bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different Munc18 Proteins Mediate Baseline and Stimulated Airway Mucin Secretion
Authors: Jaramillo Ana M. , Piccotti Lucia , Velasco Walter V. , Huerta Delgado Anna Sofia , Azzegagh Zoulikha , Chung Felicity , Nazeer Usman , Farooq Junaid , Brenner Josh , Parker-Thornburg Jan , Scott Brenton L. , Evans Christopher M. , Adachi Roberto , Burns Alan R. , Kreda Silvia M. , Tuvim Michael J. , Dickey Burton F. 
Published: October 2018

AbstractAirway mucin secretion is necessary for ciliary clearance of inhaled particles and pathogens, but can be detrimental in pathologies such as asthma and cystic fibrosis. Exocytosis in mammals requires a Munc18 scaffolding protein, and airway secretory cells express all three Munc18 isoforms. Using conditional airway epithelial deletant mice, we found that Munc18a has the major role in baseline mucin secretion, Munc18b has the major role in stimulated mucin secretion, and Munc18c does not function in mucin secretion. In an allergic asthma model, Munc18b deletion reduced airway mucus occlusion and airflow resistance. In a cystic fibrosis model, Munc18b deletion reduced airway mucus occlusion and emphysema. Munc18b deficiency in the airway epithelium did not result in any abnormalities of lung structure, particle clearance, inflammation, or bacterial infection. Our results show that regulated secretion in a polarized epithelial cell may involve more than one exocytic machine at the apical plasma membrane, and that the protective roles of mucin secretion can be preserved while therapeutically targeting its pathologic roles.
Transitions in cell potency during early mouse development are driven by Notch
Authors: Menchero Sergio , Lopez-Izquierdo Antonio , Rollan Isabel , Sainz de Aja Julio , Andreu Maria Jose , Kang Minjung , Adan Javier , Benedito Rui , Rayon Teresa , Hadjantonakis Anna-Katerina , Manzanares Miguel 
Published: October 2018

AbstractThe Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions.
Genetic transformation of the dinoflagellate chloroplast
Authors: Nimmo Isabel C. , Barbrook Adrian C. , Chen Jit Ern , Geisler Katrin , Smith Alison G. , Aranda Manuel , Saul Purton , Waller Ross F. , Nisbet R. Ellen R. , Howe Christopher J. 
Published: October 2018

AbstractCoral reefs are some of the most important and ecologically diverse marine environments. At the base of the reef ecosystem are dinoflagellate algae, living in symbiosis with coral. Efforts to understand the relationship between alga and coral have been greatly hampered by the lack of an appropriate dinoflagellate genetic transformation technology. By making use of the plasmid-like fragmented chloroplast genome, we have introduced novel genetic material into the dinoflagellate chloroplast genome. We have shown that the introduced genes are expressed and confer the expected phenotypes. Genetically modified cultures have been grown for five months with subculturing, maintaining the introduced genes and phenotypes. This indicates that cells continue to divide after transformation and that the transformation is stable.
Loss of SATB1 Induces a p21 Dependent Cellular Senescence Phenotype in Dopaminergic Neurons
Authors: Riessland Markus , Kolisnyk Benjamin , Kim Tae Wan , Cheng Jia , Ni Jason , Pearson Jordan A. , Park Emily J. , Dam Kevin , Acehan Devrim , Ramos-Espiritu Lavoisier S. , Wang Wei , Zhang Jack , Shim Jae-won , Ciceri Gabriele , Brichta Lars , Studer Lorenz , Greengard Paul 
Published: October 2018

AbstractCellular senescence is a mechanism used by mitotic cells to prevent uncontrolled cell division. As senescent cells persist in tissues, they cause local inflammation and are harmful to surrounding cells, contributing to aging. Generally, neurodegenerative diseases, such as Parkinson‘s, are disorders of aging. The contribution of cellular senescence to neurodegeneration is still unclear. SATB1 is a DNA binding protein associated with Parkinson’s disease. We report that SATB1 prevents cellular senescence in post-mitotic dopaminergic neurons. Loss of SATB1 causes activation of a cellular senescence transcriptional program in dopamine neurons, both in human stem cell-derived dopaminergic neurons and in mice. We observed phenotypes which are central to cellular senescence in SATB1 knockout dopamine neurons in vitro and in vivo. Moreover, we found that SATB1 directly represses expression of the pro-senescence factor, p21, in dopaminergic neurons. Our data implicate senescence of dopamine neurons as a contributing factor to the pathology of Parkinson’s disease.
Interplay of protein disorder in retinoic acid receptor heterodimer and its corepressor regulates gene expression
Authors: Cordeiro Tiago N. , Sibille Nathalie , Germain Pierre , Barthe Philippe , Boulahtouf Abdel , Allemand Fréderic , Bailly Rémy , Vivat Valérie , Ebel Christine , Barducci Alessandro , Bourguet William , le Maire Albane , Bernadó Pau 
Published: October 2018

AbstractThe retinoic acid receptors (RARs) form heterodimers with retinoid X receptors (RXRs) and control gene transcription in response to ligand binding and via allosteric activation of the C-termini helix (helix H12) of its ligand-binding domain. Herein we show that in the absence of ligand, helices H12 of RXR and RAR are disordered. The selective RAR agonist, Am580, induces folding of H12, whereas in the presence of the inverse agonist BMS493, H12 stays mostly disordered. These results substantiate a link between the structural dynamics of H12 and RXR/RAR heterodimer biological functions, and highlight disordered-to-order transition as an essential mechanism for retinoic acid mediated regulation. Unliganded RAR exerts a strong repressive activity allowed by the recruitment of transcriptional corepressors and establishment of a corepressor complex in the promoter region of target genes. The human regulatory complex of the RARα bound to the full-length interaction domain of the corepressor N-CoR was studied by integrating several experimental (SAXS, X-ray crystallography, NMR, CD, AUC) and computational data. Unexpectedly, we found that, while mainly intrinsically disordered, the N-CoR presents partially evolutionary conserved structured regions that are involved in transient intramolecular contacts. In the presence of RXR/RAR, we show that N-CoR exploits its multivalency to form a multi-site complex that diplays an equilibrium between different conformational states. This conformational equilibrium is modulated by cognate ligands, RAR point mutation and RXR H12 deletion. Now, we can state that, in addition to NR conformation and ligand-induced allosteric changes, intrinsic disorder is substantially embedded in the synergetic regulation of RXR/RAR activity and its resulting abilities to communicate with the intracellular components.
Testing the Gene Expression Classification of the EMT Spectrum
Authors: Jia Dongya , George Jason T. , Tripathi Satyendra C. , Kundnani Deepali L. , Lu Mingyang , Hanash Samir M. , Onuchic José N. , Jolly Mohit Kumar , Levine Herbert 
Published: October 2018

AbstractThe epithelial-mesenchymal transition (EMT) plays a central role in cancer metastasis and drug resistance – two persistent clinical challenges. Epithelial cells can undergo a partial or full EMT, attaining either a hybrid epithelial/mesenchymal (E/M) or mesenchymal phenotype, respectively. Recent studies have emphasized that hybrid E/M cells may be more aggressive than their mesenchymal counterparts. However, mechanisms driving hybrid E/M phenotypes remain largely elusive. Here, to better characterize the hybrid E/M phenotype(s) and tumor aggressiveness, we integrate two computational methods – (a) RACIPE – to identify the robust gene expression patterns emerging from the dynamics of a given gene regulatory network, and (b) EMT scoring metric - to calculate the probability that a given gene expression profile displays a hybrid E/M phenotype. We apply the EMT scoring metric to RACIPE-generated gene expression data generated from a core EMT regulatory network and classify the gene expression profiles into relevant categories (epithelial, hybrid E/M, mesenchymal). This categorization is broadly consistent with hierarchical clustering readouts of RACIPE-generated gene expression data. We show that the EMT scoring metric can be used to distinguish between samples composed of exclusively hybrid E/M cells and those containing mixtures of epithelial and mesenchymal subpopulations using the RACIPE-generated gene expression data.
Asymmetric redundancy of ZERZAUST and ZERZAUST HOMOLOG in different accessions of Arabidopsis thaliana
Authors: Vaddepalli Prasad , Fulton Lynette , Schneitz Kay 
Published: October 2018

AbstractDivergence among duplicate genes is one of the important sources of evolutionary innovation. But, the contribution of duplicate divergence to variation in Arabidopsis accessions is sparsely known. Recently, we studied the role of a cell wall localized protein, ZERZAUST (ZET), in Landsberg erecta (Ler) accession. Here, we present the study of ZET in Columbia (Col) accession, which not only showed differential expression patterns in comparison to Ler, but also revealed its close homolog, ZERZAUST HOMOLOG (ZETH). Although, genetic analysis implied redundancy, expression analysis revealed divergence, with ZETH showing minimal expression in both Col and Ler. In addition, ZETH shows relatively higher expression levels in Col compared to Ler. Our data also reveal compensatory up-regulation of ZETH in Col, but not in Ler, implying it is perhaps dispensable in Ler. However, a novel CRISPR/Cas9-induced zeth allele confirmed that ZETH has residual activity in Ler. The results provide genetic evidence for accession-specific differences in compensation mechanism and asymmetric gene contribution. Thus, our work reveals a novel example for how weakly expressed homologs contribute to diversity among accessions.
ILEX PARAGUARIENSIS, EXERCISE AND CARDIOPROTECTION: A retrospective analysis
Authors: Cahuê Fábio , Matheus Nascimento José Hamilton , Barcellos Luciane , Salerno Veronica P. 
Published: October 2018

AbstractStudies on strategies to generate cardioprotective effects have been on the rise. Previous work by our group with an ex vivo model of ischemia/reperfusion has shown that both the short-term consumption of yerba mate and exercise can each induce protection of cardiac function independently. Surprising, the two strategies together do not, with an apparent loss of their respective cardioprotection activity. To improve our understanding of the mechanisms involved without reperforming the experiments, we have conducted a retrospective data science-analysis that have produced new insights. The analysis shows that yerba mate generated reductive stress. Alone, this stress increased redox damage in the heart that appears to have led to a protective conditioning. In combination with exercise, the effects of mate inhibited the intermittent ROS generation promoted by exercise alone, which diminished the adaptive response in the heart. These results suggest that an understanding of the molecular mechanisms involved with the yerba mate-promoted reductive stress in cardiac tissue could lead to improved strategies to induce cardioprotection.
Split Selectable Markers
Authors: Jillette Nathaniel , Du Menghan , Cheng Albert 
Published: October 2018

AbstractSelectable markers are widely adopted in transgenesis and genome editing for selecting engineered cells with desired genotype but are limited in choices. We present here split selectable markers each allowing for selection of multiple “unlinked” transgenes in the context of lentivirus-mediated transgenesis as well as CRISPR/Cas-mediated biallelic knock-ins. Future development of split selectable markers may support enrichment or selection of “hyper-engineered” cells containing tens of transgenes or genetic modifications.
Total quality management practices and organizational performance in the construction chemicals companies in Jordan
Authors: Androwis Neven , Sweis Rateb J. , Tarhini Ali , Moarefi Alireza , Hosseini Amiri Mahmood 
Published: October 2018

Purpose
The purpose of this paper is to investigate the relationship between total quality management practices and the organizational performance in the Jordanian construction chemicals companies.

Design/methodology/approach
In this research, ten constructs were used to measure TQM practices, whereas six constructs were used to measure the organizational performance. A total of 160 questionnaires were distributed to 28 companies. Of these 131 questionnaires were completed and used for the analysis, representing a response rate of 81.9 percent.

Findings
Analysis has shown that TQM practices positively affect the organizational performance, with a significant value for top management commitment, customer focus, supplier management, process control and continuous improvement.

Research limitations/implications
Results were based on perceptual data provided by participants working in different sectors of the organization, which may not provide a clear picture. It would be appropriate to consider collecting information from several stakeholders such as customers and suppliers. Willingness of respondents and delivering data within time were a big challenge though efforts were made to guarantee the confidentiality of the respondents.

Practical implications
Results from this research points out that TQM is considered as a key-contributing factor to firm’s survival. It also provides empirical support that TQM implementation in manufacturing organizations contributes to the performance and survival of such organizations. This research also provides an understanding of the dynamic role of TQM practices that would help managers pay attention to the fundamental practices that have a direct impact on the firms’ performance. This will help the organizations to dedicate efforts and allocate resources to get the best long-term outcomes and to figure out their strengths and weaknesses to develop and implement a new strategy to enhance their competitive position.

Originality/value
Construction sector in Jordan is a competitive sector. Therefore, quality in such industry is vital. Many companies in Jordan have much interest in implementing TQM practices. However, research efforts related to this field are rare. No research papers investigating the relationship between TQM practices and performance in Jordanian construction chemicals companies have been found. This research, therefore, seeks to examine the relationship between TQM practices and the construction chemicals firms’ performance in Jordan.
Mapping the TQM implementation
Authors: Kumar Vimal , Sharma R.R.K. , Verma Pratima , Lai Kuei-Kuei , Chang Yu-Hsin 
Published: October 2018

PurposeCulture is considered as one of the variables that influence the total quality management (TQM) adoption process. The purpose of this paper is to explore the relationship between cultural dimensions and the strategy of the firms in TQM implementation. These relationships are the subject of prior research. Furthermore, the authors make a comparative analysis of cultural dimensions on strategic choices of the firms, i.e. innovators, prospectors and defenders in TQM implementation.Design/methodology/approachFrom the existing literature review on TQM practices and organizational culture, 14 cultural dimensions were employed with organizational strategy in this present study. By using survey data collection method, 111 Indian firms were selected. The authors considered three strategy parameters and six structural attributes to identify the strategy of the firms, namely innovators, prospectors and defenders identified using cluster analysis. Furthermore, the relationship between organizational culture and strategy was examined using one-way ANOVA approach.FindingsThe results of the study revealed that eleven of the fourteen hypotheses supported which relating the cultural dimensions to TQM implementation with the strategic orientation. With the help of significant related values of cultural dimensions to the particular strategic firms, it is also found that implementation of TQM is easy or not. Some of the organizations with a particular strategic orientation will be able to implement TQM easily and successfully but some organizations will have difficulty to implement it successfully.Practical implicationsThe firms hold their importance with respect to the different strategic orientation toward the various aspects of organizational cultures and TQM approaches in its implementation. Managerially, due to increased business competitiveness and economic pressures, top management sees the way in adopting TQM practices to achieve a competitive advantage. Apparently, it is evident that matching of TQM practices for a different strategy of the firms with various cultural dimensions leads to the smooth functioning of the organization. This study helps to the current organizations in implementing TQM with their respective culture.Originality/valueThis research can be useful for three strategic firms, namely innovators, prospectors and defenders to achieve effective implementation of TQM practices with consideration and understanding of the advantage of each culture dimension. The framework of the current study represents the effectiveness in assessing the TQM practices in individual cultural dimensions and its significant role.
Sustainability assessment in the manufacturing industry: a review of recent studies
Authors: Ahmad Shamraiz , Wong Kuan Yew 
Published: October 2018

Purpose
The purpose of this paper is to review and analyze the recent sustainability assessment studies in the manufacturing industry from the triple-bottom-line (TBL) perspective. This paper aims to depict the status quo of practical sustainability assessment, summarize the different levels and boundaries of evaluation, and highlight the difficulties and further improvements needed to make the assessment more effective in the manufacturing industry.

Design/methodology/approach
Four keywords, namely, sustainability assessment, sustainable manufacturing, TBL and green production, were used to explore and find the relevant articles. First, this paper systematically reviewed the studies and analyzed the different levels and boundaries of sustainability assessment. Following this, the reviewed studies were critically discussed along with their merits and shortcomings.

Findings
The review showed that most of the sustainability assessment studies were conducted on product, company and process levels in the manufacturing industry. Nevertheless, there is still a need to focus more on plant and process level assessments to achieve the TBL objectives. Environmental assessment is comparatively matured in manufacturing industries. However, from the economic and social viewpoints, only cost analysis and workers’ safety, respectively, were considered in most of the studies. The economic and social indicators need to be more inclusive and should be validated and standardized for manufacturing industries.

Originality/value
Unlike previous sustainability assessment reviews in manufacturing industries which were mostly based on life cycle assessment, this paper has included environmental, social and economic aspects in one comprehensive review and focused on recent studies published from 2010 to 2017. This paper has explored the recent sustainability assessment trends and provided insights into the development of sustainability assessment in the manufacturing sector.
Efficiency evaluation of accounting firm partnerships from the perspective of operating difficulties, strategies, and practices in Mainland China
Authors: Lee Chia-Chi 
Published: October 2018

Purpose
The purpose of this paper is to explore the operating efficiency of accounting firm partnerships.

Design/methodology/approach
An empirical analysis is performed with a three-stage research method: data envelopment analysis (DEA), univariate testing and regression analysis.

Findings
The results indicate that large firms are not necessarily the most efficient. Efficient accounting firms see an average 50 percent contribution from total practice revenues and a 50 percent contribution from the number of cases. The percentage of senior managers is higher for firms with poor operating efficiency than for firms with good operating efficiency. This implies that firms with poor operating efficiency have a higher expenditure in human capital. Both efficient and inefficient firms find intense market competition to be the main challenge, followed by the challenge of market recessions. Appropriate educational training should be provided to upgrade the professional expertise and competency of staff. Response to peer competition and assistance to local accountant practices are the main reasons for setting up practice in Mainland China. The main operating mode in Mainland China is bringing personnel from Taiwan.

Originality/value
Using DEA, univariate testing and regression analysis, this paper aims to help the operators of accounting firms in dealing with business difficulties, finding their own core competencies, and making up for their operating disadvantages. The findings can provide references to reviewing whether their human resource allocation is appropriate and which operational type should be adopted by the accounting firms. Hence, the accounting firms can formulate their future operational strategies.
Business environment-supply chain framework and benchmarking supply chain structures
Authors: Uluskan Meryem , Godfrey A. Blanton 
Published: October 2018

Purpose
The purpose of this paper is to develop a supply chain management framework covering different business environment levels, that is, macro, micro and supply chain levels, and also to evaluate Haiti vs China as apparel-sourcing partners by assessing macro-level, supply-chain-level and micro-level environments from the US apparel buyers’ perspective.

Design/methodology/approach
In order to achieve this, first, a framework covering these business environment levels was developed and tested through path analysis. Prior to path analysis exploratory factor analysis was conducted to verify proposed factor structures. Data were collected using face-to-face interviews with a sample of 41 apparel companies that operate in the USA and source from China and Haiti.

Findings
This study found that both supply-chain-level and micro-level environments positively impact global supply chain performance. Supply-chain-level also has a direct effect on micro-level environment and macro-level environment has only a direct effect on supply-chain-level environment. Interviews and discussions based on this framework indicate that Haiti’s proximity to the USA, price, low-wage rates, small-order sourcing opportunities and good basic sewing skills are among Haiti’s strengths.

Originality/value
This study is unique in developing a multi-level environment framework for supply chain management and in comparing Haiti and China in terms of their supply chains to evaluate the potential competitiveness of Haitian apparel supply chain.