bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell mutational profiling delineates clonal trajectories in myeloid malignancies
Authors: Miles Linde A. , Bowman Robert L. , Merlinsky Tiffany R. , Csete Isabelle S. , Ooi Aik , Durruthy-Durruthy Robert , Bowman Michael , Famulare Christopher , Patel Minal A. , Mendez Pedro , Ainali Chrysanthi , Manivannan Mani , Sahu Sombeet , Goldberg Aaron D. , Bolton Kelly , Zehir Ahmet , Rampal Raajit , Carroll Martin P. , Meyer Sara E. , Viny Aaron D. , Levine Ross L. 
Published: February 2020

SummaryMyeloid malignancies, including acute myeloid leukemia (AML), arise from the proliferation and expansion of hematopoietic stem and progenitor cells which acquire somatic mutations. Bulk molecular profiling studies on patient samples have suggested that somatic mutations are obtained in a step-wise fashion, where mutant genes with high variant allele frequencies (VAFs) are proposed to occur early in disease development and mutations with lower VAFs are thought to be acquired later in disease progression1–3. Although bulk sequencing informs leukemia biology and prognostication, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity and clone size, or offer definitive evidence of mutational order. To elucidate the clonal framework of myeloid malignancies, we performed single cell mutational profiling on 146 samples from 123 patients. We found AML is most commonly comprised of a small number of dominant clones, which in many cases harbor co-occurring mutations in epigenetic regulators. Conversely, mutations in signaling genes often occur more than once in distinct subclones consistent with increasing clonal diversity. We also used these data to map the clonal trajectory of each patient and found that specific mutation combinations (FLT3-ITD+NPM1c) synergize to promote clonal expansion and dominance. We combined cell surface protein expression with single cell mutational analysis to map somatic genotype and clonal architecture with immunophenotype. Our studies of clonal architecture at a single cell level provide novel insights into the pathogenesis of myeloid transformation and how clonal complexity contributes to disease progression.
Mapping microglia and astrocytes activationin vivousing diffusion MRI
Authors: Garcia-Hernandez Raquel , Cerdán Cerdá Antonio , Carpena Alejandro Trouve , Drakesmith Mark , Koller Kristin , Jones Derek K. , Canals Santiago , De Santis Silvia 
Published: February 2020

AbstractGlia, and particularly microglia, are increasingly implicated in the pathophysiology of psychiatric and neurodegenerative disorders. However, to date the only methods for imaging these cells in vivo involve either invasive procedures (e.g. multi-photon imaging in rodents) or TSPO-PET radiotracers, which afford low resolution and specificity, since TSPO expresses across multiple cell types. Here, we present a non-invasive diffusion-weighted MRI method to image changes in glia morphometryin vivo. Using two rat models of neuroinflammation, with and without neurodegeneration, we demonstrate that diffusion-weighted MRI carries the fingerprint of microglia and astrocytes activation, and that specific signatures from each population can be quantified non-invasively. We demonstrate that the method can further detect glia proliferation, and provide a quantitative account of neuroinflammation regardless of the existence of a concomitant neuronal loss. We prove the translational value of the approach showing significant correlations between MRI and histological microglia markers measured across different brain regions in humans. This framework holds the potential to transform basic and clinical research by providing a tool to clarify the role of inflammation in health and disease across the lifespan.
Inhibiting LXRαPhosphorylation in Hematopoietic Cells Reduces Inflammation and Attenuates Atherosclerosis and Obesity
Authors: Voisin Maud , Shrestha Elina , Rollet Claire , Josefs Tatjana , Barrett Tessa J. , Chang Hye Rim , Ruoff Rachel , Nikain Cyrus A. , Garabedian Michela L. , Brown Emily J. , Goldberg Ira J. , Pineda-Torra Inés , Fisher Edward A. , Garabedian Michael J. 
Published: February 2020

ABSTRACTAtherosclerosis and obesity share pathological features including inflammation mediated by innate and adaptive immune cells. LXRα, a nuclear receptor, plays a central role in the transcription of inflammatory and lipid metabolic genes. LXRαis modulated by phosphorylation at serine 196 (LXRαpS196), however, the functional consequences of LXRαpS196 in hematopoietic cell precursors in atherosclerosis and obesity have not been investigated. To assess the importance of LXRαphosphorylation, bone marrow from LXRαWT and S196A mice was transplanted intoLdlr-/-mice, which were fed a high fat, high cholesterol diet prior to evaluation of atherosclerosis and obesity. Plaques from S196A mice showed reduced inflammatory monocyte recruitment, lipid accumulation, and macrophage proliferation. Expression profiling of CD68+ cells from S196A mouse plaques revealed downregulation of pro-inflammatory genes and upregulation of mitochondrial genes characteristic of anti-inflammatory macrophages. Furthermore, S196A mice had lower body weight and less visceral adipose tissue; this was associated with transcriptional reprograming of the adipose tissue macrophages and resolution of inflammation resulting in less fat accumulation within adipocytes. Thus, reducing LXRαpS196 in hematopoietic cells attenuates atherosclerosis and obesity by reprogramming the transcriptional activity of LXRαto an anti-inflammatory phenotype.
Understanding the Effect of Left Prefrontal Stimulation on Positive Symptoms of Schizophrenia: A Dynamic Causal Modeling Study of Ultra-high field (7-Tesla) Resting-state fMRI
Authors: Limongi Roberto , Mackinley Michael , Dempster Kara , Khan Ali R. , Gati Joseph S. , Palaniyappan Lena 
Published: February 2020

AbstractRepetitive transcranial magnetic stimulation (rTMS), when applied to left dorsolateral prefrontal cortex (LDLPFC), reduces negative symptoms of schizophrenia, but has no effect on positive symptoms. In a small number of cases, it appears to worsen the severity of positive symptoms. It has been hypothesized that high frequency rTMS of the LDLPFC might increase the dopaminergic neurotransmission by driving the activity of the left striatum in the basal ganglia (LSTR)—increasing striatal dopaminergic activity. This hypothesis relies on the assumption that either the frontal-striatal connection or the intrinsic frontal and/or striatal connections covary with the severity of positive symptoms. The current work aimed to evaluate this assumption by studying the association between positive and negative symptoms severity and the effective connectivity within the frontal and striatal network using dynamic causal modeling (DCM) of ultra-high field (7 Tesla) resting state fMRI in a sample of 19 first episode psychosis (FEP) subjects. We found that of all core symptoms of schizophrenia, only delusions are strongly associated with the fronto striatal circuitry. Stronger intrinsic inhibitory tone of LDLPFC and LSTR, as well as a pronounced backward inhibition of the LDLPFC on the LSTR related to the severity of delusions. We interpret that an increase in striatal dopaminergic tone that underlies delusional symptoms, is likely associated with increased prefrontal inhibitory tone, strengthening the frontostriatal ‘brake’. Furthermore, based on our model, we propose that lessening of positive symptoms could be achieved by means of continuous theta-burst or low frequency (1Hz) rTMS of the prefrontal area.
Chemogenetic stimulation of mouse central amygdala corticotropin-releasing factor neurons: Effects on cellular and behavioral correlates of alcohol dependence
Authors: Kreifeldt Max , Herman Melissa A , Sidhu Harpreet , de Macedo Giovana C , Shahryari Roxana , Roberto Marisa , Contet Candice 
Published: February 2020

AbstractBackgroundCorticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) plays a critical role in rodent models of excessive alcohol drinking. However, the source of CRF acting in the CeA during alcohol withdrawal remains to be identified. In the present study, we hypothesized that CeA CRF interneurons may represent a behaviorally relevant source of CRF to the CeA increasing motivation for alcohol via negative reinforcement.MethodsWe tested this hypothesis in male mice and used chemogenetics to stimulate CeA CRF neurons in vitro and in vivo.ResultsWe first observed that Crh mRNA expression in the anterior part of the mouse CeA, at the junction with the interstitial nucleus of the posterior limb of the anterior commissure, correlates positively with alcohol intake in C57BL/6J males with a history of chronic binge drinking. We then found that chemogenetic activation of CeA CRF neurons in Crh-IRES-Cre mouse brain slices increases gamma-aminobutyric acid (GABA) release in the medial CeA in part via CRF1 receptor activation, indicating local CRF release. While chemogenetic stimulation of CeA CRF neurons exacerbated novelty-induced feeding suppression, as seen in C57BL/6J males withdrawn from chronic intermittent alcohol inhalation, it had no effect on voluntary alcohol consumption, following either acute or chronic manipulation.ConclusionsAltogether, these findings indicate that hyperactivity of CeA CRF neurons may contribute to elevated CeA GABA levels and negative affect during alcohol withdrawal but is not sufficient to drive alcohol intake escalation in dependent mice.
A comprehensive co-expression network analysis inVibrio cholerae
Authors: DuPai Cory D. , Wilke Claus O. , Davies Bryan W. 
Published: February 2020

AbstractResearch into the evolution and pathogenesis ofVibrio choleraehas benefited greatly from the generation of high throughput sequencing data to drive molecular analyses. The steady accumulation of these datasets now provides a unique opportunity forin silicohypothesis generation via co-expression analysis. Here we leverage all publishedV. choleraeRNA-sequencing data, in combination with select data from other platforms, to generate a gene co-expression network that validates known gene interactions and identifies novel genetic partners across the entireV. choleraegenome. This network provides direct insights into genes influencing pathogenicity, metabolism, and transcriptional regulation, further clarifies results from previous sequencing experiments inV. cholerae(e.g. Tn-seq and ChIP-seq), and expands upon micro-array based findings in related gram-negative bacteria.ImportanceCholera is a devastating illness that kills tens of thousands of people annually.Vibrio cholerae, the causative agent of cholera, is an important model organism to investigate both bacterial pathogenesis and the impact of horizontal gene transfer on the emergence and dissemination of new virulent strains. Despite this importance, roughly one third ofV. choleraegenes are functionally un-annotated, leaving large gaps in our understanding of this microbe. Through co-expression network analysis of existing RNA-sequencing data, this work develops an approach to uncover novel gene-gene relationships and contextualize genes with no known function, which will advance our understanding ofV. choleraevirulence and evolution.
GSK3 activity is a cell fate switch that balances the ratio of vascular cell type
Authors: Tamaki Takayuki , Oya Satoyo , Naito Makiko , Ozawa Yasuko , Furuya Tomoyuki , Saito Masato , Sato Mayuko , Wakazaki Mayumi , Toyooka Kiminori , Fukuda Hiroo , Helariutta Ykä , Kondo Yuki 
Published: February 2020

AbstractThe phloem transports photosynthetic assimilates and signalling molecules. It mainly consists of sieve elements (SEs), which act as “highways” for transport, and companion cells (CCs), which serve as “gates” to load/unload cargos. Though SEs and CCs function together, it remains unknown what determines the ratio of SE/CC in the phloem. In this study, we develop a novel culture system for CC differentiation named VISUAL-CC, which reconstitutes the SE-CC complex formation. Comparative expression analysis in VISUAL-CC reveals that SE and CC differentiation tends to show negative correlation, while total phloem differentiation is unchanged. This varying SE/CC ratio is largely dependent on GSK3 kinase activity. Indeed, gsk3 hextuple mutants possess much more SEs and less CCs in planta. Conversely, gsk3 gain-of-function mutants induced by phloem-specific promoter partially increased the CC ratio. Taken together, GSK3 activity appears to function as a cell fate switch in the phloem, thereby balancing the SE/CC ratio.
mRNA secondary structure stability regulates bacterial translation insulation and re-initiation
Authors: Chemla Yonatan , Peeri Michael , Heltberg Mathias Luidor , Eichler Jerry , Jensen Mogens Høgh , Tuller Tamir , Alfonta Lital 
Published: February 2020

AbstractIn bacteria, translation re-initiation is crucial for synthesizing proteins encoded by genes that are organized into operons. The mechanisms regulating translation re-initiation remain, however, poorly understood. We now describe the ribosome termination structure (RTS), a conserved and stable mRNA secondary structure precisely localized downstream of stop codons, which serves as the main factor governing re-initiation efficiency in a synthetic Escherichia coli operon. We further report that in 95% of 128 analyzed bacterial genomes representing all phyla, this structure is selectively depleted when re-initiation is advantageous yet selectively enriched so as to insulate translation when re-initiation is deleterious.
Shocks and entrepreneurship: a study of career shocks among newly graduated entrepreneurs
Authors: Rummel Sophie , Akkermans Jos , Blokker Rowena , Van Gelderen Marco 
Published: February 2020

PurposeThe purpose of this paper is to explore the career shocks that young, newly graduated entrepreneurs experience in the process of starting a business.Design/methodology/approachThe study adopted a qualitative approach, drawing upon 25 semi-structured interviews with entrepreneurs who recently graduated from university (up to the age of 30) in different European countries.FindingsThe analysis identifies several career shocks that can confront entrepreneurs before and after starting a business and reveals how these shocks influence graduates’ decisions to become and continue to be an entrepreneur.Research limitations/implicationsThe study sheds light on the diverse nature of career shocks and the importance of integrating agency concepts and environmental influences in career research. It identifies important factors relevant for school-to-work transition research and complements work in entrepreneurship research on necessity and opportunity entrepreneurship, push and pull motives, and entrepreneurial intentions.Practical implicationsOrganizations can use the findings to attract and retain young entrepreneurial employees, while higher education organizations can use the findings to better prepare students for a successful transition into entrepreneurship, whether in the corporate or independent form.Originality/valueThe paper integrates the concept of career shocks with literature on entrepreneurship and offers a categorization of career shocks in the pathway to entrepreneurship.
Automating construction manufacturing procedures using BIM digital objects (BDOs)
Authors: Al-Saeed Yahya , Edwards David John , Scaysbrook Stephen 
Published: February 2020

Purpose
This paper aims to present a novel proof-of-concept framework for implementing building information modeling (BIM) Digital Objects (BDO) to automate construction product manufacturers’ processes and augment lean manufacturing.

Design/methodology/approach
A mixed interpretivist and post-positivist epistemological lens is adopted to pursue the proof-of-concept’s development. From an operational perspective, a synthesis of literature using interpretivism provides the foundation for deductive research inquiry implemented within a case study approach. Within the case study, participatory action research (PAR) is implemented to test the proof of concept via three “waterfall” research phases, namely, literature diagnosis and BIM package selection, BDO development and validation and evaluation.

Findings
The findings illustrate that a BDO (which represents the digital twin of manufacturing products) can augment and drive automation processes and workflows for construction product manufacturers within a contractor’s supply chain. The developed framework illustrates the benefits of a BDO, by reducing the number of manufacturing processes to effectively eliminate early errors in the model, generates financial savings and reduces material wastage.

Originality/value
This research provides a seminal case study that implements BDO to automate construction product manufacturing processes and demonstrates the utilisation of BDO at an operational (vis-à-vis theoretical) level. Future research is proposed to implement a longitudinal approach to measure and report upon the success (or otherwise) of the proof of concept when implemented on fabrications and shop floor procedures.
Preparing future business professionals for a globalized workplace through intercultural virtual collaboration
Authors: Ferreira-Lopes Luana , Van Rompay-Bartels Ingrid 
Published: February 2020

Purpose
Universities have increasingly been adopting intercultural virtual collaboration (IVC) to connect and develop the intercultural competence of students from different locations. However, the design and implementation of IVC have proved to be challenging, and thus there is a need for sharing positive experiences. This paper explores students’ overall impressions toward their participation in an IVC project involving a Spanish and Dutch university and discusses the on-going improvement process inherent to such practice.

Design/methodology/approach
This article presents (a) the results obtained from a content analysis of students’ feedback collected through a satisfaction survey, and (b) the observations of participating teachers on the challenges encountered during the implementation of the intercultural virtual collaborative project.

Findings
The analysis shows the potential of IVC to develop different aspects of students’ intercultural competence, especially intercultural teamwork, awareness and skills. Students appreciated the experience of working in intercultural teams, “the real-life application” of the project and the opportunity to gain cultural knowledge. At the institutional level, the biggest challenge related to aligning participating institutions’ courses, schedules, and grading systems. At the classroom level, it is argued that interaction between students should happen gradually. The discussion also approaches how partnerships between universities and companies could contribute to making training in intercultural virtual collaboration more authentic.

Originality/value
Given its impact on the development of students’ intercultural competence, the intercultural virtual collaborative project has been recognized as a best-practice in both universities, being officially incorporated into the curriculum of the participating institutions and replicated to other subject areas.
Natural plants in hospitality servicescapes: the role of perceived aesthetic value
Authors: Apaolaza Vanessa , Hartmann Patrick , Fernández-Robin Cristobal , Yáñez Diego 
Published: February 2020

PurposeThis paper aims to examine the effects of natural plants on satisfaction and loyalty in the hospitality servicescape and provides a theoretical framework explaining the underlying processes.Design/methodology/approachAn experimental study (plants vs no-plants) was conducted in a restaurant with a sample of 119 individuals. Data were analyzed using ANOVA and bootstrapping moderated mediation analysis (Hayes, 2013).FindingsThe results of the study confirmed significant effects of indoor natural plants on consumers’ satisfaction and loyalty, mediated by the experiential value components of aesthetic value, service excellence and escapism. The absence of an interaction of these influences with consumers’ connectedness to nature indicates that the beneficial effects of indoor plants universally affect all individuals, independent of their personal degree of feeling connected with nature.Practical implicationsIndoor natural plants as ambient elements in restaurants can improve satisfaction and loyalty by enhancing the dimensions of aesthetics and escapism of the service experience, as well as the perception of service quality.Originality/valueThis is the first experimental study analyzing the effects of indoor plants on customer satisfaction and loyalty conducted in a real-life restaurant setting using actual plants. The findings contribute theoretically by providing an integrated conceptual model of the satisfaction and loyalty effects of atmospheric stimuli (i.e. plants) in the hospitality servicescape, which offers a process explanation based on the mediating influence of aesthetic value and the sequential mediations of aesthetic value → service excellence and aesthetic value → escapism.
Frugal innovation enablers: a comprehensive framework
Authors: Niroumand Marjan , Shahin Arash , Naghsh Amirreza , Peikari Hamid Reza 
Published: February 2020

Purpose
This paper aims to propose a framework for the dimensions of frugal innovation enablers in small and medium-sized enterprises (SMEs).

Design/methodology/approach
A mixed research approach has been applied. First, by a comprehensive literature review, the most important factors influencing frugal innovation have been identified. Then, an interview has been conducted with 18 experts who were selected by snowball sampling method. In the next step, all identified variables have been modified in a questionnaire with 48 factors, which were distributed to 200 employees and managers of SMEs in the home appliance manufacturing industry of Isfahan province, who were selected by non-random sampling. Data has been analyzed using SPSS-25 software for exploratory factor analysis.

Findings
Findings indicated that the most important enablers of frugal innovation are world-class design, human aspect, marketing, support, knowledge, social aspect, prototyping, cultural aspect, environmental aspect, distinct brand creation, core functions focus, local R&D, cost-cutting business model and low-cost production.

Practical implications
The proposed framework provides an effective basis to managers and decision-makers in the field of frugal innovation to evaluate their capabilities in implementing frugal innovation, the results of which are helpful in developing a roadmap for achieving frugal innovation in SMEs and particularly in home appliance manufacturing companies.

Originality/value
The comprehensive framework of this study has not been applied, developed or studied in the literature. The proposed framework provides new insights for future studies on the subject of frugal innovation, e.g. investigating the influence of frugal innovation on frugal innovation performance.