bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic response in symptomless roots of clubroot infected kohlrabi (Brassica oleracea var. gongylodes) mirrors resistant plants
Authors: Ciaghi Stefan , Schwelm Arne , Neuhauser Sigrid 
Published: August 2018

AbstractBackgroundClubroot disease caused by Plasmodiophora brassicae (Phytomyxea, Rhizaria) is one of the economically most important diseases of Brassica crops. The formation of hypertrophied roots accompanied by altered metabolism and hormone homeostasis is typical for infected plants. Not all roots of infected plants show the same phenotypic changes. While some roots remain uninfected, others develop galls of diverse size. The aim of this study was to analyse and compare the intra-plant heterogeneity of P. brassicae root galls and symptomless roots of the same host plants (Brassica oleracea var. gongylodes) collected from a commercial field in Austria using transcriptome analyses.ResultsTranscriptomes were markedly different between symptomless roots and gall tissue. Symptomless roots showed transcriptomic traits previously described for resistant plants. Genes involved in host cell wall synthesis and reinforcement were up-regulated in symptomless roots indicating elevated tolerance against P. brassicae. By contrast, genes involved in cell wall degradation and modification processes like expansion were up-regulated in root galls. Hormone metabolism differed between symptomless roots and galls. Brassinosteroid-synthesis was down-regulated in root galls, whereas jasmonic acid synthesis was down-regulated in symptomless roots. Cytokinin metabolism and signalling were up-regulated in symptomless roots with the exception of one CKX6 homolog, which was strongly down-regulated. Salicylic acid (SA) mediated defence response was up-regulated in symptomless roots, compared with root gall tissue. This is probably caused by a secreted benzoic acid salicylic acid methyl transferase from the pathogen (PbBSMT), which was one of the highest expressed pathogen genes in gall tissue. The PbBSMT derived Methyl-SA potentially leads to increased pathogen tolerance in uninfected roots.ConclusionsInfected and uninfected roots of clubroot infected plants showed transcriptomic differences similar to those previously described between clubroot resistant and susceptible hosts. The here described intra-plant heterogeneity suggests, that for a better understanding of clubroot disease targeted, spatial analyses of clubroot infected plants will be vital in understanding this economically important disease.
Maintaining trunk neural crest cells as crestospheres
Authors: Mohlin Sofie , Kunttas Ezgi , Persson Camilla U. , Abdel-Haq Reem , Castillo Aldo , Murko Christina , Bronner Marianne E. , Kerosuo Laura 
Published: August 2018

AbstractNeural crest cells have broad migratory and differentiative ability that differs according to their axial level of origin. However, their transient nature has limited understanding of their stem cell and self-renewal properties. While anin vitroculture method has made it possible to maintain cranial neural crest cells as self-renewing multipotent crestospheres (Kerosuo et al., 2015), these same conditions failed to preserve trunk neural crest in a stem-like state. Here we optimize culture conditions for maintenance of trunk crestospheres, comprised of both neural crest stem and progenitor cells. Trunk crestospheres display elevated expression of neural crest cell markers as compared to those characteristic of neural tube or mesodermal fates. Moreover, trunk crestospheres have increased expression of trunk-related markers as compared to cranial genes. Finally, we use lentiviral transduction as a tool to manipulate gene expression in trunk crestospheres. Taken together, this method enables long-termin vitromaintenance and manipulation of trunk neural crest cells in a premigratory stem or early progenitor state to probe the mechanisms underlying their stemness and lineage decisions.HighlightsTrunk-derived multipotent neural crest stem cells can be cultured as crestospheresTrunk-derived crestospheres require different conditions than cranialTrunk crestospheres consist of neural crest stem and progenitor cellsTrunk crestospheres can be efficiently transduced using lentiviral vectors
Supra-threshold psychoacoustics and envelope-following response relations: normal-hearing, synaptopathy and cochlear gain loss
Authors: Verhulst Sarah , Ernst Frauke , Garrett Markus , Vasilkov Viacheslav 
Published: August 2018

AbstractThe perceptual consequences of cochlear synaptopathy are presently not well understood as a direct quantification of synaptopathy is not possible in humans. To study its role for human hearing, recent studies have instead correlated changes in basic supra-threshold psychoacoustic tasks with individual differences in subcortical EEG responses, as a proxy measure for synaptopathy. It is not clear whether the reported missing relationships between the psychoacoustic quantities and the EEG are due to the adopted methods, or to a minor role of synaptopathy for sound perception. We address this topic by studying the theoretical relationship between subcortical EEG and psychoacoustic methods for different sensorineural hearing deficits.
Proteomic analysis of RNA-dependent chromatin association of nuclear proteins
Authors: Hiragami-Hamada Kyoko , Tani Naoki , Nakayama Jun-ichi 
Published: August 2018

AbstractVarious coding and non-coding transcripts are known to associate with chromatin and now there is accumulating evidence that interaction between RNA-binding proteins (RBPs) and RNA molecules regulate not only co-transcriptional mRNA processing, but also other biological processes within the nucleus. Although over a thousand of RBPs have been identified by several mass spectrometry-based methods, it is still unclear which of these RBPs actually associate with chromatin, especially through interaction with RNAs. In addition, biological outcomes of such RBP-RNA-chromatin interactions are yet to be elucidated.Here we describe a simple proteomics-based method for systematic screening of RBPs that are anchored to chromatin and/or insoluble nuclear substructures by RNA molecules. We used RNase A to release such RBPs from chromatin fraction and analyzed ‘RNase A-solubilized’ proteins by mass spectrometry. Using this method, we were able to identify 156 RNase A-solubilized proteins of which 144 were known RBPs/RBP candidates. Interestingly, several key players of the non-homologous end-joining (NHEJ) pathway were enriched in RNase A-solubilized fraction and the RNA-mediated chromatin association of these factors appeared to be dependent on transcriptional elongation. Furthermore, some enzymes involved in metabolic pathways were also released from chromatin and/or an insoluble nuclear structure by RNase A treatment. In summary, our methodology is highly versatile and is potentially a useful tool to unravel new biological functions for RBP-RNA-chromatin interactions.
Cortical circuit alterations precede disease onset in Huntington’s disease mice
Authors: Neuner Johanna , Schulz-Trieglaff Elena Katharina , Gutiérrez-Ángel Sara , Hosp Fabian , Mann Matthias , Arzberger Thomas , Klein Rüdiger , Liebscher Sabine , Dudanova Irina 
Published: August 2018

AbstractHuntington’s disease (HD) is a devastating hereditary movement disorder, characterized by degeneration of neurons in the striatum and cortex. Studies in human patients and mouse HD models suggest that disturbances of neuronal function in the neocortex play an important role in the disease onset and progression. However, the precise nature and time course of cortical alterations in HD have remained elusive. Here, we use chronicin vivotwo-photon calcium imaging to monitor the activity of single neurons in layer 2/3 of the primary motor cortex in awake, behaving R6/2 transgenic HD mice and wildtype littermates. R6/2 mice show age-dependent changes in neuronal activity with a clear increase in activity at the age of 8.5 weeks, preceding the onset of motor and neurological symptoms. Furthermore, quantitative proteomics demonstrate a pronounced downregulation of synaptic proteins in the cortex, and histological analyses in R6/2 mice and HD patient samples reveal reduced inputs from parvalbumin-positive interneurons onto layer 2/3 pyramidal cells. Thus, our study provides a time-resolved description as well as mechanistic details of cortical circuit dysfunction in HD.Significance statementFuntional alterations in the cortex are believed to play an important role in the pathogenesis of Huntington’s disease (HD). However, studies monitoring cortical activity in HD modelsin vivoat a single-cell resultion are still lacking. We have used chronic two-photon imaging to investigate changes in the activity of single neurons in the primary motor cortex of awake presymptomatic HD mice. We show that neuronal activity increases before the mice develop disease symptoms. Our histological analyses in mice and in human HD autopsy cases furthermore demonstrate a loss inhibitory synaptic terminals from parvalbimun-positive interneurons, revealing a potential mechanism of cortical circuit impairment in HD.
Uncoupled activation and cyclisation in catmint reductive terpenoid biosynthesis
Authors: Lichman Benjamin R , Kamileen Mohamed O , Titchiner Gabriel R , Saalbach Gerhard , Stevenson Clare E M , Lawson David M , O’Connor Sarah E 
Published: August 2018

AbstractTerpene synthases typically form complex molecular scaffolds by concerted activation and cyclization of linear starting materials in a single enzyme active site. Here we show that iridoid synthase, an atypical reductive terpene synthase, catalyses the activation of its substrate 8-oxogeranial into a reactive enol intermediate but does not catalyse the subsequent cyclisation into nepetalactol. This discovery led us to identify a class of nepetalactol-related short-chain dehydrogenase enzymes (NEPS) from catmint (Nepeta mussinii) which catalyse the stereoselective cyclisation of the enol intermediate into nepetalactol isomers. Subsequent oxidation of nepetalactols by NEPS1 provides nepetalactones, metabolites that are well known for both insect-repellent activity and euphoric effect in cats. Structural characterisation of the NEPS3 cyclase reveals it binds to NAD+ yet does not utilise it chemically for a non-oxidoreductive formal [4+2] cyclisation. These discoveries will complement metabolic reconstructions of iridoid and monoterpene indole alkaloid biosynthesis.
Sequence-to-structure dependence of isolated IgG Fc complex biantennary N-glycans: A molecular dynamics study
Authors: Harbison Aoife M , Brosnan Lorna P , Fenlon Keith , Fadda Elisa 
Published: August 2018

AbstractFc glycosylation of human immunoglobulins G (IgGs) is essential for their structural integrity and activity. Interestingly, the specific nature of the Fc glycoforms is known to modulate the IgG effector function. Indeed, while core-fucosylation of IgG Fc-glycans greatly affects the antibody-dependent cell-mediated cytotoxicity (ADCC) function, with obvious repercussions in the design of therapeutic antibodies, sialylation can reverse the antibody inflammatory response, and galactosylation levels have been linked to aging, to the onset of inflammation, and to the predisposition to rheumatoid arthritis. Within the framework of a structure-to-function relationship, we have studied the role of the N-glycan sequence on its intrinsic conformational propensity. Here we report the results of a systematic study, based on extensive molecular dynamics (MD) simulations in excess of 62 µs of cumulative simulation time, on the effect of sequence on the structure and dynamics of increasingly larger, complex biantennary N-glycoforms, i.e. from chitobiose to the larger N-glycan species commonly found in the Fc region of human IgGs. Our results show that while core fucosylation and sialylation do not affect the intrinsic dynamics of the isolated (unbound) N-glycans, galactosylation of the α(1-6) arm shifts dramatically its conformational equilibrium from an outstretched to a folded conformation. These findings are in agreement with and can help rationalize recent experimental evidence showing a differential recognition of positional isomers in glycan array data and also the preference of sialyltransferase for the more reachable, outstretched α(1-3) arm in both isolated and Fc-bound N-glycans.
Epigenetic inactivation of miR-203 as a key step in neural crest epithelial-to-mesenchymal transition
Authors: Sánchez-Vásquez Estefanía , Bronner Marianne E. , Strobl-Mazzulla Pablo H. 
Published: August 2018

AbstractmiR-203 is a tumor-suppressor microRNA with known functions in cancer metastasis. Here, we explore its normal developmental role in the context of neural crest development. As neural crest cells undergo an epithelial-to-mesenchymal transition to emigrate from the neural tube, miR-203 displays a reciprocal expression pattern with key regulators of neural crest delamination, Phf12 and Snail2, and interacts with their 3’UTRs. Ectopic maintenance of miR-203 inhibits neural crest migration, whereas its functional inhibition using a “sponge” vector promotes premature neural crest delamination. Bisulfite sequencing further shows that epigenetic repression of miR-203 is mediated by the de novo DNA methyltransferase DNMT3B, whose recruitment to regulatory regions on the miR-203 locus is directed by SNAIL2 in a negative feedback loop. These findings reveal an important role for miR-203 in an epigenetic-microRNA regulatory network that influences the timing of neural crest delamination.Summary statementThe EMT is a highly conserved process, involving similar levels of regulation in both neural crest and cancer cells. Our work shows an epigenetic-miRNA-gene regulatory circuit, conserved in cancer, which controls the timing of neural crest EMT as well.
Integrative analyses of multi-tissue Hi-C and eQTL data demonstrate close spatial proximity between eQTLs and their target genes
Authors: Yu Jingting , Hu Ming , Li Chun 
Published: August 2018

AbstractGene regulation is important for cells and tissues to function. At the genomic level, it has been studied from two aspects, the identification of expression quantitative trait loci (eQTLs) and identification of long-range chromatin interactions. It is important to understand their relationship, such as whether eQTLs regulate their target genes through physical chromatin interaction. Although previous studies have suggested enrichment of eQTLs in regions with a high chromatin interaction frequency, it is unclear whether this relationship is consistent across different tissues and cell lines and whether there would be any tissue-specific patterns. Here, we performed integrative analyses of eQTL and high-throughput chromatin conformation capture (Hi-C) data from 11 human primary tissue types and 2 human cell lines. We found that chromatin interaction frequency is positively correlated with the number of genes having eQTLs, and eQTLs and their target genes are more likely to fall in the same topologically associating domains than that expected from randomly generated control datasets. These results are consistent across all tissues and cell lines we evaluated. Moreover, in dorsolateral prefrontal cortex, spleen, hippocampus, pancreas and aorta, tissue-specific eQTLs are enriched in tissue-specific frequently interacting regions. These results reveal a more detailed picture of the complicated relationship between different mechanisms of gene regulation.Author summaryWhole-genome gene regulation has been studied in tissues and cell lines from multiple perspectives, including identification of expression quantitative trait loci (eQTLs) and identification of long-range chromatin interactions. These two complementary approaches focus on different aspects of gene regulation, one being statistical across individuals while the other being physical within a sample. Integrating results from these two approaches will help us understand their relationships, such as whether eQTLs regulate their target genes through physical chromatin interaction. We performed comprehensive analyses using data from multiple human tissues and cell lines, and showed that chromatin interaction frequency is positively associated with eQTL results in all evaluated tissues and cell lines. The observed relationships also displayed tissue-specific pattern in some tissues. Our results revealed a more detailed picture of the complicated relationship between the different mechanisms of gene regulation.
Institutional pressures, isomorphic changes and key agents in the transfer of knowledge of Lean in Healthcare
Authors: D’Andreamatteo Antonio , Ianni Luca , Rangone Adalberto , Paolone Francesco , Sargiacomo Massimo 
Published: August 2018

PurposeApplication of operations management in healthcare is particularly promising to improve the overall organisational performance, although the Italian system is behind in introducing related techniques and methods. One of the recent experiments in healthcare is the implementation of “Lean Thinking”. The purpose of this paper is to investigate which exogenous forces are driving knowledge transfer on Lean, both in the private and public healthcare sectors.Design/methodology/approachInformed by institutional sociology (DiMaggio and Powell, 1983; Powell and DiMaggio, 1991), the paper builds on the case study methodology (Yin, 2013) to elucidate the environmental pressures that are encouraging the adoption of Lean thinking by Italian hospitals and Local Health Authorities.FindingsThe study highlights the economic, coercive, mimetic and normative pressures that are triggering the adoption of Lean thinking in the Italian National Health System (INHS). At the same time, the authors reveal the pivotal importance and innovative roles played by diverse prominent key-actors in the different organisations investigated.Originality/valueConsidering that little is known to date regarding which exogenous forces are driving the transfer of knowledge on Lean, especially in the public healthcare sector, the paper allows scholars to focus on patterns of isomorphic change and will facilitate managers and policy makers to understand exogenous factors stimulating the transfer of Lean thinking and the subsequent innovation within health organisations and systems.
When queen bees attack women stop advancing: recognising and addressing female bullying in the workplace
Authors: Harvey Cecila 
Published: August 2018

Purpose
This paper aims to look at the implications of the “Queen Bee” syndrome in the workplace: its impact on women at work and the perception of women at work.

Design/methodology/approach
This paper draws on the author’s practical experience, observations, and studies.

Findings
The Queen Bee syndrome can have a negative impact on organizational performance and bottom-line results as well as individuals.

Research limitations/implications
The author calls for more work to done in this area to raise awareness and provide solutions.

Practical implications
This paper offers insight to help managers and organizations assess how much the Queen Bee syndrome may be at work in their own organization. It also invites women to self-reflect on their own behaviors.

Originality/value
This paper highlights an issue that can be ignored in organizations – how negative woman-to-woman behavior and/or bullying can be detrimental to individual and organizational performance.
Internationalization as a determinant of systematic risk: the role of restaurant type
Authors: Jung SoYeon , Dalbor Michael , Lee Seoki 
Published: August 2018

PurposeThe purpose of this study is twofold: to investigate the relationship between restaurant firms’ internationalization and systematic risk, and to further examine the relationship between internationalization and systematic risk based on the type of restaurant firm (i.e. limited-service vs full-service restaurants).Design/methodology/approachThis study analyzes data from US-based publicly traded restaurant firms by estimating systematic risk based on the Carhart four-factor model and by performing a two-way random-effects model.FindingsFindings support not only the risk-reduction effect of internationalization on systematic risk but also the moderating effect of the role of restaurant type on the relationship between internationalization and systematic risk. More specifically, the risk-reduction effect of internationalization on systematic risk is greater for limited-service than full-service restaurants.Practical implicationsThe findings of this study can provide restaurant executives with more confidence in pursuing internationalization as part of their risk management strategy, acknowledging that more international operations could mitigate restaurant firms’ systematic risk. More specifically, limited-service restaurants can more significantly enjoy the risk-reduction benefits by increasing their international operations than full-service restaurants based on the findings of this study. Furthermore, risk-averse investors could consider purchasing shares of limited-service multinational restaurants’ stocks to enjoy more risk-reduction benefits.Originality/valueBy focusing on the restaurant industry with consideration for the restaurant type, this study provides more tailored recommendations for implementing internationalization strategies with regard to risk management.
Intrinsically motivating idiosyncratic deals and innovative work behaviour
Authors: Kimwolo Andrew , Cheruiyot Thomas 
Published: August 2018

Purpose
This paper aims to determine the effect of intrinsically motivating idiosyncratic deals (I-deals) on innovative work behaviour (IWB) among tied life insurance agents in Kenya.

Design/methodology/approach
Standard multiple regression analysis was used to test the hypotheses from data collected from a field study from 498 employees and 48 managers.

Findings
The study findings showed a positive relationship between both flexibility I-deals and IWB (ß = 0.461, p < 0.00) and between task and responsibilities I-deals and IWB (ß = 0.171, p < 0.01).

Research/limitations/implications
The cross-sectional collection of data weakens the author’s claim of causality between the variables in focus. The study extends literature on the effects of flexibility as well as tasks and responsibilities I-deals on IWB.

Practical implications
Organizations must grant their employees with intrinsically motivating I-deals in order for display of IWB.

Social implications
These I-deals provided intrinsic motivation of the employees in displaying IWB in the organizations. The exchange relationship with the employers got enhanced through their granting motivating employees to look for new ways of doing their work.

Originality/value
This is the first study to investigate a linear relationship between intrinsically motivating I-deals and IWB.