bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic deficit of KCa3.1 channels protects against pulmonary circulatory collapse induced by TRPV4 channel activation
Authors: Wandall‐Frostholm Christine , Dalsgaard Thomas , Bajoriūnas Vytis , Oliván‐Viguera Aida , Sadda Veeruanjaneyulu , Beck Lilliana , Mogensen Susie , Stankevicius Edgaras , Simonsen Ulf , Köhler Ralf 
Published: June 2015

Background and PurposeThe intermediate conductance calcium/calmodulin‐regulated K+ channel KCa3.1 produces hyperpolarizing K+ currents that counteract depolarizing currents carried by transient receptor potential (TRP) channels, and provide the electrochemical driving force for Cl− and fluid movements. We investigated whether a deficiency in KCa3.1 (KCa3.1−/−) protects against fatal pulmonary circulatory collapse in mice after pharmacological activation of the calcium‐permeable TRP subfamily vanilloid type 4 (TRPV4) channels.Experimental ApproachAn opener of TRPV4 channels, GSK1016790A, was infused in wild‐type (wt) and KCa3.1−/− mice; haemodynamic parameters, histology and pulmonary vascular reactivity were measured; and patch clamp was performed on pulmonary arterial endothelial cells (PAEC).Key ResultsIn wt mice, GSK1016790A decreased right ventricular and systemic pressure leading to a fatal circulatory collapse that was accompanied by increased protein permeability, lung haemorrhage and fluid extravasation. In contrast, KCa3.1−/− mice exhibited a significantly smaller drop in pressure to GSK1016790A infusion, no haemorrhage and fluid water extravasation, and the mice survived. Moreover, the GSK1016790A‐induced relaxation of pulmonary arteries of KCa3.1−/− mice was significantly less than that of wt mice. GSK1016790A induced TRPV4 currents in PAEC from wt and KCa3.1−/− mice, which co‐activated KCa3.1 and disrupted membrane resistance in wt PAEC, but not in KCa3.1−/− PAEC.Conclusions and ImplicationsOur findings show that a genetic deficiency of KCa3.1 channels prevented fatal pulmonary circulatory collapse and reduced lung damage caused by pharmacological activation of calcium‐permeable TRPV4 channels. Therefore, inhibition of KCa3.1channels may have therapeutic potential in conditions characterized by abnormal high endothelial calcium signalling, barrier disruption, lung oedema and pulmonary circulatory collapse.
CD4 T cell differentiation in type 1 diabetes
Authors: Walker L S K , von Herrath M 
Published: June 2015

SummarySusceptibility to type 1 diabetes is associated strongly with human leucocyte antigen (HLA) genes, implicating T cells in disease pathogenesis. In humans, CD8 T cells predominantly infiltrate the islets, yet their activation and propagation probably requires CD4 T cell help. CD4 T cells can select from several differentiation fates following activation, and this choice has profound consequences for their subsequent cytokine production and migratory potential. In turn, these features dictate which other immune cell types T cells interact with and influence, thereby determining downstream effector functions. Obtaining an accurate picture of the type of CD4 T cell differentiation associated with a particular immune-mediated disease therefore constitutes an important clue when planning intervention strategies. Early models of T cell differentiation focused on the dichotomy between T helper type 1 (Th1) and Th2 responses, with type 1 diabetes (T1D) being viewed mainly as a Th1-mediated pathology. However, several additional fate choices have emerged in recent years, including Th17 cells and follicular helper T cells. Here we revisit the issue of T cell differentiation in autoimmune diabetes, highlighting new evidence from both mouse models and patient samples. We assess the strengths and the weaknesses of the Th1 paradigm, review the data on interleukin (IL)-17 production in type 1 diabetes and discuss emerging evidence for the roles of IL-21 and follicular helper T cells in this disease setting. A better understanding of the phenotype of CD4 T cells in T1D will undoubtedly inform biomarker development, improve patient stratification and potentially reveal new targets for therapeutic intervention.
Toward a Social Science Research Agenda for Large Marine Protected Areas
Authors: Gruby Rebecca L. , Gray Noella J. , Campbell Lisa M. , Acton Leslie 
Published: June 2015

AbstractLarge marine protected areas (LMPAs) are a high‐profile trend in global marine conservation. Although the social sciences have become well integrated into marine protected area research and practice, human dimensions considerations have not been an early priority in the development of many LMPAs. This article argues that because LMPAs exhibit unique characteristics in form, function, and/or conceptualization, they warrant a distinct social science research agenda. We outline an agenda for social science research on and for LMPAs in four related themes: scoping of human dimensions, governance, politics, and social and economic outcomes. The article is informed by interviews, participant observation at the 2014 World Parks Congress, a literature review and the authors’ research experiences. LMPAs are at an early stage in what promises to be a globally significant, long‐term project of ocean conservation and governance. There is a timely opportunity to translate relevant insights from decades of social science research to LMPAs and generate new knowledge, where necessary, to give them their best chance at biological and social success.
Impacts of inoculation withHerpotrichia pinetorum, Gremmenia infestansandGremmeniella abietinaonPinus nigrasubsp.pallasianaandCedrus libaniseedlings in the field
Authors: Doğmuş‐Lehtijärvi H. T. , Lehtijärvi A. , Woodward S. , Oskay F. 
Published: June 2015

SummaryHerpotrichia pinetorum,Gremmenia infestansandGremmeniella abietinawere inoculated onto 2‐year‐old Anatolian black pine (Pinus nigrasubsp.pallasiana) and Taurus cedar (Cedrus libani) seedlings planted in a high mountain forest (1800 m a.s.l) in south‐western Turkey, to determine the effects of these fungi during winter. In June, 8 months after inoculation, 39.9% of experimental plants were dead and 20.4% of the surviving plants failed to flush.Gremmeniella abietinaandH. pinetorumcaused the most fatalities. Prevention of new shoot formation on surviving plants, however, was mainly an effect ofG. abietinainfections, although many surviving plants inoculated withG. infestansorH. pinetorumalso failed to flush. All three pathogens had the potential to severely damage young plants ofP. nigrasubsp.pallasianaandC. libanigrowing at high elevations near to forests with heavy inoculum loads. The implications of this finding forP. nigraafforestations at high altitudes in Turkey are discussed. This study is also the first to report thatG. infestanscan infect and cause disease on youngC. libaniplants.
The Painful Legacy of Childhood Violence: Migraine Headaches Among Adult Survivors of Adverse Childhood Experiences
Authors: Brennenstuhl Sarah , Fuller‐Thomson Esme 
Published: June 2015

BackgroundChildhood adversities have been associated with adult migraine in the general population. However, most research has focused on only a few types of maltreatment and has not always controlled for factors correlated with early adversities and migraine.ObjectivesThe aim of this study was to investigate the relationship between early adversities and migraine, while controlling for a range of potential explanatory factors.MethodsWe analyzed data from the 2012 Canadian Community Health Survey – Mental Health. Using a representative sample of 10,358 men and 12,638 women, we undertook gender‐specific logistic regression analyses to determine the association between number and type of self‐reported childhood adversities (physical abuse, sexual abuse, and witnessing parental domestic violence) and migraine, while controlling for sociodemographics, comorbid adversities, health behaviors, depression, and anxiety.ResultsIn total, 6.5% of men and 14.2% of women reported migraines. All three adversities were significantly associated with migraine for both genders, even after controlling for a range of variables. The fully adjusted odds of migraine associated with physical abuse, parental domestic violence, and sexual abuse were 1.61 (95% confidence interval [CI] = 1.42‐1.83), 1.64 (95% CI = 1.39‐1.93), and 1.32 (95% CI = 1.11‐1.57), respectively, for women, and 1.50 (95% CI = 1.25‐1.80), 1.52 (95% CI = 1.16‐1.98), and 1.70 (95% CI = 1.22‐2.36) for men. Greater number of adversities was also associated with increasing odds of migraine. Men reporting all three adversities had over three times (odds ratio = 3.26; 95% CI = 2.09‐5.07) and women over two times (OR = 2.85; 95% CI = 2.25‐3.60) the odds of migraine compared with those without childhood adversities.ConclusionsNumber and type of early adversities are associated with migraine among Canadian men and women.
Detection accuracy of root fractures in cone‐beam computed tomography images: a systematic review and meta‐analysis
Authors: Ma R. H. , Ge Z. P. , Li G. 
Published: June 2015

AbstractThe aim of this review was to evaluate whetherCBCTis reliable for the detection of root fractures in teeth without root fillings, and whether the voxel size has an impact on diagnostic accuracy. The studies published in PubMed, Web of Science, ScienceDirect, Cochrane Library, Embase, Scopus,CNKIand Wanfang up to May 2014 were the data source. Studies on nonroot filled teeth with the i‐CAT(n = 8) and 3D AccuitomoCBCT(n = 5) units were eventually selected. In the studies on i‐CAT, the pooled sensitivity was 0.83 and the pooled specificity was 0.91; in the 3D Accuitomo studies, the pooled sensitivity was 0.95 and pooled specificity was 0.96. The i‐CATgroup comprised 5 voxel size subgroups and the 3D Accuitomo group contained 2 subgroups. For the i‐CATgroup, there was a significant difference amongst the five subgroups (0.125, 0.2, 0.25, 0.3 and 0.4 mm;P = 0.000). Pairwise comparison revealed that 0.125 mm voxel subgroup was significantly different from those of 0.2, 0.25 and 0.3 mm voxel subgroups, but not from the 0.4 mm voxel subgroup. There were no significant differences amongst any other two subgroups (by α′ = 0.005). No significant difference was found between 0.08 mm and 0.125 mm voxel subgroups (P = 0.320) for the 3D Accuitomo group. The present review confirms the detection accuracy of root fractures inCBCTimages, but does not support the concept that voxel size may play a role in improving the detection accuracy of root fractures in nonroot filled teeth.
Effect of an Antagonistic Yeast in Combination with Microwave Treatment on Postharvest Blue Mould Rot of Jujube Fruit
Authors: Guo Dongqi , Yang Baoqiu , Ren Xiaopu , Zhu Lixia 
Published: June 2015

AbstractThe potential of using an antagonistic yeast alone or in combination with microwave treatment for controlling blue mould rot of jujube fruit, and its effect on postharvest quality of fruit, was investigated. The results showed that the growth of Penicillium citrinum was completely inhibited by a 2450‐MHz microwave heating for 2 or more minutes in vitro. The population density of P. citrinum in surface wounds of fruit treated with microwave treatment for 2–3 min was significantly lower than that of controls. When tested on jujube fruit, antagonistic yeast or microwave treatment, as stand‐alone treatment, the disease incidence of infected wounds was reduced from 100% to 45.0% and 36.0%, and lesion diameters were reduced from 1.92 cm to 1.50 cm and 1.38 cm, respectively. However, in fruit treated with a combination of Metschnikowia pulcherrima and microwave treatment, the disease incidence of infected wounds and lesion diameters was only 21.0% and 1.00 cm, respectively. The natural decay incidence on jujube fruit treated with the combination of microwave treatment and M. pulcherrima was 6.2% after storage at 2 ± 1°C for 45 days and at 22°C for 7 days. None of the treatments impaired quality parameters of fruits. Thus, the combination of microwave treatment and M. pulcherrima could provide an alternative to synthetic fungicides for controlling postharvest blue mould rot of jujube fruit.
Cyclosporin A-sensitive cytotoxicity of flurbiprofen non-stereoselectively mediated by cytochrome P450 metabolism in three-dimensional cultured rat hepatocytes
Authors: Tanino Tadatoshi , Funakami Yoshinori , Nagai Noriaki , Kato Yoshihisa 
Published: June 2015

Abstract

Objectives
2-Arylpropionic acid (profen) drugs are associated with severe hepatotoxicity; however, risk factors are still poorly understood. Acyl-coenzyme A (acyl-CoA) thioesters of profen drugs play a more important role in the covalent binding to rat hepatocyte proteins than the respective acyl-glucuronides. Therefore, we examined whether acyl-glucuronides, acyl-CoA thioesters and oxidative metabolites of profen drugs stereoselectively participated in liver damage.

Methods
Cytotoxicity was determined by measuring lactate dehydrogenase (LDH) leakage from three-dimensional cultured rat hepatocytes.

Key findings
LDH leakage was not induced by R-2-phenylpropionic acid and R-ibuprofen greatly forming acyl-CoA thioesters. S-Naproxen metabolized mainly by Uridine 5′-diphosphate (UDP)-glucuronosyl-transferase did not enhance LDH leakage. However, flurbiprofen (FLP) induced LDH leakage. A selective cytochrome P450 (CYP) 2C11 inhibitor suppressed 40–50% of the R-FLP and S-FLP-induced cytotoxicity. Borneol non-stereoselectively accelerated the FLP-induced cytotoxicity. The R-FLP-induced cytotoxicity decreased intracellular adenosine triphosphate (ATP) levels to 50% of untreated hepatocytes. An inhibitor of mitochondrial permeability transition pore, cyclosporin A (Cys A), rescued ATP levels and LDH leakage back to control levels.

Conclusion
The reactive acyl-CoA thioesters and acyl-glucuronides were not associated with liver damage, denying one of the leading hypotheses. CYP metabolism of FLP non-stereoselectively participated in Cys A-sensitive cytotoxicity, suggesting mitochondrial injury.
The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease
Authors: Irvine Katharine M. , Wockner Leesa F. , Shanker Mihir , Fagan Kevin J. , Horsfall Leigh U. , Fletcher Linda M. , Ungerer Jacobus P. J. , Pretorius Carel J. , Miller Gregory C. , Clouston Andrew D. , Lampe Guy , Powell Elizabeth E. 
Published: June 2015

AbstractBackground and AimsCurrent tools for risk stratification of chronic liver disease subjects are limited. We aimed to determine whether the serum‐based ELF (Enhanced Liver Fibrosis) test predicted liver‐related clinical outcomes, or progression to advanced liver disease, and to compare the performance of ELF to liver biopsy and non‐invasive algorithms.MethodsThree hundred patients with ELF scores assayed at the time of liver biopsy were followed up (median 6.1 years) for liver‐related clinical outcomes (n = 16) and clear evidence of progression to advanced fibrosis (n = 18), by review of medical records and clinical data.ResultsFourteen of 73 (19.2%) patients with ELF score indicative of advanced fibrosis (≥9.8, the manufacturer's cut‐off) had a liver‐related clinical outcome, compared to only two of 227 (<1%) patients with ELF score <9.8. In contrast, the simple scores APRI and FIB‐4 would only have predicted subsequent decompensation in six and four patients respectively. A unit increase in ELF score was associated with a 2.53‐fold increased risk of a liver‐related event (adjusted for age and stage of fibrosis). In patients without advanced fibrosis on biopsy at recruitment, 55% (10/18) with an ELF score ≥9.8 showed clear evidence of progression to advanced fibrosis (after an average 6 years), whereas only 3.5% of those with an ELF score <9.8 (8/207) progressed (average 14 years). In these subjects, a unit increase in ELF score was associated with a 4.34‐fold increased risk of progression.ConclusionsThe ELF score is a valuable tool for risk stratification of patients with chronic liver disease.
Identification of novel Xanthomonas euvesicatoria type III effector proteins by a machine‐learning approach
Authors: Teper Doron , Burstein David , Salomon Dor , Gershovitz Michael , Pupko Tal , Sessa Guido 
Published: June 2015

SummaryThe Gram‐negative bacterium Xanthomonas euvesicatoria (Xcv) is the causal agent of bacterial spot disease in pepper and tomato. Xcv pathogenicity depends on a type III secretion (T3S) system that delivers effector proteins into host cells to suppress plant immunity and promote disease. The pool of known Xcv effectors includes approximately 30 proteins, most identified in the 85‐10 strain by various experimental and computational techniques. To identify additional Xcv 85‐10 effectors, we applied a genome‐wide machine‐learning approach, in which all open reading frames (ORFs) were scored according to their propensity to encode effectors. Scoring was based on a large set of features, including genomic organization, taxonomic dispersion, hypersensitive response and pathogenicity (hrp)‐dependent expression, 5′ regulatory sequences, amino acid composition bias and GC content. Thirty‐six predicted effectors were tested for translocation into plant cells using the hypersensitive response (HR)‐inducing domain of AvrBs2 as a reporter. Seven proteins (XopAU, XopAV, XopAW, XopAP, XopAX, XopAK and XopAD) harboured a functional translocation signal and their translocation relied on the HrpF translocon, indicating that they are bona fide T3S effectors. Remarkably, four belong to novel effector families. Inactivation of the xopAP gene reduced the severity of disease symptoms in infected plants. A decrease in cell death and chlorophyll content was observed in pepper leaves inoculated with the xopAP mutant when compared with the wild‐type strain. However, populations of the xopAP mutant in infected leaves were similar in size to those of wild‐type bacteria, suggesting that the reduction in virulence was not caused by impaired bacterial growth.
A Moldovan ‘sheep'? – framing Moldovan passivity
Authors: Humă Roxana Adina 
Published: June 2015

AbstractThis article offers a different perspective for understanding Moldovan discourses of passivity by turning its attention to representations of national identity. Its main focus is a Moldovan ballad, Mioriţa, and the way in which it discursively both frames and legitimises inaction. It builds on the idea that Mioriţa is a central part of the way in which Moldovans represent their identity with respect to the writings of Ion Druţă, its main promoter in Moldovan society. More importantly, the ballad is conceptually linked to national characteristics such as lamentation and kindness, characteristics that can be summed up under the headline of ‘passivity’. Thus, drawing from constructivist and post‐structuralist approaches, the article stresses how these elements inform the Moldovan view of the self, its identity and even its representations of foreign affairs, framing the Moldovan lack of agency on a discursive level.
North Africa's Spain: peripheral national identities and the nation‐state as neo‐empire
Authors: Karell Daniel 
Published: June 2015

AbstractWhen ethno‐cultural heterogeneity exists and thrives within a nation‐state, social tension and ethno‐nationalist sentiments are not considered surprising. Yet in many nation‐states, various native‐born communities have diverse and potentially contradictory national identities without the desire for self‐determination. In this paper, I explore the circumstances in which ethno‐culturally distinct, peripheral communities may develop variants of the dominant national identity – ensuring that they remain excluded from the national narrative – yet remain part of the nation‐state. To do so, I conduct a comparative analysis of the native‐born Muslim communities in Spain's two North African exclaves. I find that most Muslims are Spanish citizens yet understandings of ‘Spanish‐ness’ appear to vary between the exclaves. I use these findings to propose further steps for refining current conceptualisations of the nation‐state, in an effort to better understand cases in which variations in the dominant national identity exist, but without ethno‐nationalist sentiments.
Stochastic volatility models for theBrent oil futures market: forecasting and extracting conditional moments
Authors: Solibakke Per Bjarte 
Published: June 2015

AbstractThis paper builds and implements a multifactor stochastic volatility model for the latent (and observable) volatility from the front month future contracts at theIntercontinentalCommodityExchange (ICE),London, applyingBayesianMarkov chainMonteCarlo simulation methodologies for estimation, inference and model adequacy assessment. Stochastic volatility is the main way time‐varying volatility is modelled in financial markets. An appropriate scientific model description, specifying volatility as having its own stochastic process, broadens the applications into derivative pricing purposes, risk assessment and asset allocation and portfolio management. From an estimated optimal and appropriate stochastic volatility model, the paper reports risk and portfolio measures, extracts conditional one‐step‐ahead moments (smoothing), forecasts one‐step‐ahead conditional volatility (filtering), evaluates shocks from conditional variance functions, analyses multistep‐ahead dynamics and calculates conditional persistence measures. (Exotic) option prices can be calculated using the re‐projected conditional volatility. Observed market prices and implied volatilities establish market risk premiums. The analysis adds insight and enables forecasts to be made, building up the methodology for developing valid scientific commodity market models.
Caval agenesis in the pediatric liver donor
Authors: Khorsandi Shirin Elizabeth , Ruiz Edo Neus , Vilca‐Melendez Hector , Heaton Nigel 
Published: June 2015

AbstractThe following is the first report of a pediatric organ donor with caval agenesis and the subsequent use of this liver for transplantation. Caval embryology and potential implications of utilizing a donor liver with caval agenesis are reviewed.
Hepatitis E Virus of Subtype 3a in a Pig Farm, South‐Eastern France
Authors: Colson P. , Saint‐Jacques P. , Ferretti A. , Davoust B. 
Published: June 2015

SummaryHepatitis E virus (HEV) has emerged during the past decade as a causative agent of autochthonous hepatitis and is a clinical concern in Western developed countries. It has been increasingly recognized that pigs are a major reservoir of HEV of genotypes 3 and 4 worldwide and pig‐derived food items represent a potential source of infections by these viruses in humans. Hepatitis E virus RNA testing was performed here on faeces from rectal swabs sampled in 2012 from 50 3‐month‐old farm pigs from the same farm located in south‐eastern France than in a previous work conducted in 2007. Pig HEV sequences corresponding to genomic fragments of ORF2 and ORF1 genes were obtained after RT‐PCR amplification with in‐house protocols. Hepatitis E virus genotype was determined by phylogenetic analysis. Prevalence was similar to that determined 5 years earlier (68% versus 62%). Two robust phylogenetic clusters of HEV subtypes 3a and 3f were identified, and these sequences obtained in 2012 largely differ compared with those obtained in 2007. Notably, HEV sequences obtained in 2012 from a majority (62%) of the infected pigs belonged to subtype 3a, which was not previously described in France, including not being found in any of humans, pigs or wild boars. Further studies are needed to assess the circulation of HEV‐3a in pigs and humans in this country. In addition, along with previous findings, this study supports the need for increased information to the public on the risk of HEV infection through contacts with pigs or consumption of pig‐derived products in France.