bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep problems are associated with hypersensitivity to touch in children with autism
Authors: Orna Tzischinsky , Gal Meiri , Liora Manelis , Asif Bar-Sinai , Hagit Fluser , Analya Michaelovski , Orit Zivan , Michal Ilan , Michal Faroy , Idan Menashe , Ilan Dinstein 
Published: January 2018

AbstractBackgroundSensory abnormalities and sleep disturbances are highly prevalent in children with autism, but the potential relationship between these two domains has rarely been explored. Understanding such relationships is important for identifying children with autism who exhibit more homogeneous symptoms.MethodsHere we examined this relationship using the Caregiver Sensory Profile and the children’s sleep habit questionnaires, which were completed by parents of 69 children with autism and 62 frequency age-matched controls.ResultsIn line with previous studies, children with autism exhibited more severe sensory abnormalities and sleep disturbances than age-matched controls. The sleep disturbance scores were strongly associated with touch and oral sensitivities in the autism group and with touch and vestibular sensitivities in the control group. Hyper sensitivity towards touch, in particular, exhibited the strongest relationship with sleep disturbances in the autism group and single-handedly explained 24% of the variance in sleep disturbance scores. In contrast, sensitivity in other sensory domains such as vision and audition was not associated with sleep quality in either group.ConclusionsWhile it is often assumed that sensitivities in all sensory domains are similarly associated with sleep problems, our results suggest that hyper sensitivity towards touch exhibits the strongest relationship to sleep disturbances when examining children autism. We speculate that hyper sensitivity towards touch interferes with sleep onset and maintenance in a considerable number of children with autism who exhibit severe sleep disturbances. Studies that examine the effects of tactile sensory therapies/aids on sleep quality and behavioral improvement in these children are, therefore, highly warranted.
LiMMBo: a simple, scalable approach for linear mixed models in high-dimensional genetic association studies
Authors: Meyer Hannah Verena , Paolo Casale Francesco , Stegle Oliver , Birney Ewan 
Published: January 2018

AbstractGenome-wide association studies have helped to shed light on the genetic architecture of complex traits and diseases. Deep phenotyping of population cohorts is increasingly applied, where multi-to high-dimensional phenotypes are recorded in the individuals. Whilst these rich datasets provide important opportunities to analyse complex trait structures and pleiotropic effects at a genome-wide scale, existing statistical methods for joint genetic analyses are hampered by computational limitations posed by high-dimensional phenotypes. Consequently, such multivariate analyses are currently limited to a moderate number of traits. Here, we introduce a method that combines linear mixed models with bootstrapping (LiMMBo) to enable computationally efficient joint genetic analysis of high-dimensional phenotypes. Our method builds on linear mixed models, thereby providing robust control for population structure and other confounding factors, and the model scales to larger datasets with up to hundreds of phenotypes. We first validate LiMMBo using simulations, demonstrating consistent covariance estimates at greatly reduced computational cost compared to existing methods. We also find LiMMBo yields consistent power advantages compared to univariate modelling strategies, where the advantages of multivariate mapping increases substantially with the phenotype dimensionality. Finally, we applied LiMMBo to 41 yeast growth traits to map their genetic determinants, finding previously known and novel pleiotropic relationships in this high-dimensional phenotype space. LiMMBo is accessible as open source software (https://github.com/HannahVMeyer/limmbo).Author summaryIn multi-trait genetic association studies one is interested in detecting genetic variants that are associated with one or multiple traits. Genetic variants that influence two or more traits are referred to as pleiotropic. Multivariate linear mixed models have been successfully applied to detect pleiotropic effects, by jointly modelling association signals across traits. However, these models are currently limited to a moderate number of phenotypes as the number of model parameters grows steeply with the number of phenotypes, raising a computational burden. We developed LiMMBo, a new approach for the joint analysis of high-dimensional phenotypes. Our method reduces the number of effective model parameters by introducing an intermediate subsampling step. We validate this strategy using simulations, where we apply LiMMBo for the genetic analysis of hundreds of phenotypes, detecting pleiotropic effects for a wide range of simulated genetic architectures. Finally, to illustrate LiMMBo in practice, we apply the model to a study of growth traits in yeast, where we identify pleiotropic effects for traits with formerly known genetic effects as well as revealing previously unconnected traits.
FRMD8 promotes inflammatory and growth factor signalling by stabilising the iRhom/ADAM17 sheddase complex
Authors: Künzel Ulrike , Grieve Adam G. , Meng Yao , Cowley Sally A. , Freeman Matthew 
Published: January 2018

AbstractMany intercellular signals are synthesised as transmembrane precursors that are released by proteolytic cleavage (‘shedding’) from the cell surface. ADAM17, a membrane-tethered metalloprotease, is the primary shedding enzyme responsible for the release of the inflammatory cytokine TNFα and several EGF receptor ligands. ADAM17 exists in complex with the rhomboid-like iRhom proteins, which act as cofactors that regulate ADAM17 substrate shedding. Here we report that the poorly characterised FERM domain-containing protein FRMD8 is a new component of iRhom2/ADAM17 sheddase complex. FRMD8 binds to the cytoplasmic N-terminus of iRhoms, and is necessary to stabilise the iRhoms and ADAM17 beyond the Golgi. In the absence of FRMD8, iRhom2 and ADAM17 are degraded via the endolysosomal pathway, resulting in the reduction of ADAM17-mediated shedding. We have confirmed the pathophysiological significance of FRMD8 in iPSC-derived human macrophages and mouse tissues, thus demonstrating its role in the regulated release of multiple cytokine and growth factor signals.
Subjective confidence reveals the hierarchical nature of learning under uncertainty
Authors: Heilbron Micha , Meyniel Florent 
Published: January 2018

ABSTRACTHierarchical processing is pervasive in the brain, but its computational significance for learning in real-world conditions, with uncertainty and changes, is disputed. We show that previously proposed qualitative signatures which relied on reports of learned quantities or choices in simple experiments are insufficient to categorically distinguish hierarchical from non-hierarchical models of learning under uncertainty. Instead, we present a novel test which leverages a more complex task, whose hierarchical structure allows generalization between different statistics tracked in parallel. We use reports of confidence to quantitatively and qualitatively arbitrate between the two accounts of learning. Our results indicate that human subjects can track multiple, interdependent levels of uncertainty, and provide clear evidence for hierarchical processing, thereby challenging some influential neurocomputational accounts of learning.
Infection by a Giant Virus Induces Widespread Physiological Reprogramming inAureococcus Anophagefferens– A Harmful Bloom Algae
Authors: Moniruzzaman Mohammad , Gann Eric R. , Wilhelm Steven W. 
Published: January 2018

AbstractWhile viruses with distinct phylogenetic origins and different nucleic acid types can infect and lyse eukaryotic phytoplankton, “giant” dsDNA viruses have been found to be associated with important ecological processes, including the collapse of algal blooms. However, the molecular aspects of giant virus – host interactions remain largely unknown. AaV, a giant virus in the Mimiviridae clade, is known to play a critical role in regulating the fate of brown tide blooms caused by the pelagophyteAureococcus anophagefferens.To understand the physiological response ofA. anophagefferensCCMP1984 upon AaV infection, we studied the transcriptomic landscape of this host-virus pair over an entire infection cycle using a RNA-sequencing approach. A massive transcriptional reprogramming of the host was evident as early as 5 min post-infection, with modulation of specific processes likely related to both host defense mechanism(s) and viral takeover of the cell. InfectedAureococcusshowed a relative suppression of host-cell transcripts associated with photosynthesis, cytoskeleton formation, fatty acid and carbohydrate biosynthesis. In contrast, host cell processes related to protein synthesis, polyamine biosynthesis, cellular respiration, transcription and RNA processing were overrepresented compared to the healthy cultures at different stages of the infection cycle. A large number of redox active host-selenoproteins were overexpressed, which suggested that viral replication and assembly progresses in a highly oxidative environment. The majority (99.2%) of annotated AaV genes were expressed at some point during the infection cycle and demonstrated a clear temporal-expression pattern and an increasing relative expression for the majority of the genes through the time course. We detected a putative early promoter motif for AaV, which was highly similar to the early promoter elements of two other Mimiviridae members, indicating some degree of evolutionary conservation of gene regulation within this clade. This large-scale transcriptome study provides the insight into theAureococcus ‘virocell’, and establishes a foundation to test hypotheses regarding metabolic and regulatory processes critical for AaV and other Mimiviridae members.
What is an archaeon and are the Archaea really unique?
Authors: Harish Ajith 
Published: January 2018

AbstractThe recognition of the group Archaea as a major branch of the Tree of Life (ToL) prompted a new view of the evolution of biodiversity. The genomic representation of archaeal biodiversity has since significantly increased. In addition, advances in phylogenetic modeling of multi-locus datasets have resolved many recalcitrant branches of the ToL. Despite the technical advances and an expanded taxonomic representation, two important aspects of the origins and evolution of the Archaea remain controversial, even as we celebrate the 40th anniversary of the monumental discovery. These issues concern (i) the uniqueness (monophyly) of the Archaea, and (ii) the evolutionary relationships of the Archaea to the Bacteria and the Eukarya; both of these are relevant to the deep structure of the ToL. Here, to explore the causes for this persistent ambiguity, I examine multiple datasets that support contradicting conclusions. Results indicate that the uncertainty is primarily due to a scarcity of information in standard datasets — the core genes datasets — to reliably resolve the conflicts. These conflicts can be resolved efficiently by comparing patterns of variation in the distribution of functional genomic signatures, which are less diffused unlike patterns of primary sequence variation. Relatively lower heterogeneity in distribution patterns minimizes uncertainties, which supports statistically robust phylogenetic inferences, especially of the earliest divergences of life. This case study further highlights the limits of primary sequence data in resolving difficult phylogenetic problems and casts doubt on evolutionary inferences drawn solely from the analyses of a small set of core genes.
The role of equilibrium cost in the evolution of honest signalling: waste or optimal investment?
Authors: Számadó Szabolcs , Penn Dustin J. 
Published: January 2018

AbstractThe relationship between signal cost and honesty is a controversial and unresolved issue. The handicap principle assumes that signals must be costly at equilibrium to be honest, and the greater the cost, the more reliable the signal. However, theoretical models and simulations question the necessity of equilibrium cost for the evolution of honest signalling. Honest signals can evolve without costs, and they can evolve through differential benefits with no need for differential costs. Here we investigate the role of equilibrium signal cost in the evolution of honest signals in both differential benefit and differential cost models using an agent-based simulation. We found that there is an optimal investment paid by honest individual that allows for the highest level of honesty when there is correlation between signal cost paid by low and high-quality individuals. This holds for both differential benefit and differential cost models as long there is a correlation between signal cost paid by low and high quality individuals. However, increasing equilibrium signal cost poses an obstacle and hinders the evolution of honest signalling when there is no correlation between the cost paid by low and high-quality individuals. Last but not least, we found that the potential cost of cheating is a much better predictor of honesty than the equilibrium cost paid by honest signallers.
AMPKi overcomes the paradoxical activation of CRAF driven by RAF inhibitors through blocking the 14-3-3 binding to its carboxyl-terminus
Authors: Yuan Jimin , Ng Wan Hwa , Yap Jiajun , Chia Brandon , Huang Xuchao , Wang Mei , Hu Jiancheng 
Published: January 2018

AbstractThe paradoxical activation of RAF kinase is the predominant challenge in cancer therapies with RAF inhibitors. The inhibitor-bound RAF molecules are able to transactivate their wild-type binding partners. 14-3-3 that binds to the carboxyl-terminus of RAF kinase has been suggested to regulate the dimer-dependent activation of RAF kinase under physiological conditions, though the molecular basis is not clear. In this study, we investigated the role of 14-3-3 in the paradoxical effect of RAF inhibitors. Firstly, we found that the 14-3-3 binding to the carboxyl-terminus of CRAF was essential for its transactivation. Further, we demonstrated that this binding enhanced the dimer affinity of CRAF. Since 14-3-3 binds to the phosphorylated motif, we next investigated and identified AMPK and CRAF itself as two putative kinases that phosphorylate redundantly the 14-3-3 binding motif of CRAF. Among RAF isoforms, CRAF plays a dominant role in the paradoxical effect of RAF inhibitors, and we thus determined whether the combinatory inhibition of AMPK and CRAF would block this effect. Indeed, our data showed that AMPKi not only blocked the RAF inhibitor-driven paradoxical activation of RAF signaling and cellular overgrowth in Ras-mutated cancer cells but also reduced the drug-resistant clones derived from BRAF(V600E)-mutated cancer cells. Finally, we showed that the 14-3-3 binding to the carboxyl-terminus of CRAF was dispensable for its catalytic function in vivo. Together, our study unraveled how 14-3-3 regulates the dimerization-driven RAF activation and identified AMPKi as a potential method to relieve the drug resistance and side effect of RAF inhibitors in cancer therapy.
Limb bone scaling in hopping macropods and quadrupedal artiodactyls
Authors: Doube Michael , Felder Alessandro A , Chua Melissa Y , Lodhia Kalyani , Kłosowski Michał M , Hutchinson John R , Shefelbine Sandra J 
Published: January 2018

AbstractBone adaptation is modulated by the timing, direction, rate, and magnitude of mechanical loads. To investigate whether frequent slow, or infrequent fast, gaits could dominate bone adaptation to load, we compared scaling of the limb bones from two mammalian herbivore clades that use radically different high-speed gaits, bipedal hopping (suborder Macropodiformes; kangaroos and kin) and quadrupedal galloping (order Artiodactyla; goats, deer and kin). Forelimb and hindlimb bones were collected from 20 artiodactyl and 15 macropod species (body massM1.05 – 1536 kg) and scanned in computed tomography or X- ray microtomography. Second moment of area (Imax) and bone length (l) were measured. Scaling relations (y=axb) were calculated forlvsMfor each bone and forImaxvsMandImaxvslfor every 5% of length.ImaxvsMscaling relationships were broadly similar between clades despite the macropod forelimb being nearly unloaded, and the hindlimb highly loaded, during bipedal hopping.ImaxvslandlvsMscaling were related to locomotor and behavioural specialisations. Low-intensity loads may be sufficient to maintain bone mass across a wide range of species. Occasional high-intensity gaits might not break through the load sensitivity saturation engendered by frequent low-intensity gaits.
Deconvolution and phylogeny inference of structural variations in tumor genomic samples
Authors: Eaton Jesse , Wang Jingyi , Schwartz Russell 
Published: January 2018

AbstractPhylogenetic reconstruction of tumor evolution has emerged as a crucial tool for making sense of the complexity of emerging cancer genomic data sets. Despite the growing use of phylogenetics in cancer studies, though, the field has only slowly adapted to many ways that tumor evolution differs from classic species evolution. One crucial question in that regard is how to handle inference of structural variations (SVs), which are a major mechanism of evolution in cancers but have been largely neglected in tumor phylogenetics to date, in part due to the challenges of reliably detecting and typing SVs and interpreting them phylogenetically. We present a novel method for reconstructing evolutionary trajectories of SVs from bulk whole-genome sequence data via joint deconvolution and phylogenetics, to infer clonal subpopulations and reconstruct their ancestry. We establish a novel likelihood model for joint deconvolution and phylogenetic inference on bulk SV data and formulate an associated optimization algorithm. We demonstrate the approach to be efficient and accurate for realistic scenarios of SV mutation on simulated data. Application to breast cancer genomic data from The Cancer Genome Atlas (TCGA) shows it to be practical and effective at reconstructing features of SV-driven evolution in single tumors. All code can be found at https://github.com/jaebird123/tusv
Transforming an organization into a learning organization: Liberty Shoes Ltd, Karnal Unit
Authors: Sahoo D.P. 
Published: January 2018

Subject area
Liberty Shoes Ltd, had been experiencing falling sales and decreased production as a result of frequent strikes by workers. By 2010, total sales had fallen to INR 300 crores (from INR 500 crores in 2005). In the Annual Board meeting in 2010, Mr Shammi Bansal, the Executive Director expressed his concerns and told the board members that “they must learn to survive or be extinct”. The case study discusses how The Executive Director turned the company around and how the organization became a “learning organization”.

Study level/applicability
MBA and Executive MBA programs.

Case overview
In 2004, Liberty Shoes Ltd, had a sales turnover of INR 500 crores. In the year 2006, this dropped to INR 300 crores as a result of regular staff strikes and low morale. However, by 2013, the company had registered sales of INR 800 crores and a growth rate of around 30 per cent on a year-to-year basis. With continued focused initiatives in the organization from 2010 the management aimed to reach a sales turnover of INR 1,000 crores by March, 2014. The contributing factors to this turnaround were the leadership roles which encouraged a learning organization culture with an emphasis placed on the importance of “communication”, “employee development” and “employee empowerment”.

Expected learning outcomes
Understand the role of a business leader in building a learning organization. Understand the factors contributing to the building of a culture of a learning organization. Understand the critical aspects and benefits to the organization from becoming a learning organization.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or emailsupport@emeraldinsight.com to request teaching notes.

Subject code
CSS: 6 Human resource management.
Expanding the boundaries of brand communities: the case of Fairtrade Towns
Authors: Samuel Anthony , Peattie Ken , Doherty Bob 
Published: January 2018

Purpose
This paper aims to further the authors’ understanding of brand communities, and their role in brand co-creation, through empirical and theoretical contributions derived from researching the marketing dynamics operating within a successful but atypical form of brand community, Fairtrade Towns (FTT).

Design/methodology/approach
The paper reflects a pragmatic application of Grounded Theory, which captured qualitative data from key “insiders”, with a particular emphasis on FTT steering group members and their role as “prosumers”. Data were gathered via ethnographic involvement within one town and semi-structured interviews with participants in others.

Findings
FTTs, as brand communities, demonstrate elements of co-creation that go beyond the dominant theories and models within the marketing literature. They operate in, and relate to, real places rather than the online environments that dominate the literature on this subject. Unusually, the interactions between brand marketers and consumers are not the primary source of co-creation in FTTs. Instead, factors usually identified as merely secondary providers of additional brand knowledge become key initiators and sources of co-creation and active “citizen marketer” engagement.

Originality/value
This study demonstrates how brand co-creation can operate in physical geographical communities in ways that are formal without being managed by conventional brand managers. It conceptualises FTTs as a nested and “glocalised” brand and demonstrates how steering group members facilitate the process of co-creation as prosumers. It empirically demonstrates how FTTs have evolved to become unusually complex brand communities in terms of the variety of stakeholders and the multiplicity of brands involved, and the governance of the localised brand co-creation process.
The impact of social influence on the perceived helpfulness of online consumer reviews
Authors: Risselada Hans , de Vries Lisette , Verstappen Mariska 
Published: January 2018

PurposeThis study aims to study to what extent the helpfulness votes others attach to a review affect a consumer’s perceived helpfulness of that review. In addition, the purpose of this study is to investigate whether this social influence moderates the relationships among several content presentation factors and perceived helpfulness.Design/methodology/approachA choice-based conjoint experiment was carried out in which 201 respondents evaluated different reviews and chose the review they perceive as most helpful.FindingsConsumers perceive reviews as more (less) helpful in the presence of clearly valenced positive (negative) helpfulness votes. In addition, helpfulness votes of others diminish the positive impact of structure and the negative impact of spelling errors.Research limitations/implicationsThe experimental setup may limit the external validity of the study.Practical implicationsProviding a helpfulness button gives firms an instrument to offer content that consumers perceive as more useful and to exert some influence on the effects of content presentation factors on the review’s helpfulness.Social implicationsConsumers tend to follow other consumers’ opinions without forming their own opinion. Firms could misuse this tendency by hiring people to vote on reviews that are not necessarily helpful for consumers, but are helpful for the firm.Originality/valueThis study is the first to assess the extent to which social influence affects consumers’ evaluation of reviews. Given that consumers use helpfulness votes to distinguish reviews, it is important to understand to what extent these votes reflect the actual helpfulness of the information in the review and to what extent they reflect previous helpfulness votes.