bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAPGEF5 regulates nuclear translocation of β-catenin
Authors: Griffin John N. , Viso Florencia del , Duncan Anna R. , Robson Andrew , Kulkarni Saurabh , Liu Karen J. , Khokha Mustafa K. 
Published: June 2017

SUMMARYCanonical Wnt signaling coordinates many critical aspects of embryonic development, while dysregulated Wnt signaling contributes to common diseases, including congenital malformations and cancer. The nuclear localization of β-catenin is the defining step in pathway activation. However, despite intensive investigation, the mechanisms regulating β-catenin nuclear transport remain undefined. In a patient with congenital heart disease and heterotaxy, a disorder of left-right patterning, we previously identified the guanine nucleotide exchange factor, RAPGEF5. Here, we demonstrate that RAPGEF5 regulates left-right patterning via Wnt signaling. In particular, RAPGEF5, regulates the nuclear translocation of β-catenin independently of both β-catenin cytoplasmic stabilization and the importin β1/Ran mediated transport system. We propose a model whereby RAPGEF5 activates the nuclear GTPases, Rap1/2, to facilitate the nuclear transport of β-catenin, defining a parallel nuclear transport pathway to Ran. Our results suggest new targets for modulating Wnt signaling in disease states.
Emergent properties in complex synthetic bacterial promoters
Authors: Monteiro Lummy Maria Oliveira , Arruda Letícia Magalhães , Silva-Rocha Rafael 
Published: June 2017

SummaryRegulation of gene expression in bacteria results from the interplay between transcriptional factors (TFs) at target promoters, and how the arrangement of binding sites determines the regulatory logic of promoters is not well known. Here, we generated and fully characterized a library of synthetic complex promoters for the global regulators, CRP and IHF, inEscherichia coli, formed by a weak -35/-10 consensus sequence preceded by four combinatorial binding sites for these TFs. We found that whilecis-elements for CRP preferentially activate promoters when located immediately upstream of the promoter consensus, binding sites for IHF mainly function as “UP” elements and stimulate transcription in several different architectures in the absence of this protein. However, the combination of CRP- and IHF-binding sites resulted in emergent properties in these complex promoters, where the activity of combinatorial promoters cannot be predicted from the individual behavior of its components. Taken together, the results presented here add to the information on architecture-logic of complex promoters in bacteria.
Mechanical mismatch between Ras transformed and untransformed epithelial cells
Authors: Gullekson Corinne , Cojoc Gheorghe , Schürmann Mirjam , Guck Jochen , Pelling Andrew 
Published: June 2017

ABSTRACTThe organization of the actin cytoskeleton plays a key role in regulating cell mechanics. It is fundamentally altered during transformation, affecting how cells interact with their environment. We investigated mechanical properties of cells expressing constitutively active, oncogenic Ras (RasV12) in adherent and suspended states. To do this, we utilized atomic force microscopy and a microfluidic optical stretcher. We found that adherent cells stiffen and suspended cells soften with the expression of constitutively active Ras. The effect on adherent cells was reversed when contractility was inhibited with the ROCK inhibitor Y-27632, resulting in softer RasV12cells. Our findings suggest that increased ROCK activity as a result of Ras has opposite effects on suspended and adhered cells. Our results also establish the importance of the activation of ROCK by Ras and its effect on cell mechanics.
Effect of ownership structure and board structure on firm value: evidence from India
Authors: Mishra Rakesh , Kapil Sheeba 
Published: June 2017

PurposeThis paper aims to explore the relationship of promoter ownership and board structure with firm performance for Indian companies.Design/methodology/approachCorporate governance structures of 391 Indian companies out of CRISIL NSE Index (CNX) 500 companies listed on national stock exchange (NSE) have been studied for their impact on performance of companies. Panel data regression methodology has been used on data for five financial years from 2010 to 2014 for the selected companies. Performance measures considered are market-based measure (Tobin’s Q) and accounting-based measure (return on assets [ROA]).FindingsThe empirical findings indicate that market-based measure (Tobin’s Q) is more impacted by corporate governance than accounting-based measure. There is significant positive association between promoter ownership and firm performance. It is also indicated that the relationship between promoter ownership and firm performance is different at different levels of promoter ownership. Board size is found to be positively related to ROA; however, board independence is not found to be related to any of the performance measures.Research limitations/implicationsLimitations of the study are in terms of data methodology and possible omission of some variables. It is felt that endogeneity and reverse causality might be better addressed using simultaneous equation methodology.Originality/valueThe paper adds to the emerging body of literature on corporate governance performance relationship in Indian context using a reasonably wider and newer data set.
Identifying the factors determining cooperative innovation effect in emerging economies
Authors: Xie Xuemei , Zeng Saixing , Zang Zhipeng , Zou Hailiang 
Published: June 2017

PurposeThe purpose of this study is to identify the factors determining collaborative innovation effect of manufacturing firms in emerging economies.Design/methodology/approachBased on a survey of 1,206 Chinese manufacturing firms and using structural equation modelling, this study explores the factors determining the effect of collaborative innovation among manufacturing firms (namely, internal capabilities, government policies, collaboration mechanisms and social networks) and examines the relationship between collaborative innovation effect and innovation performance.FindingsThe study finds that there are significantly positive relationships between firms’ internal capabilities, government policies, collaboration mechanisms and social networks and collaborative innovation effect among firms.Practical implicationsThese findings reveal that policymakers should create an effective institutional culture and market environment to facilitate firms’ collaborative innovation.Originality/valueThis paper draws on the resource-based view of firms and contributes to understanding of how the development of factors determining firms’ collaborative innovation effect can improve innovation performance. This study extends established frameworks on collaborative innovation in relation to four dimensions, namely, firms’ internal capabilities, government policies, collaboration mechanisms and social networks, uniquely identifying the limits of specific dimensions. Moreover, this study addresses government policies and “Guanxi culture” specific to China that provide new insights into how firms’ collaborative innovation is improved from the perspectives of business–governmental relations and social networks.
The mediating effect of LMX in the relationship between school bureaucratic structure and teachers’ proactive behavior
Authors: Cerit Yusuf 
Published: June 2017

PurposeThe purpose of this paper is to examine the mediating effect of leader-member exchange on school bureaucratic structure and teachers’ proactive behavior.Design/methodology/approachThe study was carried out in elementary schools in Turkey. Classroom teachers proactive behavior was measured using the taking charge scale developed by Morrison and Phelps (1999), school bureaucratic structure was measured using enabling school structure scale developed by Hoy and Sweetland (2000), and LMX quality was measured using the seven-item LMX scale developed by Graen ve Uhl-bien (1995).FindingsIt was found that school bureaucratic structure had both directly and indirectly effect on teachers proactive behavior via leader-member exchange.Research limitations/implicationsThis study contributes to complete proactive behavior literature by investigating how such behavior is related to the quality of LMX relationships and school bureaucratic structure. The investigation of these relationships is likely to advance understanding of the consequences of teachers’ proactive behavior.Originality/valueThis research combines prior research streams by jointly exploring bureaucratic school structure and the quality of LMX relationships as predictors of teachers’ proactive behaviors.
Keratitis–ichthyosis–deafness syndrome accompanied by disseminated cutaneous fungal infection
Authors: Ma Han , Liang Panpan , Chen Jian , Feng Peiying , Lai Wei 
Published: June 2017

AbstractKeratitis–ichthyosis–deafness (KID) syndrome is a rare genodermatosis. It is mostly associated with mutations of the connexin 26 gene, resulting in keratitis, erythrokeratoderma and neurosensory deafness. In addition to the clinical triad, the KID syndrome patients are at high risk for infectious complications, while the mechanisms are poorly understood. In the present article, we described an Asian case of KID syndrome accompanied by fungal infection. The present study was designed to define the mutation type, and further to explore the interaction between the innate immunity response and the infectious complication of KID syndrome. Genomic DNA was extracted from peripheral blood for mutation analysis. Isolation and identification of the species were carried out to confirm the infectious microorganism. Three biopsy specimens from different parts of the body (right thigh, abdomen and forehead, respectively) were carried out for histopathological and immunohistochemical analysis. Furthermore, quantitative polymerase chain reaction (PCR) was carried out to study the expression of Toll‐like receptor 2 (TLR2) on the epidermis of the right thigh. We identified a mutation (p.G12R) in the GJB2 gene in this patient with Trichophyton rubrum infection. Immunohistochemistry staining revealed a lower expression of TLR2 and no significant difference in TLR4. Meanwhile, PCR showed a relatively slight increase of TLR2 RNA expression. These results indicated that GJB2 mutation (p.G12R) in this case of KID syndrome, which was susceptible to T. rubrum infection, might be attributed to a limited native immune response.
Efficacy and safety of ixekizumab treatment in Japanese patients with moderate‐to‐severe plaque psoriasis: Subgroup analysis of a placebo‐controlled, phase 3 study (UNCOVER‐1)
Authors: Imafuku Shinichi , Torisu‐Itakura Hitoe , Nishikawa Atsushi , Zhao Fangyi , Cameron Gregory S. ,   the Japanese UNCOVER‐1 Study Group
Published: June 2017

AbstractThe present study describes a subgroup analysis of 33 Japanese patients participating in UNCOVER‐1, an international, placebo‐controlled, phase 3 study of ixekizumab in patients with moderate‐to‐severe psoriasis. Patients were randomized to a placebo (n = 13) or ixekizumab 80 mg every 4 (IXEQ4W, n = 12) or 2 (IXEQ2W, n = 8) weeks, from week 0–12. At week 12, ixekizumab‐treated patients with a static Physician Global Assessment score 0 or 1 (sPGA [0,1]; n = 16) were re‐randomized to a placebo (n = 6), ixekizumab 80 mg every 12 (IXEQ12W, n = 5) or 4 (IXEQ4W, n = 5) weeks, from week 12–60. At week 12, more ixekizumab‐treated versus placebo‐treated patients achieved sPGA (0,1) (≥66.7% vs 0%), ≥75% improvement in Psoriasis Area and Severity Index (≥75% vs 0%), and sPGA (0) or 100% improvement in Psoriasis Area and Severity Index (both ≥33.3% vs 0%), with improved symptoms and quality of life. At week 60, 100% (IXEQ4W), 40.0% (IXEQ12W) and 16.7% (placebo) had maintained sPGA (0,1). From week 0–12, treatment‐emergent adverse events were 76.9% (placebo), 75.0% (IXEQ4W) and 87.5% (IXEQ2W), and from week 12–60 were 66.7% (placebo) and 100% (IXEQ12W, IXEQ4W). Ixekizumab‐treated patients had no severe treatment‐emergent adverse events, and one serious TEAE (IXEQ4W); infection was the most frequent treatment‐emergent adverse event. In conclusion, ixekizumab for 60 weeks was effective and safe for Japanese patients with moderate‐to‐severe psoriasis, in line with the overall findings from UNCOVER‐1.
Development of advanced practice competency standards for dietetics in Australia
Authors: Palermo Claire , Capra Sandra , Beck Eleanor J , Dart Janeane , Conway Jane , Ash Susan 
Published: June 2017

AimThis study aimed to explore the work roles, major tasks and core activities of advanced practice dietitians in Australia to define the Competency Standards for advanced practice.MethodsA qualitative approach was used to review advanced dietetic practice in Australia involving experienced professionals, mostly dietitians. Four focus groups were conducted with a total of 17 participants and an average of 20 years experience: 15 dietitian practitioners plus 2 employers (1 dietitian and 1 non‐dietitian). The focus groups explored the key purpose, roles and outcomes of these practitioners. Data from the focus groups were confirmed with in‐depth interviews about their core activities with a purposive sample of 10 individuals recently recognised as Advanced Accredited Practising Dietitians. Data from both focus groups and interviews were analysed adductively to identify key themes.ResultsThe key theme that emerged to define advanced dietetics practice was leadership, with four subthemes that described in more detail the major work roles and outcomes of advanced practice. These subthemes identified that advanced practitioners were (i) outcome‐focused, having impact; (ii) influence others and advocate; (iii) innovate and embrace change; and (iv) inspire others and are recognised for their practice. These outcomes were conceptualised within a broad generalist framework to generate revised Competency Standards.ConclusionsThis study confirmed that leadership rather than specialist practice skills is the key determinant of advanced practice.
Sulforaphane protection against the development of doxorubicin‐induced chronic heart failure is associated with Nrf2 Upregulation
Authors: Bai Yang , Chen Qiang , Sun Yun‐Peng , Wang Xuan , Lv Li , Zhang Li‐Ping , Liu Jin‐Sha , Zhao Song , Wang Xiao‐Lu 
Published: June 2017

SummaryBackgroundDoxorubicin (DOX) is an anthracycline antitumor drug. However, its clinical use is limited by dose‐dependent cardiotoxicity and even progresses to chronic heart failure (CHF).ObjectiveThis study aims to investigate whether the Nrf2 activator, sulforaphane (SFN), can prevent DOX‐induced CHF.MethodsMale Sprague‐Dawley rats which received treatment for 6 weeks were divided into four groups (n=30 per group): control, SFN, DOX and DOX plus SFN group.ResultsResults revealed that DOX induced progressive cardiac damage as indicated by increased cardiac injury markers, cardiac inflammation, fibrosis and oxidative stress. SFN significantly prevented DOX‐induced progressive cardiac dysfunction between 2‐6 weeks and prevented DOX‐induced cardiac function deterioration. Furthermore, it significantly decreased ejection fraction and increased the expression of brain natriuretic peptide. SFN also almost completely prevented DOX‐induced cardiac oxidative stress, inflammation and fibrosis. SFN upregulated NF‐E2‐related factor 2 (Nrf2) expression and transcription activity, which was reflected by the increased mRNA expression of Nrf2 and its downstream genes. Furthermore, in cultured H9c2 cardiomyocytes, the protective effect of SFN against DOX‐induced fibrotic and inflammatory responses was abolished by Nrf2 silencing.ConclusionWe arrived at the conclusion that DOX‐induced CHF can be prevented by SFN through the upregulation of Nrf2 expression and transcriptional function.
A farewell to the sum of Akaike weights: The benefits of alternative metrics for variable importance estimations in model selection
Authors: Galipaud Matthias , Gillingham Mark A. F. , Dechaume‐Moncharmont François‐Xavier 
Published: June 2017

Abstract

In a previous article, we advocated against using the sum of Akaike weights (SW) as a metric to distinguish between genuine and spurious variables in Information Theoretic (IT) statistical analyses. A recent article (Giam & Olden, Methods in Ecology and Evolution, 2016, 7, 388) criticises our finding and instead argues in favour of SW. It points out that (1) we performed a biased data‐generation procedure and (2) we erroneously evaluated SW on its capacity to estimate the proportion of variance in the data explained by a variable. We here respond to these points.

Giam and Olden's first concern is unfounded. When using the data‐generating code they proposed, SW remains very imprecise. To respond to their second concern, we first list the meanings taken by a variable's importance in the context of IT. Although, SW is presented as an estimate of variable relative importance in methodological textbooks (i.e. a variable's rank in importance or its relative contribution to the variance in the data), it is also used as a metric of variable absolute importance (i.e. a variable's absolute effect size or its statistical significance). We then compare SW to alternative metrics on its ability to estimate variable absolute or relative importance.

SW values have low repeatability across analyses. As a result, based on SW, it is hard to distinguish between variables with weak and large effects. For estimations of variable absolute importance, experimenters should prefer model‐averaged parameter estimates and/or compare nested models based on evidence ratios. Sum of Akaike weights is also a poor metric of variable relative importance. We showed that correct variable ranking in importance was generally more frequent when using model‐averaged standardised parameter estimates, than when using SW.

To avoid recurrent errors in ecology and evolution, we therefore warn against the use of SW for estimations of variable absolute and relative importance and we propose that experimenters should instead use model‐averaged standardised parameter estimates for statistical inferences.
JUXTAPOSING LITERARY AND DOCUMENTARY EVIDENCE: A NEW COPY OF THE SO-CALLED HELIODOROS STELE AND THE CORPUS INSCRIPTIONUM IUDAEAE/PALAESTINAE (CIIP)
Authors: COTTON-PALTIEL HANNAH M. , ECKER AVNER , GERA DOV 
Published: June 2017

Abstract
This article was prompted by the recent discovery of two more copies of the so-called ‘Heliodoros Stele’ from Maresha. A second one from Byblos was published in 2015. The third one, re-discovered recently and published here for the first time, also comes from Maresha. The steles bear Seleukos IV's epistolary prostagma from 178 bc to his vizier Heliodoros, and forwarded to other officials with the instruction to display it in public. It contains an appointment of one Olympiodoros to be high priest in Koele Syria and Phoenicia. Both Seleukos IV and Heliodoros also appear in the story of the plundering of the Temple related in II Maccabees 3. The existence of multiple copies, though hardly surprising, made us suspect the king's apologetic tone and identify the ‘reform’ as an attempt to embellish the withdrawal of previously bestowed privileges on the Jews (so Josephus) as well as on others.
Selective laser trabeculoplasty as replacement therapy in medically controlled glaucoma patients
Authors: De Keyser Myrjam , De Belder Maya , De Belder Jonas , De Groot Veva 
Published: June 2017

AbstractPurposeWe examined selective laser trabeculoplasty (SLT) as a replacement therapy for medically controlled open‐angle glaucoma (OAG) or ocular hypertensive patients.MethodsA prospective randomized interventional clinical trial on 143 glaucoma patients. Patients were randomized to either receiving SLT or to the control group that continued on pressure lowering medication. Data were recorded 1 hr, 1 week, 1, 3, 6, 12 and 18 months after SLT. Primary outcome was number of medications at 12 and 18 months while maintaining a predetermined target intraocular pressure (IOP).ResultsSelective laser trabeculoplasty (SLT) reduced number of medications from a mean of 1.5 at baseline, to 0.35 after 12 months and 0.29 after 18 months. Meanwhile, SLT achieved more than 20% IOP lowering in 95% of eyes and more than 30% IOP lowering in 86% of eyes after 18 months. Seventy‐seven per cent of our eyes no longer needed any medication after SLT at 18 months.ConclusionSelective laser trabeculoplasty (SLT) enabled a reduction in number of medications while maintaining good IOP control. Selective laser trabeculoplasty (SLT) was able to completely replace medical therapy in 77% of eyes after 18 months. Selective laser trabeculoplasty (SLT) as replacement therapy may reduce local and systemic side‐effects and prevent adherence issues.
The Effect of Genetic Polymorphisms in SLCO2B1 on the Lipid‐Lowering Efficacy of Rosuvastatin in Healthy Adults with Elevated Low‐Density Lipoprotein
Authors: Kim Tae‐Eun , Shin Dongseong , Gu Namyi , Jung Byung Hwa , Kim Jayoun , Cho Young Min , Yu Kyung‐Sang , Cho Joo‐Youn 
Published: June 2017

AbstractRosuvastatin is an HMG‐CoA reductase inhibitor widely used for treating hypercholesterolaemia. We investigated whether genetic polymorphisms in solute carrier organic anion transporter 2B1 (SLCO2B1) affect the lipid‐lowering effect of rosuvastatin in healthy adults with elevated low‐density lipoprotein (LDL). This study included 18 volunteers with LDL levels above 130 mg/dL. Rosuvastatin (20 mg) was administered once a day for 8 weeks. Blood samples were drawn before and after the 8‐week treatment to measure changes in lipid levels. The presence of single nucleotide polymorphisms (SNPs) of SLCO2B1 (c.935G>A and c.1457C>T), SLCO1B1 (c.521C>T, c.388A>G and c.‐11187G>A) and ABCG2 (c.421C>A) was determined by genotyping. Responses to rosuvastatin were compared between wild‐type and variant genotypes using permutation test on each polymorphism. In volunteers with SLCO2B1 c.935G>A (rs12422149) variant, rosuvastatin was less effective at lowering LDL (mean % decrease: GG 62.8% GA 50.6% AA 49.3%, p = 0.012) and apoprotein B (mean % decrease: GG 52.1% GA 42.8% AA 42.8%, p = 0.036). Regarding SLCO2B1 c.1457C>T (rs2306168) SNP, there was no significant difference between wild‐type and variant genotypes. This study demonstrated that SLCO2B1 c.935G>A (rs12422149) polymorphism influenced the lipid‐lowering effects of rosuvastatin in volunteers with hypercholesterolaemia.
Communautés francophones minoritaires : Le territoire influence‐t‐il l'identité linguistique ?
Authors: Charron Mathieu 
Published: June 2017

Messages clés

Le territoire joue un rôle dans la construction de l'identité linguistique des francophones en situation minoritaire.
L'impact du territoire est cependant plus important sur la perception de la vitalité linguistique et les pratiques linguistiques.
Les technologies d'information et de communication pourraient modifier le rôle du territoire dans la construction identitaire.