygous for deletion of β-ENaC exhibited defects in Na+/K+transport and blood pressure regulation. In response to an acute KCl infusion, +/− mice developed higher serum [K+] and excreted only 40% of the K+excreted by +/+ mice. After 6 days on a low (0.01%)-Na+diet, the cumulative Na+excretion from days 3- 6 was greater for +/− mice. This low-Na+diet caused higher serum [K+] and lower K+excretion rates in +/− mice than in +/+ mice, but the rectal potential differences were not different. Analyses of mRNA from mice on this diet showed the expected ∼50% reduction of β-ENaC in kidney and colon of +/− mice. Unexpectedly, the level of γ-ENaC mRNA was similarly reduced. NHE3 mRNA was ∼30% higher in +/− mice whereas mRNA of the Na-K-2Cl cotransporter was not different. Also unexpectedly, the amount of β-ENaC proteins was similar in both groups of mice but there was a reduction of one form of γ-ENaC in +/− mice. These experiments demonstrate that mice heterozygous for β-ENaC have a small but detectable defect in their ability to conserve Na+and a more readily apparent defect in the ability to secrete K+.
Roles of cytosolic and membrane-bound carbonic anhydrase in renal control of acid-base balance in rainbow trout,Oncorhynchus mykiss
Authors: Georgalis T. , Gilmour K. M. , Yorston J. , Perry S. F.
Published: March 2006

We tested the hypothesis that cytosolic and membrane-associated carbonic anhydrase (CA IV) are involved in renal urinary acidification and bicarbonate reabsorption in rainbow trout. With the use of homological cloning techniques, a 1,137-bp cDNA was assembled that included an open reading frame encoding for a deduced protein of 297 amino acids. Phylogenetic analysis revealed that this protein was likely a CA IV isoform. With the use of this sequence and a previously described trout cytosolic isoform [tCAc ( 13 )], tools were developed to quantify and localize mRNA and protein for the two CA isoforms. Unlike tCAc, which displayed a broad tissue distribution, trout CA IV mRNA (and to a lesser extent protein) was highly and preferentially expressed in the posterior kidney. The results of in situ hybridization, immunocytochemistry, and standard histological procedures demonstrated that CA IV was likely confined to epithelial cells of the proximal tubule with the protein being expressed on both apical and basolateral membranes. The CA IV-containing tubule cells were enriched with Na+-K+-ATPase. Similar results were obtained for tCAc except that it appeared to be present in both proximal and distal tubules. The levels of mRNA and protein for tCAc increased significantly during respiratory acidosis (hypercapnia). Although tCA IV mRNA was elevated after 24 h of hypercapnia, tCA IV protein levels were unaltered. By using F3500, a membrane-impermeant (yet filtered) inhibitor of CA, in concert with blood and urine analyses, we demonstrated that CA IV (and possibly other membrane-associated CA isoforms) plays a role in urinary acidification and renal bicarbonate reabsorption.
Hog barn dust extract increases macromolecular efflux from the hamster cheek pouch
Authors: Rubinstein Israel , Von Essen Susanna G.
Published: March 2006

The purpose of this study was to determine whether short-term exposure to an aqueous extract of hog barn dust increases macromolecular efflux from the intact hamster cheek pouch and, if so, to begin to determine the mechanism(s) underlying this response. By using intravital microscopy, we found that suffusion of hog barn dust extract onto the intact hamster cheek pouch for 60 min elicited a significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (molecular mass, 70 kDa). This response was significantly attenuated by suffusion of catalase (60 U/ml), but not by heat-inactivated catalase, and by pretreatment with dexamethasone (10 mg/kg iv) ( P < 0.05). Catalase had no significant effects on adenosine-induced increase in macromolecular efflux from the cheek pouch. Suffusion of hog barn dust extract had no significant effects on arteriolar diameter in the cheek pouch. Taken together, these data indicate that hog barn dust extract increases macromolecular efflux from the in situ hamster cheek pouch, in part, through local elaboration of reactive oxygen species that are inactivated by catalase. This response is specific and attenuated by corticosteroids. We suggest that plasma exudation plays an important role in the genesis of upper airway dysfunction evoked by short-term exposure to hog barn dust.
Load-independent index of diastolic filling: model-based derivation with in vivo validation in control and diastolic dysfunction subjects
Authors: Shmuylovich Leonid , Kovács Sándor J.
Published: March 2006

Maximum elastance is an experimentally validated, load-independent systolic function index stemming from the time-varying elastance paradigm that decoupled extrinsic load from (intrinsic) contractility. Although Doppler echocardiography is the preferred method of diastolic function (DF) assessment, all echo-derived indexes are load dependent, and no invasive or noninvasive load-independent index of filling (LIIF) exists. In this study, we derived and experimentally validated a LIIF. We used a kinematic filling paradigm (the parameterized diastolic filling formalism) to predict and derive the (dimensionless) dynamic diastolic efficiency M, defined by the slope of the peak driving force [maximum driving force ( kx o) ∝ peak atrioventricular (AV) gradient] to maximum viscoelastic resistive force [peak resistive force ( cEpeak)] relation. To validate load independence, we analyzed E-waves recorded while load was varied via tilt table (head up, horizontal, and head down) in 16 healthy volunteers. For the group, linear regression of E-wave derived kx o vs. cEpeak yielded kx o = M ( cEpeak) + B, r2 = 0.98; where M = 1.27 ± 0.09 and B = 5.69 ± 1.70. Effects of diastolic dysfunction (DD) on M were assessed by analysis of preexisting simultaneous cath-echo data in six DD vs. five control subjects. Average M for the DD group ( M = 0.98 ± 0.07) was significantly lower than controls ( M = 1.17 ± 0.05, P < 0.001). We conclude that M is a LIIF because it uncouples intrinsic DF (i.e., the pressure-flow relation) from extrinsic load (left ventricular end-diastolic pressure). Larger M values imply better DF in that increasing AV pressure gradient results in relatively smaller increases in peak resistive losses ( cEpeak). Conversely, lower M implies that increasing AV gradient leads to larger increases in resistive losses. Further prospective validation characterizing M in well-defined pathological states is warranted.
Increases in Alpha Oscillatory Power Reflect an Active Retinotopic Mechanism for Distracter Suppression During Sustained Visuospatial Attention
Authors: Kelly Simon P. , Lalor Edmund C. , Reilly Richard B. , Foxe John J.
Published: March 2006

Human electrophysiological (EEG) studies have demonstrated the involvement of alpha band (8- to 14-Hz) oscillations in the anticipatory biasing of attention. In the context of visual spatial attention within bilateral stimulus arrays, alpha has exhibited greater amplitude over parietooccipital cortex contralateral to the hemifield required to be ignored, relative to that measured when the same hemifield is to be attended. Whether this differential effect arises solely from alpha desynchronization (decreases) over the “attending” hemisphere, from synchronization (increases) over the “ignoring” hemisphere, or both, has not been fully resolved. This is because of the confounding effect of externally evoked desynchronization that occurs involuntarily in response to visual cues. Here, bilateral flickering stimuli were presented simultaneously and continuously over entire trial blocks, such that externally evoked alpha desynchronization is equated in precue baseline and postcue intervals. Equivalent random letter sequences were superimposed on the left and right flicker stimuli. Subjects were required to count the presentations of the target letter “X” at the cued hemifield over an 8-s period and ignore the sequence in the opposite hemifield. The data showed significant increases in alpha power over the ignoring hemisphere relative to the precue baseline, observable for both cue directions. A strong attentional bias necessitated by the subjective difficulty in gating the distracting letter sequence is reflected in a large effect size of 2.1 (η2 = 0.82), measured from the attention × hemisphere interaction. This strongly suggests that alpha synchronization reflects an active attentional suppression mechanism, rather than a passive one reflecting “idling” circuits.
Distinct Time Scales in Cortical Discrimination of Natural Sounds in Songbirds
Authors: Narayan Rajiv , Graña Gilberto , Sen Kamal
Published: March 2006

Understanding how single cortical neurons discriminate between sensory stimuli is fundamental to providing a link between cortical neural responses and perception. The discrimination of sensory stimuli by cortical neurons has been intensively investigated in the visual and somatosensory systems. However, relatively little is known about discrimination of sounds by auditory cortical neurons. Auditory cortex plays a particularly important role in the discrimination of complex sounds, e.g., vocal communication sounds. The rich dynamic structure of such complex sounds on multiple time scales motivates two questions regarding cortical discrimination. How does discrimination depend on the temporal resolution of the cortical response? How does discrimination accuracy evolve over time? Here we investigate these questions in field L, the analogue of primary auditory cortex in zebra finches, analyzing temporal resolution and temporal integration in the discrimination of conspecific songs (songs of the bird's own species) for both anesthetized and awake subjects. We demonstrate the existence of distinct time scales for temporal resolution and temporal integration and explain how they arise from cortical neural responses to complex dynamic sounds.
Cortical Excitatory Amino Acid Release and Cell Function during Hypotension in Near-Term Born Lambs
Authors: van Os Sandra , Ruitenbeek Wim , Hopman Jeroen , Klaessens John , van de Bor Margot
Published: March 2006

Background: Energy failure due to insufficient cerebral O2-supply leads to excess accumulation of calcium ions in presynaptic neurons, followed by excess release of excitatory amino acids, which are potent neurotoxins, into the synaptic cleft. Aim:To investigate whether electrocortical brain activity (ECBA) can provide an adequate measure for excitatory amino acid release due to hemorrhagic hypotension. Methods: Ten near-term lambs were delivered at 127 days of gestation (term: 147 days). After a stabilization period, hypotension was induced by stepwise withdrawal of blood. Cerebral microdialysis was used to measure the concentrations of glutamate and aspartate. Results:During hypotension, mean arterial blood pressure, cerebral O2-supply and ECBA decreased and the extracellular concentration of glutamate increased significantly. ECBA was significantly related to glutamate (R2: 0.67, p < 0.001) and aspartate (R2: 0.57, p < 0.001) concentrations. Conclusion:The extracellular release of glutamate and aspartate in the cerebral cortex increases after hemorrhagic hypotension in near-term born lambs. The extracellular overflow of glutamate and aspartate were significantly inversely related to ECBA.
Rac2 Concentrations in Umbilical Cord Neutrophils
Authors: Meade Virginia M. , Barese Cecilia N. , Kim Chaekyun , Njinimbam Charles G. , Marchal Christophe C. , Ingram David A. , Clapp D. Wade , Dinauer Mary C. , Yoder Mervin C.
Published: March 2006

Background: Human newborn infants display a variety of immunodeficiencies of immaturity, including diminished neutrophil adhesion, chemotaxis, and migration. Rac2, a guanosine triphosphate-binding protein, is an essential regulator of human neutrophil migration and chemotaxis. Since human subjects and mice deficient in Rac2 display deficiencies in neutrophil functions similar to newborn infants, we postulated that newborn neutrophils may be deficient in Rac2. Objectives: The aim of the study was to measure Rac1 and Rac2 concentrations in neutrophils from umbilical cord blood. Methods: Neutrophils from cord and adult blood were isolated, total cell lysates extracted, and Rac protein concentrations determined using Western blot analysis. Results: Rac2 concentrations were significantly lower in the neutrophil protein lysates isolated from cord blood compared to adult blood despite similar levels of Rac1. Conclusions: Diminished Rac2 expression in cord blood neutrophils may contribute to the defects observed in cord blood neutrophil function.
Sensori-Neural Deafness and Hypothyroidism: Autoimmunity Causing ‘Pseudo-Pendred Syndrome’
Authors: Davis Nikki , Lunardi Claudio , Shield Julian P.H.
Published: March 2006

Male, dizygotic twins were diagnosed with sensori-neural deafness at ages 5 and 21 months and later developed hypothyroidism at ages 24 and 28 months, respectively. Analysis for anti-DEP-1/CD148 autoantibodies described in Cogan syndrome proved positive. As these antibodies are directed against endothelial cells as well as sensory epithelial cells the children need long-term monitoring for associated complications.
Growth Hormone Receptor Sequence Changes Do Not Play a Role in Determining Height in Children with Idiopathic Short Stature
Authors: Hujeirat Yasir , Hess Ora , Shalev Stavit , Tenenbaum-Rakover Yardena
Published: March 2006

Background/Aims: In children with short stature, in whom growth hormone deficiency has been excluded, the presence of a normal or elevated growth hormone concentration concomitant with low insulin-like growth factor I suggests growth hormone insensitivity (GHI). Previous reports suggest that heterozygous mutations in the growth hormone receptor gene (GHR) may account for about 5% of children with idiopathic short stature (ISS). In the present study we have attempted to determine whether mutations in the GHR explain the short stature and growth retardation in a cohort of children with ISS and characteristics suggesting GHI. Methods: For the present study 33 children with clinical and biochemical characteristics of GHI were selected from a cohort of 150 children of short stature. Molecular analysis of the GHR was performed using a single-strand conformation polymorphism technique and sequencing. Ten different sequence changes in 19 (58%) out of 33 children were identified, 9 of them novel and 1 that had been described previously. Results: Two changes were found in exons 2 and 6. The known polymorphism of exon 6 (G168) was significantly more common in the control subjects than in our study group (63.5 vs. 30%; p < 0.0001). In the intronic sequences 8 previously undescribed DNA changes were found. The screening of the affected children’s family members revealed that both normal and short stature members carried the same variants. The study group did not significantly differ from the controls in retention (GHRfl) or exclusion (GHRd3) of exon 3. Conclusion: Our study suggests that sequence changes of the GHR are common in children with ISS. The presence of these sequence changes in the control subjects as well as in normal stature family members indicates that these changes represent a simple polymorphism of the GHR. Such DNA changes are more prevalent than previously recognized, and they do not seem to play a contributory role in the etiology of short stature.
Insulin Allergy and Extensive Lipoatrophy in Child with Type 1 Diabetes
Authors: Beltrand Jacques , Guilmin-Crepon Sophie , Castanet Mireille , Peuchmaur Michel , Czernichow Paul , Levy-Marchal Claire
Published: March 2006

Insulin allergy and lipoatrophy in type 1 diabetic patients have been previously reported but the mechanisms are not well documented. Here, we report a case emphasizing the role of abnormal local immune reaction associated with cytokine hyper production. The patient is a 7-year-old boy with a familial history of common variable immunodeficiency. Eight months after the diagnosis of type 1 diabetes, he developed signs of insulin allergy expressed as continuously extensive and profound lipoatrophy contrasting with a well-preserved metabolic control. Specific insulin allergy was confirmed by skin prick tests that showed lymphoid activated cells in the subcutaneous tissue at the site of insulin injection. All therapies reported in the literature (antihistaminic, local steroid, change to lispro insulin, immunosuppressive treatment, subcutaneous insulin pump, peritoneal insulin infusion) were not efficient. It is suggested that familial disorders of immune cell functions with abnormal and excessive cytokine production might explain these adverse effects triggered by insulin with severe allergic reactions and lipoatrophy.
The Timing of Neonatal Brain Damage
Authors: Bracci Rodolfo , Perrone Serafina , Buonocore Giuseppe
Published: March 2006

Although neonatal morbidity and mortality are less than in the past, the risk of pre-natal and neonatal brain damage has not been eliminated. In order to optimize pre-natal, perinatal and neonatal care, it is necessary to detect factors responsible for brain damage and obtain information about their timing. Knowledge of the timing of asphyxia, infections and circulatory abnormalities would enable obstetricians and neonatologists to improve prevention in pre-term and full-term neonates. Cardiotocography has been criticized as being too indirect a sign of fetal condition and as having various technical pitfalls, though its reliability seems to be improved by association with pulse oximetry, fetal blood pH and electrocardiography. Neuroimaging is particularly useful to determine the timing of hypoxic-ischemic brain damage. Cranial ultrasound has been used to determine the type and evolution of brain damage. Magnetic resonance has also been used to detect antenatal, perinatal and neonatal abnormalities and timing on the basis of standardized assessment of brain maturation. Advances in the interpretation of neonatal electroencephalograms have also made this technique useful for determining the timing of brain lesions. Nucleated red blood cell count in cord blood has been recognized as an important indication of the timing of pre-natal hypoxia, and even abnormal lymphocyte and thrombocyte counts may be used to establish pre-natal asphyxia. Cord blood pH and base excess are well-known markers of fetal hypoxia, but are best combined with heart rate and blood pressure. Other markers of fetal and neonatal hypoxia useful for determining the timing of brain damage are assays of lactate and markers of oxidative stress in cord blood and neonatal blood. Cytokines in blood and amniotic fluid may indicate chorioamnionitis or post-natal infections. The determination of activin and protein S100 has also been proposed. Obstetricians and neonatologists can therefore now rely on various methods for monitoring the risk of brain damage in the antenatal and post-natal periods.
Rho GTPases and Leukocyte Adhesion Receptor Expression and Function in Endothelial Cells
Authors: Cernuda-Morollón Eva , Ridley Anne J.
Published: March 2006

Rho family GTPases are key signal transducers that regulate cell adhesion and migration and a variety of other cellular responses, including changes in gene expression. In this review, we discuss how Rho GTPases regulate signaling by endothelial cell receptors involved in leukocyte extravasation. First, Rho GTPases affect the expression of some leukocyte adhesion molecules on endothelial cells, such as intracellular adhesion molecule-1 and E-selectin, that can be induced by proinflammatory mediators, hypoxia, or shear stress. Second, Rho GTPases are activated by engagement of several leukocyte adhesion receptors and contribute to both early morphological changes and subsequent alterations in gene expression. Rho GTPases are therefore candidate targets for inhibiting leukocyte transendothelial migration in heart disease and chronic inflammatory disorders.
The Rac and Rho Hall of Fame
Authors: Brown Joan Heller , Del Re Dominic P. , Sussman Mark A.
Published: March 2006

Over the last decade, the Rho family GTPases have gained considerable recognition as powerful regulators of actin cytoskeletal organization. As with many high profile signal transducers, these molecules soon attracted the attention of the cardiovascular research community. Shortly thereafter, two prominent members known as RhoA and Rac1 were linked to agonist-induced gene expression and myofilament organization using the isolated cardiomyocyte cell model. Subsequent creation of transgenic mouse lines provided evidence for more complex roles of RhoA and Rac1 signaling. Clues from in vitro and in vivo studies suggest the involvement of numerous downstream targets of RhoA and Rac1 signaling including serum response factor, NF-κB, and other transcription factors, myofilament proteins, ion channels, and reactive oxygen species generation. Which of these contribute to the observed phenotypic effects of enhanced RhoA and Rac activation in vivo remain to be determined. Current research efforts with a more translational focus have used statins or Rho kinase blockers to assess RhoA and Rac1 as targets for interventional approaches to blunt hypertrophy or heart failure. Generally, salutary effects on remodeling and ischemic damage are observed, but the broad specificity and multiple cellular targets for these drugs within the myocardium demands caution in interpretation. In this review, we assess the evolution of knowledge related to Rac1 and RhoA in the context of hypertrophy and heart failure and highlight the direction that future exploration will lead.
Oriental Despotism and European Orientalism: Botero to Montesquieu
Authors: Rubiés Joan-Pau
Published: March 2006

The issue of how European images of the East were formed, used, and contested is far from simple. The concept of oriental despotism allowed early-modern Europeans to distinguish themselves from the most powerful and impressive non-European civilizations of the Ottoman Middle East, Persia, India, and China on grounds which were neither fundamentally religious nor linked to sheer scientific and technological progress, but political and moral. However, it would be incorrect to treat this as a pure European fantasy based on the uncritical application of a category inherited from Aristotle, because both the concept and its range of application were often hotly contested. By assessing the way travel accounts helped transform the concept from the Renaissance to the Enlightenment, this article argues that oriental despotism was not a mental scheme that blinded Europeans to the perception of the true Orient, but rather a compelling tool for interpreting information gathered about the Orient, one which served a common intellectual purpose despite important differences of opinion in Europe about the nature of royal power.
Early 40s and Still Unmarried
Authors: Williams Lindy , Guest Philip , Varangrat Anchalee
Published: March 2006

In many parts of the world, including Thailand, marriage is being delayed and increasing proportions of women and men will never marry. The results reported in this article are based on microdata samples of the 1970, 1980, 1990 and 2000 Thai censuses, supplemented by focus group data. The increases in proportions never-married that had been observed between 1970 and 1990 continued through the decade of the 1990s. However, unlike earlier decades, changes in the 1990s were much greater for men than for women. Much of the difference in proportions never-married among women can probably be explained by changing socioeconomic composition of the population, but this may be less true for men. There is some evidence of a marriage squeeze for highly educated women and for men with the least formal schooling. Qualitative data suggest that while marriage may no longer be necessary, there remain abundant social pressures, particularly for women to formalize unions. Most young people still expect to get married at some point, if a suitable partner can be found, since the positive aspects of marriage still seem to outweigh the negative ones. Financial circumstances remain very important, however, in ascertaining whether one is ready or able to marry.
Durability of GFRP Rebars in Concrete Beams under Sustained Loads at Severe Environments
Authors: Almusallam Tarek H. , Al-Salloum Yousef A.
Published: March 2006

Long-term behavior of composite materials is still a controversial issue among the engineering community though fiber-reinforced polymer (FRP) reinforcements are increasingly used in infrastructure applications. The main objective of this study is to investigate the effect of different local environmental conditions on the long-term behavior of glass fiber-reinforced polymer (GFRP) bars in concrete beams subjected to sustained loads. This is achieved through testing concrete beams reinforced with GFRP bars and subjected to a certain stress level. To accelerate the reaction, all beams are either completely or partially immersed in different environments (tap water and seawater) at elevated temperature. Test results are expressed in terms of tensile strength of GFRP bars and load-deflection behavior of both unstressed and stressed beams. The results show that there is significant loss in tensile strength of GFRP bars when subjected to sustained stress for the considered exposure conditions. The results of this investigation will be very useful to engineers concerned with the design of structures using composite materials.
‘I Wanted to be a Little Lenin’: Ideology and the German International Brigade Volunteers
Authors: McLellan Josie
Published: March 2006

Around 2800 Germans joined the International Brigades and fought on the Republican side in the Spanish Civil War. Many had suffered political persecution in Germany, and the majority were already in exile when war broke out in Spain. This article asks what role ideology played in their decision to volunteer, and traces their changing motivation as they arrived in Spain, experienced combat for the first time, and eventually waited for the war to play itself out. Even amongst such politically committed soldiers, motivation was neither homogeneous nor stable. The wish to defeat fascism and return to Germany was one shared by almost all volunteers, but boredom, desire for adventure and ties to their fellow soldiers all played an important part in motivating men to fight and keeping them in the field.
Culture and Combat in the Colonies: The Indian Army in the Second World War
Authors: Barkawi Tarak
Published: March 2006

This article critiques the Eurocentric character of debates over combat motivation and battlefield conduct. It compares two approaches to these topics, the societal and the organizational, with the experience of the Indian army and other British imperial forces in the second world war. Different ways of thinking about nationalism, culture and military service are assessed against the distinctive character of colonial forces. Rather than seeing culture as derived only from ethnic heritage, as in the societal approach, the article develops a cultural analysis of the regular military institution and the ways in which it transforms people from diverse backgrounds into soldiers. This argument attends both to what soldiers share and to hybrid fusions of local and military culture.
Combat Motivation, Fear and Terror in Twentieth-century Argentinian Warfare
Authors: Robben Antonius C. G. M.
Published: March 2006

This article compares the combat motivation of Argentinian troops against guerrilla insurgents in a 1975-80 domestic counter-insurgency war with the performance of Argentinian soldiers against British forces in the 1982 Falklands war. The comparison reveals that the willingness to fire and fight differs from the desire to enter into war, and that combat motivation is not determined exclusively by mental preparedness, professional training and superior armament, but depends as much on shifting motivations and dynamic social and political circumstances during the armed conflict. Furthermore, combat motivation is also affected by the type of warfare conducted, and is only given meaning during a pause in the hostilities, when the desire to continue fighting is reassessed.
Kinetic Parameters Estimation for Thermal Degradation of Polyurethane Elastomers
Authors: Agić Ante , Bajsić Emi Govorčin , Rek Vesna
Published: March 2006

In this work, thermogravimetric analysis is used to determine the kinetic parameters of thermal degradation of polyurethane (PU) elastomers, based on poly(ether polyol) soft segment and aromatic-type diisocyanates. To determine the kinetic parameters of PU thermal decomposition, a nonlinear regression procedure is applied. Parameter estimation is obtained by minimizing the weighted quadratic output error functional with the modified Nelder-Mead simplex search algorithm. The confidence region of pre-exponential factor-activation energy are established both for the first and second steps of degradation. The effect of the soft segment molecular weight and hard segment content on the activation energy of the degradation process has been studied.
Emotions and Golf Performance
Authors: Cohen Alexander B. , Tenenbaum Gershon , English R. William
Published: March 2006

A multiple case study investigation is reported in which emotions and performance were assessed within the probabilistic individual zone of optimal functioning (IZOF) model (Kamata, Tenenbaum,& Hanin, 2002) to develop idiosyncratic emotion-performance profiles. These profiles were incorporated into a psychological skills training (PST) intervention, with a focus on three emotional dimensions, that is, arousal, pleasantness, and functionality, and several psychological strategies employed during practice and competition. Two female varsity golfers at a major Division I university in the Southeast participated in the case study during the Spring 2002 season. The PST intervention resulted in enhanced emotional self-regulation skills and improved golf performance. Directions for future research into the IZOF model and implications for practical application of the model are discussed.
The Effects of Celeration Lines on Visual Data Analysis
Authors: Normand Matthew P. , Bailey Jon S.
Published: March 2006

Previous visual analysis research reported that the overall agreement between visual analysis and statistical analysis was poor. In response, some researchers suggested the use of celeration lines to improve the accuracy and reliability of visual analysis. However, subsequent research reported little or no improvement in accuracy with such lines. The present study presented 5 board-certified behavior analysts with a series of behavioral graphs. The participants were asked to answer questions similar to those posed in previous studies but were also asked to talk aloud as they viewed each graph. Results indicate that the participants made accurate decisions for only 72% of the graphs and that celeration lines did not improve overall accuracy. The verbal protocol analysis suggests that participants were as likely to attend to trend when celeration lines were absent as they were when they were present, with the most differences attributable to varying participant competencies and not graph (i.e., celeration line) characteristics.
Behavioral Treatment of Chronic Belching Due to Aerophagia in a Normal Adult
Authors: Cigrang Jeffrey A. , Hunter Christine M. , Peterson Alan L.
Published: March 2006

Aerophagia, or excessive air swallowing, is a potential cause of belching, flatulence, bloating, and abdominal pain and may contribute to a worsening of gastrointestinal (GI) disorders. A limited number of published reports of aerophagia treatment indicate that behavioral methods may be of benefit. A case report is presented describing the behavioral treatment of chronic belching due to aerophagia in an adult female. The collaborative application of single-participant design research helped identify open-mouth, diaphragmatic breathing and minimized swallowing as an effective intervention. Belching frequency was reduced from an average rate of 18 per 5-min interval during the baseline period to 3 per 5-min period after treatment. Results were maintained at an 18-month follow-up. Recommendations for the use of a brief treatment protocol with adults referred for chronic belching or other GI complaints attributed to aerophagia are discussed.
Institutional Forces
Authors: Davidsson Per , Hunter Erik , Klofsten Magnus
Published: March 2006

Institutional theory is employed for examining how and to what extent external pressure leads to changes in the venture idea during the start-up and early life of new, knowledge-intensive ventures. From a population of 321 young, knowledge-intensive firms that underwent a training program at Linkping University, Sweden, structured telephone interview data were obtained from 167 firms. The results confirmed that the venture idea had undergone more change in ventures that had more external owners, a dominant customer, and an incubator location. The results imply that institutional theory is a meaningful tool for understanding why and how venture ideas change over time.
A Grounded Theory of Portfolio Working
Authors: Clinton Michael , Totterdell Peter , Wood Stephen
Published: March 2006

Portfolio working has been championed, most noticeably by Handy (1995), as a new way in which we should understand many working lives. It is said to be characterized by obtaining and doing a variety of pieces of work for a number of different clients or employers and is suggested by many to be an increasing practice. To understand how individuals who work in this way experience portfolio working, 26 semi-structured interviews were carried out with a range of portfolio workers and then analysed using a grounded theory technique. The model that was generated suggested that a particular combination of features characterized portfolio working: the self-management of work, the independent generation of work and income, the development of a variety of work and clients, and a working environment situated outside any single organization. The model further demonstrated how these combined features engendered three main psychological processes central to the experience of portfolio working: autonomy, uncertainty and social isolation. The nature of the processes had a subsequent impact upon the individual's work intensity, well-being and work–life balance. Personal and situational characteristics also emerged as playing a notable role in how portfolio working is experienced.
Lithium: a review of its metabolic adverse effects
Authors: Livingstone Callum , Rampes Hagen
Published: March 2006

Treatment with lithium has long been recognized to be associated with metabolic adverse effects notably hypothyroidism, hyperparathyroidism, weight gain and nephrogenic diabetes insipidus. It is important that clinicians prescribing lithium are aware of these adverse effects and have a strategy for their detection and management. We review aspects of these actions of lithium including their prevalence, risk factors, biochemical changes involved and management, and discuss some advances that have been made in their understanding in recent years.
Dysregulation of thalamic sensory ‘transmission’ in schizophrenia: neurochemical vulnerability to hallucinations
Authors: Behrendt Ralf-Peter
Published: March 2006

Cholinergic arousal mechanisms predispose thalamic and cortical neurons to fire action potentials at gamma rhythms, which have a tendency to resonate in thalamocortical networks, thereby forming coherent assemblies under constraints of sensory input to specific thalamic nuclei, on the one hand, and prefrontal and limbic attentional mechanisms, on the other. Perception may be based on sustained assemblies of coherent gamma oscillations in thalamocortical circuits. In schizophrenia, the impact of sensory input on self-organization of thalamocortical activity may be generally reduced. As a result, processes underlying perception can become uncoupled from sensory input, particularly at times of hyperarousal, leading to domination of attentional mechanisms and the emergence of hallucinations. Evidence is reviewed that implicates excessive neuronal noise in specific thalamic nuclei in the generation of hallucinations in schizophrenia. Nicotinic receptor abnormalities, dopaminergic hyperactivity and glutamate-receptor hypofunction are reconciled within a model of psychotic symptom generation that places crucial emphasis on dysfunction of the reticular thalamic nucleus.
Eating attitudes, weight concerns and beliefs about drug effects in women who use ecstasy
Authors: Curran H. Valerie , Robjant Katy
Published: March 2006

The drug ecstasy has appetite suppressant and exercise promoting effects that may appeal to young women who are concerned about weight and body image. This study therefore aimed to determine whether young women who use ecstasy differ from those who do not use this drug in concerns about eating and weight, and in beliefs about how these are affected by recreational drugs. One hundred and thirty young women, all cigarette smokers, were recruited; 73 who used ecstasy were compared with 57 who did not. All were assessed on Garnerís (1991) Eating Disorder Inventory (EDI-2), body mass index (BMI), depression and beliefs about the effects of different drugs on appetite, exercise and weight. The two groups did not differ on number of cigarettes smoked per day, depression scores, current BMI, lowest achieved BMI or ideal BMI. Ecstasy users had signi.cantly higher scores than controls on four of the 11 sub-scales of the EDI: bulimia, impulse dysregulation, social insecurity and interpersonal distrust. For ecstasy users, scores on all four scales correlated positively with frequency of ecstasy use. However there were no group differences in ëdrive for thinnessí or ëbody dissatisfactioní which may suggest that differences on other factors are related more to use of club drugs than to any speci.c eating pathology. Ecstasy users were more likely than controls to agree that ecstasy aids weight loss and that they exercise more when they use drugs. However, our .ndings indicated that women are not using ecstasy as a deliberate means of weight control.
Recreational ecstasy use and depression
Authors: Guillot Casey , Greenway David
Published: March 2006

Research in laboratory animals has shown that 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) destroys serotonergic axons in the brain at certain doses. Serotonin is known to take part in the regulation of mood in humans. Many researchers have hypothesized that if recreational ecstasy use destroys serotonergic axons, then a corresponding decline in the mood of ecstasy users should be seen. The purpose of the present study was to look at the relationship between recreational ecstasy use and depression as measured by the Beck Depression Inventory-II. No signi.cant differences were found between Beck Depression Inventory-II scores of heavy ecstasy users and ecstasynaive college students. No signi.cant relationships were found between Beck Depression Inventory-II scores and any of the measures of ecstasy use. Most ecstasy users who had been diagnosed with a psychiatric disorder reported that being diagnosed preceded their use of ecstasy.
Biocompatibility of b-Tricalcium Phosphate Root Replicas in Porcine Tooth Extraction Sockets - A Correlative Histological, Ultrastructural, and X-ray Microanalytical Pilot Study
Authors: Nair P.N.R. , Luder Hans-Ulrich , Maspero Fabrizio A. , Fischer Jürgen H. , Schug Jens
Published: March 2006

This investigation studies porcine tissue response in tooth extraction sockets treated with root replicas made out of β-tricalcium phosphate (β-TCP; β-Ca3(PO4)2) granules, molded and held together by thermal fusion of a thin film of polyglycolic-polylactic acid copolymer. Six left mandibular third incisors (n 1/4 6) of experimental pigs are treated with the root replicas and four contralateral incisors are used as nontreated controls (n 1/4 4). Two animals each were killed at 20, 40, and 60 weeks of observation periods. The mandibular jaw segments were prepared in toto for light microscopy by resin embedding and serial ground sectioning. Additionally, one β-TCP-treated socket at 60 weeks was thoroughly investigated by correlative light, electron microscopic and electron probe X-ray microanalysis to assess the bioabsorbability and host removal of the replica material from the implant site. The extraction wounds of the animals healed satisfactorily with very little histologically observable differences in the healing pattern of the test and control sites. The β-TCP was completely removed from extracellular sites, but at 60 weeks, remnants of it were found in the cytoplasm of multinucleated giant cells. The root replicas made out of β-TCP were biocompatible and bioabsorbable. Osseous healing occurred both in the test and control sockets, but the healing process was delayed due to the presence of β-TCP particles.