bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetraconatan phylogeny with special focus on Malacostraca and Branchiopoda: highlighting the strength of taxon-specific matrices in phylogenomics
Authors: Schwentner Martin , Richter Stefan , Rogers D. Christopher , Giribet Gonzalo
Published: August 2018

Understanding the evolution of Tetraconata or Pancrustacea—the clade that includes crustaceans and insects—requires a well-resolved hypothesis regarding the relationships within and among its constituent taxa. Here, we assembled a taxon-rich phylogenomic dataset focusing on crustacean lineages based solely on genomes and new-generation Illumina-generated transcriptomes, including 89 representatives of Tetraconata. This constitutes, to our knowledge, the first phylogenomic study specifically addressing internal relationships of Malacostraca (with 26 species included) and Branchiopoda (36 species). Seven matrices comprising 81–684 orthogroups and 17 690–242 530 amino acid positions were assembled and analysed under five different analytical approaches. To maximize gene occupancy and to improve resolution, taxon-specific matrices were designed for Malacostraca and Branchiopoda. Key tetraconatan taxa (i.e. Oligostraca, Multicrustacea, Branchiopoda, Malacostraca, Thecostraca, Copepoda and Hexapoda) were monophyletic and well supported. Within Branchiopoda, Phyllopoda, Diplostraca, Cladoceromorpha and Cladocera were monophyletic. Within Malacostraca, the clades Eumalacostraca, Decapoda and Reptantia were well supported. Recovery of Caridoida or Peracarida was highly dependent on the analysis for the complete matrix, but it was consistently monophyletic in the malacostracan-specific matrices. From such examples, we demonstrate that taxon-specific matrices and particular evolutionary models and analytical methods, namely CAT-GTR and Dayhoff recoding, outperform other approaches in resolving certain recalcitrant nodes in phylogenomic analyses.
Hearing through lip-reading: the brain synthesizes features of absent speech
Authors: Bourguignon Mathieu , Baart Martijn , Kapnoula Efthymia C. , Molinaro Nicola
Published: August 2018

Lip-reading is crucial to understand speech in challenging conditions. Neuroimaging investigations have revealed that lip-reading activates auditory cortices in individuals covertly repeating absent—but known—speech. However, in real-life, one usually has no detailed information about the content of upcoming speech. Here we show that during silent lip-reading ofunknownspeech, activity in auditory cortices entrains more to absent speech than to seen lip movements at frequencies below 1 Hz. This entrainment to absent speech was characterized by a speech-to-brain delay of 50–100 ms as when actually listening to speech. We also observed entrainment to lip movements at the same low frequency in the right angular gyrus, an area involved in processing biological motion. These findings demonstrate that the brain can synthesize high-level features of absent unknown speech sounds from lip-reading that can facilitate the processing of the auditory input. Such a synthesis process may help explain well-documented bottom-up perceptual effects.
Splice variants of DOMINO controlDrosophilacircadian behavior and pacemaker neuron maintenance
Authors: Liu Zhenxing , Niu Ye , Lam Vu H. , Chiu Joanna C. , Zhang Yong
Published: August 2018

Circadian clocks control daily rhythms in physiology. InDrosophila, the small ventral lateral neurons (sLNvs) expressing PIGMENT DISPERSING FACTOR (PDF) are the master pacemaker neurons. Despite the importance of sLNvs and PDF in circadian behavior, little is known about factors that control sLNvs maintenance and PDF accumulation. Here, we identify theDrosophilaSWI2/SNF2 protein DOMINO (DOM) as a key regulator of circadian behavior. Depletion of DOM eliminates morning anticipation and impairs rhythmicity. Interestingly, the two splice variants of DOM, DOM-A and DOM-B have distinct circadian functions. DOM-A depletion leads to arrhythmic behavior, while DOM-B knockdown lengthens circadian period. Both DOM-A and DOM-B bind to the promotor regions of key pacemaker genesperiodandtimeless, and regulate their protein expression. Furthermore, we identify that DOM-A is required for the maintenance of sLNvs and transcription ofpdf. Lastly, constitutive activation of PDF-receptor signaling rescued the arrhythmia and period lengthening of DOM downregulation. Taken together, our findings reveal that splice variants of DOM play distinct roles in circadian rhythms through regulating abundance of pacemaker proteins and sLNvs maintenance.
SNP Variable Selection by Generalized Graph Domination
Authors: Sun Shuzhen , Miao Zhuqi , Ratcliffe Blaise , Campbell Polly , Pasch Bret , El-Kassaby Yousry A. , Balasundaram Balabhaskar , Chen Charles
Published: August 2018

High-throughput sequencing technology has revolutionized both medical and biological research by generating exceedingly large numbers of genetic variants. The resulting datasets share a number of common characteristics that might lead to poor generalization capacity. Concerns include noise accumulated due to the large number of predictors, sparse information regarding thep≫nproblem, and overfitting and model mis-identification resulting from spurious collinearity. Additionally, complex correlation patterns are present among variables. As a consequence, reliable variable selection techniques play a pivotal role in predictive analysis, generalization capability, and robustness in clustering, as well as interpretability of the derived models.

K-dominating set, a parameterized graph-theoretic generalization model, was used to model SNP (single nucleotide polymorphism) data as a similarity network and searched for representative SNP variables. In particular, each SNP was represented as a vertex in the graph, (dis)similarity measures such as correlation coefficients or pairwise linkage disequilibrium were estimated to describe the relationship between each pair of SNPs; a pair of vertices are adjacent, i.e. joined by an edge, if the pairwise similarity measure exceeds a user-specified threshold. A minimumK-dominating set in the SNP graph was then made as the smallest subset such that every SNP that is excluded from the subset has at leastkneighbors in the selected ones. The strength of

k-dominating set selection in identifying independent variables, and in culling representative variables that are highly correlated with others, was demonstrated by a simulated dataset. The advantages ofk-dominating set variable selection were also illustrated in two applications: pedigree reconstruction using SNP profiles of 1,372 Douglas-fir trees, and species delineation for 226 grasshopper mouse samples. A C++ source code that implements SNP-SELECT and uses Gurobi™ optimization solver for thek-dominating set variable selection is available (https://github.com/transgenomicsosu/SNP-SELECT).
A population of stress-like cancer cells in melanoma promotes tumorigenesis and confers drug resistance
Authors: Baron Maayan , Tagore Mohita , Hunter Miranda V. , Kim Isabella S. , Moncada Reuben , Yan Yun , Campbell Nathaniel R. , White Richard M. , Yanai Itai
Published: August 2018

Transcriptional profiling has revealed a diverse range of cancer cell states, however an understanding of their function has remained elusive. Using a combination of zebrafish melanoma modeling and human validation, we have identified a conserved stress-like state that confers intrinsic drug resistance. The stress-like state expresses genes such asfos,hsp70andubb, all required for adaptation to diverse cellular stresses, and we confirmed its existence using immunofluorescence and spatial transcriptomics. We provide evidence that this state has a higher tumor seeding capabilities compared to non-stressed cells, and confers intrinsic resistance to MEK inhibitors, a commonly used melanoma therapeutic. Furthermore, the stress-like program can be induced by extrinsic processes such as heat shock, and confers resistance to both MEK and BRAF inhibitors in both zebrafish and human melanomas. Collectively, our study suggests that the transcriptional states associated with therapeutic failure are established during the earliest steps of tumorigenesis.
A de novoEDA-variant in a litter of shorthaired standard Dachshunds with X-linked hypohidrotic ectodermal dysplasia
Authors: Vasiliadis Danae , Hewicker-Trautwein Marion , Klotz Daniela , Fehr Michael , Ruseva Stefka , Arndt Jennifer , Metzger Julia , Distl Ottmar
Published: August 2018

In this study, we present a detailed phenotype description and genetic elucidation of the first case of X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund. This condition is characterized by partial alopecia, missing and malformed teeth and a lack of eccrine sweat glands. Clinical signs including dental X-raying and histopathological findings were consistent with an ectodermal dysplasia. Pedigree analysis supported an X-recessive mode of inheritance. Whole-genome sequencing of one affected puppy and his dam identified a 1-basepair deletion within theectodysplasin-Agene (CM000039.3:g.54509504delT, PRJEB27789). Sanger sequencing of further family members confirmed the PRJEB27789-variant. Validation in all available family members, 37 unrelated shorthaired standard Dachshunds, 128 Dachshunds from all other breeds and samples from 34 dog breeds revealed the PRJEB27789 variant to be private for this family. Two heterozygous females showed very mild alopecia but normal dentition. Since the dam is demonstrably the only heterozygous animal in the ancestry of the affected animals, we assume that the PRJEB27789-variant arose in the germline of the granddam or in an early embryonic stage of the dam. In conclusion, we detected a very recent de-novoEDAmutation causing X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund.
Gene target discovery with network analysis inToxoplasma gondii
Authors: Alonso Andres M. , Corvi Maria M. , Diambra Luis
Published: August 2018

Infectious diseases are of great relevance for global health, but needed drugs and vaccines have not been developed yet or are not effective in many cases. In fact, traditional scientific approaches with intense focus on individual genes or proteins have not been successful in providing new treatments. Hence, innovations in technology and computational methods provide new tools to further understand complex biological systems such as pathogens biology. In this work, we propose a system biology approach to analyze transcriptomic data of the parasiteToxoplasma gondii. By means of an optimization procedure, the phenotypic transitions between the stages associated with the life cycle of the parasite were embedded into the dynamics of a gene network model. Thus, through this methodology we were able to reconstruct a gene regulatory network able to emulate the life cycle of the pathogen. The community network analysis has revealed that nodes of the network can be organized in seven communities which allow us to assign putative functions to 339 previously uncharacterized genes, 25 of which are predicted as new pathogenic factors. Furthermore, we identified a small subnetwork module that controls the parasite’s life cycle. These new findings can contribute to understand of parasite pathogenesis.
Zero-preserving imputation of scRNA-seq data using low-rank approximation
Authors: Linderman George C. , Zhao Jun , Kluger Yuval
Published: August 2018

Single cell RNA-sequencing (scRNA-seq) methods have revolutionized the study of gene expression but are plagued by dropout events, a phenomenon where genes actually expressed in a given cell are incorrectly measured as unexpressed. We present a method based on low-rank approximation which successfully replaces these dropouts (zero expression levels of unobserved expressed genes) by nonzero values, while preserving biologically non-expressed genes (true biological zeros) at zero expression levels. We validate our approach and compare it to two state-of-the-art methods. We show that it recovers true expression of marker genes while preserving biological zeros, increases separation of known cell types and improves correlation of simulated cells to their true profiles. Furthermore, our method is dramatically more scalable, allowing practitioners to quickly and easily recover expression of even the largest scRNA-seq datasets.
Genome Scale Epigenetic Profiling Reveals Five Distinct Subtypes of Colorectal Cancer
Authors: Fennell Lochlan , Dumenil Troy , Hartel Gunter , Nones Katia , Bond Catherine , McKeone Diane , Bowdler Lisa , Montgomery Grant , Wockner Leesa , Klein Kerenaftali , Hoffmann Isabell , Patch Ann-Marie , Kazakoff Stephen , Pearson John , Waddell Nicola , Wirapati Pratyaksha , Lochhead Paul , Imamura Yu , Ogino Shuji , Shao Renfu , Tejpar Sabine , Leggett Barbara , Whitehall Vicki
Published: August 2018

BACKGROUND:

Colorectal cancer is an epigenetically heterogeneous disease, however the extent and spectrum of the CpG Island Methylator Phenotype (CIMP) is not clear.

RESULTS

An unselected cohort of 216 colorectal cancers clustered into five clinically and molecularly distinct subgroups using Illumina 450K DNA methylation arrays. CIMP-High cancers were most frequent in the proximal colons of female patients. These dichotomised into CIMP-Hl and CIMP-H2 based on methylation profile which was supported by over representation ofBRAF(74%, P<0.0001) orKRAS(55%, P<0.0001) mutation, respectively. Congruent with increasing methylation, there was a stepwise increase in patient age from 62 years in the CI MP-Negative subgroup to 75 years in the CIMP-Hl subgroup (P<0.0001). There was a striking association between PRC2-marked loci and those subjected to significant gene body methylation in CIMP-type cancers (P<1.6xl078). We identified oncogenes susceptible to gene body methylation and Wnt pathway antagonists resistant to gene body methylation. CIMP cluster specific mutations were observed for genes involved in chromatin remodelling, such as in the SWI/SNF and NuRD complexes, suggesting synthetic lethality.

CONCLUSION

There are five clinically and molecularly distinct subgroups of colorectal cancer based on genome wide epigenetic profiling. These analyses highlighted an unidentified role for gene body methylation in progression of serrated neoplasia. Subgroup-specific mutation of distinct epigenetic regulator genes revealed potentially druggable vulnerabilities for these cancers, which may provide novel precision medicine approaches.
GxEMM: Extending linear mixed models to general gene-environment interactions
Authors: Dahl Andy , Cai Na , Flint Jonathan , Zaitlen Noah
Published: August 2018

Gene-environment interaction (GxE) is a well-known source of non-additive inheritance. GxE can be important in applications ranging from basic functional genomics to precision medical treatment. Further, GxE effects elude inherently-linear LMMs and may explain missing heritability. We propose a simple, unifying mixed model for polygenic interactions (GxEMM) to capture the aggregate effect of small GxE effects spread across the genome. GxEMM extends existing LMMs for GxE in two important ways. First, it extends to arbitrary environmental variables, not just categorical groups. Second, GxEMM can estimate and test for environment-specific heritability. In simulations where the assumptions of existing methods do not hold, we show that GxEMM improves estimates of ordinary and GxE heritability and increases power to test for polygenic GxE. We then use GxEMM to prove that the heritability of major depression (MD) is reduced by stress, which we previously conjectured but could not prove with prior methods, and that a tail of polygenic GxE effects remains unexplained by MD GWAS.
Systematic evaluation of the causal relationship between DNA methylation and C-reactive protein
Authors: Walton Esther , Hemani Gibran , Dehghan Abbas , Relton Caroline , Smith George Davey
Published: August 2018

Elevated C-reactive protein (CRP) levels are an indicator of chronic low-grade inflammation. Epigenetic modifications, including DNA methylation, have been linked to CRP, but systematic investigations into potential underlying causal relationships have not yet been performed.

We systematically performed two-sample Mendelian randomization and colocalization analysis between CRP and DNA methylation levels, using GWAS and EWAS summary statistics as well as individual level data available through the ARIES subset of the Avon Longitudinal Study of Parents and Children (ALSPAC; 1,616 participants).

We found no convincing examples for a causal association from CRP to DNA methylation. Testing for the reverse (a putative causal effect of DNA methylation on CRP), we found three CpG sites that had shared genetic effects with CRP levels after correcting for multiple testing (cg26470501 (offspring: beta=0.07 [0.03, 0.11]; mothers: beta=0.08 [0.04, 0.13]), cg27023597 (offspring: beta=0.18 [0.10, 0.25]; mothers: beta=0.20 [0.12, 0.28]) and cg12054453 (offspring: beta=0.09 [0.05, 0.13])) influenced CRP levels. For all three CpG sites, linked to the genes TMEM49, BCL3 and MIR21, increased methylation related to an increase in CRP levels. Two CpGs (cg27023597 and cg12054453) were influenced by SNPs in genomic regions that had not previously been implicated in CRP GWASs, implicating them as novel genetic associations.

Overall, our findings suggest that CRP associations with DNA methylation are more likely to be driven by either confounding or causal influences of DNA methylation on CRP levels, rather than the reverse.
Combinatorial recognition of clustered RNA elements by a multidomain RNA-binding protein, IMP3
Authors: Schneider Tim , Hung Lee-Hsueh , Aziz Masood , Wilmen Anna , Thaum Stephanie , Wagner Jacqueline , Janowski Robert , Müller Simon , Hüttelmaier Stefan , Niessing Dierk , Sattler Michael , Schlundt Andreas , Bindereif Albrecht
Published: August 2018

How multidomain RNA-binding proteins recognize their specific target sequences, based on a combinatorial code, represents a fundamental unsolved question and has not been studied systematically so far. Here we focus on a prototypical multidomain RNA-binding protein, IMP3 (also called IGF2BP3), which contains six RNA-binding domains (RBDs): four KH and two RRM domains. We have established an integrative systematic strategy, combining single-domain-resolved SELEX-seq, motif-spacing analyses,in vivoiCLIP, functional validation assays, and structural biology. This approach identifies the RNA-binding specificity and RNP topology of IMP3, involving all six RBDs and a cluster of up to five distinct and appropriately spaced CA-rich and GGC-core RNA elements, covering a >100 nucleotide-long target RNA region. Our generally applicable approach explains both specificity and flexibility of IMP3-RNA recognition, providing a paradigm for the function of multivalent interactions with multidomain RNA-binding proteins in gene regulation.
LION/web: a web-based ontology enrichment tool for lipidomic data analysis
Authors: Molenaar Martijn R. , Jeucken Aike , Wassenaar Tsjerk A. , van de Lest Chris H. A. , Brouwers Jos F. , Helms J. Bernd
Published: August 2018

A major challenge for lipidomic analyses is the handling of the large amounts of data and the translation of results to interpret the involvement of lipids in biological systems. We built a new lipid ontology (LION) that associates over 50,000 lipid species to biophysical, chemical and cell biological features. By making use of enrichment algorithms, we used LION to develop a web-based interface (LION/web, www.lipidontology.com) that allows identification of lipid-associated terms in lipidomes. LION/web was validated by analyzing a lipidomic dataset derived from well-characterized sub-cellular fractions of RAW 264.7 macrophages. Comparison of isolated plasma membranes with the microsomal fraction showed a significant enrichment of relevant LION-terms including ‘plasma membrane’, ‘headgroup with negative charge, ‘glycerophosphoserines’, ‘above average bilayer thickness’, and ‘below average lateral diffusion’. A second validation was performed by analyzing the membrane fluidity of CHO cells incubated with arachidonic acid. An increase in membrane fluidity was observed both experimentally by using pyrene decanoic acid and by using LION/web, showing significant enrichment of terms associated with high membrane fluidity ('above average’, 'very high’ and 'high lateral diffusion’, and 'below average transition temperature’). The results demonstrate the functionality of LION/web, which is freely accessible in a platform-independent way.
Hypomethylation ofSTAT1andHLA-DRB1is associated with type-I interferon-dependentHLA-DRB1expression in lupus CD8+ T cells
Authors: Miller Shaylynn , Coit Patrick , Gensterblum-Miller Elizabeth , Renauer Paul , Kilian Nathan C , Schonfeld Mark , Tsou Pei-Suen , Sawalha Amr H
Published: August 2018

Objective

We examined genome-wide DNA methylation changes in CD8+ T cells from lupus patients and controls, and investigated the functional relevance of some of these changes in lupus.

Methods

Genome-wide DNA methylation of lupus and age, sex, and ethnicity-matched control CD8+ T cells was measured using the Infinium MethylationEPIC arrays. Measurement of relevant cell subsets was performed via flow cytometry. Gene expression was quantified by qPCR.

Results

Lupus CD8+ T cells had 188 hypomethylated CpG sites compared to healthy matched controls. Among the most hypomethylated were sites associated withHLA-DRB1. Genes involved in the type-I interferon response, includingSTAT1, were also found to be hypomethylated. IFNα upregulated HLA-DRB1 expression on lupus but not control CD8+ T cells. Lupus and control CD8+ T cells significantly increased STAT1 mRNA levels after treatment with IFNα. The expression of CIITA, a key interferon/STAT1 dependent MHC-class II regulator, is induced by IFNα in lupus CD8+ T cells, but not healthy controls. Co-incubation of naïve CD4+ T cells with IFNα-treated CD8+ T cells led to CD4+ T cell activation, determined by increased expression of CD69, in lupus patients but not in healthy controls. This can be blocked by neutralizing antibodies targeting HLA-DR.

Conclusions

Lupus CD8+ T cells are epigenetically primed to respond to type-I interferon. We describe an HLA-DRB1+ CD8+ T cell subset that can be induced by IFNα in lupus patients. A possible pathogenic role for CD8+ T cells in lupus that is dependent upon a high type-I interferon environment and epigenetic priming warrants further characterization.
Synthetic and genomic regulatory elements reveal aspects of cis regulatory grammar in Mouse Embryonic Stem Cells
Authors: King Dana M. , Maricque Brett B. , Cohen Barak A.
Published: August 2018

In embryonic stem cells (ESCs), a core network of transcription factors establish and maintain the gene expression program necessary to grow indefinitely in cell culture and generate all three primary germ layers. To understand how interactions between four key pluripotency transcription factors (TFs), SOX2, POU5F1 (OCT4), KLF4, and ESRRB, contribute to cis-regulation in mouse ESCs, we assayed two massively parallel reporter assay (MPRA) libraries composed of different combinations of binding sites for these TFs. One library was an exhaustive set of synthetic cis-regulatory elements and the second was a set of genomic sequences with comparable configurations of binding sites. Comparisons between the libraries allowed us to determine the regulatory grammar requirements for these binding sites in constrained synthetic contexts versus genomic sequence contexts. We found that binding site quality is a common attribute for active elements in both the synthetic and genomic contexts. For synthetic regulatory elements, the level of expression is mostly determined by the number of binding sites but is tuned by a grammar that includes position effects. Surprisingly, this grammar appears to only play a small role in setting the output levels of genomic sequences. The relative activity of genomic sequences is best explained by the predicted affinity of binding sites, regardless of identity, and optimized spacing between sites. Our findings highlight the need for detailed examinations of complex sequence space when trying to understand cis-regulatory grammar in the genome.
Effect of Platelet-activating factor on barrier function of ARPE-19 cells
Authors: Zhang Fan , Liu Lei , Zhang Han , Liu Zhe-Li
Published: August 2018

PURPOSE:

To examine the effects of platelet-activating factor (PAF) on tight junction permeability in cultured retinal pigment epithelial (RPE) cells.

METHODS:

A human RPE cell line (ARPE-19) cultured on microporous filter supports was used. PAF and WEB2086, which is a specific PAF-receptor (PAF-R) antagonist, were added to the culture medium. RPE monolayer permeability was measured using transepithelial electrical resistance (TER) and sodium fluorescein flux. The expression of the tight junction protein zonula occludens (ZO)-1 was assessed using immunohistochemistry. We also measured the vascular endothelial growth factor (VEGF) level in cultures treated with PAF, and RPE monolayer permeability was measured again in the presence of neutralizing antibodies to VEGF.

RESULTS:

PAF significantly decreased the TER of the RPE monolayer and enhanced sodium fluorescein flux. ZO-1 expression was downregulated in PAF-supplemented medium. These effects were abolished with PAF-R blockage. PAF stimulation increased VEGF expression in RPE cells, and neutralization of VEGF with antibodies caused partial recovery of barrier properties.

CONCLUSIONS:

The tight junctions of ARPE-19 cells are altered by PAF, and these effects are partly mediated by the upregulation of VEGF expression in these cells. Our results contribute to growing evidence supporting the role of PAF in choroidal neovascularization, and our findings suggest that PAF is a novel therapeutic target for increased permeability of the RPE monolayer.
STAT3 is a master regulator of epithelial identity and KRAS-driven tumorigenesis
Authors: D'Amico Stephen , Shi Jiaqi , Martin Benjamin L. , Crawford Howard C. , Petrenko Oleksi , Reich Nancy C.
Published: August 2018

A dichotomy exists regarding the role of signal transducer and activator of transcription 3 (STAT3) in cancer. Functional and genetic studies demonstrate either an intrinsic requirement for STAT3 or a suppressive effect on common types of cancer. These contrasting actions of STAT3 imply context dependency. To examine mechanisms that underlie STAT3 function in cancer, we evaluated the impact of STAT3 activity in KRAS-driven lung and pancreatic cancer. Our study defines a fundamental and previously unrecognized function of STAT3 in the maintenance of epithelial cell identity and differentiation. Loss of STAT3 preferentially associates with the acquisition of mesenchymal-like phenotypes and more aggressive tumor behavior. In contrast, persistent STAT3 activation through Tyr705 phosphorylation confers a differentiated epithelial morphology that impacts tumorigenic potential. Our results imply a mechanism in which quantitative differences of STAT3 Tyr705 phosphorylation, as compared with other activation modes, direct discrete outcomes in tumor progression.
Phenotypically distinct female castes in honey bees are defined by alternative chromatin states during larval development
Authors: Wojciechowski Marek , Lowe Robert , Maleszka Joanna , Conn Danyal , Maleszka Ryszard , Hurd Paul J.
Published: August 2018

The capacity of the honey bee to produce three phenotypically distinct organisms (two female castes; queens and sterile workers, and haploid male drones) from one genotype represents one of the most remarkable examples of developmental plasticity in any phylum. The queen–worker morphological and reproductive divide is environmentally controlled during post-embryonic development by differential feeding. Previous studies implicated metabolic flux acting via epigenetic regulation, in particular DNA methylation and microRNAs, in establishing distinct patterns of gene expression underlying caste-specific developmental trajectories. We produce the first genome-wide maps of chromatin structure in the honey bee at a key larval stage in which developmental canalization into queen or worker is virtually irreversible. We find extensive genome-wide differences in H3K4me3, H3K27ac, and H3K36me3, many of which correlate with caste-specific transcription. Furthermore, we identify H3K27ac as a key chromatin modification, with caste-specific regions of intronic H3K27ac directing the worker caste. These regions may harbor the first examples of caste-specific enhancer elements in the honey bee. Our results demonstrate a key role for chromatin modifications in the establishment and maintenance of caste-specific transcriptional programs in the honey bee. We show that at 96 h of larval growth, the queen-specific chromatin pattern is already established, whereas the worker determination is not, thus providing experimental support for the perceived timing of this critical point in developmental heterochrony in two types of honey bee females. In a broader context, our study provides novel data on environmentally regulated organismal plasticity and the molecular foundation of the evolutionary origins of eusociality.
Classification of ab initio models of proteins restored from small-angle X-ray scattering
Authors: Oide Mao , Sekiguchi Yuki , Fukuda Asahi , Okajima Koji , Oroguchi Tomotaka , Nakasako Masayoshi
Published: August 2018

In structure analyses of proteins in solution by using small-angle X-ray scattering (SAXS), the molecular models are restored by using ab initio molecular modeling algorithms. There can be variation among restored models owing to the loss of phase information in the scattering profiles, averaging with regard to the orientation of proteins against the direction of the incident X-ray beam, and also conformational fluctuations. In many cases, a representative molecular model is obtained by averaging models restored in a number of ab initio calculations, which possibly provide nonrealistic models inconsistent with the biological and structural information about the target protein. Here, a protocol for classifying predicted models by multivariate analysis to select probable and realistic models is proposed. In the protocol, each structure model is represented as a point in a hyper-dimensional space describing the shape of the model. Principal component analysis followed by the clustering method is applied to visualize the distribution of the points in the hyper-dimensional space. Then, the classification provides an opportunity to exclude nonrealistic models. The feasibility of the protocol was examined through the application to the SAXS profiles of four proteins.
Keep them on-board! How organizations can develop employee embeddedness to increase employee retention
Authors: Ma Qing Kathy , Mayfield Milton , Mayfield Jacqueline
Published: August 2018

Purpose

This paper aims to examine how companies can increase employee retention through job embeddedness.

Design/methodology/approach

The authors adopted a job embeddedness perspective to explain how different components of job embeddedness-fit, links, and sacrifice can contribute to employee retention.

Findings

The authors developed a practical model of employee retention by building job embeddedness into employee recruitment, selection, training, and development processes and provided a variety of easy-to-implement organizational practices.

Originality/value

This paper introduced job embeddedness as a new way to increase employee retention and developed a practical model for managers to develop HR practices for retaining their top talent.
Modified chain sampling plan for assuring percentile life under Weibull distribution and generalized exponential distribution
Authors: P. Jeyadurga , Mahalingam Usha , Balamurali Saminathan
Published: August 2018

Purpose

The purpose of this paper is to design a modified chain sampling plan for assuring the product percentile life where the lifetime follows Weibull or generalized exponential distributions (GEDs). In order to reduce the cost of inspection when implementing the proposed modified chain sampling plan, it is also considered the economic aspect of designing of proposed plan in this paper.

Design/methodology/approach

The authors have designed the proposed plan on the basis of two points on the operating characteristic (OC) curve approach. The optimization problem is used to determine the plan parameters of the proposed plan so that the specified values of producer’s risk and consumer’s risk are satisfied simultaneously.

Findings

The results we have obtained, confirm that the proposed plan will be very effective in reducing the sample size rather than other existing sampling plans. The OC curves of proposed plan, chain sampling plan and zero acceptance number single sampling plan show that the performance of proposed plan in discriminating the good and poor quality lots is better than other two plans. In this paper, it is proved that the value of number of preceding lots required for current lot disposition plays an important role.

Originality/value

The proposed modified chain sampling plan for assuring the percentile lifetime of the products under Weibull or GEDs is not available in the literature. The proposed plan can be used in all the manufacturing industries to assure the product percentile lifetime with minimum sample size as well as minimum cost.
Assessing risk through composite FMEA with pairwise matrix and Markov chains
Authors: Brun Alessandro , Savino Matteo Mario
Published: August 2018

Purpose

Failure mode and effect analysis (FMEA) is an analysis technique for identifying and eliminating known and/or potential failures and problems from products, processes or systems. Notwithstanding its diffusion, traditional FMEA has several limitations. Lately, scientific research has been focused on improving said limitations, yet the process is still ongoing. The purpose of this paper is to support developments in this area.

Design/methodology/approach

The paper improves the conventional FMEA by using the method of pairwise comparison to establish the relative importance of the input factors in risk priority number calculation, and Markov chains to calculate risk distributions in the long term.

Findings

The functioning and usefulness of the proposed methodology is demonstrated through an application to the construction industry, one of the world’s biggest industrial sectors, dogged by a high rate of work-related injuries and casualties.

Originality/value

Having demonstrated the applicability of the novel methodology to a real domain, the paper contributes to the process of overcoming traditional FMEA limitations.
Total productive maintenance, kaizen event, and performance
Authors: Habidin Nurul Fadly , Hashim Suzaituladwini , Fuzi Nursyazwani Mohd , Salleh Mad Ithnin
Published: August 2018

Purpose

The purpose of this paper is to determine the relationship between total productive maintenance (TPM), kaizen event (KE) and innovation performance (IP) for Malaysian automotive industry using structural equation modeling (SEM).

Design/methodology/approach

The samples were selected from the list of Proton and Perodua automotive industry. The number of collected respondents was 238 respondents. An SEM technique was used in the study. In order to test the reliability and validity of the instrument, reliability analysis, exploratory and confirmatory factor analysis were conducted.

Findings

Based on the results, KE does not affect the relationship between TPM and IP. However, the impact of TPM on IP increases with mediating of KE for Malaysian automotive industry. Thus, this study has shown that empirical test results prove that the implementation of TPM and KE has improved the IP for Malaysian automotive industry.

Research limitations/implications

This study only focused on the Malaysian automotive industry. The other limitation in this research is the number of factors and limited measurement in this study. Only a few TPM, KE and IP measurements were considered. By using the SEM technique, four TPM constructs, three for KE constructs and three for IP measures were developed and verified. Therefore, this study can assist the researchers and practitioners to the practice of TPM, KE and IP for Malaysian automotive industry.

Originality/value

This research provides fundamental knowledge and direction for researchers in further research as well as practitioners to constantly improve IP through the implementation of TPM and KE for Malaysian automotive industry.
Optimal composition of hybrid/blended real estate portfolios
Authors: Ametefe Frank Kwakutse , Devaney Steven , Stevenson Simon Andrew
Published: August 2018

Purpose

The purpose of this paper is to establish an optimum mix of liquid, publicly traded assets that may be added to a real estate portfolio, such as those held by open-ended funds, to provide the liquidity required by institutional investors, such as UK defined contribution pension funds. This is with the objective of securing liquidity while not unduly compromising the risk-return characteristics of the underlying asset class. This paper considers the best mix of liquid assets at different thresholds for a liquid asset allocation, with the performance then evaluated against that of a direct real estate benchmark index.

Design/methodology/approach

The authors employ a mean-tracking error optimisation approach in determining the optimal combination of liquid assets that can be added to a real estate fund portfolio. The returns of the optimised portfolios are compared to the returns for portfolios that employ the use of either cash or listed real estate alone as a liquidity buffer. Multivariate generalised autoregressive models are used along with rolling correlations and tracking errors to gauge the effectiveness of the various portfolios in tracking the performance of the benchmark index.

Findings

The results indicate that applying formal optimisation techniques leads to a considerable improvement in the ability of the returns from blended real estate portfolios to track the underlying real estate market. This is the case at a number of different thresholds for the liquid asset allocation and in cases where a minimum return requirement is imposed.

Practical implications

The results suggest that real estate fund managers can realise the liquidity benefits of incorporating publicly traded assets into their portfolios without sacrificing the ability to deliver real estate-like returns. However, in order to do so, a wider range of liquid assets must be considered, not just cash.

Originality/value

Despite their importance in the real estate investment industry, comparatively few studies have examined the structure and operation of open-ended real estate funds. To the authors’ knowledge, this is the first study to analyse the optimal composition of liquid assets within blended or hybrid real estate portfolios.
Dependency of flow and transport properties on aperture distributions and compression states
Authors: Ma Joseph H.Y. , Li Yunyue Elita , Cheng Arthur
Published: August 2018

Fluid conductivity and elastic properties in fractures depend on the aperture geometry – in particular, the roughness of fracture surfaces. In this study, we have characterized the surface roughness with a log‐normal distribution and investigated the transport and flow behaviour of the fractures with varying roughness characteristics. Numerical flow and transport simulations have been performed on a single two‐dimensional fracture surface, whose aperture geometry changes with different variances and correlation lengths in each realization. We have found that conventional measurement of hydraulic conductivity alone is insufficient to determine these two parameters. Transient transport measurements, such as the particle breakthrough time, provide additional constraints to the aperture distribution. Nonetheless, a unique solution to the fracture aperture distribution is still under‐determined with both hydraulic conductivity and transport measurements. From numerical simulations at different compression states, we have found that the flow and transport measurements exhibit different rates of changes with respect to changes in compression. Therefore, the fracture aperture distribution could be further constrained by considering the flow and transport properties under various compression states.
Primary Contact Occupational Therapy Hand Clinics: The pull of an occupational perspective
Authors: Burley Samantha , Cox Ruth , Di Tommaso Amelia , Molineux Matthew
Published: August 2018

Background/aim

Primary contact models of care are an emerging area of occupational therapy practice that aim to respond to the changing health‐care landscape. There is a dearth of literature exploring an occupational perspective in primary contact roles, and literature in the broader scope of hand therapy has recognised that occupational therapists’ practice often aligns with the biomedical worldview. Therefore, this study aimed to explore the practice of occupational therapists within Primary Contact Occupational Therapy Hand (PCOTH) Clinics from an occupational perspective.

Method

This ethnographic study gathered in‐depth data through observations of primary contact hand therapy sessions, review of progress notes and interviews with occupational therapists. Qualitative data analysis was conducted using a three‐stage process first at the item level, then pattern level and finally at the structural level. The research team collaboratively discussed all codes and then themes.

Results

The push of the biomedical culture and the pull of an occupational perspective was conceptualised as an overarching theme shaping occupational therapists’ practice in the primary contact clinics. Five themes emerged: bottom‐up approach to an occupational perspective, an occupational perspective via informal discussion, occupational therapists’ expectations of patients, occupational perspective on autopilot and blurred professional identity.

Conclusion

Occupational therapists working in primary contact roles were pushed by the biomedical culture of the setting. Despite this, there was still a pull towards an occupational perspective. This research provides an initial exploration of primary contact clinics, and highlighted the added bonus of an occupational perspective. The findings present a timely opportunity for occupational therapists to critically reflect on practice in PCOTH clinics.
Hume, Bishop Butler, and the Revival of Ritual in Anglophone Protestantism
Authors: Savonius‐Wroth Celestina
Published: August 2018

A sweeping reassessment of the role of ritual, ceremony, and aesthetics took place in anglophone Protestantism between the late eighteenth and the late nineteenth centuries. While the nineteenth‐century developments themselves have been extensively studied, little scholarly attention has been paid to the importance of the earlier emergence of philosophical language capable of explaining and justifying, in a Protestant context, the ritual and aesthetic dimensions of religious practice. I argue that this language, paradoxically, grew out of a symbiosis of sceptical modernity, traditional religious apologetics, and the religious “enthusiasm” of the early eighteenth century. I approach the topic through the interconnected oeuvres (and careers) of David Hume and Joseph Butler, presenting the first synoptic account of their ideas about the psychological underpinnings of religious worship, and the use made of their ideas by later generations of anglophone Protestants. As mainstream Anglicans, Episcopalians, and Presbyterians confronted the challenges presented by Methodism and Evangelicalism, they found support in a synthesis of Butler's and Hume's ideas. Eventually, the beneficial role of ritual and aesthetics in religious worship came to be widely accepted throughout the anglophone Protestant world.
Milner and the Miraculous in Post‐Enlightenment England
Authors: DeStefano Michael
Published: August 2018

In post‐Enlightenment England Catholic Bishop John Milner wrote repeatedly about miracles. He defended the continuation of miracles in contrast to Protestant thinkers who believed that miracles had ceased after the apostolic age. Milner held that miracles supported the truth of Catholicism, distinguished it from Protestantism and provided consolation to Catholics. Milner criticised a report in which fellow Catholic Joseph Berington rejected the miraculous nature of events at Ancona, Italy in 1796 where a painting of the Virgin Mary purportedly moved its eyes. Upon becoming a bishop he investigated a cure that occurred at St Winefrid's Holywell and found that the cure was miraculous. Milner participated in the debate over the miracles of Prince Hohenlohe, the wonder‐working German priest, and found in the priest's favour. Given that Protestants for three hundred years had attacked post‐scriptural miracles, and that modern philosophers rejected all miracles, Milner's views appeared to be reactionary. Nevertheless, his views were not immune to historical developments, and he thought of himself as a sharp critic of excessive belief in miracles. Although his views anticipated a revival of miracle piety in English Catholicism, he could not prevent the long‐term decline of the miracle apologetic.
Complex in memory, mind in matter: walking hand in hand
Authors: Caetano Aurea Afonso , Machado Teresa Cristina
Published: August 2018

This paper aims to highlight four major points: first: a ‘Jungian attitude’ understood as a viewpoint which enables work with interconnectedness through various fields of knowledge. Second, that complexes are dynamic, as is memory, and that both are transformed by experience and develop hand in hand with each other i.e., the transformation of the complex occurs through the transformation of memory as embodied in internal working models, and vice versa. Third, complexes and archetypes are linked to each other in matrices of one form or another and lead to the complexity of the psyche, which is a developing system. Fourth, the analytical process provides an arena that enables and consolidates interconnections that foster a better intrapsychic transition. The analytic meeting promotes profound changes, redesigning our neural architecture as well as our psychic landscape.
Admission cardiotocography versus intermittent auscultation of the fetal heart in low‐risk pregnancy during evaluation for possible labour admission – a multicentre randomised trial: the ADCAR trial
Authors: Smith V , Begley C , Newell J , Higgins S , Murphy DJ , White MJ , Morrison JJ , Canny S , O'Donovan D , Devane D
Published: August 2018

Objective

To assess the effect of admission cardiotocography (ACTG) versus intermittent auscultation (IA) of the fetal heart (FH) in low‐risk pregnancy during assessment for possible labour on caesarean section rates.

Design

A parallel multicentre randomised trial.

Setting

Three maternity units in the Republic of Ireland.

Population

Healthy, low‐risk pregnant women, at term and ≥ 18 years old, who provided written informed consent.

Methods

Women were randomised to receive IA of the FH or 20 minutes ACTG on admission for possible labour onset, using remote telephone randomisation. Both groups received IA during labour, with conversion to continuous CTG as clinically indicated.

Main outcome measures

Caesarean section (primary outcome), obstetric interventions (e.g. continuous CTG during labour, fetal blood sampling, augmentation of labour) and neonatal morbidity (e.g. metabolic acidosis, admission to the neonatal intensive care unit, neonatal death).

Results

Based on 3034 women (1513 and 1521 randomised to IA and ACTG, respectively), there was no statistical difference between the groups in caesarean section [130 (8.6%) and 105 (6.9%) for IA and ACTG groups, respectively; relative risk (RR) 1.24; 95% CI 0.97–1.58], or in any other outcome except for use of continuous CTG during labour, which was lower in the IA group (RR 0.90, 95% CI 0.86–0.93).

Conclusion

Our study demonstrates no differences in obstetric or neonatal outcomes between IA and ACTG for women with possible labour onset, other than an increased risk for continuous CTG in women receiving ACTG.

Tweetable abstract

No differences in outcomes between intermittent auscultation and admission cardiotocography for women with possible labour onset.