bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cargo receptor SURF4 promotes the efficient cellular secretion of PCSK9
Authors: Emmer Brian T. , Hesketh Geoffrey G. , Kotnik Emilee , Tang Vi T. , Lascuna Paul J. , Xiang Jie , Gingras Anne-Claude , Chen Xiao-Wei , Ginsburg David 
Published: May 2018

ABSTRACTProprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that plays an important role in regulating plasma cholesterol and cardiovascular disease risk. PCSK9 secretion uniquely depends on the cytoplasmic COPII protein SEC24A, suggesting the presence of a transmembrane ER cargo receptor mediating this interaction. Here, we report a novel approach that combines proximity-dependent biotinylation and proteomics together with genome-scale CRISPR screening to identify proteins that facilitate the efficient secretion of PCSK9 heterologously expressed in HEK293T cells. We first identified 35 candidate proteins that were labeled by BirA* fusions to PCSK9 and either COPII component SAR1A or SAR1B. We then performed genome-scale pooled CRISPR mutagenesis to identify genes whose perturbation resulted in intracellular accumulation of PCSK9-eGFP but not the control A1AT-mCherry. The 4 most enriched sgRNAs in this screen all targeted SURF4, a homologue of the yeast endoplasmic reticulum (ER) cargo receptor Erv29p and the only candidate also identified by proximity-dependent biotinylation. The functional contribution of SURF4 to PCSK9 secretion was confirmed with multiple independent SURF4-targeting sgRNAs, clonal SURF4-deficient cell lines, and functional rescue with SURF4 cDNA. Compatible with a function of SURF4 as a cargo receptor for PCSK9, fluorescence microscopy localized SURF4 to the early secretory pathway, coimmunoprecipitation revealed a physical interaction between SURF4 and PCSK9, and SURF4 deletion resulted in decreased extracellular secretion of PCSK9 and PCSK9 accumulation in the ER. Taken together, these findings support a model in which SURF4 functions as an ER cargo receptor for the efficient cellular secretion of PCSK9.
Force localization modes in dynamic epithelial colonies
Authors: Schaumann Erik N. , Staddon Michael F. , Gardel Margaret L. , Banerjee Shiladitya 
Published: May 2018

AbstractCollective cell behaviors, including tissue remodeling, morphogenesis and cancer metastasis rely on dynamics between cells, their neighbors and the extracellular matrix. The lack of quantitative models precludes understanding of how cell-cell and cell-matrix interactions regulate tissue-scale force transmission to guide morphogenic processes. We integrate biophysical measurements on model epithelial tissues and computational modelling to explore how cell-level dynamics alter mechanical stress organization at multicellular scales. We show that traction stress distribution in epithelial colonies can vary widely for identical geometries. For colonies with peripheral localization of traction stresses, we recapitulate previously described mechanical behavior of cohesive tissues with a continuum model. By contrast, highly motile cells within colonies produce traction stresses that fluctuate in space and time. To predict the traction force dynamics, we introduce an Active Adherent Vertex Model (AAVM) for epithelial monolayers. AAVM predicts that increased cellular motility and reduced intercellular mechanical coupling localize traction stresses in the colony interior, in agreement with our experimental data. Furthermore, the model captures a wide spectrum of localized stress production modes that arise from individual cell activities including cell division, rotation, and polarized migration. This approach provides a robust quantitative framework to study how cell-scale dynamics influence force transmission in epithelial tissues.
Parallel sexual and parasexual population genomic structure inTrypanosoma cruzi
Authors: Schwabl Philipp , Imamura Hideo , Van den Broeck Frederik , Costales Jaime A. , Maiguashca Jalil , Miles Michael A. , Andersson Bjorn , Grijalva Mario J. , Llewellyn Martin S. 
Published: June 2018

AbstractGenetic exchange and hybridization in parasitic organisms is fundamental to the exploitation of new hosts and host populations. Variable mating frequency often coincides with strong metapopulation structure, where patchy selection or demography may favor different reproductive modes. Evidence for genetic exchange inTrypanosoma cruziover the last 30 years has been limited and inconclusive. The reproductive modes of other medically important trypanosomatids are better established, although little is known about their variability on a spatio-temporal scale. Targeting a contemporary focus ofT. cruzitransmission in southern Ecuador, we present compelling evidence from 45 sequenced genomes thatT. cruzi(discrete typing unit I) maintains sexual populations alongside others that represent clonal bursts of parasexual origin. Strains from one site exhibit genome-wide Hardy-Weinberg equilibrium and intra-chromosomal linkage decay consistent with meiotic reproduction. Strains collected from adjacent areas (>6 km) show excess heterozygosity, near-identical haplo-segments, common mitochondrial sequences and levels of aneuploidy incompatible with Mendelian sex. Certain individuals exhibit trisomy in as many as fifteen chromosomes. Others present fewer, yet shared, aneuploidies reminiscent of mitotic genome erosion and parasexual genetic exchange. Genomic and intra-genomic phylogenetics as well as haplotype co-ancestry analyses indicate a clear break in gene-flow between these distinct populations, despite the fact that they occasionally co-occur in vectors and hosts. We propose biological explanations for the fine-scale disconnectivity we observe and discuss the epidemiological consequences of flexible reproductive modes and their genomic architecture for this medically important parasite.
The Dimer-dependent Catalytic Activity of RAF Family Kinases Is Revealed Through Characterizing Their Oncogenic Mutants
Authors: Yuan Jimin , Ng Wan Hwa , Lam Paula Y.P. , Wang Yu , Xia Hongping , Yap Jiajun , Guan Shou Ping , Lee Ann S.G. , Wang Mei , Baccarini Manuela , Hu Jiancheng 
Published: June 2018

AbstractAlthough extensively studied for three decades, the molecular mechanisms that regulate the RAF/MEK/ERK kinase cascade remain ambiguous. Recent studies identified the dimerization of RAF as a key event in the activation of this cascade. Here, we show that in-frame deletions in the β3-αC loop activate ARAF as well as BRAF and other oncogenic kinases by enforcing homodimerization. By characterizing these RAF mutants, we find that ARAF has less allosteric and catalytic activity than the other two RAF isoforms, which arises from its non-canonical APE motif. Further, these RAF mutants exhibit a strong oncogenic potential, and a differential inhibitor resistance that correlates with their dimer affinity. Using these unique mutants, we demonstrate that active RAFs, including the BRAF(V600E) mutant, phosphorylate MEK in a dimer-dependent manner. This study characterizes a special category of oncogenic kinase mutations, and elucidates the molecular basis that underlies the differential ability of RAF isoforms to stimulate MEK-ERK pathway. Further, this study reveals a unique catalytic feature of RAF family kinases that can be exploited to control their activities for cancer therapies.
H3K9me3 is Required for Inheritance of Small RNAs that Target a Unique Subset of Newly Evolved Genes
Authors: Lev Itamar , Gingold Hila , Rechavi Oded 
Published: June 2018

AbstractIn Caenorhabditis elegans, RNA interference (RNAi) responses can transmit across generations via small RNAs. RNAi inheritance is associated with Histone-3-Lysine-9 tri-methylation (H3K9me3) of the targeted genes. In other organisms, maintenance of silencing requires a feed-forward loop between H3K9me3 and small RNAs. Here we show that in C. elegans not only is H3K9me3 unnecessary for inheritance, the modification’s function depends on the identity of the RNAi-targeted gene. We found an asymmetry in the requirement for H3K9me3 and the main worm H3K9me3 methyltransferases, SET-25 and SET-32. Both methyltransferases promote heritable silencing of the foreign gene gfp, but are dispensable for silencing of the endogenous gene oma-1. Genome-wide examination of heritable endogenous small interfering RNAs (endo-siRNAs) revealed that the SET-25-dependent heritable endo-siRNAs target newly acquired and highly H3K9me3 marked genes. Thus, “repressive” chromatin marks could be important specifically for heritable silencing of genes which are flagged as “foreign”, such as gfp.
Small Molecule Inhibition of the Innate Immune Response Increases Transgene Expression
Authors: Spivack Kyle , Muzzelo Christine , Neely Christopher , Vanzelli Julia , Kurt Evan , Elmer Jacob 
Published: June 2018

AbstractForeign molecules like plasmid DNA trigger a complex and potent innate immune response comprised of highly redundant signal transduction cascades that result in the activation of transcription factors and the production of inflammatory cytokines. Unfortunately, this defense mechanism can hinder gene therapy by inhibiting transgene expression. The goal of this study was to increase transgene expression by inhibiting key components of the innate immune response (β-catenin, NF-κB/AP1, TBK1, TLR9, and p38 MAPK) with small molecule inhibitors (iCRT-14, curcumin, BX-795, E6446, and VX-702 respectively). The effects of each drug on transgene (luciferase) expression, inflammatory cytokine (IL-6) levels, and cell viability were quantified in prostate (PC3), breast (MCF-7), and murine bladder (MB49) cancer cell lines. The β-catenin inhibitor iCRT-14 (1 μM) provided the highest enhancement of 35.5 ± 19-fold in MCF-7 cells, while the other inhibitors increased transgene expression at a more modest level (2-9 fold). The optimal concentrations of iCRT-14, curcumin, and VX-702 showed no significant effect on cell proliferation; however, optimal concentrations of BX-795 and E6446 did significantly reduce cell proliferation. Nonetheless, inhibition of the innate immune response by iCRT-14 and curcumin was confirmed by a concomitant decrease in IL-6 production in PC3 cells. These results demonstrate that these inhibitors can improve gene therapy by preventing an inflammatory innate immune response.
Image, performance, attitudes, trust, and loyalty in financial services
Authors: Akhgari Mehdi , Bruning Edward R. , Finlay Jesse , Bruning Nealia S. 
Published: May 2018

PurposeThe purpose of this paper is twofold: first, to determine the extent to which hedonic and utilitarian attitudes and loyalty are influenced by perceived financial performance (PFP) and executive compensation plan image (ECPI) in financial services; second, the authors evaluate relationships among hedonic and utilitarian attitudes, trust, and loyalty.Design/methodology/approachUsing a quasi-experimental design in Study 1 the authors test the relationship between antecedents (PFP and ECPI) and relational elements (attitudes, trust, and loyalty) to address the first objective. To accomplish the second objective, the authors employ structural equation modeling in Study 2 to test the relationship among hedonic and utilitarian attitudes, trust, and loyalty.FindingsStudy 1 confirms that PFP and ECPI positively impact both hedonic and utilitarian attitudes but do not directly affect loyalty. Study 2 demonstrates a positive association between utilitarian attitudes and trust, although the hedonic attitudes-trust relationship is negative. Hedonic attitudes are also significantly related to utilitarian attitudes. Finally, trust mediates the relationship between attitudes and loyalty.Practical implicationsBuilding customer trust is an important correlate of loyalty, and emphasizing an attribute-based aspect of perceived financial service generates greater trust compared to enhancing a non-attribute aspect (i.e. minimizing negative effects on image of executive compensation plans).Originality/valueThe authors link attitude research to service/relationship quality research and discover that attitudes are indirectly related to loyalty through increases in trust. The findings suggest that perceived image and performance of financial services are important to relationship quality when applied to financial services.
Development of a Green Lean Six Sigma model for public sectors
Authors: Sreedharan V. Raja , G. Sandhya , Raju R. 
Published: June 2018

PurposeThe purpose of this paper is to improve the operational excellence of public sector services such as construction, telecommunication and health care. To achieve this endeavor, the study explores the structural attributes and obstacles in the public services and develops a Green Lean Six Sigma (GLSS) model for the public sector.Design/methodology/approachThe study involved two stages: first, structured literature reviews; second, a focus group study involving Black Belts and supply chain practitioners. Using the results from the literature reviews and focus group study, the researchers have developed a Green Lean Six Sigma (GLSS) model for the public sectors.FindingsBlack belts and supply chain practitioners have identified the success in deploying Lean Six Sigma with green supply chain management. This leads to eradicating the obstacles faced by the public sector, leading to process improvement.Practical implicationsThis study proposed an approach for developing a GLSS model for the public services, which can be applicable for other public service organizations.Originality/valueThe current paper presents a predictive model for process improvement in the public sector by integrating green supply chain management with Lean Six Sigma.
Springing from where? How emerging market firms become multinational enterprises
Authors: Hennart Jean-François 
Published: May 2018

Purpose
The purpose of this paper is to show that existing theories, principally Dunning’s OLI model, Mathews LLL model and Rugman’s version of internalization theory are unable to explain the rise of emerging market multinationals (EMNEs). The reason is that they over-emphasize the strategic importance of intangibles and ignore that of complementary local assets. Taking complementary local assets into account makes it possible to understand why EMNEs are able to finance their intangible-buying sprees and, often with the help of their governments, to swap market access for technology.

Design/methodology/approach
This is a conceptual paper based on the bundling model (JIBS 2009) and backed by the case histories of four EMNEs.

Findings
The author shows that EMNEs have much better prospects vis-à-vis established MNEs than generally thought in Western Europe and the USA and that they will become serious competitors.

Originality/value
This is, as far as the author knows, the first explanation of why EMNEs have the bargaining power and the resources necessary to swap or buy technology from established MNEs.
Lost in the transition from cash to accrual accounting
Authors: Gigli Sabrina , Mariani Laura 
Published: June 2018

PurposeThe purpose of this paper is to examine the change from cash accounting to accrual accounting, identifying and assessing the institutional and organisational barriers that may affect this process. A specific focus on knowledge gaps is provided.Design/methodology/approachThe study employs a mixed method design, combining action research activities, a survey, and in-depth qualitative interviews in the setting of Italian public universities.FindingsThe findings highlight a low degree of compliance with the accrual accounting system and budgeting system, which is the result of the lack of an accrual accounting culture in the Italian public sector.Originality/valueThe analysis confirms some barriers to the transition highlighted by previous literature and also adds further explanations of such limitations in terms of the lack of skills and accounting knowledge of the universities’ administrative staff possesses.
Ge-whiz! How students choose their general education classes
Authors: Seeley Eugene Lyle , Goddard Todd , Mellado Miller Ronald 
Published: May 2018

PurposeThe purpose of this paper is to understand how students choose their general education elective courses.Design/methodology/approachA survey was given to 12,000 undergraduate students at Utah Valley University (UVU) that asked about how they selected distribution courses to fulfill the requirements for the general education. UVU offers 113 different courses in the general education distribution area, but only six are needed to meet the requirements. Students were asked to both select all methods that they used and then to rank their selected methods. The results were analyzed usingχ2methods.Findings“Personal interest” and “What best fit my schedule” were the top choices and where chosen as a method used by 69 and 67 percent of the students respectively. When asked to rank the methods, “Personal interest” ranked first most frequently at 32 percent and “What best fits my schedule” was ranked first by 29 percent of students. The results indicate that although personal interest is the most used method for choosing these classes, it does not dominate, and schedule remains a significant factor for students at UVU.Originality/valueThe data provide a look into the perceptions and attitudes of students at what is predominately a commuter school. This research provides the first step in understanding student motives in selecting elective classes.
Are two heads better than one? Intellectual capital, learning and knowledge sharing in a dyadic interdisciplinary relationship
Authors: Wang Jue-Fan JF , Tarn David DC 
Published: June 2018

PurposePast studies have paid extensive attention to investigate learning issues in individual, organizational and team contexts. Learning activities in the workplace, however, often occur in the interdisciplinary dyadic context. Hence, the purpose of this paper is to clarify what factors make interdisciplinary dyads lead to better learning effects. The authors attempted to clarify two major agendas: What knowledge factors (intellectual capitals) owned by the parties of the dyads can induce better learning effects? What contextual factors (learning tasks) can make better learning effects during the dyadic learning process?Design/methodology/approachTo examine the previous agendas, the authors first conducted in-depth interviews and an exploratory survey so that a four-element dyadic intellectual capital (DIC) architecture was circumscribed: knowledge interdependency, expertise similarity, collaborative routines and mutual trust. Dyadic learning tasks were classified as exploitative and exploratory learning. The authors then sampled 248 respondents for the formal empirical survey to examine the relationship between DIC, dyadic learning tasks and knowledge sharing.FindingsThe statistical evidences confirmed the positive relationships between DIC and knowledge sharing, and the results also signified the previous relationships with a mediating effect from exploratory learning, while the effect of exploitative learning was not supported. Thus, only dyads (the two heads) with knowledge interdependency and mutual trust can make the exploratory task better than that of one individual (the one head).Originality/valueThis study provides a new insight into the learning issue with an interdisciplinary dyadic perspective to supplement the existing gap between academic efforts and learning practices in the workplace.
A holistic model for inter-plant knowledge transfer within an international manufacturing network
Authors: Noruzi Farhad , Stenholm Daniel , Sjögren Peter , Bergsjö Dag 
Published: May 2018

PurposeThis paper aims to provide a holistic view to support the choice of appropriate strategy for conducting a knowledge transfer (KT) project in an international manufacturing network (IMN) environment. It proposes a model that includes multiple aspects of a KT project along with guidelines on each aspect.Design/methodology/approachTo achieve the research goals, multiple case study method was adopted. Data have been collected by conducting semi-structured interviews regarding five KT projects in three multinational corporations. Data were triangulated by means of comparisons to complementary data acquired through observations and archival documents.FindingsThe results of this paper detail the key issues of five KT projects. Furthermore, the paper proposes an aggregated model comprising the main aspects and strategies for a KT project within an IMN.Research limitations/implicationsDespite the abundant research on KT area, not many research projects provide holistic views on KT process. The focus has rather been sectional and concentrated on each specific aspect within the KT.Practical implicationsThe paper guides practitioners to identify multiple aspects in KT that will eventually increase the odds for successfully performing such projects.Originality/valueThe proposed learning network model improves the performance of KT projects by providing a holistic view including several factors that the organization should emphasize to succeed with inter-plant KT.
Development programs, household income and economic vulnerability
Authors: Mamun Abdullah Al , Ibrahim Mohd Asrul Hery Bin , Muniady Rajennd , Ismail Mohammad Bin , Nawi Noorshella Binti Che , Nasir Noorul Azwin Binti Md 
Published: June 2018

Purpose
The purpose of this paper is to improve the socio-economic condition of low-income households in Malaysia, many products and services are available, including access to working capital and enterprise development training programs. This study examined the impact of access to working capital and micro-enterprise development training programs on household income and economic vulnerability among participants of development initiatives in the eKasih (national poverty data bank) in Peninsular Malaysia.

Design/methodology/approach
Adopting a cross-sectional design, the authors collected data randomly from the selected 300 micro-entrepreneurs from the list of development organizations available in the eKasih (national poverty data bank) located in four states of Peninsular Malaysia. Quantitative data were collected through structured interviews with the respondents from October to November 2017.

Findings
Both the length of participation and total amount of economic loan were found to increase the household income. However, there was no positive and significant impact of total number of training hours on household income. Interestingly, length of participation was found to reduce the level of economic vulnerability, except total amount of economic loan, and total number of training hours.

Originality/value
Despite the overwhelming empirical evidence, the findings indicated that the impact of enterprise development training programs was inconclusive. The effect of total amount of loan on economic vulnerability was also inconclusive. Hence, both policy makers and development organizations should understand how their programs benefit the poor households that can be improved through new implementation strategies.
Isolation, identification and screening of high‐quality yeast strains for the production of milk beer
Authors: Wang Liang , Gao Enyan , Hu Man , Oladejo Ayobami , Gong Xiaofen , Wang Jiangyue , Zhong Hao 
Published: May 2018

The aim of this study was to screen yeast strains from kefir grains for good fermentation abilities to produce milk beer. Molecular identification tests revealed the 17 yeast strains isolated belonged to four different species [Kluyveromyces marxianus (4/17), Pichia kudriavzevii (6/17), Dekkera anomala (1/17), Kazachstania unispora (6/17)]. Through physical and chemical testing of the 17 fermentation sample strains, five strains met the standard for milk beer production. Of the five strains, three strains showed better characteristics based on sensory evaluation and volatile components analysis. Based on principal component analysis, strain MJ1 (K. marxianus) performed the best and was deemed the most suitable for milk beer fermentation.