bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological Restoration of Visual Function in a Zebrafish Model of von-Hippel Lindau Disease
Authors: Ward Rebecca , Slater Kayleigh , Ali Zaheer , Reynolds Alison L , Jensen Lasse D , Kennedy Breandán N 
Published: December 2018

AbstractVon Hippel-Lindau (VHL) syndrome is rare, autosomal dominant disorder, characterized by hypervascularised tumour formation in multiple organ systems. Vision loss associated with retinal capillary hemangioblastomas remains one of the earliest complications of VHL disease. The mortality ofVhl-/-micein uterorestricted modelling of VHL disease in this mammalian model. Zebrafish harbouring a recessive germline mutation in thevhlgene represent a viable, alterative vertebrate model to investigate associated ocularloss-of-functionphenotypes. Previous studies reported neovascularization of the brain, eye and trunk together with odema in thevhl-/-zebrafish eye. In this study, we demonstratevhl-/-zebrafish almost entirely lack visual function. Furthermore, hyaloid vasculature networks in thevhl-/-eye are improperly formed and this phenotype is concomitant with development of an ectopic intraretinal vasculature. Sunitinib, a multi tyrosine kinase inhibitor, market authorised for cancer, reversed the ocular behavioural and morphological phenotypes observed invhl-/-zebrafish. We conclude that the zebrafishvhlgene contributes to the endogenous molecular barrier that prevents development of intraretinal vasculature and that sunitinib can improve visual function and hyaloid vessel patterning while reducing abnormally formed ectopic intraretinal and choroidal vessels invhl-/-zebrafish.
Leaf economics guides slow-fast adaptation across the geographic range of A. thaliana
Authors: Sartori Kevin , Vasseur François , Violle Cyrille , Baron Etienne , Gerard Marianne , Rowe Nick , Ayala-Garay Oscar , Christophe Ananda , JalÓN Laura Garcia De , Masclef Diane , Harscouet Erwan , Granado Maria Del Rey , Chassagneux Agathe , Kazakou Elena , Vile Denis 
Published: December 2018

SummaryThe slow-fast continuum describes how resource allocation constrains life-history strategies in many organisms. In plants, it is reflected by a trade-off at the leaf level between the rate of carbon assimilation and lifespan, the so-called Leaf Economics Spectrum (LES). However, it is still unclear how the LES is connected to the slow-fast syndrome, and reflects adaptation to climate. Here, we measured growth, morpho-physiological and life-history traits at both leaf and whole-plant levels in 384 natural accessions of Arabidopsis thaliana. We examined the extent to which the LES continuum parallels the slow-fast continuum, and compared trait variation to neutral genetic differentiation between lineages. We found that the LES is tightly linked to variation in whole-plant functioning, relative growth rate and life history. A genetic analysis further suggested that phenotypic differentiation is linked to the evolution of different slow-fast strategies in contrasted climates. Together, our findings shed light on the physiological bases of the slow-fast continuum, and its role for plant adaptation to climate.
Natural selection contributed to immunological differences between human hunter-gatherers and agriculturalists
Authors: Harrison Genelle F , Sanz Joaquin , Boulais Jonathan , Mina Michael J , Grenier Jean-Christophe , Leng Yumei , Dumaine Anne , Yotova Vania , Bergey Christina M. , Elledge Stephen J. , Schurr Erwin , Quintana-Murci Lluis , Perry George H. , Barreiro Luis B. 
Published: December 2018

AbstractThe shift from a hunter-gatherer (HG) to an agricultural (AG) mode of subsistence is believed to have been associated with profound changes in the burden and diversity of pathogens across human populations. Yet, the extent to which the advent of agriculture may have impacted the evolution of the human immune system remains unknown. Here we present a comparative study of variation in the transcriptional responses of peripheral blood mononuclear cells to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda. We observed increased divergence between hunter-gatherers and agriculturalists in the transcriptional response to viruses compared to that for bacterial stimuli. We demonstrate that a significant fraction of these transcriptional differences are under genetic control, and we show that positive natural selection has helped to shape population differences in immune regulation. Across the set of genetic variants underlying inter-population immune response differences, however, the signatures of positive selection were disproportionately observed in the rainforest hunter-gatherers. This result is counter to expectations based on the popularized notion that shifts in pathogen exposure due to the advent of agriculture imposed radically heightened selective pressures in agriculturalist populations.
Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells
Authors: Nguyen Quynh P.H. , Liu Zhen , Nanjundappa Rashmi , Megherbi Alexandre , Delgehyr Nathalie , Ouyang Hong , Zlock Lorna , Coyaud Etienne , Laurent Estelle , Dell Sharon , Finkbeiner Walter , Moraes Theo , Raught Brian , Czymmek Kirk , Munier Alice , Mahjoub Moe R. , Mennella Vito 
Published: December 2018

AbstractMotile cilia are beating machines that play a critical role in airway defense. During airway cell differentiation, hundreds of motile cilia are templated from basal bodies that extend a basal foot, an appendage that links motile cilia together to ensure beating coordination. This assembly has thus far escaped structural analysis because its size is below the resolution limit. Here, we determine the molecular architecture and identify basal foot proteins using a super-resolution-driven approach. Quantitative super-resolution image analysis shows that the basal foot is organized in three main regions linked by elongated coiled-coil proteins. FIB-SEM tomography and comparative super-resolution mapping of basal feet reveal that, among hundreds of motile cilia of an airway cell, a hybrid cilium with features of primary and motile cilia is harbored. The hybrid cilium is conserved in mammalian multiciliated cells and originates from parental centrioles. We further demonstrate that this novel cilium is a signalling centre whose cellular position is dependent on flow.
Differences in high-definition transcranial direct current stimulation over the motor hotspot versus the premotor cortex on motor network excitability
Authors: Lefebvre Stephanie , Jann Kay , Schmiesing Allie , Ito Kaori , Jog Mayank , Schweighofer Nicolas , Wang Danny JJ , Liew Sook-Lei 
Published: December 2018

AbstractThe effectiveness of transcranial direct current stimulation (tDCS) placed over the motor hotspot (thought to represent the primary motor cortex (M1)) to modulate motor network excitability is highly variable. The premotor cortex—particularly the dorsal premotor cortex (PMd)—may be a promising alternative target to more effectively modulate motor excitability, as it influences motor control across multiple pathways, one independent of M1 and one with direct, modulating connections to M1. This double-blind, placebo-controlled study aimed to differentially excite motor and premotor regions using high-definition tDCS (HD-tDCS) with concurrent functional magnetic resonance imaging (fMRI). HD-tDCS applied over either the motor hotspot or the premotor cortex demonstrated high inter-individual variability in changes on cortical motor excitability. However, HD-tDCS over the premotor cortex led to a higher number of responders and greater changes in local fMRI-based complexity than HD-tDCS over the motor hotspot. Furthermore, an analysis of individual motor hotspot anatomical locations revealed that, in more than half of the participants, the motor hotspot is not located over anatomical M1 boundaries, despite using a canonical definition of the motor hotspot. This heterogeneity in stimulation site may contribute to the variability of tDCS results. Altogether, these findings provide new considerations to enhance tDCS reliability.
Golden magic: RSH enzymes for (p)ppGpp metabolism in the diatom Phaeodactylum tricornutum
Authors: Avilan L , Puppo C , Villain A , Bouveret E , Menand B , Field B , Gontero B 
Published: December 2018

AbstractThe nucleotides guanosine tetraphosphate and pentaphosphate (together known as (p)ppGpp or magic spot) are produced in plant plastids from GDP/GTP and ATP by RelA-SpoT homologue (RSH) enzymes. In the model plant Arabidopsis (p)ppGpp regulates chloroplast transcription and translation to affect growth, and is also implicated in acclimation to stress. However, little is known about (p)ppGpp metabolism or its evolution in other photosynthetic eukaryotes. Here we studied (p)ppGpp metabolism in the golden-coloured marine diatom Phaeodactylum tricornutum. We identified three expressed RSH genes in the P. tricornutum genome, and determined the enzymatic activity of the corresponding enzymes by heterologous expression in bacteria. We showed that two P. tricornutum RSH are (p)ppGpp synthetases, despite substitution of a residue within the active site believed critical for activity, and that the third RSH is a bifunctional (p)ppGpp synthetase and hydrolase, the first of its kind demonstrated in a photosynthetic eukaryote. A broad phylogenetic analysis then showed that diatom RSH belong to novel algal RSH clades. Together our work significantly expands the horizons of (p)ppGpp signalling in the photosynthetic eukaryotes by demonstrating an unexpected functional, structural and evolutionary diversity in RSH enzymes from organisms with plastids derived from red algae.HighlightWe discover RSH enzymes for (p)ppGpp metabolism in the diatom Phaeodactylum tricornutum and show that they have surprising functional and structural features, and belong to novel red-plastid lineage RSH clades.
Components from the human c-myb transcriptional regulation system reactivate epigenetically repressed transgenes
Authors: Barrett Cassandra M. , McCracken Reilly , Elmer Jacob , Haynes Karmella A. 
Published: December 2018

ABSTRACTEpigenetic silencing of transgenes has been a persistent challenge for mammalian cell engineering. Foreign DNA can be incorporated into closed chromatin before and after it has been integrated into a host cell’s genome. To identify elements that mitigate epigenetic silencing, we tested components from the c-myb and NF-kB transcriptional regulation systems in transiently transfected DNA and at chromosomally integrated transgenes in PC-3 and HEK293 cells. DNA binding sites for MYB (c-myb) placed upstream of a minimal promoter strongly enhanced expression from transiently transfected plasmid DNA. We targeted p65 and MYB fusion proteins to chromosomal transgenes that were silenced by ectopic Polycomb chromatin or by uncharacterized endogenous chromatin. Transient expression of Gal4-MYB induced sustained activation of the Polycomb-silenced UAS-Tk-luciferase transgene. We used custom guide RNAs and dCas9-MYB to target MYB to different sites. Transgene activation within ectopic Polycomb chromatin required proximity of dCas9-MYB to the transcriptional start site, while activation at the naturally repressed transgene was position-independent. Our report is the first to demonstrate the use of MYB in the context of the CRISPR-activation system. The results demonstrate that DNA elements and fusion proteins derived from c-myb can mitigate epigenetic silencing to improve transgene expression in engineered cell lines.
Ancient DNAs and the Neolithic Chinese super-grandfather Y haplotypes
Authors: Zhang Ye , Lei Xiaoyun , Chen Hongyao , Zhou Hui , Huang Shi 
Published: December 2018

AbstractPrevious studies identified 3 Neolithic Han Chinese super-grandfather Y haplotypes, O2a2b1a1a-F5, O2a2b1a2a1-F46, and O2a1b1a1a1a-F11, but their relationships with the archaeological and written records remain unexplored. We here report genome wide DNA data for 12 ancient samples (0.02x-1.28x) from China ranging from 6500 to 2500 years before present (YBP). They belonged to 4 different genetic groups, designated as Dashanqian (DSQ) of Xiajiadian Culture in the Northeast, Banpo (BP) of middle Yangshao Culture in the Central West, Zhengzhou Xishan (ZX) of Miaodigou Culture in the Central Plains, and Others. Present day F5 samples were closer in autosomal distances to the ZX and DSQ groups while F11, C, O1, and O2 samples were closer to the BP group. We also sequenced the Y chromosome of one of these ancient samples K12 from DSQ and found both K12 and a previously reported ~4000 year old sample MG48 from Northwest China to have the O2a2b1a1a1a2a-F2137 haplotype, belonging to the most prolific branch O2a2b1a1a1-F438 immediately under F5. We further found close relationships between ZX and DSQ and between ZX and ancient M117 Tibetans or present day Southwest Dai Chinese carrying the F5 subtype O2a2b1a1a6, implicating radiations of F5 subtypes from the putative place of F5 origin in ZX. These results are remarkably consistent with archaeological and written records.
Entrepreneurial response to changing opportunity structures
Authors: Kazlou Aliaksei , Klinthall Martin 
Published: December 2018

PurposeThe purpose of this paper is to analyse how the introduction of a liberalised regime for labour immigration in Sweden affected the self-selection of new immigrant entrepreneurs and to what extent the changes in entrepreneurial income among new immigrants was due to self-selection or to a changing business environment.Design/methodology/approachBased on rich microdata from Swedish administrative registers, this paper investigates how incomes changed during the years before and after the migration policy reform. By decomposing the income differential of new immigrant entrepreneurs arriving before and after the reform, this study estimates the contribution of a changed composition of migrants to the changing entrepreneurial income.FindingsEntrepreneurial income among self-employed new immigrants improved after the reform, narrowing the immigrant–native income gap, while among employees, the income gap remained during the whole period of the study. Out of the total 10.9 per cent increase in log income, the authors find that 2.7 per cent was due to selectivity, i.e., changing characteristics of new immigrant entrepreneurs. The remaining 8.2 per cent was due to increased returns to characteristics, i.e., the characteristics of new immigrant entrepreneurs were better rewarded in the markets in the latter period. Hence, increases in entrepreneurial income among new immigrants were due both to self-selection and changes in the business environment.Practical implicationsThe authors find that the migration policy reform had the effect of attracting successful immigrant entrepreneurs. Hence, the findings have implications for migration policy as well as for growth and employment policy.Originality/valueThis paper reveals a positive trend regarding income from the entrepreneurship of new immigrants after the liberalisation of labour immigration policy in Sweden. Theoretically and methodologically, the authors combine self-selection theory and the mixed-embeddedness perspective in a novel way, using rich data and a quantitative approach.
Digital health technology enhances resilient behaviour: evidence from the ward
Authors: Rubbio Iacopo , Bruccoleri Manfredi , Pietrosi Astrid , Ragonese Barbara 
Published: December 2018

PurposeIn the healthcare management domain, there is a lack of knowledge concerning the role of resilience practices in improving patient safety. The purpose of this paper is to understand the capabilities that enable healthcare resilience and how digital technologies can support these capabilities.Design/methodology/approachWithin- and cross-case research methodology was used to study resilience mechanisms and capabilities in healthcare and to understand how digital health technologies impact healthcare resilience. The authors analyze data from two Italian hospitals through the lens of the operational failure literature and anchor the findings to the theory of dynamic capabilities.FindingsFive different dynamic capabilities emerged as crucial for managing operational failure. Furthermore, in relation to these capabilities, medical, organizational and patient-related knowledge surfaced as major enablers. Finally, the findings allowed the authors to better explain the role of knowledge in healthcare resilience and how digital technologies boost this role.Practical implicationsWhen trying to promote a culture of patient safety, the research suggests healthcare managers should focus on promoting and enhancing resilience capabilities. Furthermore, when evaluating the role of digital technologies, healthcare managers should consider their importance in enabling these dynamic capabilities.Originality/valueAlthough operations management (OM) research points to resilience as a crucial behavior in the supply chain, this is the first research that investigates the concept of resilience in healthcare systems from an OM perspective, with only a few authors having studied similar concepts, such as “workaround” practices.
Antecedents and consequences of virtual customer co-creation behaviours
Authors: Frasquet-Deltoro Marta , Alarcón-del-Amo María-del-Carmen , Lorenzo-Romero Carlota 
Published: December 2018

PurposeThe purpose of this paper is to compare the antecedents and consequences of two distinct types of virtual co-creation behaviours that require different degree of effort from the customer, i.e. customer participation (CPB), and customer citizenship (CCB) behaviour, in a cross-cultural study.Design/methodology/approachA survey was conducted among members of online panels in the UK and Spain, reaching a sample of 800 online individuals who participate in online co-creation processes with fashion retailers. This design allows us to test the cross-cultural effects. Multi-group structural equations modelling was used to analyse the data.FindingsVirtual co-creation behaviours are driven by perceived ease-of-use of the co-creation platform, electronic word-of-mouth (e-WOM) quality and fashion involvement; however, the effects are different on CPB, affected by perceived ease-of-use more strongly, and on CCB, driven by e-WOM quality and fashion involvement more strongly. Higher level of co-creation increases satisfaction with co-creation, which mediates the effect on engagement and intention of future co-creation. The cross-cultural design reveals that most relationships hold in both countries, with the exception of the influence of fashion involvement on CPB, while some differences in the size of the effects appear between countries.Originality/valueThis study contributes to increasing our knowledge on online co-creation in several ways. First, the authors investigate, in the online environment, two co-creation behaviours, CPB and CCB, and compare their antecedents. This paper provides a cross-cultural validation of the relationships between CPB and CCB’s antecedents and consequences, identifying the different effects due to culture.
Fuzzy front end of innovation: a dual theoretical rationale
Authors: Zhang Qingyu , Cao Mei , Doll William 
Published: December 2018

PurposeThe uncertainties, ambiguities and unknown issues that characterize the beginning of a new product development project have led practitioners and scholars to coin the term “fuzzy front end” to refer to this seminal stage. The causes of many product failures can be traced back to this fuzzy front end. Despite a growing realization of its importance, the meaning of the term “front-end fuzziness” itself remains vague. A theory-based framework is not available to guide thinking and research on this important topic. The purpose of this paper is to create a conceptual framework for fuzzy front end.Design/methodology/approachThis paper applies Daft and Lengel’s (1986) theory of organizational information processing to create a framework for research on the fuzzy front end of product innovation. This framework is used to clarify the concept of front-end fuzziness and identify three sources of fuzziness in the project team’s task environment.FindingsContrary to the current literature, the authors argue that equivocality rather than uncertainty is the dominant cause of front-end fuzziness. This new conceptualization: appropriately broadens the concept of front-end fuzziness; identifies new problem areas; highlights the need for new solutions; and suggests the need to focus on team vision as a front-end deliverable.Practical implicationsThe previous literature used a single uncertainty reduction rationale for integrative mechanisms. Thus, it did not consider that the implementation might change from front end to downstream. The dual theoretical rationale suggests that integrative mechanisms can be implemented differently to focus either on uncertainty or equivocality reduction. In the front end, equivocality is the dominant issue and mechanisms should be implemented in ways that create a rich channel to identify issues and share perspectives. In downstream activities where the dominant issue is uncertainty reduction, mechanisms might be implemented in ways that provide greater quantities of information on known issues.Originality/valueThis new conceptualization of front-end fuzziness provides a better theoretical rationale for how integrative mechanisms enable a project team to work through the fuzziness it faces, creating a clear team vision that guides its downstream efforts.
Is there evidence of PHH in developing Asia?
Authors: Miniesy Rania S. , Tarek MennaTallah 
Published: December 2018

PurposeThis paper aims to test the pollution haven hypothesis (PHH) in developing Asian countries by examining whether lax environmental laws are a determinant of foreign direct investment (FDI) inflows into these countries, which are characterised by being the largest FDI recipients among developing countries and also by being among the most highly polluted and the highest carbon dioxide (CO2) emitters worldwide.Design/methodology/approachPanel data for the main determinants of FDI inflows including a carbon dioxide emissions and an agglomeration variable are collected for all developing Asian countries for the 1996-2016 period and a fixed effects model with robust standard errors is used.FindingsResults show that lax environmental laws are a significant determinant of FDI inflows for the selected Asian countries as a whole. A closer look shows that this result cannot be generalised for the whole region, but applies particularly to three countries China, Hong Kong and the Philippines. PHH is thus only partially supported.Originality/valueFDI is a main engine of growth for developing countries. However, it might adversely affect them, specifically in terms of environmental deterioration in the absence of stringent and well-enforced environmental policies. Some developing countries might even deliberately relax their environmental policies to attain comparative advantage especially in polluting industries and thus attract FDI. This leads to serious repercussions and might eventually limit growth, where augmenting it was the intention in the first place.