bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actions of hydrogen sulphide on ion transport across rat distal colon
Authors: Hennig B , Diener M 
Published: September 2009

Background and purpose: The aim of this study was to identify the actions of H2S on ion transport across rat distal colon.Experimental approach: Changes in short‐circuit current (Isc) induced by the H2S‐donor, NaHS, were measured in Ussing chambers. Cytosolic Ca2+concentration was evaluated using fura‐2.Key results: NaHS concentration‐dependently induced a change in Isc, that was only partially inhibited by the neurotoxin, tetrodotoxin. Lower concentrations (≤10−3 mol·L−1) of NaHS induced a monophasic increase in Isc, whereas higher concentrations induced an additional, secondary fall of Isc, before a third phase when Isc rose again. Blockers of H2S‐producing enzymes (expression demonstrated immunohistochemically) decreased basal Isc, suggesting that endogenous production of H2S contributes to spontaneous anion secretion. The positive Isc phases induced by NaHS were due to Cl‐secretion as shown by anion substitution and transport inhibitor experiments, whereas the transient negative Isc induced by higher concentrations of the H2S‐donor was inhibited by mucosal tetrapentylammonium suggesting a transient K+secretion. When applied from the serosal side, glibenclamide, an inhibitor of ATP‐sensitive K+channels, and tetrapentylammonium, a blocker of Ca2+‐dependent K+channels, suppressed NaHS‐induced Cl‐secretion suggesting different types of K+channels are stimulated by the H2S‐donor. NaHS‐induced increase in cytosolic Ca2+concentration was confirmed in isolated, fura‐2‐loaded colonic crypts. This response was not dependent on extracellular Ca2+, but was inhibited by blockers of intracellular Ca2+channels present on Ca2+storage organelles.Conclusions and implications: H2S induces colonic ion secretion by stimulation of apical as well as basolateral epithelial K+channels.
Activation of the lung S1P1 receptor reduces allergen‐induced plasma leakage in mice
Authors: Blé F‐X , Cannet C , Zurbruegg S , Gérard C , Frossard N , Beckmann N , Trifilieff A 
Published: September 2009

Background and purpose:  It has been suggested that intratracheal administration of the immunomodulator, FTY720, could have anti‐inflammatory effects without causing a decrease in blood lymphocyte counts. However, the receptor responsible for this effect has not been defined.Experimental approach:  We have described, in a mouse model of allergen‐induced inflammation, the use of proton magnetic resonance imaging to non‐invasively assess lung fluid accumulation and inflammation. Here, we used this model to investigate the sphingosine‐1‐phosphate (S1P) receptor responsible for the anti‐inflammatory effect of FTY720.Key results:  When given intranasally, FTY720 (3 and 10 µg·kg−1) inhibited by approximately 50% the allergen‐induced accumulation of fluid in the lung detected by magnetic resonance imaging, but had no effect on the cellular inflammation in the airway space or on circulating blood lymphocytes. Inhibition of the infiltration of inflammatory cells into the airways was only observed at a dose of FTY720 that induced lymphopenia (100 µg·kg−1). Similar results were observed in S1P3‐deficient mice. The effect of FTY720 was mimicked by intranasal treatment of wild‐type mice with a S1P1‐specific agonist, AUY954.Conclusions and implications:  Thus, in contrast to previously published work, our results suggest that systemic exposure of FTY720 is necessary to obtain an airway anti‐inflammatory effect. On the contrary, inhibition of the allergen‐induced accumulation of fluid in the lung, via activation of the S1P1 receptor, is obtainable without systemic effects.
Integrated risk assessment and predictive value to humans of non‐clinical repolarization assays
Authors: Wallis Robert M 
Published: September 2009

The potential for drugs to be associated with the life‐threatening arrhythmia, Torsades de Pointes (TdeP), continues to be a topic of regulatory, academic and industrial concern. Despite being an imperfect biomarker, prolongation of the QT interval of the surface ECG is used to assess the risk of a drug being associated with TdeP such that a thorough examination of drug effects on the QT interval is required for all new chemical entities. Numerous studies have investigated the relationship between non‐clinical findings and the risk of TdeP and QT prolongation in the general population. There are many literature references supporting the strong correlation between the clinical safety margin over humanether‐a‐go‐go(hERG) inhibitory potency and the risk of drug‐induced arrhythmia and sudden death. A quantitative analysis of the relationship between non‐clinical studies and the outcome of a human Thorough QT study has also been reported. In the current manuscript, based on the outcome of the non‐clinical assays the sensitivity and specificity of each assay and an integrated risk assessment for predicting the outcome of the human Thorough QT study has been conducted. The data suggest that for QT prolongation mediated through inhibition of the hERG current the non‐clinical assays are highly predictive of drug effects on the QT interval. Based on the literature review and specific quantitative analysis reported above it is concluded that non‐clinical assays predict the risk of compounds to prolong the QT interval and cause TdeP in humans if the mechanism is through inhibition of the hERG current.This article is part of a themed section on QT safety. To view this issue visithttp://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010
Phosphorylation alters the pharmacology of Ca2+‐activated Cl‐ channels in rabbit pulmonary arterial smooth muscle cells
Authors: Wiwchar M , Ayon R , Greenwood IA , Leblanc N 
Published: September 2009

Background and purpose:  Ca2+‐activated Cl‐ currents (ICl(Ca)) in arterial smooth muscle cells are inhibited by phosphorylation. The Ca2+‐activated Cl‐ channel (ClCa) blocker niflumic acid (NFA) produces a paradoxical dual effect on ICl(Ca), causing stimulation or inhibition at potentials below or above 0 mV respectively. We tested whether the effects of NFA on ICl(Ca) were modulated by phosphorylation.Experimental approach:  ICl(Ca) was elicited with 500 nM free internal Ca2+ in rabbit pulmonary artery myocytes. The state of global phosphorylation was altered by cell dialysis with either 5 mM ATP or 0 mM ATP with or without an inhibitor of calmodulin‐dependent protein kinase type II, KN‐93 (10 µM).Key results:  Dephosphorylation enhanced the ability of 100 µM NFA to inhibit ICl(Ca). This effect was attributed to a large negative shift in the voltage‐dependence of block, which was converted to stimulation at potentials <−50 mV, ∼70 mV more negative than cells dialysed with 5 mM ATP. NFA dose‐dependently blocked ICl(Ca) in the range of 0.1–250 µM in cells dialysed with 0 mM ATP and KN‐93, which contrasted with the stimulation induced by 0.1 µM, which converted to block at concentrations >1 µM when cells were dialysed with 5 mM ATP.Conclusions and implications:  Our data indicate that the presumed state of phosphorylation of the pore‐forming or regulatory subunit of ClCa channels influenced the interaction of NFA in a manner that obstructs interaction of the drug with an inhibitory binding site.
Long‐term blockade of L/N‐type Ca2+channels by cilnidipine ameliorates repolarization abnormality of the canine hypertrophied heart
Authors: Takahara A , Nakamura Y , Wagatsuma H , Aritomi S , Nakayama A , Satoh Y , Akie Y , Sugiyama A 
Published: September 2009

Background and purpose: The heart of the canine model of chronic atrioventricular block is known to have a ventricular electrical remodelling, which mimics the pathophysiology of long QT syndrome. Using this model, we explored a new pharmacological therapeutic strategy for the prevention of cardiac sudden death.Experimental approach: The L‐type Ca2+channel blocker amlodipine (2.5 mg·day−1), L/N‐type Ca2+channel blocker cilnidipine (5 mg·day−1), or the angiotensin II receptor blocker candesartan (12 mg·day−1) was administered orally to the dogs with chronic atrioventricular block for 4 weeks. Electropharmacological assessments with the monophasic action potential (MAP) recordings and blood sample analyses were performed before and 4 weeks after the start of drug administration.Key results: Amlodipine and cilnidipine decreased the blood pressure, while candesartan hardly affected it. The QT interval, MAP duration and beat‐to‐beat variability of the ventricular repolarization period were shortened only in the cilnidipine group, but such effects were not observed in the amlodipine or candesartan group. Plasma concentrations of adrenaline, angiotensin II and aldosterone decreased in the cilnidipine group. In contrast, plasma concentrations of angiotensin II and aldosterone were elevated in the amlodipine group, whereas in the candesartan group an increase in plasma levels of angiotensin II and a decrease in noradrenaline and adrenaline concentrations were observed.Conclusions and implications: Long‐term blockade of L/N‐type Ca2+channels ameliorated the ventricular electrical remodelling in the hypertrophied heart which causes the prolongation of the QT interval. This could provide a novel therapeutic strategy for the treatment of cardiovascular diseases.
Evidence that 5‐hydroxytryptamine7 receptors play a role in the mediation of afferent transmission within the nucleus tractus solitarius in anaesthetized rats
Authors: Oskutyte Diana , Jordan David , Ramage Andrew G 
Published: September 2009

Background and purpose:  Central 5‐hydroxytryptamine (5‐HT)‐containing pathways utilizing 5‐HT7 receptors are known to be critical for the mediation of cardiovascular reflexes. The nucleus tractus solitarius (NTS) is a site involved in the integration of cardiovascular afferent information. The present experiments examined the involvement of the 5‐HT7 receptor in the processing of cardiovascular reflexes in the NTS.Experimental approach:  In anaesthetized rats extracellular recordings were made from 104 NTS neurones that were excited by electrical stimulation of the vagus nerve and/or activation of cardiopulmonary afferents. Drugs were applied ionophoretically in the vicinity of these neurones.Key results:  The non‐selective 5‐HT7 receptor agonist 5‐carboxamidotryptamine maleate (5‐CT) applied to 78 neurones increased the firing rate in 18 by 59% and decreased it in 38 neurones by 47%. Similarly, the 5‐HT1A agonist 8‐OH‐DPAT applied to 20 neurones had an excitatory (8), inhibitory (7) or no effect (5) on the 20 neurones tested. In the presence of the 5‐HT7 antagonist SB 258719 the 5‐CT excitation was attenuated. Furthermore, the excitatory response of NTS neurones evoked by electrical stimulation of the vagus nerve or activation of cardiopulmonary afferents with intra atrial phenylbiguanide was attenuated by SB 258719. The inhibitory action of 5‐CT was unaffected by SB 258719 and the 5‐HT1A antagonist WAY‐100635. WAY‐100635 failed to have any effect on 5‐CT and vagal afferent‐evoked excitations.Conclusions and implications:  Vagal afferent‐evoked excitation of NTS neurones can be blocked by SB 258719, a selective 5‐HT7 antagonist. This observation further supports the involvement of 5‐HT neurotransmission in NTS afferent processing.
GENETIC MAPPING OF THE LAMINARIA JAPONICA (LAMINARALES, PHAEOPHYTA) USING AMPLIFIED FRAGMENT LENGTH POLYMORPHISM MARKERS1
Authors: Liu Fuli , Wang Xiuliang , Liu Jidong , Fu Wandong , Duan Delin , Yang Yingxia 
Published: September 2009

To establish a molecular‐marker‐assisted system of breeding and genetic study for Laminaria japonica Aresch., amplified fragment length polymorphism (AFLP) was used to construct a genetic linkage map of L. japonica featuring 230 progeny of F2 cross population. Eighteen primer combinations produced 370 polymorphic loci and 215 polymorphic loci segregated in a 3:1 Mendelian segregation ratio (P ≤ 0.05). Of the 215 segregated loci, 142 were ordered into 27 linkage groups. The length of the linkage groups ranged from 6.7 to 90.3 centimorgans (cM) with an average length of 49.6 cM, and the total length was 1,085.8 cM, which covered 68.4% of the estimated 1,586.9 cM genome. The number of mapped markers on each linkage group ranged from 2 to 12, averaging 5.3 markers per group. The average density of the markers was 1 per 9.4 cM. Based on the marker density and the resolution of the map, the constructed linkage map can satisfy the need for quantitative trait locus (QTL) location and molecular‐marker‐assisted breeding for Laminaria.
ULTRASTRUCTURE AND LSU rDNA–BASED REVISION OF PERIDINIUM GROUP PALATINUM (DINOPHYCEAE) WITH THE DESCRIPTION OF PALATINUS GEN. NOV.1
Authors: Craveiro Sandra C. , Calado António J. , Daugbjerg Niels , Moestrup Øjvind 
Published: September 2009

The name Peridinium palatinum Lauterborn currently designates a freshwater peridinioid with 13 epithecal and six cingular plates, and no apical pore complex. Freshwater dinoflagellate floras classify it in Peridinium group palatinum together with P. pseudolaeve M. Lefèvre. General ultrastructure, flagellar apparatus, and pusular components of P. palatinum were examined by serial section TEM and compared to P. cinctum (O. F. Müll.) Ehrenb. and Peridiniopsis borgei Lemmerm., respectively, types of Peridinium and Peridiniopsis. Partial LSU rDNA sequences from P. palatinum, P. pseudolaeve and several peridinioids, woloszynskioids, gymnodinioids, and other dinoflagellates were used for a phylogenetic analysis. General morphology and tabulation of taxa in group palatinum were characterized by SEM. Differences in plate numbers, affecting both the epitheca and the cingulum, combine with differences in plate ornamentation and a suite of internal cell features to suggest a generic‐level distinction between Peridinium group palatinum and typical Peridinium. The branching pattern of the phylogenetic tree is compatible with this conclusion, although with low support from bootstrap values and posterior probabilities, as are sequence divergences estimated between species in group palatinum, and typical Peridinium and Peridiniopsis. Palatinus nov. gen. is proposed with the new combinations Palatinus apiculatus nov. comb. (type species; syn. Peridinium palatinum), P. apiculatus var. laevis nov. comb., and P. pseudolaevis nov. comb. Distinctive characters for Palatinus include a smooth or slightly granulate, but not areolate, plate surface, a large central pyrenoid penetrated by cytoplasmic channels and radiating into chloroplast lobes, and the presence of a peduncle‐homologous microtubular strand. Palatinus cells exit the theca through the antapical‐postcingular area.
Blood Pressure and Brain Injury in Older Adults: Findings from a Community‐Based Autopsy Study
Authors: Wang Lucy Y. , Larson Eric B. , Sonnen Joshua A. , Shofer Jane B. , McCormick Wayne , Bowen James D. , Montine Thomas J. , Li Ge 
Published: September 2009

OBJECTIVES: To examine correlations between blood pressure (BP) and dementia‐related pathological brain changes in a community‐based autopsy sample.DESIGN: Prospective cohort study.SETTING: A large health maintenance organization in Seattle, Washington.PARTICIPANTS: A cohort of 250 participants aged 65 and older and cognitively normal at time of enrollment in the Adult Changes in Thought (ACT) Study and who underwent autopsy.MEASUREMENTS: BP and history of antihypertensive treatment were taken at enrollment. A linear regression model was used to examine the relationship between BP (systolic (SBP) and diastolic (DBP)) at enrollment and pathological changes in the cerebrum (cystic macroscopic infarcts, microinfarcts, neuritic plaques, neurofibrillary tangles, and cortical Lewy bodies).RESULTS: The presence of more than 2 microinfarcts, but not any other pathological change, was independently associated with SBP in younger participants (65–80, n=137) but not in older participants (>80, n=91). The relative risk (RR) for more than two microinfarcts with each 10‐mmHg increase in SBP was 1.15 (95% confidence interval (CI)=1.00–1.33) in the younger participants, adjusted for age at entry, sex, and time to death. This RR was particularly strong in younger participants not taking antihypertensive medications (RR=1.48, 95% CI=1.21, 1.81); significant associations were not observed in participants treated for hypertension. Findings for DBP were negative.CONCLUSION: The association between high SBP and cerebrovascular damage in untreated older adults (65–80) suggests that adequate hypertension treatment may reduce dementia risk by minimizing microvascular injury to cerebrum.
The Vulnerable Elders‐13 Survey Predicts 5‐Year Functional Decline and Mortality Outcomes in Older Ambulatory Care Patients
Authors: Min Lillian , Yoon William , Mariano Jeff , Wenger Neil S. , Elliott Marc N. , Kamberg Caren , Saliba Debra 
Published: September 2009

OBJECTIVES: To test the predictive properties of the Vulnerable Elders‐13 Survey (VES‐13) a short tool that predicts functional decline and mortality over a 1‐ to 2‐year follow‐up interval over a 5‐year interval.DESIGN: Longitudinal evaluation with mean follow‐up of 4.5 years.SETTING: Two managed‐care organizations.PARTICIPANTS: Six hundred forty‐nine community‐dwelling older adults (≥75) enrolled in the Assessing Care of Vulnerable Elders observational study who screened positive for symptoms of falls or fear of falling, bothersome urinary incontinence, or memory problems.MEASUREMENTS: VES‐13 score (range 1–10, higher score indicates worse prognosis), functional decline (decline in count of 5 activities of daily living or nursing home entry), and deaths.RESULTS: Higher VES‐13 scores were associated with greater predicted probability of death and decline in older patients over a mean observation period of 4.5 years. For each additional VES‐13 point, the odds of the combined outcome of functional decline or death was 1.37 (95% confidence interval (CI)=1.25–1.50), and the area under the receiver operating curve was 0.75 (95% CI=0.71–0.80). In the Cox proportional hazards model predicting time to death, the hazard ratio was 1.23 (95% CI=1.19–1.27) per additional VES‐13 point.CONCLUSION: This study extends the utility of the VES‐13 to clinical decisions that require longer‐term prognostic estimates of functional status and survival.
The On‐Road Difficulties of Older Drivers and Their Relationship with Self‐Reported Motor Vehicle Crashes
Authors: Wood Joanne M. , Anstey Kaarin J. , Lacherez Philippe F. , Kerr Graham K. , Mallon Kerry , Lord Stephen R. 
Published: September 2009

OBJECTIVES: To quantify the driving difficulties of older adults using a detailed assessment of driving performance and to link this with self‐reported retrospective and prospective crashes.DESIGN: Prospective cohort study.SETTING: On‐road driving assessment.PARTICIPANTS: Two hundred sixty‐seven community‐living adults aged 70 to 88 randomly recruited through the electoral roll.MEASUREMENTS: Performance on a standardized measure of driving performance.RESULTS: Lane positioning, approach, and blind spot monitoring were the most common error types, and errors occurred most frequently in situations involving merging and maneuvering. Drivers reporting more retrospective or prospective crashes made significantly more driving errors. Driver instructor interventions during self‐navigation (where the instructor had to brake or take control of the steering to avoid an accident) were significantly associated with higher retrospective and prospective crashes; every instructor intervention almost doubled prospective crash risk.CONCLUSION: These findings suggest that on‐road driving assessment provides useful information on older driver difficulties, with the self‐directed component providing the most valuable information.
1. The Role of Land Markets in Economic Crises
Authors: Gaffney Mason 
Published: September 2009

AbstractIt is widely recognized that the economic crisis of 2009 was caused by unsound lending for real estate. Largely ignored, however, is that this contraction was easily predicted on the basis of a well‐established pattern of land speculation, premature subdivision, and excessive building on marginal land that recurs approximately once every 18 years. Capital locked up in projects that are started during a land bubble is effectively lost during the downturn, leaving the nation without sufficient capital to finance ordinary business operations during the recovery period. The best instrument for avoiding this boom‐bust cycle is the property tax and, more specifically, the portion that falls on land. We explore here the ways in which the property tax influences the intensity, timing, and location of development. We also examine why frequent and accurate assessment are essential to make the property tax an effective method of preventing speculative real estate bubbles.
Why Do U.S. Firms Hold So Much More Cash than They Used To?
Authors: BATES THOMAS W. , KAHLE KATHLEEN M. , STULZ RENÉ M. 
Published: September 2009

ABSTRACTThe average cash‐to‐assets ratio for U.S. industrial firms more than doubles from 1980 to 2006. A measure of the economic importance of this increase is that at the end of the sample period, the average firm can retire all debt obligations with its cash holdings. Cash ratios increase because firms' cash flows become riskier. In addition, firms change: They hold fewer inventories and receivables and are increasingly R&D intensive. While the precautionary motive for cash holdings plays an important role in explaining the increase in cash ratios, we find no consistent evidence that agency conflicts contribute to the increase.
Credit Contagion from Counterparty Risk
Authors: JORION PHILIPPE , ZHANG GAIYAN 
Published: September 2009

ABSTRACTStandard credit risk models cannot explain the observed clustering of default, sometimes described as “credit contagion.” This paper provides the first empirical analysis of credit contagion via direct counterparty effects. We find that bankruptcy announcements cause negative abnormal equity returns and increases in CDS spreads for creditors. In addition, creditors with large exposures are more likely to suffer from financial distress later. This suggests that counterparty risk is a potential additional channel of credit contagion. Indeed, the fear of counterparty defaults among financial institutions explains the sudden worsening of the credit crisis after the Lehman bankruptcy in September 2008.
The Relation between Price and Performance in the Mutual Fund Industry
Authors: GIL‐BAZO JAVIER , RUIZ‐VERDÚ PABLO 
Published: September 2009

ABSTRACTGruber (1996)drew attention to the puzzle that investors buy actively managed equity mutual funds, even though on average such funds underperform index funds. We uncover another puzzling fact about the market for equity mutual funds: Funds with worse before‐fee performance charge higher fees. This negative relation between fees and performance is robust and can be explained as the outcome of strategic fee‐setting by mutual funds in the presence of investors with different degrees of sensitivity to performance. We also find some evidence that better fund governance may bring fees more in line with performance.
Business Networks, Corporate Governance, and Contracting in the Mutual Fund Industry
Authors: KUHNEN CAMELIA M. 
Published: September 2009

ABSTRACTBusiness connections can mitigate agency conflicts by facilitating efficient information transfers, but can also be channels for inefficient favoritism. I analyze these two effects in the mutual fund industry and find that fund directors and advisory firms that manage the funds hire each other preferentially based on the intensity of their past interactions. I do not find evidence that stronger board‐advisor ties correspond to better or worse outcomes for fund shareholders. These results suggest that the two effects of board‐management connections on investor welfare—improved monitoring and increased potential for collusion—balance out in this setting.