bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTThe 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

ABSTRACTPluripotent 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

AbstractThe 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.ImportanceMycobacterium 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

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

AbstractCell 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.
Genotype networks of 80 quantitativeArabidopsis thalianaphenotypes reveal phenotypic evolvability despite pervasive epistasis
Authors: Schweizer Gabriel , Wagner Andreas 
Published: February 2020

AbstractWe 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 summaryHow 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

PurposeEducation 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/approachQualitative data from the feedback of students regarding their simulation experience in an advanced marketing course were collected and analyzed.FindingsThe 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/implicationsFirst, 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/valueBy 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

PurposeThis 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/approachThis 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).FindingsThe 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/valueThe 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

PurposeAn 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/approachA 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.FindingsCategories 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/implicationThe 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/valueCBE has not previously been studied from an organizational learning perspective.