bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional phenomics: An emerging field integrating high-throughput phenotyping, physiology, and bioinformatics
Authors: York Larry M. 
Published: July 2018

HighlightFunctional phenomics is an emerging field in plant biology that relies on high-throughput phenotyping, big data analytics, controlled manipulative experiments, and simulation modelling to increase understanding of plant physiology.AbstractThe emergence of functional phenomics signifies the rebirth of physiology as a 21st century science through the use of advanced sensing technologies and big data analytics. Functional phenomics highlights the importance of phenotyping beyond only identifying genetic regions because a significant knowledge gap remains in understanding which plant properties will influence ecosystem services beneficial to human welfare. Here, a general approach for the theory and practice of functional phenomics is outlined including exploring the phene concept as a unit of phenotype. The functional phenomics pipeline is proposed as a general method for conceptualizing, measuring, and validating utility of plant phenes. The functional phenomics pipeline begins with ideotype development. Second, a phenotyping platform is developed to maximize the throughput of phene measurements. A mapping population is screened measuring target phenes and indicators of plant performance such as yield and nutrient composition. Traditional forward genetics allows genetic mapping, while functional phenomics links phenes to plant performance. Based on these data, genotypes with contrasting phenotypes can be selected for smaller yet more intensive experiments to understand phene-environment interactions in depth. Simulation modeling can be used to understand the phenotypes and all stages of the pipeline feed back to ideotype and phenotyping platform development.
MSTD: an efficient method for detecting multi-scale topological domains from symmetric and asymmetric 3D genomic maps
Authors: Ye Yusen , Gao Lin , Zhang Shihua 
Published: July 2018

AbstractThe chromosome conformation capture (3C) technique and its variants have been employed to reveal the existence of a hierarchy of structures in three-dimensional (3D) chromosomal architecture, including compartments, topologically associating domains (TADs), sub-TADs and chromatin loops. However, existing methods for domain detection were only designed based on symmetric Hi-C maps, ignoring long-range interaction structures between domains. To this end, we proposed a generic and efficient method to identify multi-scale topological domains (MSTD), including cis- and trans-interacting regions, from a variety of 3D genomic datasets. We first applied MSTD to detect promoter-anchored interaction domains (PADs) from promoter capture Hi-C datasets across 17 primary blood cell types. The boundaries of PADs are significantly enriched with one or the combination of multiple epigenetic factors. Moreover, PADs between functionally similar cell types are significantly conserved in terms of domain regions and expression states. Cell type-specific PADs involve in distinct cell type-specific activities and regulatory events by dynamic interactions within them. We also employed MSTD to define multi-scale domains from typical symmetric Hi-C datasets and illustrated its distinct superiority to the-state-of-art methods in terms of accuracy, flexibility and efficiency.
The phospholamban pentamer interacts with the sarcoplasmic reticulum calcium pump SERCA
Authors: Glaves J. P. , Primeau J. O. , Espinoza-Fonseca L. M. , Lemieux M. J. , Young H. S. 
Published: July 2018

ABSTRACTThe interaction of phospholamban with the sarcoplasmic reticulum calcium pump (SERCA) is a major regulatory axis in cardiac muscle contractility. The prevailing model involves reversible inhibition of SERCA by monomeric phospholamban and storage of phospholamban as an inactive pentamer. However, this paradigm has been challenged by studies demonstrating that phospholamban remains associated with SERCA and that the phospholamban pentamer is required for cardiac contractility. We have previously used two-dimensional crystallization and electron microscopy to study the interaction between SERCA and phospholamban. To further understand this interaction, we compared small helical crystals and large two-dimensional crystals of SERCA in the absence and presence of phospholamban. In both crystal forms, SERCA molecules are organized into identical anti-parallel dimer ribbons. The dimer ribbons pack together with distinct crystal contacts in the helical versus large two-dimensional crystals, which allow phospholamban differential access to potential sites of interaction with SERCA. Nonetheless, we show that a phospholamban oligomer interacts with SERCA in a similar manner in both crystal forms. In the two-dimensional crystals, a phospholamban pentamer interacts with transmembrane segments M3 of SERCA and participates in a crystal contact that bridges neighboring SERCA dimer ribbons. In the helical crystals, an oligomeric form of phospholamban also interacts with M3 of SERCA, though the phospholamban oligomer straddles a SERCA-SERCA crystal contact. We conclude that the pentameric form of phospholamban interacts with SERCA, and that it plays distinct structural and functional roles in SERCA regulation.
Receptor-ligand rebinding kinetics in confinement
Authors: Erbaş A. , Olvera de la Cruz M. , Marko J. F. 
Published: July 2018

ABSTRACTRebinding kinetics of molecular ligands plays a critical role in biomachinery, from regulatory networks to protein transcription, and is also a key factor for designing drugs and high-precision biosensors. In this study, we investigate initial release and rebinding of ligands to their binding sites grafted on a planar surface, a situation commonly observed in single molecule experiments and which occurs during exocytosisin vivo. Via scaling arguments and molecular dynamic simulations, we analyze the dependence of non-equilibrium rebinding kinetics on two intrinsic length scales: average separation distance between the binding sites and dimensions of diffusion volume (e.g., height of the experimental reservoir in which diffusion takes place or average distance between receptor-bearing surfaces). We obtain time-dependent scaling laws for on rates and for the cumulative number of rebinding events (the time integral of on rates) for various regimes. Our analyses reveal that, for diffusion-limited cases, the on rate decreases via multiple power law regimes prior to the terminal steady-state regime, in which the on rate becomes constant. At intermediate times, at which particle density has not yet become uniform throughout the reservoir, the number of rebindings exhibits a distinct plateau regime due to the three dimensional escape process of ligands from their binding sites. The duration of this regime depends on the average separation distance between binding sites. Following the three-dimensional diffusive escape process, a one-dimensional diffusive regime describes on rates. In the reaction-limited scenario, ligands with higher affinity to their binding sites (e.g., longer residence times) delay the power laws. Our results can be useful for extracting hidden time scales in experiments where kinetic rates for ligand-receptor interactions are measured in microchannels, as well as for cell signaling via diffusing molecules.
A novel virulence phenotype rapidly assesses Candida fungal pathogenesis in healthy and immunocompromised Caenorhabditis elegans hosts
Authors: Feistel Dorian J. , Elmostafa Rema , Nguyen Nancy , Penley McKenna , Morran Levi , Hickman Meleah A. 
Published: July 2018

AbstractThe yeast Candida albicans is an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. While C. albicans is the predominant species isolated in the human mycobiome and implicated in fungal infection, infections due to non-albicans Candida species are rapidly rising. Studying the factors that contribute to virulence is often challenging and frequently depends on many contexts including host immune status and pathogen genetic background. Here, we utilize the nematode Caenorhabditis elegans as a perspicuous and efficient model host system to study fungal infections of Candida pathogens. We find that in addition to reducing lifetime host survival, exposure to C. albicans results in delayed reproduction, which significantly reduced lineage growth over multiple generations. Furthermore, we assessed fungal pathogen virulence in C. elegans hosts compromised for innate immune function and detected increased early mortality, reduced brood sizes and delayed reproduction relative to infected healthy hosts. Importantly, by assessing virulence in both healthy and immunocompromised host backgrounds we reveal the pathogen potential in non-albicans Candida species. Taken together, we present a novel lineage growth assay to measure reduction in host fitness associated with fungal infection and demonstrate significant interactions between pathogen and host immune function that contribute to virulence.
Study of Sterilization Effects on Marine Vibrio sp. using Interaction of Cavitation with Shock Wave in a Narrow Water Chamber
Authors: Wang J. , Abe A. , Koita T. , Sun M. , Wang Y. , Huang C. 
Published: July 2018

AbstractWhen underwater shock waves are generated by an electric discharge in a narrow water chamber, the instant release of a great amount of energy causes the propagation of a shear wave in wall material with the deformation of the chamber wall. The shear waves produce decompression in water and result in the growth of bubble nuclei. Subsequently, those oscillating cavitation bubbles are exposed to the shock pressures, and thus free radicals and rebound shock waves are generated due to their violent collapses. Eventually, marine bacteria around them are inactivated by these productions. In the present study, we investigate the sterilization effects of these oscillating bubbles and cavitation-shock interaction by bio-experiments, respectively. Furthermore, the chemical action of free radicals on marine bacteria is discussed. The generation of the OH radicals is clarified by measuring the concentration of the H2O2. To estimate the generation condition of the OH radicals, a bubble dynamic model consisting of an oscillation model for the growth of bubble nuclei and an impact model to describe the cavitation-shock interaction is developed. Finally, the theoretical estimation by the bubble dynamic model is discussed under the conditions of the present experiments.
Massively parallel characterization of regulatory dynamics during neural induction
Authors: Inoue Fumitaka , Kreimer Anat , Ashuach Tal , Ahituv Nadav , Yosef Nir 
Published: July 2018

AbstractThe molecular components governing neural induction remain largely unknown. Here, we applied a suite of genomic and computational tools to comprehensively identify these components. We performed RNA-seq, ChIP-seq (H3K27ac, H3K27me3) and ATAC-seq on human embryonic stem cells (hESCs) at seven early neural differentiation time points (0-72 hours) and identified thousands of induced genes and regulatory regions. We analyzed the function of ~2,500 selected regions using massively parallel reporter assays at all time points. We found numerous temporal enhancers that correlated with similarly timed epigenetic marks and gene expression. Development of a prioritization method that incorporated all genomic data identified key transcription factors (TFs) involved in neural induction. Individual overexpression of eleven TFs and several combinations in hESCs found novel neural induction regulators. Combined, our results provide a comprehensive map of genes and functional regulatory elements involved in neural induction and identify master regulator TFs that are instrumental for this process.One Sentence SummaryUsing numerous genomic assays and computational tools we characterized the dynamic changes that take place during neural induction.
Toxoplasma does not secrete the GRA16 and GRA24 effectors beyond the parasitophorous vacuole membrane of tissue cysts
Authors: Krishnamurthy Shruthi , Saeij Jeroen PJ 
Published: July 2018

AbstractAfter invasion, Toxoplasma resides in a parasitophorous vacuole (PV) that is surrounded by the PV membrane (PVM). Once inside the PV, tachyzoites secrete dense granule proteins (GRAs) of which some, such as GRA16 and GRA24, are transported beyond the PVM likely via a putative translocon. However, once tachyzoites convert into bradyzoites within cysts, it is not known if secreted GRAs can traffic beyond the cyst wall membrane. We used the tetracycline inducible system to drive expression of HA epitope tagged GRA16 and GRA24 after inducing stage conversion and show that these proteins are not secreted beyond the cyst wall membrane.
Forecasting autism gene discovery with machine learning and genome-scale data
Authors: Brueggeman Leo , Koomar Tanner , Michaelson Jacob J 
Published: July 2018

AbstractBackgroundGenes are one of the most powerful windows into the biology of autism, and it has been estimated that perhaps a thousand or more genes may confer risk. However, less than 100 genes are currently viewed as having robust enough evidence to be considered true "autism genes". Massive genetic studies are underway to produce data to implicate additional genes, but this approach, although necessary, is costly and slow-moving.MethodsWe approach autism gene discovery as a machine learning problem, rather than a genetic association problem, and use genome-scale data as predictors for identifying further genes that have similar properties in the feature space compared to established autism risk genes. This approach, which we call forecASD, integrates spatiotemporal gene expression, heterogeneous network data, and previous gene-level predictors of autism association into an ensemble classifier that yields a single score that indexes each gene’s evidence for being involved in the etiology of autism.ResultsWe demonstrate that forecASD has substantially increased sensitivity and specificity compared to previous gene-level predictors of autism association, including genetic measures such as TADA. On an independent test set, consisting of newly-released pilot data from the SPARK Genomics Consortium, we show that forecASD best predicts which genes will have an excess of likely gene disrupting (LGD) de novo mutations. We further use independent data from a recent post mortem study of case/control gene expression to show that forecASD is also a significant predictor of genes implicated in ASD through differential expression. Using forecASD results, we show which molecular pathways are currently under-represented in the autism literature and likely represent under-appreciated biological mechanisms of autism. Finally, forecASD correctly predicted 12 of 16 genes implicated at FDR=0.2 by the latest ASD gene discovery study, while also identifying the most likely false positives among the candidate genes.ConclusionsThese results demonstrate that forecASD bridges the gap between genetic- and expression-based ASD gene discovery, and provides a data-driven replacement to much of the manual filtering and curation that is a critical step in ensuring the robustness of gene discovery studies.
The glue that holds an organization together: building organizational vision with top management teams
Authors: Lattuch Frank , Dankert Patricia 
Published: July 2018

Purpose
Top-management teams often have no shared understanding of the organizational vision, or they find it unhelpful for decision-making due to its vague and uninspiring style. The purpose of this paper is to test a theory-based workshop to effectively develop a shared vision for organizational development and learning.

Design/methodology/approach
Based on the Collins and Porras (2008) vision framework, the authors tested a workshop design with top management teams.

Findings
The outlined vision workshop is a useful tool to develop a shared organizational vision in a systematic way.

Originality/value
This paper provides a practical approach to vision building that is relevant and shared by top management teams. Lessons drawn from the case analysis provide insights into the means by which organizations can shape their development through a compelling, guiding force.
Automatic enrolment to pension plans in small organisations: a research agenda
Authors: Maloney Maureen , McCarthy Alma 
Published: July 2018

PurposeThe purpose of this paper is to analyse how firm size impacts pension workforce coverage with a particular focus on automatic enrolment (AE) to pension plans in small organisations.Design/methodology/approachThe paper examines the alignment of government AE interests with those of small employers, their employees and pension providers to better understand how firm size impacts pension workforce coverage.FindingsThe alignment of interests between stakeholders (government, pension providers, employers and employees) differs between large and small organisations, and empirical findings from large organisations cannot be assumed to apply in small organisations.Research limitations/implicationsThe paper calls attention to the need for future empirical research and identifies a number of research questions for further analysis to examine how AE impacts pension participation in small organisations and advance the field.Originality/valueThe policy of automatically enroling employees into occupational pension plans, recently legislated for all eligible workers in the UK and under consideration in the USA and Ireland, was developed from research conducted in a small number of large organisations. Pension coverage is particularly inadequate for the large number of employees working in small organisations (1–49 employees). However, little research attention has been focussed on pensions in small organisations with pension policy makers assuming that legislated AE will work as effectively in small organisations as it did in large organisations. This paper addresses this gap in the field.
Earning tenure with outstanding teaching
Authors: Leech Nancy L. , Schnittka Jessica , Haug Carolyn A. 
Published: July 2018

Purpose
The purpose of this paper is to investigate motivation to teach for higher education faculty within schools of education.

Design/methodology/approach
This study utilized survey research methods to collect data from higher education faculty at nine universities identified from the Carnegie Foundation for the Advancement of teaching website.

Findings
The predictor variables of gender, years of teaching in higher education, percent of overall workload devoted to teaching and two dummy variables for type of institution (i.e. doctoral granting and research II institution) when considered together did not statistically significantly predict whether or not a faculty person achieved tenure with outstanding teaching. In total, 14 of the factors influencing teaching (FIT)-choice scale components statistically significantly predicted whether or not a faculty person achieved tenure with outstanding teaching, only social dissuasion statistically significantly added to the model.

Originality/value
This is the first study to use the FIT-choice scale with university education faculty, and the findings suggest that higher education faculty may be motivated to produce high-quality instruction based on different factors than K-12 teachers.
Regulating bank leverage
Authors: Bleck Alexander 
Published: July 2018

Purpose
This paper aims to study the design of bank capital regulation and points out a conceptual downside of risk-sensitive regulation. The author argues that when a bank is better informed about its risk than the regulator, designing regulation is subject to the Lucas critique. The second-best regulation could be risk-insensitive, which provides an explanation for the leverage ratio as a backstop to risk-based capital requirements. This paper offers empirical predictions and implications for policy.

Design/methodology/approach
The argument in the paper is based on analytical results from mechanism design.

Findings
Optimal bank regulation could be risk-insensitive, as is observed in practice in the form of the leverage ratio rule.

Originality/value
Counter to conventional wisdom, the paper argues and provides a new explanation for why bank regulation should not be sensitive to the risk of the bank. The paper then offers empirical predictions and implications for policy.
Determinants of employee trust during organisational change in higher institutions
Authors: Vosse Bart Jeroen Franciscus , Aliyu Olayemi Abdullateef 
Published: July 2018

PurposeThe researchers in this study aim to understand the impact of a recent merger between two high performing institutions, on employee trust and well-being. The purpose of this paper is to quantitatively test the relationships between communication initiatives, human resource management initiatives, and cultural congruence and their impact on employee trust during organisational change.Design/methodology/approachTo empirically validate these hypothesised relationships, 139 employees of the organisation were surveyed; the data were analysed using structural equation modelling.FindingsThe results indicate that HR planning and successful communication by the organisation are vital if a merger is to achieve the gains envisioned at its inception.Research limitations/implicationsFuture research may explore longitudinal study to establish time of how employee trust are affected from the early merger announcement stage, during the merger-related activities and most importantly the post-merger period. The researchers are of the opinion, that understanding the impacts of change and how employee trust is affected during change is vital. The scope of this study permitted only three independent variables, consideration should be given for further research to explore the influence other activities may have on trust such as policy, government restraint, governance and internationalisation.Practical implicationsThese results further establish the need for educational and commercial organisations to focus on internal and external relationship management and on communication strategies that can affect employees before, during and after a merger.Social implicationsUnderstanding factors that will influence employee vulnerability is important for any organisation as it is possibly the first step to understanding what planning needs to take place to foster change and consider contingencies pre, during and post-merger related change. Considerable thought and planning should be given to the re building of culture and regaining of lost trust post-merger.Originality/valueThis is the first empirical research that quantitatively test the relationships between communication initiatives, human resource initiatives, cultural congruence and their impact on employee trust during organisational change in higher academic institution. This particular study has further add value to change management research, particularly from New Zealand perspective where there is little literature on the current Institute of Technology and Polytechnic sector merger.