bluuebunny/crossref_metadata_2025_split huggingface dataset:
YAP independently regulates cell size and population growth dynamics via non-cell autonomous mediators
Authors: Mugahid Douaa , Kalocsay Marian , Gruver Scott , Peshkin Leonid , Kirschner Marc W. 
Published: November 2018

SummaryThe Hippo pathway, in which changes at the cell surface and in the extracellular environment control the activity of a downstream transcription factor, known as YAP in mammalian cells and Yorkie in Drosophila, has recently taken center-stage as perhaps the most important pathway in metazoans for controlling organ size. In intact tissues YAP activity is inhibited and the organ does not overgrow. When the organ is damaged, YAP is active and necessary for growth and regeneration to occur. The exact process by which YAP drives organ and tissue growth is not fully understood, although it is known to affect both cell size and cell number. Since cell size and proliferation are highly interdependent in many cultured cell studies, we investigated the role of YAP in the simultaneous regulation of both cell size and number. Our experiments reveal that YAP controls both cell size and cell proliferation by independent circuits, and that it affects each process non-cell autonomously via extracellular mediators. We identify that CYR61, a known secreted YAP target, is the major regulator of the non-cell autonomous increase in cell number, but does not affect cell size. The molecular identity of the non-cell autonomously acting mediator of cell size is yet to be identified.
Network-based identification of genetic factors in Ageing, lifestyle and Type 2 Diabetes that Influence in the progression of Alzheimer’s disease
Authors: Chowdhury Utpala Nanda , Ahmad Shamim , Islam M. Babul , Huq Fazlul , Quinn Julian M.W. , Moni Mohammad Ali 
Published: November 2018

AbstractMotivationAlzheimer’s disease (AD) is currently incurable and the causative risk factors are still poorly understood, which impedes development of effective prevention and treatment strategies. We propose a network-based quantitative framework to reveal details of the complex interaction between the various genetic contributors to AD susceptibility. We analyzed gene expression microarray data from tissues affected by AD, advanced ageing, high alcohol consumption, type II diabetes, high body fat, high dietary fat, obesity, high dietary red meat intake, sedentary lifestyle, smoking, and control datasets. We developed genetic associations and diseasome networks for these factors and AD using the neighborhood-based benchmarking and multilayer network topology approaches.ResultsThe study identified 484 genes differentially expressed between AD and controls. Among these, 27 genes showed elevated expression both in individuals in AD and in smoker datasets; similarly 21 were observed in AD and type II diabetes datasets and 12 for AD and sedentary lifestyle datsets. However, AD shared less than ten such elevated expression genes with other factors examined. 3 genes, namely HLA-DRB4, IGH and IGHA2 showed increased expression among the AD, type II diabetes and alcohol consumption datasets; 2 genes, IGHD and IGHG1, were commonly up-regulated among the AD, type II diabetes, alcohol consumption and sedentary lifestyle datasets. Protein-protein interaction networks identified 10 hub genes: CREBBP, PRKCB, ITGB1, GAD1, GNB5, PPP3CA, CABP1, SMARCA4, SNAP25 and GRIA1. Ontological and pathway analyses genes, including Online Mendelian Inheritance in Man (OMIM) and dbGaP databases were used for gold benchmark gene-disease associations to validate the significance of these putative target genes of AD progression.ConclusionOur network-based methodologies have uncovered molecular pathways that may influence AD development, suggesting novel mechanisms that contribute to AD risk and which may form the basis of new therapeutic and diagnostic approaches.Contactmohammad.moni@sydney.edu.au
Early Detection of Neurological Dysfunction Using Blood Cell Transcript Profiles
Authors: Moni Mohammad Ali , Rana Humayan Kabir , Islam M. Babul , Ahmed Md Bashir , Liò Pietro , Huq Fazlul , Quinn Julian M.W. 
Published: November 2018

AbstractIdentification of genes whose regulation of expression is similar in both brain and blood cells could enable monitoring of significant neurological traits and disorders by analysis of blood samples. We thus employed transcriptional analysis of pathologically affected tissues, using agnostic approaches to identify overlapping gene functions and integrating this transcriptomic information with expression quantitative trait loci (eQTL) data. Here, we estimate the correlation of genetic expression in the top-associated cis-eQTLs of brain tissue and blood cells in Parkinson’s (PD).We introduced quantitative frameworks to reveal the complex relationship of various biasing genetic factors in PD, a neurodegenerative disease. We examined gene expression microarray and RNA-Seq datasets from human brain and blood tissues from PD-affected and control individuals. Differentially expressed genes (DEG) were identified for both brain and blood cells to determine common DEG overlaps. Based on neighborhood-based benchmarking and multilayer network topology aproaches we then developed genetic associations of factors with PD.Overlapping DEG sets underwent gene enrichment using pathway analysis and gene ontology methods, which identified candidate common genes and pathways. We identified 12 significantly dysregulated genes shared by brain and blood cells, which were validated using dbGaP (gene SNP-disease linkage) database for gold-standard benchmarking of their significance in disease processes. Ontological and pathway analyses identified significant gene ontology and molecular pathways that indicate PD progression.In sum, we found possible novel links between pathological processes in brain and blood cells by examining cell path-way commonalities, corroborating these associations using well validated datasets. This demonstrates that for brain-related pathologies combining gene expression analysis and blood cell cis-eQTL is a potentially powerful analytical approach. Thus, our methodologies facilitate data-driven approaches that can advance knowledge of disease mechanisms and may enable prediction of neurological dysfunction using blood cell transcript profiling.
On Using Local Ancestry to Characterize the Genetic Architecture of Human Phenotypes: Genetic Regulation of Gene Expression in Multiethnic or Admixed Populations as a Model
Authors: Zhong Yizhen , Perera Minoli , Gamazon Eric R. 
Published: November 2018

AbstractBackgroundUnderstanding the nature of the genetic regulation of gene expression promises to advance our understanding of the genetic basis of disease. However, the methodological impact of use of local ancestry on high-dimensional omics analyses, including most prominently expression quantitative trait loci (eQTL) mapping and trait heritability estimation, in admixed populations remains critically underexplored.ResultsHere we develop a statistical framework that characterizes the relationships among the determinants of the genetic architecture of an important class of molecular traits. We estimate the trait variance explained by ancestry using local admixture relatedness between individuals. Using National Institute of General Medical Sciences (NIGMS) and Genotype-Tissue Expression (GTEx) datasets, we show that use of local ancestry can substantially improve eQTL mapping and heritability estimation and characterize the sparse versus polygenic component of gene expression in admixed and multiethnic populations respectively. Using simulations of diverse genetic architectures to estimate trait heritability and the level of confounding, we show improved accuracy given individual-level data and evaluate a summary statistics based approach. Furthermore, we provide a computationally efficient approach to local ancestry analysis in eQTL mapping while increasing control of type I and type II error over traditional approaches.ConclusionOur study has important methodological implications on genetic analysis of omics traits across a range of genomic contexts, from a single variant to a prioritized region to the entire genome. Our findings highlight the importance of using local ancestry to better characterize the heritability of complex traits and to more accurately map genetic associations.
Immunological Diversity with Similarity
Authors: Arora Rohit , Burke Harry M. , Arnaout Ramy 
Published: November 2018

AbstractA diverse immune repertoire is considered a hallmark of good health, but measuring diversity requires a framework that incorporates not only sequences’ relative frequencies but also their functional similarity to each other. Using experimentally measured dissociation constants from over 1,300 antibody-antigen and T-cell receptor (TCR)-peptide pairs, we developed a framework for functional immunological diversity based on binding and applied it to nearly 400 high-throughput antibody and TCR repertoires to reveal patterns in immunological memory, infection, vaccination, and aging. We show that functional diversity adds information that is not captured by raw diversity, revealing signatures of e.g. clonal selection, and that unlike raw diversity, functional diversity is a robust measure that does not require correction for sampling error. Finally, we show that according to functional diversity, unlike raw diversity, individuals’ repertoires overlap substantially, indicating a definable ceiling for the functional diversity of human adaptive immunity. Similarity redefines diversity in complex systems.
Computational psychiatry 2.0 and implications for stress research
Authors: Pashkov Anton A. , Berebin Mikhail A. 
Published: November 2018

AbstractStress-related disorders are highly prevalent in modern society and pose significant challenge to human’s health. Being recently emerged branch of psychiatry, computational psychiatry is geared toward mathematical modeling of psychiatric disorders. Harnessing power of computer sciences and statistics may bridge the complex nature of psychiatric illnesses with hidden brain computational mechanisms. Stress represents an adaptive response to environmental threats but, while getting chronic, it leads to progressive deflection from homeostasis or result in buildup of allostatic load, providing researches with unique opportunity to track patterns of deviations from adaptive responding toward full-blown disease development. Computational psychiatry toolkit enables us to quantitatively assess the extent of such deviations, to explicitly test competing hypotheses which compare the models with real data for goodness-of-fit and, finally, to tethering these computational operations to structural or functional brain alterations as may be revealed by non-invasive neuroimaging and stimulation techniques.It is worth noting that brain does not directly face environmental demands imposed on human or animal, but rather through detecting signals and acting out via bodily systems. Therefore, it is of critical importance to take homeostatic and allostatic mechanisms into account when considering sophisticated interactions between brain and body and how their partnership may result in establishment of stress-susceptible or resilient profiles.In this article, with a particulate focus on brain-gut interactions, we outline several possible directions to widen the scope of application of computational approach in mental health care field trying to integrate computational psychiatry, psychosomatics and nutritional medicine
Hypoxic environment promotes barrier formation in human intestinal epithelial cells through regulation of miRNA-320a expression
Authors: Muenchau Stephanie , Deutsch Rosalie , Hielscher Thomas , Heber Nora , Niesler Beate , Stanifer Megan L. , Boulant Steeve 
Published: November 2018

AbstractIntestinal epithelial cells (IECs) are exposed to the low-oxygen environment present in the lumen of the gut. These hypoxic conditions are on one hand fundamental for the survival of the commensal microbiota, and on the other hand, favor the formation of a selective semipermeable barrier allowing IECs to transport essential nutrients/water while keeping the sterile internal compartments separated from the lumen containing commensals. The hypoxia-inducible factor (HIF) complex, which allows cells to respond and adapt to fluctuations in oxygen levels, has been described as a key regulator in maintaining IEC barrier function by regulating their tight junction integrity. In this study, we sought to better evaluate the mechanisms by which low oxygen conditions impact the barrier function of human IECs. By profiling miRNA expression in IECs under hypoxia, we identified miRNA-320a as a novel barrier formation regulator. Using pharmacological inhibitors and short hairpin RNA-mediated silencing we could demonstrate that expression of this miRNA was HIF-dependent. Importantly, using over-expression and knock-down approaches of miRNA-320a we could confirm its direct role in the regulation of barrier functions in human IECs. These results reveal an important link between miRNA expression and barrier integrity, providing a novel insight into mechanisms of hypoxia-driven epithelial homeostasis.
Serum-dependent and independent regulation of PARP2
Authors: Sun Qizhi , Gatie Mohamed I. , Kelly Gregory M. 
Published: November 2018

AbstractPARP2 belongs to a family of proteins involved in cell differentiation, DNA damage repair, cellular energy expenditure, chromatin modeling and cell differentiation. In addition to these overlapping functions with PARP1, PARP2 participates in spermatogenesis, T-cell maturation, extraembryonic endoderm formation and adipogenesis. The function(s) of PARP2 is far from complete, and the mechanism(s) by which the gene and protein are regulated are unknown. In this study, we found that two different mechanisms are usedin vitroto regulate PARP2 levels. In the presence of serum, PARP2 is degraded through the ubiquitin-proteasome pathway, however, when serum is removed, PARP2 is rapidly sequestered into an SDS- and urea-insoluble fraction. This sequestration is relieved by serum in a dose-dependent manner, and again PARP2 is detected by immunoblotting. Furthermore, and despite the presence of a putative serum response element in thePARP2gene, transcription is not affected by serum deprivation. These observations that PARP2 is tightly regulated by distinct pathways highlights the critical roles PARP2 plays under different physiological conditions.
Time-resolved digital immunoassay for rapid and sensitive quantitation of procalcitonin with plasmonic imaging
Authors: Jing Wenwen , Wang Yan , Yang Yunze , Wang Yi , Ma Guangzhong , Wang Shaopeng , Tao Nongjian 
Published: November 2018

AbstractTimely diagnosis of acute diseases improves treatment outcomes and saves lives, but it requires fast and precision quantification of biomarkers. Here we report a time-resolved digital immunoassay based on plasmonic imaging of binding of single nanoparticles to biomarkers captured on a sensor surface. The real-time and high contrast of plasmonic imaging lead to fast and precise counting of the individual biomarkers over a wide dynamic range. We demonstrated the detection principle, evaluated the performance of the method using procalcitonin (PCT) as an example, and achieved a limit of detection of ~ 3 pg/mL, dynamic range of 4-12500 pg/mL, for a total detection time of ~ 25 mins.
Oculomotor nerve requires an early interaction with muscle precursors for nerve guidance and branch patterning
Authors: Bjorke Brielle , Weller Katherine G. , Robinson G. Eric , Vesser Michelle , Chen Lisheng , Gage Philip J. , Gould Thomas W. , Mastick Grant S. 
Published: November 2018

AbstractMuscle function is dependent on innervation by the correct motor nerves. Motor nerves are composed of motor axons that extend through peripheral tissues as a compact bundle, but then diverge to create nerve branches to specific muscle targets. A transition point typically occurs as motor nerves grow near their targets, where the fasciculated nerve halts further growth, then later initiates branching to muscles. The motor nerve transition point is potentially an intermediate target acting as a guidepost to present specific cellular and molecular signals for navigation. Here we describe the navigation of the oculomotor nerve with respect to eye muscle precursor cells in mouse embryos. We found that the oculomotor nerve initially grew to the eye three days prior to the appearance of any eye muscles. The oculomotor axons spread to form a plexus within a mass of eye muscle precursors, then the nerve growth paused for more than two days. This plexus persisted during primary extraocular myogenesis, with a subsequent phase in which the nerve branched out to specific muscles. To test the functional significance of the nerve-precursor contact in the plexus, we genetically ablated muscle precursors early in nerve development, prior to nerve contact. Ablation of muscle precursors resulted in oculomotor nerve fibers failing to stop to form the plexus, but instead growing past the eye. In contrast, ablating the precursor pool at later stages, after the nerve has contacted the precursor cells, results in ectopic branching restricted near the eye. These results demonstrate that muscle precursors act as an intermediate target for nerve guidance, and are required for the oculomotor nerve to transition between nerve growth and distinct stages of terminal axon branching.
Trans-omics analyses revealed differences in hormonal and nutritional status between wild and cultured female Japanese eel (Anguilla japonica)
Authors: Higuchi Masato , Mekuchi Miyuki , Hano Takeshi , Imaizumi Hitoshi 
Published: November 2018

AbstractLong-term stock decline in the Japanese eel (Anguilla japonica) is a serious issue. To reduce natural resource utilization in Japan, artificial hormonal induction of maturation and fertilization in the Japanese eel has been intensively studied. Recent experiment on feminized (by feeding a commercial diet containing estradiol-17β for first half year) cultured eels have shown ovulation problem, which is seldom observed in captured wild eels. In this study, we tried to investigate causes of ovulation problem frequently seen in cultured eels by comparative trans-omics analyses.The omics data showed low growth hormone and luteinizing hormone transcription levels in the brain and low sex hormone–binding globulin transcription levels in the liver of the cultured eels. In addition, we found high accumulation of glucose-6-phosphate and, maltose in the cultured eel liver. We also found that docosahexaenoic (DHA) acid, eicosapentaenoic acid (EPA) and arachidonic acid (ARA) ratios in cultured eels were quite different from wild eels.The data suggested that ovulation problem is due to prolonged intake of a high-carbohydrate diet and/or unbalanced DHA/EPA/ARA ratios in diet.
Measuring emotions toward dining alone by frequency of single dining events
Authors: Kim Hyeyeon , Choi Jinkyung 
Published: November 2018

Purpose
The growing prevalence of single-person households in South Korea has started to affect the country’s restaurant business. The phenomenon has led to changes in how the interiors of food service establishments are designed. The purpose of this paper is to measure consumers’ emotions when they ate alone and when they saw someone else eating alone to investigate how these emotions can be used in marketing strategies.

Design/methodology/approach
The data were collected via self-administered surveys to individuals in Daejeon in South Korea. A total of 163 respondents were surveyed and divided into two groups on the basis of their frequency of eating alone: low frequency of eating alone and high frequency of eating alone (HEA). The HEA group was further sub-divided to identify significant differences in greater detail. An independent t-test and descriptive analyses were conducted on the data.

Findings
Significant differences were observed in the emotions of “be proud of oneself,” “sadness,” “extroversion,” and “loneliness.” A majority of the respondents ate alone because it saved them time. They also preferred to eat home meal replacements when they ate alone.

Originality/value
The results of this study help understand consumers’ emotions when eating alone in relation to their behaviors at food service establishments. They can inform decisions on market strategies developed by food businesses targeting single consumers.
Role of designers in developing new products: an innovation turn in transformational economies
Authors: Gasparin Marta 
Published: November 2018

PurposeThe purpose of this paper is to present a critical literature review on design management.Design/methodology/approachThe map of the field is based on the analysing the chain of associations between the papers (Latour, 1987). The strategy for this review is informed by the methodology described by Callonet al.(1986) on following the construction of the arguments. The first search was conducted in EBESCO and Web of Science looking for papers dealing with design management; “design management”; innovat* and design* in the management, including title, keywords and abstract. It resulted in 8,216 articles that were exported and downloaded in a database.FindingsFive groups emerged: design as rational decision making, industrial design, managing as designing, design as proposals of new meaning and design as a network construction.Originality/valueThis paper maps the role of designers in innovation and design management literature. Design management is a variegated field of research, and the focus of this paper has been on product design in business and management literature. To begin with, the research philosophy which was inferred by analysing the preferred methodology in the papers belonging to five perspectives was analysed, and the ontology, essence, metaphysics delineated. Then, a map of the field of on the role of designers was proposed. The author concluded with a reflection of a possible research agenda in design management, focussing on investigating the role of designers in transformational economies, such as Vietnam.
Making it tangible: hybrid card sorting within qualitative interviews
Authors: Conrad Lettie Y. , Tucker Virginia M. 
Published: November 2018

PurposeQualitative researchers and information practitioners often investigate questions that probe the underlying mental models, nuanced perspectives, emotions and experiences of their target populations. The in-depth qualitative interview is a dominant method for such investigations and the purpose of this paper is to demonstrate how incorporating hybrid card-sorting activities into interviews can enable deeper participant reflections and generate rich data sets to increase understanding.Design/methodology/approachFollowing a review of relevant literature, the case illustration presented is a grounded theory study into the student-researcher information experience with personal academic information management. This study uses hybrid card sorting within in-depth, semi-structured interviews, a unique adaptation that extends multi-disciplinary awareness of the benefits of card-sort exercises for qualitative research.FindingsEmerging from diverse fields, ranging from computer science, engineering, psychology and human–computer interaction, card sorting seeks to illuminate how participants understand and organise concepts. The case illustration draws largely on methods used in interaction design and information architecture. Using either open or fixed designs, or hybrid variations, card-sort activities can make abstract concepts more tangible for participants, offering investigators a new approach to interview questions with the aid of this interactive, object-based technique.Originality/valueOpening with a comprehensive review of card-sort studies, the authors present an information experience case illustration that demonstrates the rich data generated by hybrid card sorting within qualitative interviews, or interactive interviews. This is followed by discussion of the types of research questions that may benefit from this original method.