bluuebunny/crossref_metadata_2025_split huggingface dataset:
Voltage‐operated Ca2+ currents and Ca2+‐activated Cl– currents in single interstitial cells of the guinea‐pig prostate
Authors: Lang Richard J. , Tonta Mary A. , Takano Hiromichi , Hashitani Hikaru 
Published: January 2014

ObjectiveTo investigate the expression of ‘T‐type’ and ‘L‐type’ voltage‐operated Ca2+ channels in single interstitial cells of the guinea‐pig prostate.Material and MethodsWhole‐cell and perforated patch‐clamp techniques were applied to prostatic interstitial cells (PICs) dispersed using collagenase.ResultsIn contrast to prostatic myocytes, PICs under voltage clamp and filled with K+ (130 mm) were distinguished by the absence of a voltage‐operated transient outward K+ current or spike discharge upon membrane depolarisation when under current clamp. Depolarisation of Cs+‐filled PICs evoked an inward current at potentials positive to −60 mV, which peaked in amplitude near 0 mV. This inward current increased when Ba2+ (5 mm) replaced the external Ca2+ (1.5 mm) and displayed a variable sensitivity to the inhibitory actions of conditioning depolarisations to −40 mV applied before the test depolarisation or to 1 μm nifedipine, the ‘L‐type’ Ca2+ channel blocker. A residual inward current recorded in nifedipine was blocked by 10 μm Ni2+. Cs+‐filled PICs also displayed a slowly inactivating outward current that was little affected by nifedipine, reduced by the Cl– channel blocker, niflumic acid (10 μm) and blocked by Ba2+ or a conditioning depolarisation.ConclusionPICs express both a small ‘T‐type’ Ca2+ channel current (ICa) and a large ‘L‐type’ ICa. Ca2+ influx through ‘T‐type’ ICa was an essential trigger for the activation of a Ca2+‐activated Cl–‐selective current. The dependence of PIC Ca2+ signalling on ‘T‐type’ and ‘L‐type’ ICa is unique compared with other interstitial cells of the urogenital tract and may well be pharmaceutically exploitable.
Sex differences in endothelial function in porcine coronary arteries: a role for H2O2 and gap junctions?
Authors: Wong P S , Roberts R E , Randall M D 
Published: January 2014

Background and PurposeCardiovascular risk is higher in men and postmenopausal women compared with premenopausal women. This may be due to sex differences in endothelial function. Here, sex differences in endothelial function of porcine coronary arteries (PCAs) were investigated.Experimental ApproachDistal PCAs were studied under myographic conditions and after precontraction with U46619. Concentration‐response curves to bradykinin were constructed in the presence of a range of inhibitors.Key ResultsIn male and female PCAs, bradykinin produced comparable vasorelaxant responses. Inhibition of NO and prostanoid synthesis produced greater inhibition in males compared with females. Removing H2O2 with PEG‐catalase reduced the maximum relaxation in the absence, but not the presence of L‐NAME and indomethacin in females, and had no effect in males. Blocking gap junctions with 100 µM carbenoxolone or 18α‐glycyrrhetinic acid further inhibited the endothelium‐derived hyperpolarization (EDH)‐mediated response in females but not in males. In female PCAs, the maximum EDH‐mediated response was reduced by inhibiting SKCa with apamin and by inhibiting IKCa with TRAM‐34, or with both. In male PCAs, at maximum bradykinin concentration, the EDH‐mediated response was reduced in the presence of apamin but not TRAM‐34. Western blot did not detect any differences in connexins 40 or 43 or in IKCa expression between male and female PCAs.Conclusions and ImplicationsH2O2 mediated some part of endothelium‐dependent vasorelaxation in female PCAs and EDH was more important in females, with differences in the contribution of gap junctions and IKCa channels. These findings may contribute to understanding vascular protection in premenopausal women.
Heart ischaemia–reperfusion induces local up‐regulation of vasoconstrictor endothelin ETB receptors in rat coronary arteries downstream of occlusion
Authors: Skovsted G F , Kruse L S , Larsen R , Pedersen A F , Trautner S , Sheykhzade M , Edvinsson L 
Published: January 2014

Background and PurposeEndothelins act via two receptor subtypes, ETA and ETB. Under physiological conditions in coronary arteries, ETA receptors expressed in smooth muscle cells mediate vasoconstriction whereas ETB receptors mainly found in endothelial cells mediate vasorelaxation. However, under pathophysiological conditions, ETB receptors may also be expressed in vascular smooth muscle cells mediating vasoconstriction. Here, we have investigated whether vasoconstrictor ETB receptors are up‐regulated in coronary arteries after experimental myocardial ischaemia in rats.Experimental ApproachMale Sprague‐Dawley rats were subjected to either heart ischaemia–reperfusion (15 min ischaemia and 22 h reperfusion), permanent ischaemia (22 h) by ligation of the left anterior descending coronary artery, or sham operation. Using wire myography, the endothelin receptor subtypes mediating vasoconstriction were examined in isolated segments of the left anterior descending and the non‐ligated septal coronary arteries. Endothelin receptor‐mediated vasoconstriction was examined with cumulative administration of sarafotoxin 6c (ETB receptor agonist) and endothelin‐1 (with or without ETA or ETB receptor blockade). The distribution of ETB receptors was localized with immunohistochemistry and quantified by Western blot.Key ResultsEndothelin ETB receptor‐mediated vasoconstriction and receptor protein levels were significantly augmented in coronary arteries situated downstream of the occlusion after ischaemia–reperfusion compared with non‐ischaemic arteries. In contrast, the ETA receptor‐mediated vasoconstriction was unaltered in all groups.Conclusions and ImplicationsIschaemia–reperfusion induced local up‐regulation of ETB receptors in the smooth muscle cells of coronary arteries in the post‐ischaemic area. In contrast, in non‐ischaemic areas, ETB receptor function was unaltered.
Luteolin is effective in the non‐small cell lung cancer model with L858R/T790M EGF receptor mutation and erlotinib resistance
Authors: Hong Zhuan , Cao Xiang , Li Na , Zhang Yizhou , Lan Lei , Zhou Yi , Pan Xiaolong , Shen Lei , Yin Zhimin , Luo Lan 
Published: January 2014

Background and PurposeNon‐small cell lung cancer (NSCLC) is one of the most commonly diagnosed malignancies in the world. Small‐molecule inhibitors of the EGF receptor's tyrosine kinase domain (TKIs), including gefitinib and erlotinib, have been widely used for treating NSCLC. Unfortunately, nearly all patients after initially experiencing a marked improvement while on these drugs, eventually progress to acquire resistance to TKIs. Because there is no effective therapeutic strategy to treat TKI‐resistant NSCLC, we evaluated the effects of luteolin, a naturally occurring flavanoid, on T790M mutant NSCLC cells.Experimental ApproachThe effect of luteolin on the viability of NSCLC and normal cell lines was investigated using the Cell Counting Kit‐8 (CCK‐8) assay. Luteolin‐induced apoptosis was assessed by bivariate FITC‐annexin V/PI assay, and Western blots were used to measured apoptotic proteins. Co‐immunoprecipitation was used to determine the effect of luteolin on the interaction between Hsp90 and mutant EGF receptors. The effect of luteolin on the Akt/mTOR pathway was studied using Western blotting analysis. Its anti‐tumour efficacy in vivo was examined in a mouse xenograft model.Key ResultsLuteolin exerted significant anti‐tumourigenic effects on the EGF receptor L858R/T790M mutation and erlotinib‐resistant NSCLC both at the cellular and animal levels. Mechanistically, luteolin induced degradation of the EGF receptor by inhibiting the association of Hsp90 with the mutant EGF receptor, and, therefore, prevented PI3K/Akt/mTOR signalling, which resulted in NSCLC cell apoptosis.Conclusion and ImplicationsLuteolin may be a potential candidate for NSCLC therapy, especially for treatment of patients with acquired erlotinib‐resistant NSCLC.
Psychiatric disease in late adolescence and young adulthood. Foetal programming by maternal hypothyroidism?
Authors: Andersen Stine Linding , Olsen Jørn , Wu Chun Sen , Laurberg Peter 
Published: January 2014

SummaryObjectiveLack of maternal thyroid hormones during foetal brain development may lead to structural abnormalities in the brain. We hypothesized that maternal hypothyroidism during the pregnancy could programme the foetus to development of psychiatric disease later in life.DesignDanish nationwide register study.ParticipantsSingletons live‐born 1980–1990.MeasurementsCox proportional hazards model was used to estimate adjusted hazard ratio (aHR) with 95% confidence interval for offspring redemption of ≥2 prescriptions of a psychiatric drug from age 15 to 31 years.ResultsAmong 542 100 adolescents and young adults included, altogether 3979 (0·7%) were born to mothers with hypothyroidism registered before 1996. In crude analyses, the use of a psychiatric drug was more frequent in late adolescence and young adulthood when the mother had hypothyroidism (P < 0·001); however, several possible confounders had to be taken into account. For example, mothers with hypothyroidism often also had a psychiatric registration (38·5% vs 27·7%, P < 0·001) and the use of psychiatric drugs changed over time. After adjustment for confounders including birth year, maternal age and maternal psychiatric history, maternal hypothyroidism was associated with an increased risk of having redeemed prescriptions of anxiolytics [aHR 1·23 (1·03–1·48)] and antipsychotics [aHR 1·22 (1·03–1·44)] in late adolescence and young adulthood. For antidepressants, aHR was 1·07 (0·98–1·17).ConclusionsThe association between maternal hypothyroidism and the use of a psychiatric drug in late adolescence and young adulthood was partly confounded by maternal psychiatric history, but foetal programming by maternal hypothyroidism may be part of the mechanisms leading to the use of anxiolytics and antipsychotics.
One and Done? Optimal Decisions From Very Few Samples
Authors: Vul Edward , Goodman Noah , Griffiths Thomas L. , Tenenbaum Joshua B. 
Published: January 2014

AbstractIn many learning or inference tasks human behavior approximates that of a Bayesian ideal observer, suggesting that, at some level, cognition can be described as Bayesian inference. However, a number of findings have highlighted an intriguing mismatch between human behavior and standard assumptions about optimality: People often appear to make decisions based on just one or a few samples from the appropriate posterior probability distribution, rather than using the full distribution. Although sampling‐based approximations are a common way to implement Bayesian inference, the very limited numbers of samples often used by humans seem insufficient to approximate the required probability distributions very accurately. Here, we consider this discrepancy in the broader framework of statistical decision theory, and ask: If people are making decisions based on samples—but as samples are costly—how many samples should people use to optimize their total expected or worst‐case reward over a large number of decisions? We find that under reasonable assumptions about the time costs of sampling, making many quick but locally suboptimal decisions based on very few samples may be the globally optimal strategy over long periods. These results help to reconcile a large body of work showing sampling‐based or probability matching behavior with the hypothesis that human cognition can be understood in Bayesian terms, and they suggest promising future directions for studies of resource‐constrained cognition.
Identifying realistic recovery targets and conservation actions for tigers in a human‐dominated landscape using spatially explicit densities of wild prey and their determinants
Authors: Harihar Abishek , Pandav Bivash , MacMillan Douglas C. 
Published: January 2014

AbstractAimSetting realistic population targets and identifying actions for site and landscape‐level recovery plans are critical for achieving the global target of doubling wild tiger numbers by 2022. Here, we estimate the spatially explicit densities of wild ungulate prey across a gradient of disturbances in two disjunct tiger habitat blocks (THBs) covering 5212 km2, to evaluate landscape‐wide conditions for tigers and identify opportunities and specific actions for recovery.LocationWestern Terai Arc Landscape, India.MethodsData generated from 96 line transects in 15 systematically selected geographical cells (166.5 km2) were used to estimate spatially explicit densities of six wild ungulate prey species at a fine scale (1 km2). Employing distance‐based density surface models, we derived species‐specific estimates within three major forest land management categories (inviolate protected areas (PA),PAs with settlements and multiple‐use forests). By scaling estimated prey densities using an established relationship, we predicted the carrying capacity for tigers within eachTHB.ResultsSpecies‐specific responses of the six wild ungulates to natural‐habitat and anthropogenic covariates indicated the need for targeted prey recovery strategies. InviolatePAs supported the highest prey densities compared withPAs with settlements and multiple‐use forests, and specifically benefited the principal tiger prey species (chitalAxis axisand sambarRusa unicolor). The estimated mean prey density of 35.16 (±5.67) individuals per km2can potentially support 82 (62–106) and 299 (225–377) tigers acrossTHBI andTHB II, which currently support 2 (2–7) and 225 (199–256) tigers, respectively. This suggests a potentialc. 68% increase in population size given existing prey abundances. Finally, whileTHBI represents a potential tiger recovery site given adequate prey,PAs where resettlement of pastoralists is underway represent potential prey recovery sites inTHB II.Main conclusionsThis systematic approach of setting realistic population targets and prioritizing spatially explicit recovery strategies should aid in developing effective landscape conservation plans towards achieving global tiger conservation targets.
Lower urinary tract symptoms and urodynamic dysfunction in clinically isolated syndromes suggestive of multiple sclerosis
Authors: Di Filippo M. , Proietti S. , Gaetani L. , Gubbiotti M. , Di Gregorio M. , Eusebi P. , Calabresi P. , Sarchielli P. , Giannantoni A. 
Published: January 2014

Background and purposeUrinary symptoms associated with multiple sclerosis (MS) are common and negatively impact on quality of life, representing a considerable psychosocial and economic burden, often requiring care and hospitalization. Although the importance of identifying and adequately treating urinary symptoms in MS is now well recognized, there is no information, to date, about the real prevalence and impact of bladder symptoms in patients with clinically isolated syndromes (CISs) suggestive of MS.MethodsThe aim of the present study was to investigate, in a cohort of patients with a diagnosis of CIS suggestive of MS, the prevalence of urinary tract symptoms, their impact on quality of life measures and their association with functional urodynamic dysfunctions. Patients underwent a complete neurological and urological visit, urodynamic investigation and the MSQoL‐54 questionnaire.ResultsTwenty‐eight consecutive patients presenting with CISs were enrolled in the study; 53.6% of CIS patients reported urinary symptoms, 46.7% reporting irritative symptoms, 33.3% both irritative and obstructive symptoms and 20% obstructive symptoms alone. Urodynamic abnormalities were observed in 57.1% of the CIS patients. In 17.9% of the CIS patients urodynamic dysfunctions were asymptomatic. The presence of urinary symptoms was associated with lower scores on specific quality of life domains, particularly in women with obstructive symptoms.ConclusionsA high prevalence of urinary symptoms and urodynamic dysfunctions in patients with CISs and an association of urinary symptoms with quality of life measures were found. These results highlight the importance of identifying and optimally treating urinary symptoms also at the very early stages of MS.
Performance selection for Thoroughbreds racing in Hong Kong
Authors: Velie B. D. , Hamilton N. A. , Wade C. M. 
Published: January 2014

SummaryReasons for performing studyDifferent indicators of racing performance are commonly used in the racing industry to assess the genetic superiority of racing Thoroughbreds. However, how well these indicators predict the performance of future progeny or siblings varies depending on the population and circumstances in which the indicators were recorded or achieved.ObjectivesTo identify heritable indicators of racing performance for horses racing in Hong Kong.Study designHeritability analysis of racing performance traits.MethodsPerformance data on the population of Thoroughbreds racing in Hong Kong between 3 September 2000 and 12 March 2011 (n = 4947) were acquired and used to estimate the heritabilities and probability values of fixed effects and covariates for a range of racing performance traits. Heritabilities for all performance traits were estimated using a single trait animal model. Each model included, as a minimum, the effects of sex, region of origin and trainer.ResultsHeritability estimates for traits relating to finish position ranged from 0.01 to 0.06. Average handicap weight had a heritability of 0.07 ± 0.03. The effects of sex (fixed) and trainer (random) were significant (P<0.05) for all performance traits relating to earnings measures, handicap weights and finish positions. The heritability of win time at 1600 m was 0.52 ± 0.06 and was the only significant estimate of heritability for win time in the current study.ConclusionsAlthough significantly affected by multiple environmental factors, certain indicators of Hong Kong racing performance can be reliably used to predict the performance of the individual's progeny or siblings. However, despite Hong Kong's controlled racing environment, these indicators appear to be no more heritable than in other less controlled racing environments.
Pre‐Service Foreign Language Teachers' Perspectives on Learning With Technology
Authors: Sardegna Veronica G. , Dugartsyrenova Vera A. 
Published: January 2014

AbstractThis study explores pre‐service foreign language teachers' (N = 25) beliefs about the value and usefulness of employing technology‐enhanced activities (discussion forums, blogs, wikis, e‐portfolios, videotape recordings) in a methods course, and their perceptions of how these activities supported their learning. Likert‐scale items from an anonymous questionnaire indicated that participants found those activities beneficial for bridging theory and practice, enhancing critical thinking, and promoting professional growth. A qualitative analysis of participants' reflections revealed that, despite technology‐related challenges and preferences for other coursework activities, participants believed that the technology‐based activities provided increased opportunities for varied and richer interactions, peer feedback, and reflection; helped develop their learner autonomy and sense of belonging to a community of learners; modeled effective technology uses; and fostered a deeper appreciation of technology‐enriched practices.
Migration model of post‐smolt Atlantic salmon (Salmo salar) in the Gulf of Maine
Authors: Byron Carrie J. , Pershing Andrew J. , Stockwell Jason D. , Xue Huijie , Kocik John 
Published: January 2014

AbstractUnderstanding how oceanographic factors independently and interactively influence fish behavior, physiology, and survival is essential for predicting the impact of climate change on fish. Such predictions are especially challenging for highly migratory species such as salmon that experience a broad range of conditions. We applied a novel modeling approach that combines an individual‐based particle model with a bioenergetics model to evaluate the effects of oceanographic variability on migration of post‐smolt Atlantic salmon (Salmo salar). Interannual variability in the surface current velocity and sea surface temperature differentially influenced post‐smolt salmon migration. The magnitude, duration, and direction of the currents relative to a fish's intended swimming direction had the strongest influence on migration. Changes in ocean circulation led to changes in currents at a regional scale that have a similar, relative effect across multiple populations during out‐migration. Results of this study suggest that the Nova Scotia Coastal Current has a strong influence on the migration pathways of migrating salmon through the Gulf of Maine. The influx of cool fresh water from the Arctic, observed in the early 1990s, changed the Nova Scotia Coastal Current and, as suggested by model results, could have dramatically influenced post‐smolt salmon migration success. There was a trade‐off between arriving at the destination quickly but at a small size and not arriving at the destination at all. Fish that took a long time to migrate had more opportunities to feed and encountered warmer summer waters, increasing their overall growth.
Morphology, metabolism and behaviour: responses of three fishes with different lifestyles to acute hypoxia
Authors: Dwyer Georgia K. , Stoffels Rick J. , Pridmore Peter A. 
Published: January 2014

Summary

Behavioural responses to changing environments affect community composition, so the identification of associations between environmental gradients, behavioural traits and physiological traits makes a significant contribution to the quest for trait‐based rules of community change.

We tested the hypothesis that fish morphology and lifestyle are associated with metabolic rate, hence oxygen demand, and behavioural response to gradual hypoxia [low dissolved oxygen (DO)], using respirometry and behavioural experiments. Three species fell along different points of the fast–slow lifestyle continuum: Melanotaenia fluviatilis, a pelagic fish adapted to endurance swimming, lies at the fast end of the lifestyle continuum, while Mogurnda adspersa, a benthic fish adapted to burst swimming, lies at the other end. The benthopelagic Hypseleotris sp. has an intermediate lifestyle.

Standard and routine metabolic rates varied strongly among the species and were associated with lifestyle according to the inequality M. fluviatilis > Hypseleotris > M. adspersa. As DO declined, aquatic surface respiration behaviour also varied significantly among the species and indicated a sensitivity to hypoxia described by the same inequality. As hypoxia ensued, changes in habitat were also linked to lifestyle, but changes in activity level among species were not neatly correlated with lifestyle.

Overall, our experiments imply that there are significant links between morphology, lifestyle, metabolism and behavioural response to hypoxia in these three species of fish.