bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limits of Devolution: Localism, Economics and Post‐democracy
Authors: Tomaney John 
Published: July 2016

AbstractThis article challenges the narrowly founded but untroubled consensus about the alleged benefits of the Conservative government's devolution programme. It suggests that too much attention has been paid to purported benefits and too little regard to the potential risks, and draws attention to international evidence that suggests that the distribution of the benefits of devolution is crucially dependent on its design. It critically examines the case for the currently offered model of devolution and finds the underpinning economic model and limited forms of democratic accountability are likely to produce regressive social outcomes and the reinforcement of existing local elites. It calls for a wider public debate and fuller democratic scrutiny of the model of devolution on offer.
Species diversity can be overestimated by a fixed empirical threshold: insights from DNA barcoding of the genus Cletus (Hemiptera: Coreidae) and the meta‐analysis of COI data from previous phylogeographical studies
Authors: Zhang Hai‐Guang , Lv Min‐Hua , Yi Wen‐Bo , Zhu Wei‐Bing , Bu Wen‐Jun 
Published: July 2016

AbstractThe use of genetic distances to identify species within the framework of DNA barcoding has to some extent improved the development of biodiversity studies. However, using a fixed empirical threshold to delimit species may lead to overestimating species diversity. In this study, we use a new data set of COI sequences for 366 specimens within the genus of Cletus as well as conduct an analysis on the same genetic data for collected morphologically defined species from previous phylogeographical studies, to test whether high intraspecific genetic divergences are common with the premises of comprehensive sampling. The results indicate C. graminis Hsiao & Cheng , is the same species with C. punctiger (Dallas, 1852) and should be synonymized and that the distributional record of C. pugnator (Fabricius, 1787) in China is correct. High intraspecific genetic differentiations (0%–4.35%) were found in C. punctiger. Furthermore, as to the mined data, the maximum intraspecific K2P distances of 186 species (48.44% of 384) exceed 3%, and 101 species (26.30%) can be divided into two or more clusters with a threshold of 3% in cluster analysis. If genetic distance is used to delimit species boundaries, the minimum interspecific K2P distance of the congeneric species should be considered rather than only using the fixed empirical value; otherwise, the species richness may be overestimated in some cases.
Medial Prefrontal Cortical Dopamine Responses During Operant Self‐Administration of Sweetened Ethanol
Authors: Doherty James M. , Schier Christina J. , Vena Ashley A. , Dilly Geoffrey A. , Gonzales Rueben A. 
Published: July 2016

BackgroundMedial prefrontal cortex (mPFC) dysfunction is present in heavy alcohol consumers. Dopamine signaling in mPFC is associated with executive functioning and affects drinking behavior; however, direct measurement of extracellular mPFC dopamine during appetitive and consummatory ethanol (EtOH) self‐administration behavior has not been reported.MethodsWe used in vivo microdialysis in freely behaving, adult, male, Long Evans rats to determine extracellular dopamine concentration in the mPFC during operant self‐administration of an EtOH‐plus‐sucrose or sucrose solution. The model separated appetitive/seeking from consummatory phases of the operant session. Dopamine was also monitored in an untrained handling control group, and dialysate EtOH was measured in the EtOH‐drinking group.ResultsHome cage baseline dopamine was lower in rats that experienced a week of drinking sweetened EtOH compared with sucrose‐drinking and handling controls. Transfer into the operant chamber and the initiation of consumption stimulated a relatively higher change in dopamine over baseline in the sweetened EtOH group compared with sucrose and handling controls. However, all groups show a dopamine response during transfer into the operant chamber, and the sucrose group had a relatively higher change in dopamine over baseline during initiation of consumption compared with handling controls. The time courses of dopamine and EtOH in the mPFC differ in the EtOH‐consuming rats.ConclusionsDifferences in extracellular mPFC dopamine between EtOH drinkers compared with control groups suggest that mPFC dopamine is involved in the mechanism of operant self‐administration of sweetened EtOH and sucrose. Furthermore, the increase in dopamine during consumption is consistent with a role of mPFC dopamine in reward prediction.
Nuclear Thioredoxin‐1 Overexpression Attenuates Alcohol‐Mediated Nrf2 Signaling and Lung Fibrosis
Authors: Sueblinvong Viranuj , Mills Stephen T. , Neujahr David C. , Go Young‐Mi , Jones Dean P. , Guidot David M. 
Published: July 2016

BackgroundAlcohol abuse, which impairs antioxidant defenses and promotes acute lung injury, increases Nrf2 nuclear translocation but nevertheless inhibits its activation of the antioxidant response element (ARE). Thioredoxin‐1 (Trx1) is required for optimal Nrf2 binding and activation of the ARE, and we hypothesized that its inhibition contributes to impaired Nrf2‐ARE signaling in the alcoholic lung.MethodsLung tissue and primary lung fibroblasts (PLFs) were isolated from C57/BL6 wild‐type (WT) and transgenic mice overexpressing the human Trx1 gene with a nuclear localizing sequence (NLS‐Tg); some mice consumed alcohol in water prior to lung tissue and PLF isolation; in some mice, acute lung injury was induced with intratracheal bleomycin. In other experiments, PLFs were isolated from WT and NLS‐Tg mice and then exposed to alcohol. Finally, PLF isolated from WT mice were transfected with Trx1 expression vector containing either a cytosolic localized sequence (NES) or a nuclear localized sequence (NLS) prior to alcohol exposure.ResultsAlcohol treatment in vivo or in vitro decreased Trx1 expression, and bleomycin‐treated alcohol‐fed mice had fibrotic disrepair in their lungs. In parallel, whereas alcohol exposure in vitro increased TGFβ1 expression and decreased Nrf2‐ARE activity in PLF from WT mice, these effects were not observed in PLF from NLS‐Tg mice. Finally, selective overexpression of Trx1 in the nucleus but not in the cytosol preserved Nrf2‐ARE activity during alcohol exposure.ConclusionsAlthough alcohol‐induced redox stress actually promotes Nrf2 nuclear translocation, the coincident suppression of Trx1 impairs Nrf2‐ARE activity within the nuclear compartment. Nuclear overexpression of Trx1 restored Nrf2‐ARE activity and attenuated alcohol‐induced TGFβ1 expression and alcohol‐induced exaggerate response to bleomycin‐induced acute lung injury.
Identification and differential expression of microRNAs in the ovaries of pigs (Sus scrofa) with high and low litter sizes
Authors: Huang L. , Yin Z. J. , Feng Y. F. , Zhang X. D. , Wu T. , Ding Y. Y. , Ye P. F. , Fu K. , Zhang M. Q. 
Published: July 2016

SummaryLitter size affects profitability in the swine industry. Mammalian ovaries play important roles during reproduction, including ovulation and hormone secretion, which are tightly regulated by specific microRNAs (miRNAs). In this study, we investigated the effects of specific miRNAs on porcine litter size. We compared the ovarian miRNAs of Yorkshire pigs with high (YH) and low (YL) litter sizes using Solexa sequencing technology. We identified 327 and 320 miRNAs in the ovaries of YH and YL pigs respectively. A total of 297 miRNAs were co‐expressed; 30 and 23 miRNAs respectively were specifically expressed in the two libraries. A total of 83 novel miRNAs were predicted; 37 specific miRNAs were obtained, of which 21 miRNAs were upregulated and 16 miRNAs were downregulated in YH compared with YL. Additionally, 19 628 and 19 250 target genes were predicted in the two libraries respectively. The results revealed that specific miRNAs (i.e., miR‐224, miR‐99a, let‐7c, miR‐181c, miR‐214 and miR‐21) may affect porcine litter size. The results of this study will help in gaining understanding of the role of miRNAs in porcine litter size regulation.
The Mendelian inheritance of rare flesh and shell colour variants in the black‐lipped pearl oyster (Pinctada margaritifera)
Authors: Ky Chin‐Long , Nakasai Seiji , Pommier Steve , Sham Koua Manaarii , Devaux Dominique 
Published: July 2016

SummaryPinctada margaritifera is French Polynesia's most economically important aquaculture species. This pearl oyster has the specific ability to produce cultured pearls with a very wide range of colours, depending on the colour phenotypes of donor oysters used. Its aquaculture is still based on natural spat collection from wild stocks. We investigated three rare colour variants of P. margaritifera – orange flesh, and red and white shell colour phenotypes – in comparison with the wild‐type black flesh and shell commonly found in this species. The study aimed to assess the geographic distribution and genetic basis of these colour variants. Colour frequencies were evaluated during transfer and graft processes of pearl oyster seed captured at collector stations. Among the collection locations studied, Mangareva Island showed the highest rate of the orange flesh phenotype, whereas Takaroa and Takume atolls had relatively high rates of red and white shell phenotypes respectively. Broodstocks were made of these rare colour variants, and crosses were performed to produce first‐ and second‐generation progenies to investigate segregation. The results were consistent with Mendelian ratios and suggest a distinct model with no co‐dominance: (i) a two‐allele model for flesh trait, whereby the orange allele is recessive to the black fleshed type, and (ii) a three‐allele model for shell trait, whereby the black wild‐type allele is dominant to the red coloration, which is dominant to the white shell. Furthermore, the proposed model provides the basis for producing selected donor pearl oyster lines through hatchery propagation.
Variations at regulatory regions of the milk protein genes are associated with milk traits and coagulation properties in the Sarda sheep
Authors: Noce A. , Pazzola M. , Dettori M. L. , Amills M. , Castelló A. , Cecchinato A. , Bittante G. , Vacca G. M. 
Published: July 2016

SummaryRegulatory variation at the ovine casein genes could have important effects on the composition and coagulation properties of milk. Herewith, we have partially resequenced the promoters and the 3′‐UTR of the four casein genes in 25 Sarda sheep. Alignment of these sequences allowed us to identify a total of 29 SNPs. This level of polymorphism (one SNP every 250 bp) is remarkably high if compared with SNP densities estimated in human genic regions (approximately one SNP per bp). The 29 SNPs identified in our resequencing experiment, plus three previously reported SNPs mapping to the lactalbumin, alpha (LALBA) and β‐lactoglobulin (BLG, also known as progestagen‐associated endometrial protein, PAEP) genes, were genotyped with a multiplex TaqMan Open Array Real‐Time PCR assay in 760 Sarda sheep with records for milk composition and coagulation properties. Association analysis revealed the existence of significant associations of CSN1S2 and CSN3 genotypes with milk protein and casein contents. Moreover, genotypes at CSN1S1 were significantly associated with rennet coagulation time, curd firming time and curd firmness, whereas CSN2 was associated with curd firming time. These results suggest that SNPs mapping to the promoters and 3′‐UTRs of ovine casein genes may exert regulatory effects on gene expression and that they could be used for improving sheep milk quality and technological traits at the population level through marker assisted selection.
A20 SNP rs77191406 may be related to secondary cancer for rheumatoid arthritis and systemic lupus erythematosus patients
Authors: Zhu Lihua , Zhou Lingling , Wang Liang , Li Zhaoxia , Lu Shuai , Yang Lijian , Chen Shaohua , Li Bo , Wu Xiuli , Zhou Yi , Li Yangqiu 
Published: July 2016

AbstractAimAn increased risk for malignancy for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients may be related to factors that play a critical role in the regulation of T‐cell activation. A20 is an important negative immunoregulatory factor that was found to be associated with lymphoma and the development of numerous solid tumors. Previous studies have implicated the A20 locus in RA susceptibility. In this study, we investigated polymorphisms in the A20 3′ UTR and explored whether there was an association between these polymorphisms and malignancy risk in autoimmune diseases.MethodsPCR and sequencing were used to identify A20 gene polymorphisms in peripheral blood mononuclear cells (PBMCs) from 99 RA cases, 37 SLE cases and 99 healthy individuals. Pearson's Chi square test was used for statistical analysis.ResultsOnly one SNP (rs77191406) and one new mutation (20132 A>G) in A20 gene were identified in RA and SLE patients and healthy individuals. Heterozygous rs77191406 was identified in just 1 of 99 RA patients and 2 of 37 SLE patients. More importantly, a RA patient who was heterozygous for rs77191406 developed colon cancer 10 years after the RA diagnosis. Similarly, two SLE patients carrying rs77191406 (heterozygous) had severe disease or developed bladder cancer 5 years after SLE diagnosis.ConclusionsThese findings suggest that rs77191406 may be a prognostic marker for a high risk for rapid malignancy progression, poor survival and refractory disease and a new molecular marker associated with autoimmune diseases transforming into a secondary cancer.
Combining genomewide association study and lung eQTL analysis provides evidence for novel genes associated with asthma
Authors: Nieuwenhuis M. A. , Siedlinski M. , van den Berge M. , Granell R. , Li X. , Niens M. , van der Vlies P. , Altmüller J. , Nürnberg P. , Kerkhof M. , van Schayck O. C. , Riemersma R. A. , van der Molen T. , de Monchy J. G. , Bossé Y. , Sandford A. , Bruijnzeel‐Koomen C. A. , Gerth van Wijk R. , ten Hacken N. H. , Timens W. , Boezen H. M. , Henderson J. , Kabesch M. , Vonk J. M. , Postma D. S. , Koppelman G. H. 
Published: July 2016

AbstractBackgroundGenomewide association studies (GWASs) of asthma have identified single‐nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis‐eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor's diagnosed) asthma to our GWAS of asthma with BHR.MethodsA GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts, and lung cis‐eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data.ResultsA total of 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genomewide significance after meta‐analysis. Five of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma‐associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL‐33 and GSDMB, showed larger effect sizes in our data compared to published literature.ConclusionsCombining GWAS with subsequent lung eQTL analysis revealed disease‐associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor's diagnosed) asthma.
On Longitudinal Prediction with Time-to-Event Outcome: Comparison of Modeling Options
Authors: Maziarz Marlena , Heagerty Patrick , Cai Tianxi , Zheng Yingye 
Published: July 2016

Summary
Long-term follow-up is common in many medical investigations where the interest lies in predicting patients’ risks for a future adverse outcome using repeatedly measured predictors over time. A key quantity is the likelihood of developing an adverse outcome among individuals who survived up to time s given their covariate information up to time s. Simple, yet reliable, methodology for updating the predicted risk of disease progression using longitudinal markers remains elusive. Two main approaches have been considered in the literature. One approach, based on joint modeling (JM) of failure time and longitudinal covariate process (Tsiatis and Davidian, 2004), derives such longitudinal predictive probability from the joint probability of a longitudinal marker and an event at a given time. A second approach, the partly conditional (PC) modeling (Zheng and Heagerty, 2005), directly models the predictive probability conditional on survival up to a landmark time and information accrued by that time. In this article, we propose new PC models for longitudinal prediction that are more flexible than joint modeling and improve the prediction accuracy over existing PC models. We provide procedures for making inference regarding future risk for an individual with longitudinal measures up to a given time. In addition, we conduct simulations to evaluate both JM and PC approaches in order to provide practical guidance on modeling choices. We use standard measures of predictive accuracy adapted to our setting to explore the predictiveness of the two approaches. We illustrate the performance of the two approaches on a dataset from the End Stage Renal Disease Study (ESRDS).
Pragmatic randomized controlled trial of an allergy intervention for children aged 6–16 with asthma and rhinitis in general practice
Authors: Smith H. , Horney D. , Jones C. , Goubet S. , Mukhopadhyay S. , Frew A. 
Published: July 2016

SummaryBackgroundIt is widely believed that for allergic rhinitis and asthma, avoidance of specific triggers can improve symptom control. Whilst many children with asthma or rhinitis are sensitized to airborne allergens, primary care diagnostic and management decisions are often made without a detailed history of the allergic triggers or allergy testing. Thus, treatment decisions are empirical and allergen avoidance advice is either not given or, if given, not tailored to the child's sensitivities.ObjectiveTo ascertain whether allergy assessment and tailored advice in general practice enhances outcomes of children with asthma and rhinitis.MethodPragmatic RCT of allergy intervention (structured allergy history, skin prick testing and appropriate allergy avoidance advice) vs. usual care in children with asthma and/or rhinoconjunctivitis. A blinded observer assessed outcomes at 12 months. Main outcome measures were symptom scores and disease‐specific health‐related QoL. Secondary outcomes were healthcare utilization, days unable to pursue usual activities and self‐rated improvement.ResultsA total of 335 participants were randomized to formal allergy assessment or normal care. There were no differences in participants’ demographic or clinical characteristics at baseline (all P > 0.05). At 12 months, participants receiving the allergy intervention had fewer rhinitis symptoms (MD − 3.14, 95% CI − 6.01, − 0.81) and an improvement in QoL (MD − 0.50, 95% CI 0.32, 0.68). There were no significant changes in asthma symptoms, healthcare utilization or number of days unable to pursue usual activities.ConclusionAmongst children with known asthma and/or rhinitis in primary care, taking a structured allergy history with skin prick testing and tailored advice on allergy avoidance resulted in reduced symptoms of rhinitis and improved QoL.
Why western spruce budworms travel so far for the winter
Authors: NEALIS VINCENT G. , RÉGNIÈRE JACQUES 
Published: July 2016

1. Conifer‐feeding budworms (Choristoneura) hibernate in sheltered locations on their host trees from late summer of 1 year to spring of the next. During this period, they do not feed but rely on sustenance provided in the egg. Overwinter survival is dependent on the rate of consumption of these limited reserves.2. A process model was developed that quantifies the relationship between the rate of consumption and survival at variable temperatures and exposure times for western spruce budworm. The model supported physiological evidence that warm weather conditions early in the diapause period have a dominant influence on overwinter survival. Output compared favourably with field observations of poorer budworm survival at lower elevations where late‐summer and autumn temperatures were warmer compared to those overwintering at cooler, higher elevations.3. Field experiments demonstrated these weather‐dependent rates of survival were modulated significantly by the degree of shelter experienced by hibernating budworms.4. Dissection of whole trees harbouring overwintering western spruce budworms showed a significant portion of the population had travelled a considerable distance from the periphery of the tree canopy where eggs were laid to overwinter successfully on the tree bole where sheltered niches are common.5. Thus, budworms will travel relatively long distances and risk increased mortality during this dispersal to find adequate shelter to overwinter.
A systematic review of the benefits and harms of dipeptidyl peptidase‐4 inhibitor for chronic kidney disease
Authors: Kamiya Hiroyuki 
Published: July 2016

AbstractIntroduction: Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) and the optimal glycemic control is key to delay the progression of the disease and prevent major complications. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors have emerged as a promising therapeutic option. However, the benefits and harms of the treatment have yet to be clarified for diabetic patients with CKD. Methods: Type 2 diabetic patients with moderate to severe CKD including end‐stage renal disease were eligible and randomized controlled trials comparing DPP‐4 inhibitors with no treatment or placebo or other antihyperglycemic agents were included. A systematic electronic search was conducted through the Medline Ovid, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. Findings: Six placebo/open and 2 active controlled trials (1747 participants) were included. The adjusted mean difference of hemoglobin A1c between DPP‐4 inhibitors and placebo ranged from −0.60% to −0.42%. The odds ratio of hypoglycemia, mortality and severe adverse effects due to all types of DPP‐4 inhibitors were 1.35 (95% CI: 0.98–1.84), 0.88 (95% CI: 0.42–1.86) and 0.86 (95% CI: 0.65–1.15), respectively while that due to DPP‐4 inhibitors with renal clearance were 1.40 (95% CI: 0.87 to 2.24), 0.85 (95% CI: 0.35 to 2.04) and 0.91 (95% CI: 0.63 to 1.32), respectively. Discussion: DPP‐4 inhibitors demonstrated beneficial effects on the glycemic control for diabetic patients with CKD without causing any additional adverse effects. However, a definitive conclusion has yet to be drawn due to serious methodological problems and a small number of studies.