bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful Correction of ALD Patient-derived iPSCs Using CRISPR/Cas9
Authors: Jung Eul Sik , Quan Zhejiu , Chang Mi-Yoon , Hong Wonjun , Kim Ji Hun , Kim Seung Hyun , You Seungkwon , Kim Dae-Sung , Jang Jiho , Lee Sang-Hun , Kim Hyongbum (Henry) , Kang Hoon Chul
Published: February 2020

X-linked adrenoleukodystrophy (ALD) caused by theABCD1mutation, is the most common inherited peroxisomal disease. It is characterized by three phenotypes: inflammatory cerebral demyelination, progressive myelopathy, and adrenal insufficiency, but there is no genotype-phenotype correlation. Hematopoietic stem cell transplantation can only be used in a few patients in the early phase of cerebral inflammation; therefore, most affected patients have no curative option. Previously, we reported the generation of an ALD patient-derived iPSC model and its differentiation to oligodendrocytes. In this study, we have performed the first genome editing of ALD patient-derived iPSCs using homology-directed repair (HDR). The mutation site, c.1534G>A [GenBank:NM_000033.4], was corrected by introducing ssODN and the CRISPR/Cas9 system. The cell line exhibited normal ALD protein expression following genome editing. We differentiated the intermediate oligodendrocytes from mutation-corrected iPSCs and the metabolic derangement of ALD tended to correct but was not statistically significant. Mutation-corrected iPSCs from ALD patient can be used in research into the pathophysiology of and therapeutics for ALD.
The virulence of theCryptococcus neoformansVNIa-5 lineage is highly plastic and associated with isolate background
Authors: Hai Trieu Phan , Tuan Thanh Lam , Van Anh Duong , Mai Trinh Nguyen , Phu Huong Lan Nguyen , Thwaites Guy E. , Johnson Errin , Van Vinh Chau Nguyen , Baker Stephen , Ashton Philip M. , Day Jeremy N.
Published: February 2020

Cryptococcus neoformansmost frequently causes disease in immunocompromised patients. However, in Vietnam and east Asia, disease is frequently reported in apparently immunocompetent patients. We have previously shown that almost all such disease is due to a specific lineage ofC. neoformans– VNIa-5. However, in HIV-infected patients, infections due to this lineage are not associated with worse outcomes. Here, we demonstrate that the VNIa-5 lineage presents different virulence phenotypes depending on its source. Isolates derived from immunocompetent patients are more virulent than those from HIV-infected patients or the environment. Moreover, the virulence phenotype is plastic – sterile culture filtrate from highly virulent VNIa-5 strains can induce increased virulence in less virulent VNIa-5 isolates, which in turn can then induce increased virulence in their low virulence states. We present evidence that this phenomenon is driven by secreted proteins associated with extra-cellular vesicles.
Genomic Prediction with Genotype by Environment Interaction Analysis for Kernel Zinc Concentration in Tropical Maize Germplasm
Authors: Mageto Edna K. , Crossa Jose , Pérez-Rodríguez Paulino , Dhliwayo Thanda , Palacios-Rojas Natalia , Lee Michael , Guo Rui , Vicente Félix San , Zhang Xuecai , Hindu Vemuri
Published: February 2020

Zinc (Zn) deficiency is a major risk factor for human health, affecting about 30% of the world’s population. To study the potential of genomic selection (GS) for maize with increased Zn concentration, an association panel and two doubled haploid (DH) populations were evaluated in three environments. Three genomic prediction models, M (M1: Environment + Line, M2: Environment + Line + Genomic, and M3: Environment + Line + Genomic + Genomic x Environment) incorporating main effects (lines and genomic) and the interaction between genomic and environment (G x E) were assessed to estimate the prediction ability (rMP) for each model. Two distinct cross-validation (CV) schemes simulating two genomic prediction breeding scenarios were used. CV1 predicts the performance of newly developed lines, whereas CV2 predicts the performance of lines tested in sparse multi-location trials. Predictions for Zn in CV1 ranged from −0.01 to 0.56 for DH1, 0.04 to 0.50 for DH2 and −0.001 to 0.47 for the association panel. For CV2,rMPvalues ranged from 0.67 to 0.71 for DH1, 0.40 to 0.56 for DH2 and 0.64 to 0.72 for the association panel. The genomic prediction model which included G x E had the highest averagerMPfor both CV1 (0.39 and 0.44) and CV2 (0.71 and 0.51) for the association panel and DH2 population, respectively. These results suggest that GS has potential to accelerate breeding for enhanced kernel Zn concentration by facilitating selection of superior genotypes.
Expecting the unexpected: the paranoid style of belief updating across species
Authors: Reed Erin J. , Uddenberg Stefan , Mathys Christoph D. , Taylor Jane R. , Groman Stephanie M. , Corlett Philip R.
Published: February 2020

Paranoia is the belief that harm is intended by others. It may arise from selective pressures to infer and avoid social threats, particularly in ambiguous or changing circumstances. We propose that uncertainty may be sufficient to elicit learning differences in paranoid individuals, without social threat. We used reversal learning behaviour and computational modelling to estimate belief updating across individuals with and without mental illness, online participants, and rats exposed to chronic methamphetamine, an elicitor of paranoia in humans. Paranoia is associated with a strong but immutable prior on volatility, accompanied by elevated sensitivity to perceived changes in the task environment. Methamphetamine exposure in rats recapitulates this impaired uncertainty-driven belief updating and rigid anticipation of a volatile environment. Our work provides evidence of fundamental, domain-general learning differences in paranoid individuals. This paradigm enables further assessment of the interplay between uncertainty and belief-updating across individuals and species.
Convergent evolution of niche structure in Northeast Pacific kelp forests
Authors: Starko Samuel , Demes Kyle W. , Neufeld Christopher J. , Martone Patrick T.
Published: February 2020

Much of the morphological and ecological diversity present on earth is believed to have arisen through the process of adaptive radiation. Yet, this is seemingly at odds with substantial evidence that niches tend to be similar among closely related species (i.e., niche conservatism). Identifying the relative importance of these opposing processes in different circumstances is therefore essential to our understanding of the interaction between ecological and evolutionary phenomena.

In this study, we make use of recent advances in our understanding of the phylogeny of kelps (Laminariales) to investigate niche evolution in one of the most important groups of benthic habitat-forming organisms on the planet. We quantify functional traits and use community sampling data from a kelp diversity hotspot to determine which traits are responsible for the habitat (β) niche of kelps and whether they are labile or conserved across the kelp phylogeny.

We find that combinations of functional traits have evolved convergently across kelp subclades and that these traits are significant predictors of community structure. Specifically, traits associated with whole-kelp structural reinforcement and material properties were found to be significantly correlated with species distributions along a gradient of wave disturbance and thus predict the outcome of environmental filtering. However, kelp assemblages were made up of species that are more phylogenetically distinct than predicted from null models (i.e., phylogenetic overdispersion), suggesting that niche partitioning along this gradient of wave disturbance has been an important driver of divergence between close relatives.

These results collectively demonstrate that environmental filtering by waves plays an essential role in determining the habitat niche of kelps across local communities and further suggest that this community-level process can drive phenotypic divergence between close relatives. We propose that parallel adaptive radiation of kelp subclades has shaped the diversity and species composition of kelp forests in the Northeast Pacific and we discuss how evidence from the literature on incipient or ongoing speciation events support this hypothesis.
Mustache: Multi-scale Detection of Chromatin Loops from Hi-C and Micro-C Maps using Scale-Space Representation
Authors: Ardakany Abbas Roayaei , Gezer Halil Tuvan , Lonardi Stefano , Ay Ferhat
Published: February 2020

We present Mustache, a new method for multi-scale detection of chromatin loops from Hi-C and Micro-C contact maps. Mustache employs scale-space theory, a technical advance in computer vision, to detect blob-shaped objects in a multi-scale representation of chromatin contact maps parametrized by the size of the smoothing kernel. When applied to high-resolution Hi-C and Micro-C data, Mustache detects loops at a wide range of genomic distances, identifying potential structural and regulatory interactions that are supported by independent conformation capture experiments as well as by known correlates of loop formation such as CTCF binding, enhancers and promoters. Unlike the commonly used HiCCUPS tool, Mustache runs on general-purpose CPUs and it is very time efficient with a runtime of only a few minutes per chromosome for 5kb-resolution human genome contact maps. Extensive experimental results show that Mustache reports two to three times the number of HiCCUPS loops, which are reproducible across replicates. It also recovers a larger proportion of published ChIA-PET and HiChIP loops than HiCCUPS. A comparative analysis of Mustache’s experimental results on Hi-C and Micro-C data confirms strong agreement between the two datasets with Micro-C providing better power for loop detection. Overall, our experimental results show that Mustache enables a more efficient and comprehensive analysis of the chromatin looping from high-resolution Hi-C and Micro-C datasets. Mustache is freely available at https://github.com/ay-lab/mustache.
Predicting TUG score from gait characteristics with video analysis and machine learning
Authors: Jian MA
Published: February 2020

Fall is a leading cause of death which suffers the elderly and society. Timed Up and Go (TUG) test is a common tool for fall risk assessment. In this paper, we propose a method for predicting TUG score from gait characteristics extracted from video with computer vision and machine learning technologies. First, 3D pose is estimated from video captured with 2D and 3D cameras during human motion and then a group of gait characteristics are computed from 3D pose series. After that, copula entropy is used to select those characteristics which are mostly associated with TUG score. Finally, the selected characteristics are fed into the predictive models to predict TUG score. Experiments on real world data demonstrated the effectiveness of the proposed method. As a byproduct, the associations between TUG score and several gait characteristics are discovered, which laid the scientific foundation of the proposed method and make the predictive models such built interpretable to clinical users.
Intracranial-EEG evidence for medial temporal pole driving amygdala activity induced by multi-modal emotional stimuli
Authors: Sonkusare Saurabh , Nguyen Vinh Thai , Moran Rosalyn , van der Meer Johan , Ren Yudan , Koussis Nikitas , Dionisio Sasha , Breakspear Michael , Guo Christine
Published: February 2020

The temporal pole (TP) is an associative cortical region required for complex cognitive functions such as social and emotional cognition. However, functional mapping of the TP with functional magnetic resonance imaging is technically challenging and thus understanding of its interaction with other key emotional circuitry, such as the amygdala, remain elusive. We exploited the unique advantages of stereo-electroencephalography (SEEG) to assess the responses of the TP and the amygdala during the perception of emotionally salient stimuli of pictures, music and movies. These stimuli consistently elicited high gamma responses (70-140 Hz) in both the TP and the amygdala, accompanied by functional connectivity in the low frequency range (2-12 Hz). Computational analyses suggested the TP driving this effect in the theta-alpha frequency range and which was modulated by the emotional salience of the stimuli. Of note, cross-frequency analysis indicated the phase of theta-alpha oscillations in the TP modulated the amplitude of high gamma activity in the amygdala. These results were reproducible with three types of stimuli including naturalistic stimuli suggesting a hierarchical influence of the TP over the amygdala in non-threatening stimuli.
Signatures of selection in the coral holobiont reveal complex adaptations to inshore environments driven by Holocene climate change
Authors: Cooke Ira , Ying Hua , Forêt Sylvain , Bongaerts Pim , Strugnell Jan , Simakov Oleg , Zhang Jia , Field Matt A. , Rodriguez-Lanetty Mauricio , Bell Sara C. , Bourne David G. , van Oppen Madeleine JH , Ragan Mark A. , Miller David J.
Published: February 2020

Climate change at the Pleistocene/Holocene boundary reshaped many coastal landscapes, and provides an opportunity to study recent adaptive processes in marine species and ecosystems including coral reefs. On the Great Barrier Reef (GBR) sea level rise flooded a vast shelf creating a distinct inshore region which now harbours extensive coral assemblages despite being subject to relatively high turbidity, freshwater input and thermal fluctuations. To investigate how the coral holobiont has adapted to these conditions we first generated a highly contiguous genome assembly forAcropora tenuisbased on long-read sequencing, and then used shallow whole-genome resequencing of 148Acropora tenuiscolonies from five inshore locations to model demographic history, identify signatures of selection and profile symbiont communities. We show that corals from Magnetic Island, located in the central inshore region of the GBR, are genetically distinct from those 50-500km further north, reflecting a Pleistocene (250-600Kya) split, whereas photosymbiont genotypes differ between reefs in a pattern more likely to reflect contemporary (Holocene) conditions. We also identified loci in the coral host genome with signatures of positive selection in the northern population and used coalescent simulations to show that these are unlikely to be accounted for by demographic history. Genes at these loci have roles in a diverse range of processes that includes heterotrophic nutrition, osmotic regulation, skeletal development and the establishment and maintenance of symbiosis. Our results show that, in the case ofA. tenuisholobionts from the inshore GBR, the genomes of both the coral host and the primary photosymbiont of have been significantly shaped by their environment and illustrate the complexity of adaptations that have occurred in response to past climate change.
The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment
Authors: Legal Thibault , Hayward Daniel , Gluszek-Kustusz Agata , Blackburn Elizabeth A. , Spanos Christos , Rappsilber Juri , Gruneberg Ulrike , Welburn Julie P.I.
Published: February 2020

During cell division, misaligned chromosomes are captured and aligned by motors before their segregation. The CENP-E motor is recruited to polar unattached kinetochores, to facilitate chromosome alignment. The spindle checkpoint protein BubR1 has been reported as a CENP-E interacting partner, but to what extent, if at all, BubR1 contributes to CENP-E localization at kinetochores, has remained controversial. Here we define the molecular determinants that specify the interaction between BubR1 and CENP-E. The basic C-terminal helix of BubR1 is necessary but not sufficient for CENP-E interaction, while a minimal key acidic patch on the kinetochore-targeting domain of CENP-E, is also essential. We then demonstrate that BubR1 is required for the recruitment of CENP-E to kinetochores to facilitate chromosome alignment. This BubR1-CENP-E axis is critical to align chromosomes that have failed to congress through other pathways and recapitulates the major known function of CENP-E. Overall, our studies define the molecular basis and the function for CENP-E recruitment to BubR1 at kinetochores during mammalian mitosis.
Automated joint skull-stripping and segmentation with Multi-Task U-Net in large mouse brain MRI databases
Authors: De Feo Riccardo , Shatillo Artem , Sierra Alejandra , Valverde Juan Miguel , Gröhn Olli , Giove Federico , Tohka Jussi
Published: February 2020

Skull-stripping and region segmentation are fundamental steps in preclinical magnetic resonance imaging (MRI) studies, and these common procedures are usually performed manually. We present Multi-task U-Net (MU-Net), a convolutional neural network designed to accomplish both tasks simultaneously. MU-Net achieved higher segmentation accuracy than state-of-the-art multi-atlas segmentation methods with an inference time of 0.35 seconds and no pre-processing requirements. We evaluated the performance of our network in the presence of skip connections and recently proposed framing connections, finding the simplest network to be the most effective. We tested MU-Net with an unusually large dataset combining several independent studies consisting of 1,782 mouse brain MRI volumes of both healthy and Huntington animals, and measured average Dice scores of 0.906 (striati), 0.937 (cortex), and 0.978 (brain mask). These high evaluation scores demonstrate that MU-Net is a powerful tool for segmentation and skull-stripping, decreasing inter and intra-rater variability of manual segmentation. The MU-Net code and the trained model are publicly available athttps://github.com/Hierakonpolis/MU-Net.
General anaesthesia disrupts complex cortical dynamics in response to intracranial electrical stimulation in rats
Authors: Arena A. , Comolatti R. , Thon S. , Casali A.G. , Storm J.F.
Published: February 2020

The capacity of the human brain to sustain complex dynamics consistently drops when consciousness fades. Several recent studies in humans found a remarkable reduction of the complexity of cortical responses to local stimulation during dreamless sleep, general anaesthesia, and coma. So far, this perturbational complexity has never been estimated in non-human animalsin vivo. Here, we quantify the complexity of electroencephalographic responses to intracranial electrical stimulation in rats, comparing wakefulness to propofol, sevoflurane, and ketamine anaesthesia. We confirm the changes previously observed in humans: from highly complex evoked activity during wakefulness, to simpler responses, suppression of high frequencies, and reduced phase-locking with propofol and sevoflurane. We then deepen our mechanistic understanding by analyzing functional connectivity, and by showing how these parameters dissociate with ketamine, and depend on intensity and site of stimulation. This approach opens the way for further direct investigations of the mechanisms underlying brain complexity and consciousness.
Profiling of the reprogramome and quantification of fibroblast reprogramming to pluripotency
Authors: Hu Kejin , Ianov Lara , Crossman David
Published: February 2020

Pluripotent state can be established via reprogramming of somatic nuclei by factors within an oocyte or by ectopic expression of a few transgenes. Considered as being extensive and intensive, the full complement of genes to be reprogrammed, however, has never been defined, nor has the degree of reprogramming been determined quantitatively. Here, we propose a new concept of reprogramome, which is defined as the full complement of genes that need to be reprogrammed to the expression levels found in pluripotent stem cells (PSCs). This concept in combination with RNA-seq enables us to precisely profile reprogramome and sub-reprogramomes, and study the reprogramming process with the help of other available tools such as GO analyses. With reprogramming of human fibroblasts into PSCs as an example, we have defined the full complement of the human fibroblast-to-PSC reprogramome. Furthermore, our analyses of the reprogramome revealed that WNT pathways and genes with roles in cellular morphogenesis have to be extensively and intensely reprogrammed for the establishment of pluripotency. We further developed the first mathematical model to quantitate the overall reprogramming, as well as reprogramming in a specific cellular feature such as WNT signaling pathways and genes regulating cellular morphogenesis. We anticipate that our concept and mathematical model may be applied to study and quantitate other reprogramming (pluripotency reprogramming from other somatic cells, and lineage reprogramming), as well as transcriptional and epigenetic differences between any two types of cells including cancer cells and their normal counterparts.
Mucosal delivery of a multistage subunit vaccine promotes development of lung-resident memory T cells and affords interleukin-17-dependant protection against pulmonary tuberculosis
Authors: Counoupas Claudio , Ferrell Kia , Ashhurst Anneliese , Bhattacharyya Nayan , Nagalingam Gayathri , Feng Carl G. , Petrovsky Nikolai , Britton Warwick J. , Triccas James A.
Published: February 2020

The development of effective vaccines against bacterial lung infections requires the induction of protective, pathogen-specific immune responses without deleterious inflammation within the pulmonary environment. Here, we made use of a polysaccharide-adjuvanted vaccine approach to elicit resident pulmonary T cells to protect against aerosolMycobacterium tuberculosisinfection. Intratracheal administration of the multistage fusion protein CysVac2 and the delta-inulin adjuvant Advax™ (formulated with a TLR9 agonist) provided superior protection against aerosolM. tuberculosisinfection in mice, compared to parenteral delivery. Surprisingly, removal of the TLR9 agonist did not impact vaccine protection despite a reduction in cytokine-secreting T cell subsets, particularly CD4+IFN-γ+IL-2+TNF+multifunctional T cells. CysVac2/Advax-mediated protection was associated with the induction of lung-resident, antigen-specific memory CD4+T cells that expressed IL-17 and RORγt, the master transcriptional regulator of Th17 differentiation. IL-17 was identified as a key mediator of vaccine efficacy, with blocking of IL-17 duringM. tuberculosischallenge reducing phagocyte influx, suppressing priming of pathogen-specific CD4+T cells in local lymph nodes and ablating vaccine-induced protection. These findings suggest that tuberculosis vaccines such as CysVac2/Advax that are capable of eliciting Th17 lung-resident memory T cells are promising candidates for progression to human trials.

Importance

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), kills more individuals each year than any other single pathogen. The only approved vaccine, BCG, administered intradermally, is unreliable in protecting against pulmonary TB, therefore a more effective vaccine is critical for global control of the disease. Vaccination in the lung would be a rational way of inducing a local memory immune response to TB, however vaccine platforms would need to deliver antigens to delicate mucosal surfaces without inducing deleterious inflammatory responses. We developed a safe mucosal vaccine which induced protection against TB lung infection in mice by inducing high levels of lung-resident T cells expressing the cytokine IL-17. Removal of IL-17 limited the influx of phagocytic cells to the lung and completely ablated protection afforded by the vaccine. This study provides new insights into mechanisms of protection againstM. tuberculosisand provides a promising candidate to protect against TB in humans.
Standard Flow Multiplexed Proteomics (SFloMPro) – An Accessible and Cost-Effective Alternative to NanoLC Workflows
Authors: Jenkins Conor , Orsburn Ben
Published: February 2020

Multiplexed proteomics using isobaric tagging allows for simultaneously comparing the proteomes of multiple samples. In this technique, digested peptides from each sample are labeled with a chemical tag prior to pooling sample for LC-MS/MS with nanoflow chromatography (NanoLC). The isobaric nature of the tag prevents deconvolution of samples until fragmentation liberates the isotopically labeled reporter ions. To ensure efficient peptide labeling, large concentrations of labeling reagents are included in the reagent kits to allow scientists to use high ratios of chemical label per peptide. The increasing speed and sensitivity of mass spectrometers has reduced the peptide concentration required for analysis, leading to most of the label or labeled sample to be discarded. In conjunction, improvements in the speed of sample loading, reliable pump pressure, and stable gradient construction of analytical flow HPLCs has continued to improve the sample delivery process to the mass spectrometer. In this study we describe a method for performing multiplexed proteomics without the use of NanoLC by using offline fractionation of labeled peptides followed by rapid “standard flow” HPLC gradient LC-MS/MS. Standard Flow Multiplexed Proteomics (SFloMPro) enables high coverage quantitative proteomics of up to 16 mammalian samples in about 24 hours. In this study, we compare NanoLC and SFloMPro analysis of fractionated samples. Our results demonstrate that comparable data is obtained by injecting 20 μg of labeled peptides per fraction with SFloMPro, compared to 1 μg per fraction with NanoLC. We conclude that, for experiments where protein concentration is not strictly limited, SFloMPro is a competitive approach to traditional NanoLC workflows with improved up-time, reliability and at a lower relative cost per sample.

Data are available via ProteomeXchange with identifier PXD016704.

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Control of tissue development by cell cycle dependent transcriptional filtering
Authors: Chakra Maria Abou , Isserlin Ruth , Tran Thinh , Bader Gary D.
Published: February 2020

Cell cycle duration changes dramatically during development, starting out fast to generate cells quickly and slowing down over time as the organism matures. The cell cycle can also act as a transcriptional filter to control the expression of long genes which are partially transcribed in short cycles. Using mathematical simulations of cell proliferation, we identify an emergent property, that this filter can act as a tuning knob to control cell fate, cell diversity and the number and proportion of different cell types in a tissue. Our predictions are supported by comparison to single-cell RNA-seq data captured over embryonic development. Evolutionary genome analysis shows that fast developing organisms have a narrow genomic distribution of gene lengths while slower developers have an expanded number of long genes. Our results support the idea that cell cycle dynamics may be important across multicellular animals for controlling gene expression and cell fate.
The impact of colonization history on the composition of ecological systems
Authors: Zhao Nannan , Saavedra Serguei , Liu Yang-Yu
Published: February 2020

Observational studies of ecological systems have shown that different species compositions can arise from distinct species arrival orders during community assembly—also known as colonization history. However, it is still unclear under which conditions colonization history will dominate community composition. Yet, this is important in order to understand and anticipate the impact of species arrivals on the biodiversity that we observe in both nature and experiments. To address this fundamental question, here we develop a testable theory linking colonization history and community composition. First, we prove two general theorems to determine whether the composition of a community will depend on its colonization history. For communities governed by Lotka-Volterra dynamics, we further simplify the two theorems into a corollary that is easy for numerical test. Second, we show, via extensive numerical simulations, that the probability that community composition is dominated by colonization history increases monotonically with community size and species connectivity. Third, we show that this probability significantly increases with the variation of intrinsic growth rates across species. These results reveal that community composition is a probabilistic process mediated by ecological dynamics via the interspecific variation and the size of regional pools.
Genotype networks of 80 quantitativeArabidopsis thalianaphenotypes reveal phenotypic evolvability despite pervasive epistasis
Authors: Schweizer Gabriel , Wagner Andreas
Published: February 2020

We study the genotype-phenotype maps of 80 quantitative phenotypes in the model plantArabidopsis thaliana,by representing the genotypes affecting each phenotype as a genotype network. In such a network, each vertex or node corresponds to an individual’s genotype at all those genomic loci that affect a given phenotype. Two vertices are connected by an edge if the associated genotypes differ in exactly one nucleotide. The 80 genotype networks we analyze are based on data from genome-wide association studies of 199A. thalianaaccessions. They form connected graphs whose topography differs substantially among phenotypes. We focus our analysis on the incidence of epistasis (non-additive interactions among mutations) because a high incidence of epistasis can reduce the accessibility of evolutionary paths towards high or low phenotypic values. We find epistatic interactions in 67 phenotypes, and in 51 phenotypes every pairwise mutant interaction is epistatic. Moreover, we find phenotype-specific differences in the fraction of accessible mutational paths to maximum phenotypic values. However, even though epistasis affects the accessibility of maximum phenotypic values, the relationships between genotypic and phenotypic change of our analyzed phenotypes are sufficiently smooth that some evolutionary paths remain accessible for most phenotypes, even where epistasis is pervasive. The genotype network representation we use can complement existing approaches to understand the genetic architecture of polygenic traits in many different organisms.

Author summary

How genotypic change relates to phenotypic change is a fundamental problem in evolutionary biology. A smooth relationship between genotypic and phenotypic change facilitates phenotypic evolution, whereas a rugged one hampers it, because evolutionary change on a rugged landscape does not allow a monotonic increase or decrease in phenotypic value. We use data from multiple genome-wide association studies for 80 different phenotypes in the thale cressArabidopsis thalianato construct 80 genotype-phenotype maps for these phenotypes. We use a network representation for each map, where a vertex corresponds to a genotype, and where two vertices are connected if they differ in a single nucleotide. We study the incidence of non-additive interactions between mutations as a proxy for the ease to reach extreme phenotypic values of these maps. This incidence varies greatly among phenotypes, but even where it is highest, some monotonic pathways to high or low phenotypic values exist for the vast majority of phenotypes, such that the underlying phenotypes are accessible to adaptive evolution.
Lessons from within: redesigning higher education
Authors: Hale Annie , Archambault Leanna , Wenrick Lukas
Published: February 2020

Purpose

The purpose of this study is to examine real experiences and challenges from personnel engaged in reforming and transforming the higher education ecosystem at a major university in the desert southwest.

Design/methodology/approach

Through a case study approach, we use narrative analysis and a constant comparative method with three researchers who work closely in this space.

Findings

Ten categories were identified through a close review of collected data from ten participants through an IRB approved process. Recommendations include clarifying the purpose and using transparent terminology for both implementers and learners as well as figuring out ways to help learners navigate learning pathways. Personnel yearn to be involved early and often to be able to shape major transformations that make use of their efforts and expertise.

Research limitations/implications

Exploring phenomenon in context at one university can highlight nuances that exist at this particular case study site and may not be generalizable.

Practical implications

Sharing real experiences and challenges from those who have begun to implement change in higher education is critical and will bolster those working to push learning forward into the 21st century. To meet the needs of learners at the pre-college, college, and post-college levels, universities need to innovate beyond the traditional modes of education.

Originality/value

It is not often that researchers explore and analyze the struggles and successes of personnel on the ground, working to actualize a major educational shift in higher education. The ten categories denoted in this paper are a pivotal entry point for review that can support others who are engaging or beginning to make changes in their context – pushing one beyond known considerations.
What are your “odds-of-success”? Reflecting on the role of adaptive leadership in Leicester City’s (2015/16) English Football Premier League Title win
Authors: Coleman Andy
Published: February 2020

Purpose

This article utilizes the concept of adaptive leadership to explore how Leicester City, a small, provincial football club, defied odds of 5000-1 to became only the sixth winners of the English Premier League. It examines two research questions: 1. can adaptive leadership be used to explain how the club developed the conditions for the team’s success? and; 2. what practical lessons can be learned from this?

Design/methodology/approach

This case study utilizes secondary material, published from 2011-2019, including interviews with players and staff, recordings of press conferences, club announcements, match programmes, books, magazine and newspaper articles, television reports, and social media coverage.

Findings

Adaptive leadership provides a mechanism for understanding the organizational change necessary for Leicester City’s title victory. Three core elements of adaptive leadership are identified: 1. the “change leader’s” deliberate decision to engage others across the organization in a process of “intelligent reflection,” to identify the required approach to address an identified organizational objective; 2. an organization-wide focus on building leadership capacity, to promote continuous improvement through personal and organizational learning; 3. a long term commitment by the most senior organizational leader to elements of the change process, thereby ensuring new ways of working became normalized over the longer term.

Originality/value

While theoretically well-developed, the practice of adaptive leadership remains under-researched (Yukl and Mahsud, 2010). Leicester City’s Premier League victory illustrates several key aspects of adaptive leadership in action, in a way that many people can easily relate to. The efficacious and team learning aspects of Leicester City’s success story are important for organizational development scholars and practitioners alike. In summary, the key findings and lessons within this article can be metaphorically transferred to other team-based learning organization, i.e. including and beyond the world of sport!.
Enhancing students' entrepreneurial capacity through marketing simulation games
Authors: Thanasi-Boçe Marsela
Published: February 2020

Purpose

Education can cultivate a variety of skills for future entrepreneurs. The purpose of this study was to explore the role of a marketing simulation game as a pedagogical tool to enhance the entrepreneurial mind-set and boost the predisposition of postgraduate students to become entrepreneurs.

Design/methodology/approach

Qualitative data from the feedback of students regarding their simulation experience in an advanced marketing course were collected and analyzed.

Findings

The reports showed that, in a simulation setting, entrepreneurial learning can develop students' entrepreneurial skills and encourage them to undertake entrepreneurial activities. The simulation experience allowed students to face challenges, overcome limitations, improve their analytical skills, and enhance their business knowledge.

Research limitations/implications

First, these findings cannot be generalized as they are based on a small sample of students. Second, qualitative research is very reliant on the individual characteristics of students. Because of the restricted time of the module, the students were only allowed to run six rounds (the minimum) out of 10. More rounds would have benefitted student learning and increased the likelihood of capturing more of their insights.

Originality/value

By using qualitative research, this study provides more thoughtful insights into students' perceptions of entrepreneurial skills and competency improvements by using simulation as a pedagogical tool. Following the suggestions of Fayolle et al. (2016), this study underlines the entrepreneurship education outcomes in terms of students' reflections on understanding their capability and their predisposition to take entrepreneurial actions in the future. Also, the role of education in fostering entrepreneurship is highlighted.
Developing a comprehensive life cycle framework for social media research in hospitality and tourism
Authors: Nusair Khaldoon
Published: February 2020

Purpose

This paper aims to provide a comprehensive bibliometric analysis of the current state of social media literature by examining co-word network analysis and thematic keyword analysis of both scholars and hospitality and tourism journals in three sub-periods (2002-2006, 2007-2012 and 2013-2018).

Design/methodology/approach

This research used a bibliometric analysis of social media literature in the field of hospitality and tourism by synthesizing the literature of a large sample of 601 studies over an extended time period (2002-2018).

Findings

The jump in the number of examined contexts, platforms, methodological approaches and research implications during 2007-2012 has marked the start of social media as a new phenomenon in hospitality and tourism research. Interestingly,International Journal of Contemporary Hospitality Managementwas a leading contributor to social media research between 2017 and 2018. The period 2013-2018 has witnessed newly emerging trends such as “big data,” “e-tourism,” “green experience” and “smart tourism.” This study’s analysis indicated that few keywords in social media appeared in the maturity stage. New platforms such as “Expedia,” “Foursquare,” “Flickr,” “Pinterest,” “Couchsurfing” and “Twitter” appeared between 2013 and 2018.

Originality/value

The scope of past research on the evolution of social media was limited to either a few of the most popular cited journals and/or analysis within a narrow time span. In contrast, the present study aims to uncover the rapid progress in social media research between 2002 and 2018, addressing growth in breadth and depth of thematic areas. Finally, this paper concluded with the proposal of knowledge-based life cycle framework that identifies key themes related to social media research. This framework provided insights into what has been addressed in previous literature (maturity and decline stages) and reported the topics that have been under-researched (introduction and growth stages).
Organizational learning in consciousness-based education schools: a multiple-case study
Authors: Lagrosen Yvonne , Lagrosen Stefan
Published: February 2020

Purpose

An innovative technology called consciousness-based education (CBE) is being introduced in schools worldwide. The approach includes both an experiential and an intellectual component. However, research studies exploring learning in CBE are rare. The purpose of the paper is to explore how organizational learning takes place in schools, which adopt CBE in addition to their ordinary curriculum. Moreover, the ambition of the approach regarding quality is examined.

Methodology/approach

A multiple-case study has been carried out. Four schools using CBE have been studied: a private school in Fairfield, Iowa, USA; a governmentally funded free school in Skelmersdale, United Kingdom; an independent school in Melbourne, Australia, and a primary school in Lelystad, the Netherlands. In total, 26 in-depth interviews have been performed, mainly with teachers and students but also with principals and experts in the CBE pedagogy. In addition, three focus-group interviews with primary school pupils were conducted and observation during classes was included. The data were analyzed by the constant comparative technique from the grounded theory approach.

Findings

Categories characterizing organizational learning in the CBE schools have been identified. These findings are related to theories of the learning organization, resulting in a framework depicting different components of learning.

Research limitation/implication

The study provides a framework illustrating organizational learning in schools that utilize CBE which affords an overview of the technology and can serve as a vantage point for further research. Since this is a qualitative case study, the effectiveness of the CBE approach and its impact on learning outcomes were not assessed, and the possibilities to generalize the findings are limited.

Originality/value

CBE has not previously been studied from an organizational learning perspective.
The prevalence of ill-treatment and bullying at work in Ireland
Authors: Hogan Victoria , Hodgins Margaret , Lewis Duncan , Maccurtain Sarah , Mannix-McNamara Patricia , Pursell Lisa
Published: February 2020

Purpose

The purpose of this paper is to examine the prevalence of ill-treatment and bullying experienced by Irish workers and to explore individual and organisational predictors. The most recent national figures available are specific to bullying and predate the economic recession; therefore, this study is timely and investigates a broader range of negative behaviours.

Design/methodology/approach

A questionnaire survey study on a national probability sample of Irish employees was conducted (N = 1,764). The study design replicated the methodology employed in the British workplace behaviour study.

Findings

The results showed that 43% of Irish workers had experienced ill-treatment at work over the past two years, with 9% meeting the criteria for experiencing workplace bullying. A number of individual and organisational factors were found to be significantly associated with the experience of ill-treatment at work.

Research limitations/implications

This study provides national-level data on workplace ill-treatment and bullying that are directly comparable to British study findings.

Practical implications

The findings indicate that a significant number of Irish workers experience ill-treatment at work, and that workplace bullying does not appear to have decreased since the last national study was conducted in Ireland.

Social implications

This study is of use to the Irish regulator and persons responsible for managing workplace bullying cases, as it identifies high-risk work situations and contributing individual factors.

Originality/value

This study provides national Irish data on workplace behaviour and ill-treatment following a severe economic recession.
Exploring the effect of an enhanced e-commerce institutional mechanism on online shopping intention in the context of e-commerce poverty alleviation
Authors: Han Feiyan , Li Bo
Published: February 2020

Purpose

E-commerce poverty alleviation (EPA) is an innovative poverty alleviation model in China. The institutional mechanisms of the e-commerce platform improve the effect of EPA and exert online shopping purchase power in rural China. From a socio-technical perspective, this paper used adoption readiness of farmers and perceived risk to construct an integrated model to discern the effect of enhanced e-commerce institutional mechanisms on farmers' online shopping intention in the context of EPA.

Design/methodology/approach

The survey included 832 valid samples from rural farmers in Shanxi province. This study analyses using structural equation modelling (SEM) and bootstrap methods used to empirically test the model.

Findings

Findings suggest that enhanced e-commerce institutional mechanisms have significant direct and indirect positive impacts on farmers' online shopping intention; adoption readiness and perceived risk play partial mediation roles in determining the relationship between farmers' online shopping intention and enhanced e-commerce institutional mechanisms; and the indirect mediation effect of adoption readiness is greater than that of perceived risk.

Research limitations/implications

Although the proposed model was supported in the questionnaire survey, the investigation method was not completely excluded. Future research can combine the method of panel data and apply the framework to other e-commerce platforms, as well as to other cultural settings.

Practical implications

The study suggests that enhanced e-commerce institutional mechanisms that are based on the needs of farmers from poverty-stricken areas change the shopping habits of farmers. Moreover, enhanced e-commerce institutional mechanisms should allow farmers' perceived adoption readiness to play its promoting role and reduce the impeding role of perceived risk. The results of this study are conducive to the intensive implementation of the ‘Three Rural Issues’ strategy in China.

Originality/value

A new model to generate a two-factor mediation effect model by integrating the perceived effectiveness of enhanced e-commerce institutional mechanisms with farmers, farmers' adoption readiness, perceived risk and online shopping intention. The study explored the relationship between enhanced e-commerce institutional mechanisms and farmers' online shopping intention, bridging the gap in related empirical studies. Besides, this study first proposed farmers' adoption readiness and clarifies the mediating role of farmers' adoption readiness and perceived risk, which highlights the previously unnoticed role of farmers' adoption readiness.
Macroeconomic and macro-financial factors as leading indicators of non-performing loans
Authors: Staehr Karsten , Uusküla Lenno
Published: February 2020

Purpose

Large or increasing stocks of non-performing loans in the banking sector constitute threats to financial stability. This paper considers to which extent various macroeconomic and macro-financial factors may serve as leading indicators for the dynamics of the ratio of non-performing loans to total loans.

Design/methodology/approach

The paper estimates panel data models for all EU countries and two groups of EU countries using quarterly data over approximately 20 years.

Findings

The estimations show that many macroeconomic and macro-financial variables are leading indicators for non-performing loans in the EU countries, even years ahead. Higher GDP growth, lower inflation and lower debt are robust leading indicators of a lower ratio of non-performing loans in the future. The current account balance and real house prices are important indicators for the Western European group but not for the Central and Eastern European group.

Research limitations/implications

The estimations are carried out for panels of EU countries and the effects may hence be seen as averages for the countries in the particular panel and may not apply for individual countries.

Practical implications

National and international authorities have brought in systems to detect and address imbalances and emerging problems in the financial sectors. Many of the measures operate with long lags, and so it is important to assess whether various macroeconomic and macro-financial variables may serve as leading indicators for future developments of non-performing loans.

Originality/value

The main contribution of the paper is that it estimates models meant expressly for predicting non-performing loans several years ahead. The results are thus of practical use for national and international authorities which typically have access to measures that operate with a long delay. The analysis also includes more macroeconomic and macro-financial variables as leading indicators than have typically been used in earlier studies.