bluuebunny/crossref_metadata_2025 huggingface dataset:
A CRISPR-based yeast two-hybrid system for investigating RNA-protein interactions
Authors: Hass Evan P. , Zappulla David C.
Published: May 2017

Despite the great importance of RNA-protein interactions in cells, there is a very limited set of approaches available for identifying proteins that bind to a specific RNA. We report here combining the use of CRISPR technology with the yeast two-hybrid protein-protein interaction system in order to create an advantageous method for investigating RNA-protein interactions. In thisCRISPR-assistedRNA/RBPyeast (CARRY) two-hybrid system, an RNA of interest is targeted to the promoters of standard yeast two-hybrid reporter genes by fusing it to the CRISPR guide RNA in a strain expressing catalytically deactivated Cas9 (dCas9). If the promoter-tethered RNA binds to a protein fused to Gal4 transcriptional activation domain (GAD), then the reporter genes become transcribed, just as in the standard protein-protein yeast two-hybrid assay. We used the CARRY two-hybrid system to analyze MS2 bacteriophage RNA hairpin binding to the MS2 coat protein (MCP). We tested MS2 hairpin mutants with a range of biochemically determined binding affinities for MCP and found that CARRY two-hybrid detected all binding interactions with dissociation constants ≤300 nM. In summary, this new CRISPR-based yeast two-hybrid system provides an easily operable, much-needed new tool for identifying proteins that bind to a particular RNA.
Changes of gene expression but not cytosine methylation are associated with plasticity of male parental care reflecting behavioural state, social context, and individual flexibility
Authors: Cunningham CB , Ji L , McKinney EC , Benowitz KM , Schmitz RJ , Moore AJ
Published: May 2017

Behaviour is often on the front line of plasticity in response to different environments. At the genetic level, behavioural changes are likely to be associated with changes of gene expression. Most studies to date have focused on gene expression differences associated with discrete behavioural states reflecting development or age-related changes, such as honey bee castes. However, more rapidly flexible behaviour is often observed in response to social context or simple individual variation. The differences in genetic influences for the different forms of plasticity are poorly understood. In this study we contrasted gene expression during male parental care of the burying beetle,Nicrophorus vespilloides, in a factorial design. MaleN. vespilloidesmales typically do not provide care when females are present. However, male care is inducible by the removing female and has parental effects equivalent to female care. We used this experimental manipulation to isolate gene expression and cytosine methylation associated with differences of behavioural state, differences of social context, or differences of individual flexibility for expressing care. The greatest number of differentially expressed genes was associated with behavioural state, followed by differences of social contexts, and lastly differences of individual variation. DNA methylation has been hypothesized to regulate the transcriptional architecture that regulates behavioural transitions. We tested this hypothesis by quantifying differences of cytosine methylation that were associated with differences of behavioural state and individual flexibility. Changes of cytosine methylation were not associated with changes of gene expression. Our results suggest a hierarchical association between gene expression and the different sources of variation that influence behaviour, but that this process is not controlled by DNA methylation despite reflecting levels of plasticity in behaviour. Our results further suggest that the extent that a behaviour is transient plays an underappreciated role in determining the molecular mechanisms that underpin the behaviour.
NQO1 binds and supports SIRT1 function
Authors: Tsvetkov Peter , Adler Julia , Adamovich Yaarit , Asher Gad , Reuven Nina , Shaul Yosef
Published: May 2017

Silent information regulator 2-related enzyme 1 (SIRT1) is an NAD+-dependent class III deacetylase and a key component of the cellular metabolic sensing pathway. The requirement of NAD+for SIRT1 activity led us to assume that NQO1, an NADH oxidoreductase producing NAD+, regulates SIRT1 activity. We show here that SIRT1 is capable of increasing NQO1 (NAD(P)H Dehydrogenase Quinone 1) transcription and protein levels. NQO1 physically interacts with SIRT1 but not with an enzymatically dead SIRT1 H363Y mutant. The interaction of NQO1 with SIRT1 is markedly increased under mitochondrial inhibition. Interestingly, under this condition the nuclear pool of NQO1 is elevated. Depletion of NQO1 compromises the role of SIRT1 in inducing transcription of several target genes and eliminates the protective role of SIRT1 following mitochondrial inhibition. Our results suggest that SIRT1 and NQO1 form a regulatory loop where SIRT1 regulates NQO1 expression and NQO1 binds and mediates the protective role of SIRT1 during mitochondrial stress. The interplay between an NADH oxidoreductase enzyme and an NAD+dependent deacetylase may act as a rheostat in sensing mitochondrial stress.
Microfluidic immobilization and subcellular imaging of developingCaenorhabditis elegans
Authors: Shivers Jordan , Uppaluri Sravanti , Brangwynne Clifford P.
Published: May 2017

C. eleganshas been an essential model organism in the fields of developmental biology, neuroscience, and aging. However, these areas have been limited by our ability to visualize and track individualC. elegansworms, especially at the subcellular scale, over the course of their lifetime. Here we present a microfluidic device to culture individualC. elegansin parallel throughout post-embryonic development. The device allows for periodic mechanical immobilization of the worm, enabling 3D imaging at subcellular precision. The immobilization is sufficient to enable fluorescence recovery after photobleaching (FRAP) measurements on organelles and other substructures within the same specific cells, throughout larval development, without the use of chemical anesthetics. Using this device, we measure FRAP recovery of two nucleolar proteins in specific intestinal cells within the same worms during larval development. We show that these exhibit different fluorescence recovery as they grow, suggesting differential protein interactions during development. We anticipate that this device will help expand the possible uses ofC. elegansas a model organism, enabling its use in addressing fundamental questions at the subcellular scale, including the role of phase transitions in driving spatiotemporal intracellular organization within multicellular organisms.
Systematic analysis of RNA-seq-based gene co-expression across multiple plants
Authors: Yu Hua , Jiao Bingke , Liang Chengzhi
Published: May 2017

The complex cellular network was formed by the interacting gene modules. Building the high-quality RNA-seq-based Gene Co-expression Network (GCN) is critical for uncovering these modules and understanding the phenotypes of an organism. Here, we established and analyzed the RNA-seq-based GCNs in two monocot species rice and maize, and two eudicot speciesArabidopsisand soybean, and subdivided them into co-expressed modules. Taking rice as an example, we associated these modules with biological functions and agronomic traits by enrichment analysis, and discovered a large number of conditin-specific or tissue-specific modules. In addition, we also explored the regulatory mechanism of the modules by enrichment of the known cis-elements, transcription factors and miRNA targets. Their coherent enrichment with the inferred functions of the modules revealed their synergistic effect on the gene expression regulation. Moreover, the comparative analysis of gene co-expression was performed to identify conserved and species-specific functional modules across 4 plant species. We discovered that the modules shared across 4 plants participate in the basic biological processes, whereas the species-specific modules were involved in the spatiotemporal-specific processes linking the genotypes to phenotypes. Our research provides the massive modules relating to the cellular activities and agronomic traits in several model and crop plant species.
CRootBox: A structural-functional modelling framework for root systems
Authors: Schnepf Andrea , Leitner Daniel , Landl Magdalena , Lobet Guillaume , Mai Trung Hieu , Morandage Shehan , Sheng Cheng , Zörner Mirjam , Vanderborght Jan , Vereecken Harry
Published: May 2017

Background and Aims

Root architecture development determines the sites in soil where roots provide input of carbon and take up water and solutes. However, root architecture is difficult to determine experimentally when grown in opaque soil. Thus, root architectural models have been widely used and been further developed into functional-structural models that simulate the fate of water and solutes in the soil-root system. We present a root architectural model, CRootBox, as a flexible framework to model architecture and its interactions with static and dynamic soil environments.

Methods

CRootBox is a C++ -based root architecture model with Python binding, so that CRootBox can be included via a shared library into any Python code. Output formats include VTP, DGF, RSML and CSV. We further created a database of published root architectural parameters. The capabilities of CRootBox for the unconfined growth of single root systems, as well as the different parameter sets, are highlighted into a freely available web application.

Key results

We demonstrate the use of CRootBox for 5 different cases (1) free growth of individual root systems (2) growth of root systems in containers as a way to mimic experimental setups, (3), field scale simulation, (4) root growth as affected by heterogeneous, static soil conditions, and (5) coupling CRootBox with Soil Physics with Python code to dynamically compute water flow in soil, root water uptake, and water flow inside roots.

Conclusions

In conclusion, we present a fast and flexible functional-structural root model which is based on state-of-the-art computational science methods. Its aim is to facilitate modelling of root responses to environmental conditions as well as the impact of root on soil. In the future, we plan to extend this approach to the aboveground part of the plant.
Side effects and the need for secrecy: characterising discontinuation of modern contraception and its causes in Ethiopia using mixed methods
Authors: Alvergne Alexandra , Stevens Rose , Gurmu Eshetu
Published: May 2017

Background

Contraceptive discontinuation is a major barrier to reducing global unmet needs for family planning, but the reasons why women discontinue contraception are poorly understood. Here we use data from Ethiopia to investigate (i) the magnitude of contraceptive discontinuation in 2005-2011, (ii) how the risk of discontinuation varies with method type and education level and (iii) the barriers to continuation. Our main hypothesis is that contraceptive discontinuation is driven by the experience of physiological side-effects associated with the use of hormonal contraception, rather than a lack of education.

Methods

We used a mixed methods explanatory sequential design to explain the quantitative results in more details through the qualitative data. First, we analysed quantitative data from the 2011 Ethiopian Demographic and Health Survey to study patterns of contraceptive discontinuation and method choice using multilevel multiprocess models. Second, we conducted semi-structured interviews and focus group discussions in the 3 most populated regions of Ethiopia with individuals of reproductive age and health professionals.

Results

The analysis of EDHS data shows that the rate of discontinuation has not reduced in the period 2005-2011 and remains high. Discontinuation mainly takes the form of abandonment, and is a function of method type and wealth but not of educational level. Interviews with women and health professionals reveal that the experience of debilitating physiological side effects, the need for secrecy and poverty are important barriers to continuation.

Conclusions

Our findings together suggest that physiological and social side-effects of contraceptive use, not education, are the root causes of contraceptive discontinuation in Ethiopia. We argue that to tackle discontinuation due to side-effects, dispelling misconceptions through educating women is not addressing the root causes of discontinuation, and that priority should be given to both engaging men and questioning the appropriateness of medical technology to the physiology of Ethiopian women, especially those living in poverty.
Cell dynamics underlying oriented growth of theDrosophilawing imaginal disc
Authors: Dye Natalie A. , Popović Marko , Spannl Stephanie , Etournay Raphaël , Kainmüller Dagmar , Myers Eugene W. , Jülicher Frank , Eaton Suzanne
Published: May 2017

Quantitative analysis of the dynamic cellular mechanisms shaping theDrosophilawing during its larval growth phase has been limited, impeding our ability to understand how morphogen patterns regulate tissue shape. Such analysis requires imaging explants under conditions that maintain both growth and patterning, as well as methods to quantify how much cellular behaviors change tissue shape. Here, we demonstrate a key requirement for the steroid hormone 20-hydroxyecdysone (20E) in the maintenance of numerous patterning systemsin vivoand in explant culture. We find that low concentrations of 20E support prolonged proliferation in explanted wing discs in the absence of insulin, incidentally providing novel insight into the hormonal regulation of imaginal growth. We use 20E-containing media to directly observe growth and apply recently developed methods for quantitatively decomposing tissue shape changes into cellular contributions. We discover that while cell divisions drive tissue expansion along one axis, their contribution to expansion along the orthogonal axis is cancelled by cell rearrangements and cell shape changes. This finding raises the possibility that anisotropic mechanical constraints contribute to growth orientation in the wing disc.
Control of AMPA receptor activity by the extracellular loops of auxiliary proteins
Authors: Riva Irene , Eibl Clarissa , Volkmer Rudolf , Carbone Anna L. , Plested Andrew J. R.
Published: May 2017

At synapses throughout the mammalian brain, AMPA receptors form complexes with auxiliary proteins, including TARPs. However, how TARPs modulate AMPA receptor gating remains poorly understood. We built structural models of TARP-AMPA receptor complexes for TARPs γ2 and γ8, combining recent structural studies and de novo structure predictions. These models, combined with peptide binding assays, provide evidence for multiple interactions between GluA2 and variable extracellular loops of TARPs. Substitutions and deletions of these loops had surprisingly rich effects on the kinetics of glutamate-activated currents, without any effect on assembly. Critically, by altering the two interacting loops of γ2 and γ8, we could entirely remove all allosteric modulation of GluA2, without affecting formation of AMPA receptor-TARP complexes. Likewise, substitutions in the linker domains of GluA2 completely removed any effect of Y2 on receptor kinetics, indicating a dominant role for this previously overlooked site proximal to the AMPA receptor channel gate.
Oligomeric states in sodium ion–dependent regulation of cyanobacterial histidine kinase-2
Authors: Ibrahim Iskander M. , Wang Liang , Puthiyaveetil Sujith , Krauß Norbert , Nield Jon , Allen John F.
Published: May 2017

Two-component signal transduction systems (TCSs) consist of sensor histidine kinases and response regulators. TCSs mediate adaptation to environmental changes in bacteria, plants, fungi, and protists. Histidine kinase 2 (Hik2) is a sensor histidine kinase found in all known cyanobacteria and as chloroplast sensor kinase in eukaryotic algae and plants. Sodium ions have been shown to inhibit the autophosphorylation activity of Hik2 that precedes phosphoryl transfer to response regulators, but the mechanism of inhibition has not been determined. We report on the mechanism of Hik2 activation and inactivation probed by chemical crosslinking and size exclusion chromatography together with direct visualisation of the kinase using negative-stain transmission electron microscopy of single particles. We show that the functional form of Hik2 is a higher order oligomer such as a hexamer or octamer. Increased NaCl concentration converts the active hexamer into an inactive tetramer. Furthermore, the action of NaCl appears to be confined to the Hik2 kinase domain.

IMPORTANCE

Bacteria sense change and respond to it by means of two-component regulatory systems. The sensor component is a protein that becomes covalently modified by a phosphate group on a histidine side chain. The response regulator accepts the phosphate group onto an aspartate, with structural and functional consequences, often for gene transcription. Histidine kinase 2 is a sensor of sodium ion concentration and redox potential, regulating transcription of genes for light-harvesting and reaction center proteins of photosynthesis in cyanobacteria and chloroplasts of algae and plants. Using radiolabeling, chemical crosslinking, chromatography and electron microscopy, we find that sodium ion concentration governs the oligomeric state of Histidine Kinase 2 and its phosphorylation by ATP.
Identification of jellyfish neuropeptides that act directly as oocyte maturation inducing hormones
Authors: Takeda Noriyo , Kon Yota , Quiroga Artigas Gonzalo , Lapébie Pascal , Barreau Carine , Koizumi Osamu , Kishimoto Takeo , Tachibana Kazunori , Houliston Evelyn , Deguchi Ryusaku
Published: May 2017

Oocyte meiotic maturation is a critical process for sexually reproducing animals, and its core cytoplasmic regulators are highly conserved between species. In contrast, the few known Maturation Inducing Hormones (MIHs) that act on oocytes to initiate this process have highly variable molecular natures. Using the hydrozoan jellyfish speciesClytiaandCladonema, which undergo oocyte maturation in response to dark-light and light-dark transitions respectively, we deduced from gonad transcriptome data amidated tetrapeptide sequences and found that synthetic peptides could induce maturation of isolated oocytes at nanomolar concentrations. Antibody preabsorption experiments conclusively demonstrated that these W/RPRPamide-related neuropeptides account for endogenous MIH activity produced by isolated gonads. We further showed that the MIH peptides are synthesised by neural-type cells in the gonad, are released following dark-light / light-dark transitions, and probably act on the oocyte surface. They are produced by male as well as female jellyfish and can trigger both sperm and egg release, suggesting a role in spawning coordination. We propose an evolutionary link between hydrozoan MIH and the neuropeptide hormones that regulate reproduction upstream of MIH in bilaterian species.
In vivophenotyping of Parkinson-specific stem cells reveals increased a-Synuclein levels but no spreading
Authors: Hemmer Kathrin , Smits Lisa M. , Bolognin Silvia , Schwamborn Jens C.
Published: May 2017

Parkinson′s disease is a progressive age-associated neurological disorder. One of the major neuropathological hallmarks of Parkinson’s disease is the appearance of protein aggregates, mainly consisting of the protein alpha-Synuclein. These aggregates have been described both in genetic as well as idiopathic forms of the disease. Currently, Parkinson’s disease patient-specific induced pluripotent stem cells (iPSCs) are mainly used forin vitrodisease modeling or for experimental cell replacement approaches. Here, we demonstrate that these cells can be used forin vivodisease modeling. We show that Parkinson’s disease patient-specific, iPSC-derived neurons carrying the LRRK2-G2019S mutation show an upregulation of alpha-Synuclein after transplantation in the mouse brain. However, further investigations indicate that the increased human alpha-Synuclein levels fail to induce spreading or aggregation in the mouse brain. We therefore conclude that grafting of these cells into the mouse brain is suitable for cell autonomousin vivodisease modeling but has strong limitations beyond that. Furthermore, our results support the hypothesis that there might be a species barrier between human to mouse concerning alpha-Synuclein spreading.
The resistome of common human pathogens
Authors: Munck Christian , Hashim Ellabaan Mostafa M. , Klausen Michael Schantz , Sommer Morten O.A.
Published: May 2017

Genes capable of conferring resistance to clinically used antibiotics have been found in many different natural environments. However, a concise overview of the resistance genes found in common human bacterial pathogens is lacking, which complicates risk ranking of environmental reservoirs. Here, we present an analysis of potential antibiotic resistance genes in the 17 most common bacterial pathogens isolated from humans. We analyzed more than 20,000 bacterial genomes and defined a clinical resistome as the set of resistance genes found across these genomes. Using this database, we uncovered the co-occurrence frequencies of the resistance gene clusters within each species enabling identification of co-dissemination and co-selection patterns. The resistance genes identified in this study represent the subset of the environmental resistome that is clinically relevant and the dataset and approach provides a baseline for further investigations into the abundance of clinically relevant resistance genes across different environments. To facilitate an easy overview the data is presented at the species level atwww.resistome.biosustain.dtu.dk.
Ccr4 and Pop2 control poly(A) tail length inSaccharomyces cerevisiae
Authors: Balagopal Vidya , Bolisetty Mohan , Al Husaini Najwa , Coller Jeff , Graveley Brenton R.
Published: May 2017

Messenger RNA degradation is an important aspect of post-transcriptional gene regulation and shortening the poly(A) tail is suggested to be the rate-limiting step in mRNA degradation. InSaccharomyces cerevisiae, the Ccr4-Not complex is the major deadenylase and contains two subunits with exoribonuclease domains, Ccr4 and Pop2. Although the role of Ccr4 and Pop2 in deadenylation has previously been studied using individual reporter mRNAs, their activity has not been studied transcriptome-wide. Here, we describe END-seq, a method to accurately measure poly(A) tail lengths of individual mRNAs transcriptome-wide, and have used this assay to examine the impact of deleting or mutatingCCR4andPOP2on steady state poly(A) tail length. We found that Ccr4 and Pop2 have differential effects on the poly(A) tail lengths of individual mRNAs. Additionally, though Pop2 has previously been reported to have exonuclease activity, mutations that render it catalytically inactive have no effect on steady-state poly(A) tail lengths. Furthermore, mutations that disrupt the interaction between Ccr4 and Pop2 result in longer poly(A) tails. We also observe an inverse correlation between codon optimality and poly(A) tail length – transcripts containing predominantly optimal codons display fewer changes in poly(A) tail length upon deletion of Ccr4 or Pop2 than those containing less optimal codons. Together, these results indicate that Pop2 modulates poly(A) tail length, at least partially, via its association with Ccr4 and that Pop2 improves the function of Ccr4 in regulating poly(A) tail length. These data provide important insights into poly(A) tail length dynamics in yeast and demonstrate that END-seq is an efficient and accurate method to study poly(A) tail length.
A gonad-expressed opsin mediates light-induced spawning in the jellyfishClytia
Authors: Quiroga Artigas Gonzalo , Lapébie Pascal , Leclère Lucas , Takeda Noriyo , Deguchi Ryusaku , Jékely Gáspár , Momose Tsuyoshi , Houliston Evelyn
Published: May 2017

Across the animal kingdom, environmental light cues are widely involved in regulating gamete release, but the molecular and cellular bases of the photoresponsive mechanisms are poorly understood. In hydrozoan jellyfish, spawning is triggered by dark-light or light-dark transitions acting on the gonad, and is mediated by oocyte maturation-inducing neuropeptide hormones (MIHs) released from the ectoderm. We determined inClytia hemisphaericathat blue-cyan light triggers spawning in isolated gonads. A candidate opsin (Opsin9) was found co-expressed with MIH within specialised ectodermal cells.Opsin9knockout jellyfish generated by CRISPR/Cas9 failed to undergo oocyte maturation and spawning, a phenotype reversible by synthetic MIH. Gamete maturation and release inClytiais thus regulated by gonadal photosensory-neurosecretory cells that secrete MIH in response to light via Opsin9. Similar cells in ancestral eumetazoans may have allowed tissue-level photo-regulation of diverse behaviours, a feature elaborated in cnidarians in parallel with expansion of the opsin gene family.
Interactive phenotyping of large-scale histology imaging data with HistomicsML
Authors: Nalisnik Michael , Amgad Mohamed , Lee Sanghoon , Halani Sameer H. , Vega Jose Velazquez , Brat Daniel J , Gutman David A , Cooper Lee AD
Published: May 2017

Whole-slide imaging of histologic sections captures tissue microenvironments and cytologic details in expansive high-resolution images. These images can be mined to extract quantitative features that describe histologic elements, yielding measurements for hundreds of millions of objects. A central challenge in utilizing this data is enabling investigators to train and evaluate classification rules for identifying objects related to processes like angiogenesis or immune response. Here we present HistomicsML, an interactive machine-learning framework for large whole-slide imaging data. HistomicsML uses active learning direct user feedback, making classifier training efficient and scalable in datasets containing 108+ histologic objects. We demonstrate how HistomicsML can be used to phenotype microvascular structures in gliomas to predict survival, and to explore the molecular pathways associated with these phenotypes. Our approach enables researchers to unlock phenotypic information from digital pathology datasets to investigate prognostic image biomarkers and genotype-phenotype associations.
An inference approach combines spatial and temporal gene expression data to predict gene regulatory networks in Arabidopsis stem cells
Authors: de Luis Balaguer Maria Angels , Fisher Adam P. , Clark Natalie M. , Fernandez-Espinosa Maria Guadalupe , Möller Barbara K. , Weijers Dolf , Lohmann Jan U. , Williams Cranos , Lorenzo Oscar , Sozzani Rosangela
Published: May 2017

Identifying the transcription factors (TFs) and associated networks involved in stem cell regulation is key for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. For this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network (GRN) inference algorithm that combines clustering with Dynamic Bayesian Network (DBN) inference. We leveraged the topology of our networks to infer potential key regulators. The results presented in this work show that our combination of molecular biology approaches, computational biology and mathematical modeling was key to identify candidate factors that function in the stem cells. Specifically, through experimental validation and mathematical modeling, we identifiedPERIANTHIA (PAN)as an important molecular regulator of quiescent center (QC) function.
Daam2 Driven Degradation of VHL Promotes Gliomagenesis
Authors: Zhu Wenyi , Krishna Saritha , Garcia Cristina , John Lin Chia-Ching , Scott Ken , Mohila Carrie A , Creighton Chad J , Yoo Seung-Hee , Lee Hyun Kyoung , Deneen Benjamin
Published: May 2017

Von Hippel-Landau (VHL) protein is a potent tumor suppressor regulating numerous pathways that drive cancer, but mutations in VHL are restricted to limited subsets of malignancies. Here we identified a novel mechanism for VHL suppression in tumors that do not have inactivating mutations. Using developmental processes to uncover new pathways contributing to tumorigenesis, we found that Daam2 promotes glioma formation. Protein expression screening identified an inverse correlation between Daam2 and VHL expression across a host of cancers, including glioma. Thesein silicoinsights guided corroborating functional studies, which revealed that Daam2 promotes tumorigenesis by suppressing VHL expression. Furthermore, biochemical analyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation. Together, these studies are the first to define an upstream mechanism regulating VHL suppression in cancer and describe the role of Daam2 in tumorigenesis.

Statement of Significance

We found that the glial developmental factor Daam2 promotes glioma tumorigenesis by suppressing VHL expression. Our studies show, for the first time, a regulatory mechanism that operates upstream of VHL in cancer and provides an explanation for how VHL expression is extinguished in tumors that do not have inactivating mutations.
Service quality, perceived value, satisfaction and intention to pay
Authors: Londoño Beatriz , Prado Yesica , Salazar Viviana
Published: May 2017

Objective

The purpose of this paper is to examine the relations between the concepts of service quality, perceived value, satisfaction and intention to pay in the context of theatrical services in the city of Medellín, Colombia.

Design/methodology

Quantitative research was carried out on a sample of 274 individuals who had attended the theatre at least once in the previous year. The information was gathered in October 2014 using an online survey. Confirmatory factor analysis was used to test the validity and reliability of the measurement scales, and a structural equations model was developed to test the hypotheses.

Findings

Satisfaction with overall service and with the central service (i.e. with the performance itself) was the major predictors of consumer intention to pay.

Limitations/implications of the research

Future research could replicate the analysis presented here for other cultural services and different geographical contexts.

Practical implications

Theatres should focus their efforts on offering a basic service (a theatrical presentation) that meets the cultural and artistic expectations of the public, but should also bear in mind that audiences expect to be treated well when they go out and want to feel comfortable.

Originality/value

This paper contributes to understand the factors that influence theatre clients’ intention to pay by taking into account the factors that affect satisfaction and perceived value of the theatregoing experience. It also contributes to academic reflections on the cultural consumption in the field of the theatrical arts in the Latin American region, where this is a new field of research.
Development, implementation and evaluation of nurse-led integrated, person-centred care with long-term conditions
Authors: Harvey Clare Lynette , Sibley Jonathan , Palmer Janine , Phillips Andrew , Willis Eileen , Marshall Robert , Thompson Shona , Ward Susanne , Forrest Rachel , Pearson Maria
Published: May 2017

Purpose

The purpose of this paper is to outline a conceptual plan for innovative, integrated care designed for people living with long-term conditions (LTCs).

Design/methodology/approach

The conceptual plan delivers a partnership between the health system, the person with LTCs (chronic), their family, and the community. The partnership aims to support people at home with access to effective treatment, consistent with the New Zealand Government Health Strategy. This concept of people-owned care is provided by nurses with advanced practice skills, who coordinate care across services, locations and multiple LTCs.

Findings

With the global increase in numbers of people with multiple chronic conditions, health services are challenged to deliver good outcomes and experience. This model aims to demonstrate the effective use of healthcare resources by supporting people living with a chronic condition, to increase their self-efficacy and resilience in accordance with personal, cultural and social circumstance. The aim is to have a model of care that is replicable and transferable across a range of health services.

Social implications

People living with chronic conditions can be empowered to manage their health and well-being, whilst having access to nurse-led care appropriate to individual needs.

Originality/value

Although there are examples of case management and nurse-led coordination, this model is novel in that it combines a liaison nursing role that works in partnership with patients, whilst ensuring that care across a number of primary and secondary care services is truly integrated and not simply interfaced.
Interest groups and policy volatility
Authors: Breunig Christian , Koski Chris
Published: May 2017

We offer a model of how interest groups affect policy stability. The relationship between interest group density and policy volatility is concave because of two forces: (a) the number and interaction of interest groups in a policy domain and (b) the effect of this interaction on policy image and attention. After laying out the logics of both processes, we identify three ideal type situations: (a) capture (low interest group density, low attention) and (b) deadlock (high interest group density, high attention) lead to low levels of policy volatility while (c) lability (medium interest group density, intermittent attention) leads to high levels of policy volatility. For our empirical evidence, we rely on all budget functions in the American states from 1984 to 2010 and employ generalized additive regression modeling. The article contributes to the literature on understanding interest group strategies, interest group influence in policy making, and broader questions of deliberative democracy.
Bureaucratic Speech: Language Choice and Democratic Identity in the Taipei Bureaucracy
Authors: Bernstein Anya
Published: May 2017

This article illuminates the social nature of bureaucratic practice by analyzing the everyday speech of bureaucrats in a polyglossic society. My ethnographic analysis shows how Taipei city government administrators mobilize ideologies associated with Taiwan's two primary languages, and stereotypes associated with bureaucracy, to undermine both. Instead, they present themselves as a postethnonational and postbureaucratic avant‐garde of their new democracy. In doing so, they draw on local values and tropes of legitimation, which place a premium on the personalistic relations and social imbrication of government actors—relations that democracy, for all its potential to spawn dangerous chaos, is seen to facilitate. They represent their government employer not by claiming a superordinate status for it but by situating it as one participant within a complex of institutions, networks, and values. In illuminating both the internally and the externally social nature of government bureaucracy, I highlight the creative and progressive possibilities hidden within the drab government office.
Imaging and Peritoneal Dialysis Catheters
Authors: Ash Stephen , Sequeira Adrian , Narayan Rajeev
Published: May 2017

The placement of a peritoneal dialysis (PD) catheter by interventionalists demands not only procedural skill but also an ability to decipher real‐time ultrasonographic and fluoroscopic images. In this article, we discuss how imaging assists in PD placement and recognition of complications. To aid this endeavor, we have provided images and video clips that should assist interventionalists. Compared with the fluoroscopic technique, peritoneoscopic PD catheter placement provides direct visual imaging to also aid placement of the initial trocar and the peritoneal catheter.
Introduction
Authors: Sousa Lisa
Published: May 2017

Chapter 1 provides an introduction to major themes of the study and to the historical background of the indigenous groups of central Mexico and Oaxaca--the Nahua, Ñudzahui (Mixtec), Bènizàa (Zapotec), and Ayuk (Mixe) peoples--that are the focus of the book. The chapter lays out the dramatic changes that took place in native communities in the decades following the Spanish conquest (1519-21), including depopulation, sociopolitical reorganization, imposition of Christianity, and economic reorientation. Chapter 1 provides a general overview of social structure and gender relations in the post-classic and colonial periods. The Introduction places the work and its contributions in the context of the scholarship on colonial Mexican ethnohistory and Latin American women’s history, and discusses the sources and methods used in the study.
Gender and the Body
Authors: Sousa Lisa
Published: May 2017

Chapter 2 draws on theories of the body, gender performativity, and dress, to show how gender was inscribed on the body to create the appearance of difference, which, in turn, shaped all social relations. The chapter analyzes aspects of indigenous gender ideology and concepts of the body as expressed in life-cycle rituals, native-language metaphors and terminology, and beliefs pertaining to the calendar, tonalism, and nahualism. The chapter argues that concepts concerning the fluidity of the body and gender identity undermined essentializing ideologies. The work examines the construction of gender through labor, drawing on Nahua and Bènizàa rituals as two central case studies. The chapter also considers clothing and adornment and speech and behavior, which served as mechanisms to stabilize the body and impose identity. Chapter 2 concludes with a discussion of cross-gendering which occurred when individuals adopted the dress, labor roles, and mannerisms of the “opposite sex.”
Rebellious Women
Authors: Sousa Lisa
Published: May 2017

Chapter 9 studies women’s participation in public protests and acts of civil disobedience, including riots. It shows how threats to the integrity of the household and community, such as increased demands for tribute and labor, disputes over land and natural resources, and Spanish attempts to remove local officials from office, led men and women to seek legal redress, to protest, and at times to rebel against colonial authorities. The chapter traces women’s efforts to organize acts of resistance, such as the refusal to pay tribute, and their leadership roles in local riots. While women did not hold political office, they were aware of controversies over lands, resources, and legal suits to protect these assets. Chapter 9 argues that women’s participation in efforts to defend their homes, communities, and allies reveals a broader consciousness that has been overlooked or underestimated in previous studies.
Trust between Adversaries and Allies: President George H. W. Bush, Trust, and the End of the Cold War
Authors: Rofe J. Simon
Published: May 2017

This chapter investigates the central role of trust-building for the George H. W. Bush administration and its crucial significance in navigating the political transformations of 1990–91. Portraying Bush's foreign policy as driven by an effort to establish trust among adversaries to minimize risk and maintain order, this chapter shows how Bush and his key advisers, Secretary of State James A. Baker III and National Security Advisor Brent Scowcroft, crafted a strategy of personal diplomacy and caution. Analyzing in particular the demise of the Soviet Union in late 1991 as well as the 1990–91 Kuwait crisis, the chapter highlights the Bush administration's prioritization of reliability, steadfastness, and personal relationships in fostering a culture of mutual trust as key assets for U.S. foreign policy before.
Not Quite “Brothers in Arms”: East Germany and People’s Poland between Mutual Dependency and Mutual Distrust, 1975–1990
Authors: Boysen Jens
Published: May 2017

This chapter assesses the relationship between East Germany and Poland during the last phase of the Cold War. It explains how the historical legacy of German–Polish relations infused the relationship of both countries with mistrust, despite the officially proclaimed brotherhood of a “socialist community” mandated from Moscow. Personal enmity between communist leaders Walter Ulbricht and Władysław Gomułka, conceptual differences of notions of statehood, and rivaling foreign policy goals and ideas about tolerance for domestic opposition since the end of the 1970s only exacerbated these tensions, which not even successful military cooperation under the Warsaw Pact umbrella was able to alleviate. Held together by their relationship to the Soviet hegemon, the officially required “trust” between the two countries fully disintegrated in the second half of the 1980s.
Institutionalizing Trust? Regular Summitry (G7s and European Councils) from the Mid-1970s until the Mid-1980s
Authors: Bonhomme Noël , Mourlon-Druol Emmanuel
Published: May 2017

This chapter describes how the maintenance and fostering of trust was a crucial element in founding both the G7 summits and the European Council in the mid-1970s. Deeply anchored in the strong friendship between West German chancellor Helmut Schmidt and French president Valéry Giscard d'Estaing, both initiatives sought to deepen interpersonal relations as well as recover systemic trust in the Western (economic) systems in an informal, multilateral setting. The institutionalization and frequency of these meetings not only allowed for the development of a framework of informal coordination even in the absence of trust; it also provided a platform for the socialization of new leaders and a ritualistic display of Western unity, thus addressing potential international and domestic deficits of trust by “formalizing informality.”
Jewish Christian Sects in Southern Russia
Authors: Schainker Ellie R.
Published: May 2017

Chapter 6 charts the proliferation of Jewish-Christian sects in southern Russia in the 1880s and the confessional journeys of their leaders and adherents who were in conversation with contemporary sectarian and revolutionary political movements. These sects provided a forum for a cross-cultural conversation in the public press on Jewish and Russian fears of conversion, cultural hybridity, and trespassing the boundaries of imperial confessions. The liminal space occupied by the sects highlighted the tension between tolerated confession and personal faith in the empire, and the question of where converts and schismatics communally belonged.
Epilogue
Authors: Schainker Ellie R.
Published: May 2017

The epilogue summarizes how the phenomenon of Russian Jewish conversion, though marginal in number, left an outsized imprint on the cultural map of East European Jews who grappled with questions of Jewish identity and the role of religion in the increasingly powerful Jewish secular nationalist ideologies of the late nineteenth and early twentieth centuries. The epilogue explores evolving Jewish attitudes towards baptism, interfaith sociability, and cultural mobility in the late-imperial period, and it puts conversions from Judaism in imperial Russia in conversation with conversions from Judaism in the modern period more broadly. Finally, the epilogue looks ahead to the inter-revolutionary period (1906-1917) and the Soviet period when conversions from Judaism accelerated, accompanied by a growing ethnic conception of Jewish identity whereby national Jewishness found explicit harmony with Christian religious adherence.
Ukraine’s Politicized Courts
Authors: Popova Maria
Published: May 2017

Many other aspects of reform, including economic reform and democratization, depend in large part on a functioning judicial system. Maria Popova’s findings reported in this chapter on politicized prosecution in Ukraine are sobering. Looking at a series of cases from 2001 to 2010, she determines that under the Yanukovych administration, political prosecution became a more effective means to sideline one’s rivals. While this might be explained in terms of Yanukovych’s greater enmity to democracy, Popova hypothesizes that a process of authoritarian learning is at work, in that Yanukovych and others have learned over time how to use the prosecution process more effectively. This outcome highlights that not all actors are interested in reform; and that policy innovation can be for the worse as well as the better.
Oligarchs, the Partial Reform Equilibrium, and the Euromaidan Revolution
Authors: Kuzio Taras
Published: May 2017

In contrast to many other scholars, Taras Kuzio shows how the corruption, shadow economy, and organized crime that plague Ukraine today emerged in the late Soviet period and then took advantage of the collapse of the Soviet Union. Through a detailed analysis of oligarchs’ roles in a wide range of enterprises, he shows empirically how corruption works at the micro-level. He also shows why the foundations of the Donetsk group in organized crime networks prepared it to outcompete the Dnipropetrovsk oligarchs for power in post-Soviet Ukraine. Kuzio’s chapter leaves it clear that the current patterns of “non-reform” that we see in Ukraine are deeply entrenched and resistant to change. While the 2014 revolution opened space for reform, many actors are striving to take advantage of the current turmoil to gain control over economic assets.
Economic Reforms in Ukraine in Comparative Perspective: Formal and Informal Dimensions
Authors: Libman Alexander , Obydenkova Anastassia
Published: May 2017

Alexander Libman and Anastassia Obydenkova set out inductively to identify the countries whose economies are most similar to Ukraine’s using a hierarchical cluster analysis of indicators of the micro-level institutions, such as obtaining permits, registering property, and enforcing contracts. This analysis indicates that in terms of formal institutions, Ukraine performs like a country of southeastern Europe, while in informal terms, it looks more like the other post-Soviet states. While the formal institutional environment in Ukraine has improved, perceptions of the business climate have worsened. This highlights the disconnect between formal institutions and informal practices. They stress that government cannot directly change informal practices—it can only change formal rules or personnel.
The Poetry and the Prose of the Future
Authors: Lehman Robert S.
Published: May 2017

The Introduction examines three moments that have proven foundational for the fraught relationship between poetry and history. The first occurs in the fourth century B. C. in Aristotle’s Poetics, the earliest attempt to provide a systematic definition of the structure and effects of poetry and, consequently, the origin of all later crises of verse. The second appears in Marx’s Eighteenth Brumaire, a text that offers a complicated poetic response to a moment of crisis in Marx’s own historical method. The third appears in the early writings of Friedrich Nietzsche, where, against the onset of the nineteenth-century science of history, the demand to see history become poetry is made explicit. Focusing on these three moments, the Introduction establishes the intellectual-historical coordinates of the poetico-historical problem that T. S. Eliot and Walter Benjamin inherit.
Questions About Footbinding
Authors: Bossen Laurel , Gates Hill
Published: May 2017

This chapter challenges assumptions that footbinding was confined to the urban elite and that women with bound feet were unproductive. On the contrary, footbinding was very common among poor villagers who could not afford to support unproductive members. Examining the enormous historical importance of women’s work in China’s handcraft textile production, this chapter argues for the importance of handwork performed by footbound daughters. Emphasizing the work girls performed before marriage, this chapter also considers the misdirections and omissions that have sidetracked queries about a practice that debilitated hundreds of millions of Chinese girls and women. Feminist historians and economic historians alike have underestimated the significance of hand labor by young girls and failed to examine its links to footbinding.