bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of Operational Tolerance Signatures Are Limited by Variability and Type of Immunosuppression in Renal Transplant Recipients: A Cross-Sectional Study
Authors: Bottomley Matthew J. , Chen Mian , Fuggle Sue , Harden Paul N. , Wood Kathryn J. 
Published: December 2016

Background
Renal transplant recipients (RTR) frequently develop complications relating to chronic immunosuppression. Identifying RTR who could safely reduce immunosuppression is therefore highly desirable. We hypothesized that “signatures” described in RTR who have stopped immunosuppression but maintained stable graft function (“operational tolerance”) may enable identification of immunosuppressed RTR who are candidates for immunosuppression minimization. However, the effect of immunosuppression itself on these signatures and circulating B-cell populations is currently unknown.

Methods
We undertook a cross-sectional study of 117 RTR to assess the effect of immunosuppression upon circulating B cell populations, humoral alloresponse and 2 previously published “signatures” of operational tolerance.

Results
Immunosuppression associated with alterations in both published “signatures.” Azathioprine associated with a decrease in transitional and naive B-cell numbers and calcineurin inhibition associated with an increase in the number of circulating plasmablasts. However, only azathioprine use associated with the presence of donor-specific anti-HLA IgG antibodies. Calcineurin inhibition associated with an increase in total serum IgM but not IgG. Data were corrected for age, time since last transplant, and other immunosuppression.

Conclusions
Current signatures of operational tolerance may be significantly affected by immunosuppressive regimen, which may hinder use in their current form in clinical practice. Calcineurin inhibition may prevent the development of long-lasting humoral alloresponses, whereas azathioprine therapy may be associated with donor specific antibody development.
Analysis of copy number variants on chromosome 21 in Down syndrome-associated congenital heart defects
Authors: Rambo-Martin Benjamin L. , Mulle Jennifer G. , Cutler David J. , Bean Lora J.H. , Rosser Tracie C. , Dooley Kenneth J. , Cua Clifford , Capone George , Maslen Cheryl L. , Reeves Roger H. , Sherman Stephanie L. , Zwick Michael E. 
Published: December 2016

AbstractOne in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2,000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: 1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and 2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 198 case individuals with DS+AVSD and 211 control individuals with DS and a normal heart using a custom microarray with dense probes tiled on chromosome 21 for array CGH. We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. Pathway analyses indicated copy number perturbations of genes involved in protein heterotrimerization and histone methylating proteins. Finally, we showed that previously DS+AVSD-associated common CNVs on chromosome 21 are likely false positives. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population.
Assembly of photoactive Orange Carotenoid Protein from its domains unravels a carotenoid shuttle mechanism
Authors: Moldenhauer Marcus , Sluchanko Nikolai N. , Buhrke David , Zlenko Dmitry V. , Tavraz Neslihan N. , Schmitt Franz-Josef , Hildebrandt Peter , Maksimov Eugene G. , Friedrich Thomas 
Published: December 2016

AbstractThe Orange Carotenoid Protein (OCP) is indispensable for cyanobacterial photoprotection by quenching phycobilisome fluorescence upon photoconversion from the orange OCPOto the red OCPRform. Cyanobacterial genomes frequently harbor, besides genes for Orange Carotenoid Proteins (OCPs), several genes encoding homologs of OCP’s N- or C-terminal domains (NTD, CTD). Unlike the well-studied NTD homologs, called Red Carotenoid Proteins (RCPs), the role of CTD homologs remains elusive. We show how OCP can be reassembled from its functional domains. Expression ofSynechocystisOCP-CTD in carotenoid-producingEscherichia coliyielded violet-colored proteins, which, upon mixing with the RCP-apoprotein, produced an orange-like photoswitchable form that further photoconverted into a species spectroscopically indistinguishable from RCP, thus demonstrating a unique carotenoid shuttle mechanism. The CTD itself is a novel, dimeric carotenoid-binding protein, which effectively quenches singlet oxygen and interacts with the Fluorescence Recovery Protein, assigning physiological roles to CTD homologs and explaining the evolutionary process of OCP formation.One Sentence SummaryThe C-domain of cyanobacterial OCP dimerizes, binds a carotenoid, and delivers it to the N-domain forming photoactive OCP.
Ecological speciation within thePhytophthoragenus
Authors: Mideros M. F. , Turissini D. A. , Guayazán N. , Danies G. , Cárdenas M. , Myers K. , Tabima J. , Goss E. M. , Bernal A. , Lagos L. E. , Grajales A. , Gonzalez L. N. , Cooke D. E. L. , Fry W. E. , Grünwald N. , Matute D. R. , Restrepo S. 
Published: December 2016

AbstractOver the past few years, symptoms akin to late blight disease have been reported on a variety of crop plants in South America. Despite the economic importance of these crops, the causal agents of the diseases belonging to the genusPhytophthorahave not been completely characterized. In this study, we used an integrative approach that leveraged morphological, ecological, and genetic approaches to explore cryptic speciation withinP. infestans sensu lato. We described a newPhytophthoraspecies collected in Colombia from tree tomato (Solanum betaceum), a semi-domesticated fruit. All morphological traits and population genetic analyses, using microsatellite data and a reduced representation of single nucleotide polymorphism (SNP) data, support the description of the new species,Phytophthora betaceisp. nov. We have demonstrated that ecological differences are important in the persistence ofP. infestansandP. betaceias genetically isolated units across an overlapping area in the northern Andes.
HILAQ: A Novel Strategy for Newly Synthesized Protein Quantification
Authors: Ma Yuanhui , McClatchy Daniel B. , Barkallah Salim , Wood William W. , Yates John R. 
Published: December 2016

AbstractHere we describe a new strategy, HILAQ (HeavyIsotopeLabeledAzidohomoalanineQuantification), to rapidly quantify the molecular vulnerability profile to oxytosis. HILAQ quantified more than 1,900NewlySynthesizedProteins (NSP) after 1h pulse labeling in HEK293T cell line. Compared with the previous published QuaNCAT protocol, the HILAQ strategy simplifies newly synthesized proteome analysis and achieves higher sensitivity.
Dynamics of Cortical Dendritic Membrane Potential and Spikes in Freely Behaving Rats
Authors: Moore Jason J. , Ravassard Pascal M. , Ho David , Acharya Lavanya , Kees Ashley L. , Vuong Cliff , Mehta Mayank R. 
Published: December 2016

AbstractNeural activityin vivois primarily measured using extracellular somatic spikes, which provide limited information about neural computation. Hence, it is necessary to record from neuronal dendrites, which generate dendritic action potentials (DAP) and profoundly influence neural computation and plasticity. We measured neocortical sub- and supra-threshold dendritic membrane potential (DMP) from putative distal-most dendrites using tetrodes in freely behaving rats over multiple days with a high degree of stability and sub-millisecond temporal resolution. DAP firing rates were several fold larger than somatic rates. DAP rates were modulated by subthreshold DMP fluctuations which were far larger than DAP amplitude, indicting hybrid, analog-digital coding in the dendrites. Parietal DAP and DMP exhibited egocentric spatial maps comparable to pyramidal neurons. These results have important implications for neural coding and plasticity.One Sentence SummaryMeasurement of cortical dendritic membrane potential for several days in freely behaving rats reveals disproportionate dendritic spiking and analog and digital coding.
Hnf4a mediates microbial control of intestinal gene expression and inflammation
Authors: Davison James M. , Lickwar Colin R. , Song Lingyun , Breton Ghislain , Crawford Gregory E. , Rawls John F. 
Published: December 2016

ABSTRACTMicrobiota influence diverse aspects of intestinal epithelial physiology and disease in part by controlling tissue-specific transcription of host genes. However, host genomic mechanisms mediating microbial control of host gene expression are poorly understood. Using an unbiased screening strategy, we found that the zebrafish Hepatic nuclear factor 4 alpha (Hnf4a) transcription factor specifically binds and activates a microbiota-suppressed intestinal epithelial transcriptional enhancer. Genetic analysis disclosed that zebrafishhnf4aactivates nearly half of the genes that are suppressed by microbiota, suggesting microbiota negatively regulate Hnf4a. In support, analysis of genomic architecture in mouse intestinal epithelial cells revealed that microbiota colonization leads to activation or inactivation of hundreds of enhancers along with drastic genome-wide reduction of Hnf4a and Hnf4g occupancy. Interspecies meta-analysis suggests Hnf4a may mediate microbial contributions to inflammatory bowel disease pathogenesis. These results indicate Hnf4a plays a critical conserved role in maintaining intestinal homeostasis in response to microbiota and inflammation.
Bio.Ontology - Python tools for enrichment analysis and visualization of ontologies
Authors: Koziara Kamil , Herman-Izycka Julia , Wilczynski Bartek 
Published: December 2016

AbstractMotivationFunctional annotation and enrichment analysis based on ontologies has become one of the standard methods of analysis of experimental results. Over the past decade, many methods have been proposed for statistical quantification of enrichment of different functional terms and many implementations of these methods are available. As the popularity of these methods grows, the need for tools facilitating their automation increases.ResultsWe present a complete Python library for statistical enrichment analysis of gene sets and gene rankings compatible with most available biological ontologies. It allows the user to perform all necessary steps: reading the ontologies and gene annotations in multiple formats; performing enrichment analysis using various methods and visualizing the results as readable reports. Importantly, our library includes methods for correcting for multiple hypotheses testing including computation of False Discovery Rates.AvailabilityThe library is compatible with recent versions of python interpreter (≥ 2.6 or ≥ 3.3) and is available on github at:https://github.com/regulomics/biopythontogether with an API documentation and a tutorial. The sample galaxy installation can be found athttp://regulomics.mimuw.edu.pl/wp/GO/.Contactbartek@mimuw.edu.pl
DNA damage in 3D constricted migration or after lamin-A depletion in 2D: shared mechanisms of repair factor mis-localization under nuclear stress
Authors: Xia Yuntao , Irianto Jerome , Pfeifer Charlotte R. , Ji Jiazheng , Ivanovska Irena L. , Tewari Manu , Bennett Rachel R. , Harding Shane M. , Liu Andrea J. , Greenberg Roger A. , Discher Dennis E. 
Published: December 2016

AbstractCells that migrate through small, rigid pores and that have normal levels of the nuclear structure protein lamin-A exhibit an increase in DNA damage, which is also observed with lamin-A depletion in diseases such as cancer and with many lamin-A mutations. Here we show nuclear envelope rupture is a shared feature that increases in standard culture after lamin-A knockdown, which causes nuclear loss of multiple DNA repair factors and increased DNA damage. Some repair factors are merely mis-localized to cytoplasm whereas others are partially depleted unless rescued by lamin-A expression. Compared to standard cultures on rigid glass coverslips, the growth of lamin-A low cells on soft matrix relaxes cytoskeletal stress on the nucleus, suppresses the mis-localization of DNA repair factors, and minimizes DNA damage nearly to wildtype levels. Conversely, constricted migration of the lamin-A low cells causes abnormally high levels of DNA damage, consistent with sustained loss of repair factors. The findings add insight into why monogenic progeroid syndromes that often associate with increased DNA damage and predominantly impact cells in stiff tissues result from mutations only in lamin-A or DNA repair factors.
A Data Citation Roadmap for Scholarly Data Repositories
Authors: Fenner Martin , Crosas Mercè , Grethe Jeffrey , Kennedy David , Hermjakob Henning , Rocca-Serra Philippe , Durand Gustavo , Berjon Robin , Karcher Sebastian , Martone Maryann , Clark Timothy 
Published: December 2016

AbstractThis article presents a practical roadmap for scholarly data repositories to implement data citation in accordance with the Joint Declaration of Data Citation Principles, a synopsis and harmonization of the recommendations of major science policy bodies. The roadmap was developed by the Repositories Expert Group, as part of the Data Citation Implementation Pilot (DCIP) project, an initiative of FORCE11.org and the NIH BioCADDIE (https://biocaddie.org) program. The roadmap makes 11 specific recommendations, grouped into three phases of implementation: a) required steps needed to support the Joint Declaration of Data Citation Principles, b) recommended steps that facilitate article/data publication workflows, and c) optional steps that further improve data citation support provided by data repositories.
Identification of the maize Mediator CDK8 module, andDissociationinsertional mutagenesis ofZmMed12a
Authors: Núñez-Ríos Tania , Ahern Kevin R. , Alonso-Nieves Ana Laura , Lepe-Soltero Daniel , Martínez-Camacho Carol , García-Aguilar Marcelina , Brutnell Thomas P. , Gillmor C. Stewart , Sawers Ruairidh James Hay 
Published: December 2016

ABSTRACTMediator is a conserved transcriptional co-activator that links transcription factors bound at enhancer elements to RNA Polymerase II. Mediator-RNA Polymerase II interactions can be sterically hindered by the Cyclin Dependent Kinase 8 (CDK8) module, a submodule of Mediator that acts to repress transcription in response to discrete cellular and environmental cues. The CDK8 module is conserved in all eukaryotes and consists of 4 proteins: CDK8, CYCLIN C (CYCC), MED12, and MED13. In this study, we have characterized the CDK8 module of Mediator in maize. The maize genome contains single copy genes forCdk8, CycC,andMed13,and two genes forMed12.Analysis of expression data for the CDK8 module demonstrated that all five genes are broadly expressed in maize tissues, withZmMed12a, ZmMed12b,andZmMed13exhibiting similar expression patterns. We performed aDissociation (Ds)insertional mutagenesis, recovering two independent insertions in theZmMed12agene. One of theseDsinsertions results in a truncation of theZmMed12atranscript. Our molecular characterization of the maize CDK8 module, as well as transposon tagging ofZmMed12a,establish the basis for molecular and functional studies of these important transcriptional regulators inZea mays.
Contesting China’s engagement with neoliberal urbanism
Authors: Li Lingyue , Chan Roger C.K. 
Published: December 2016

PurposeThe purpose of this paper is to contribute to an in-depth understanding of China’s ongoing urban development by engaging with the theoretical dialogue of neoliberalism. It takes decentralization and marketization as the governance background to examine the evolving policy of land, housing and public service in China, with a particular focus on Chongqing. The mismatches experienced under the evolving policy are also discussed.Design/methodology/approachBy reviewing and consulting related literature, archives, statistical yearbooks, government reports, local newspapers and urban planning documents, this paper offers an overview of urban policy in China. The authors have also taken two field trips and conducted interviews in Chongqing in Summer 2012 and Winter 2013.FindingsThis paper finds that urban China’s land, housing and public service markets have been re-regulated, with a rescaling of statehood, recalibration of central-local relations and reinvented urban governance in the post-reform era. These policies have evolved from the market-oriented principles of early reforms to a more hybrid approach for which the policies have matured and state intervention has been reintroduced. Mismatches have been generated by this evolution.Originality/valueThis paper provides an up-to-date examination of new initiatives for policy adjustment in urban China, with a closer look at Chongqing, one of the most dynamic contemporary metropolises in the country. It has important implications for the debate over China’s engagement with neoliberal urbanism. Also, it empirically reveals the mismatches created by the latest policy initiatives.
Foreword to the special edition, the return to Europe: a generation of re-inventing national identities
Authors: Brunet-Thornton Richard 
Published: December 2016

Purpose
Readers from outside the region may not be familiar with the subject matter, therefore, the purpose of this paper is to serve as a foundation for the further reading and appreciation of the submitted manuscripts.

Design/methodology/approach
Based on a pertinent literature review, the foreword addresses the general subject matter of this special edition. The approach used was to introduce the reader to the contents as well as to complement and introduce the contributions.

Findings
The literature review substantiates the varied positions adopted and exposed by the contributing authors.

Originality/value
The contents are derived from original research. The value, as mentioned above, positions the reader to better understand the subject matter at hand.
Ideological shift and employees’ relationships: evidence from Ukraine
Authors: Bogodistov Yevgen , Lizneva Anzhela 
Published: December 2016

PurposeThe purpose of this paper is to investigate the employees’ identities shift in Ukraine based on the relational model theory. The paper concentrates on the role which culture and history play in the use of relational models in firms on different organizational levels.Design/methodology/approachThe proposed hypotheses were tested by multivariate analysis of variance and covariance tests with the data from 99 surveys of Ukrainian firms describing 219 intraorganizational relationships.FindingsThe results showed that culture and history play a significant role for the preference of a certain relational model. Position in the organization and gender influence the choice of the relational model.Research limitations/implicationsThe sample of only Ukrainian employees restricts generalizability of the results. This study applies relational models theory in business domain and provides an alternative explanation of employees’ identities shift due to cultural differences and ideological past. Relational models are investigated on different organizational levels shedding light on models of relationships employees prefer in different settings.Practical implicationsManagers working in international settings should pay more attention to patterns of relationships in the target country since they are not freely chosen but partially predestined by the cultural background and the historical and ideological past. Relationships in firms are path dependent, whereby employees inherit models from their peers to apply them to their subordinates. Ukrainian female and male employees have different preferences concerning relational models.Originality/valueThis study is unique in that it applies an anthropological theory to relationships on different organizational levels and tests it in a business domain of a country in an ideological transition.
Responding to NAMAs and preparing for INDCs/NDCs
Authors: Lin Jui-Chu , Chen Wei-Ming , Chen Ding-Jang 
Published: December 2016

PurposeIn this paper, the international progress of Nationally Appropriate Mitigation Actions (NAMAs), Intended Nationally Determined Contributions (INDCs), and Nationally Determined Contributions (NDCs) under the United Nations Framework Convention on Climate Change are reviewed. The content of Taiwan’s NAMAs and INDCs are also investigated, especially with reference to actions for the electricity sector. To better understand the greenhouse gas (GHG) reduction contribution from the electricity sector, this paper aims to examine challenges and solutions for implementing a carbon trading mechanism in Taiwan’s monopolistic electricity market under the newly passed Greenhouse Gases Emissions Reduction and Management Act (GHG ERMA).Design/methodology/approachCarbon reduction strategies for the electricity sector are discussed by examining and explaining Taiwan’s official documents and the law of GHG ERMA.FindingsThis study finds that market mechanisms should be utilized to allocate appropriate costs and incentives for GHG reductions to transform Taiwan into a low-carbon society.Originality/valueThis study identifies strategies for the electricity sector to reduce GHG emissions, especially the operation of a carbon-trading scheme under a non-liberalized electricity market.
Corporate governance reforms and shareholders’ confidence in emerging markets
Authors: Rahman Haseeb-Ur- , Ibrahim Mohd. Yussoff , Ahmad Ayoib Che 
Published: December 2016

Purpose
The purpose of this paper is to investigate the relation of corporate governance (CG) attributes, such as separate leadership (SL) structure, independent chair (IC) of the board, and the proportion of independent directors on the board (Bind) recommended by the new Malaysian Code on Corporate Governance (2012), with firms’ market performance measured by share market price.

Design/methodology/approach
The paper uses a randomly selected sample of 150 non-financial Malaysian listed companies. To find the distinct impact of the code, the paper explicitly divides the sample into two-year pre-context (2010-2011) and two-year post-context (2013-2014) of the code. Besides descriptive statistics, the study also employs correlation and multiple regression estimators.

Findings
By comparing the pre-context and post-context of the code, the study found that SL and Bind have a significant positive relation while IC of the board has a significant negative relation with share market price after enactment of the code.

Research limitations/implications
The paper has a limitation of using only two years of data due to its non-availability particularly after enactment of the code. The findings show that the new code slightly improved compliance to the CG attributes investigated. Based on findings, the study also recommends further improvement in compliance to CG codes and other voluntary regulations in Malaysia.

Originality/value
Besides contributing to the limited and incongruent literature in pre-context and post-context of CG regulations, the paper also provides important insights for regulators and policy makers of the emerging markets like Malaysia.