bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three enzymes and one substrate; regulation of flux through the glyoxylate shunt in the opportunistic pathogen,Pseudomonas aeruginosa
Authors: Crousilles Audrey , Dolan Stephen K. , Brear Paul , Chirgadze Dimitri Y. , Welch Martin 
Published: May 2018

AbstractThe glyoxylate shunt bypasses the oxidative decarboxylation steps of the tricarboxylic acid (TCA) cycle, thereby conserving carbon skeletons for biosynthesis. The branchpoint between the TCA cycle and the glyoxylate shunt is therefore widely considered to be one of the most important junctions in the whole of microbial metabolism. InEscherichia coli, AceK-mediated phosphorylation and inactivation of the TCA cycle enzyme,isocitrate dehydrogenase (ICD), is necessary to redirect flux through the first enzyme of the glyoxylate shunt,isocitrate lyase (ICL). In contrast, Mycobacterial species lack AceK and employ a phosphorylation-insensitiveisocitrate dehydrogenase (IDH) at the branchpoint. Flux partitioning here is controlled “rheostatically” through cross-activation of IDH by the product of ICL activity, glyoxylate. However, the opportunistic human pathogen,Pseudomonas aeruginosa, expresses IDH, ICD, ICL and AceK. Here, we present the structure, kinetics and regulation of each branchpoint enzyme. We show that flux partitioning is coordinated through reciprocal regulation of the enzymes involved, beautifully linking carbon flux with the availability of key gluconeogenic precursors in a way that cannot be extrapolated from an understanding of the branchpoint enzymes in other organisms.
Long-term expanding human airway organoids for disease modelling
Authors: Sachs Norman , Zomer-van Ommen Domenique D. , Papaspyropoulos Angelos , Heo Inha , Böttinger Lena , Klay Dymph , Weeber Fleur , Huelsz-Prince Guizela , Iakobachvili Nino , Viveen Marco C. , Lyubimova Anna , Teeven Luc , Derakhshan Sepideh , Korving Jeroen , Begthel Harry , Kumawat Kuldeep , Ramos Emilio , van Oosterhout Matthijs F.M. , Olimpio Eduardo P. , de Ligt Joep , Dijkstra Krijn K. , Smit Egbert F. , van der Linden Maarten , Voest Emile E. , van Moorsel Coline H.M. , van der Ent Cornelis K. , Cuppen Edwin , van Oudenaarden Alexander , Coenjaerts Frank E. , Meyaard Linde , Bont Louis J. , Peters Peter J. , Tans Sander J. , van Zon Jeroen S. , Boj Sylvia F. , Vries Robert G. , Beekman Jeffrey M. , Clevers Hans 
Published: May 2018

AbstractOrganoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here we describe a method to establish long-term-expanding human airway organoids from broncho-alveolar biopsies or lavage material. The pseudostratified airway organoid epithelium consists of basal cells, functional multi-ciliated cells, mucus-producing goblet cells, and CC10-secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoid culture conditions also allow gene editing as well as the derivation of various types of lung cancer organoids. Respiratory syncytial virus (RSV) infection recapitulated central disease features and dramatically increases organoid cell motility, found to be driven by the non-structural viral NS2 protein. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.
Local Contractions Regulate E-Cadherin Adhesions, Rigidity Sensing and Epithelial Cell Sorting
Authors: Yang Yian , Nguyen Emmanuelle , Narayana Gautham Hari Narayana Sankara , Heuzé Melina , Mège René-Marc , Ladoux Benoit , Sheetz Michael P. 
Published: May 2018

AbstractE-cadherin is a major cell-cell adhesion molecule involved in mechanotransduction at cell-cell contacts in tissues. Since epithelial cells respond to rigidity and tension in the tissue through E-cadherin, there must be active processes that test and respond to the mechanical properties of these adhesive contacts. Using sub-micrometer, E-cadherin-coated PDMS pillars, we find that cells generate local contractions between E-cadherin adhesions and pull to a constant distance for a constant duration, irrespective of pillar rigidity. These cadherin contractions require non-muscle myosin IIB, tropomyosin 2.1, α-catenin and binding of vinculin to α-catenin; plus, they are correlated with rigidity-dependent cell spreading. Without contractions, cells fail to spread to different areas on soft and rigid surfaces and to maintain monolayer integrity. We further observe that cadherin contractions enable cells to test myosin IIA-mediated tension of neighboring cells, and sort out myosin IIA-depleted cells. Thus, we suggest that epithelial cells test and respond to the mechanical characteristics of neighboring cells through cadherin contractions.
Integrin and ligand-independent PDGFr signaling synergistically contribute to directional migration ofXenopusmesendoderm
Authors: Richardson Crystal M. , Dzamba Bette J. , Sonavane Pooja R. , DeSimone Douglas W. 
Published: May 2018

AbstractBoth PDGF signaling and adhesion to fibronectin (FN) matrix have been implicated in the directional collective migration ofXenopusmesendoderm cells at gastrulation. However, mesendoderm explants cultured on FN-coated substrates migrate directionally even in the absence of a source of PDGF. Integrin adhesion has been reported to up-regulate PDGF ligand-independent signaling through the PDGF receptor (PDGFr) in cultured mammalian cells. In order to address whether a similar mechanism stimulates PDGFr signaling in the absence of PDGF-A ligand in amphibian mesendoderm, isolated cells were cultured on bacterial fusion proteins containing the Type-III repeats 9-11 of FN (GST-9.11). Type III9-11contains the RGD and “synergy” (PPSRN) sites required for integrin α5β1 adhesion and activation but lacks the PDGF-A ligand-binding site present in the full-length FN protein. In order to ensure mesendoderm was not exposed to PDGFin vivoprior to removal and culturein vitro, antisense morpholinos were used to inhibit normal expression of PDGF-A ligand in embryos. P-Akt levels were reduced two-fold when either the PDGFr-α was knocked down or when cells were plated on GST-9.11a, which contains a point mutation (PPSRN>PPSAN) that prevents both full activation of integrin α5β1 and cell spreading. Reduced expression of PDGFr-α was accompanied by perturbations in tissue migration, cytoskeletal organization, polarity of cell protrusions, and focal adhesion area. Mesendoderm cells became rounded, and the actin and cytokeratin filaments appeared collapsed and often colocalized near the cell center. Taken together, these findings suggest that integrin adhesion to FN, acting in synergy with PDGFr-α, is sufficient to elevate PI3K-Akt signaling in the mesendoderm even in the absence of the PDGF-A ligand, and to promote forward-directed protrusions and directional tissue migration.
Gold Cup: human resources as sources of competitive advantage and superior performance
Authors: Omondi-Ochieng Peter 
Published: May 2018

PurposeThe purpose of this paper is twofold: first, to evaluate the association between human resources and qualification for the 2017 Gold Cup, and second, to examine if human resources could predict qualification for the 2017 Gold Cup.Design/methodology/approachGuided by four competitive advantage (CA) theories related to the human resources, the study utilized archival data of 35 male Gold Cup national football teams. The dependent variable was qualifications for 2017 Gold Cup and the independent variables were football-specific human capital measured by ranked number of football amateurs, professionals and officials. Statistical analysis was performed using Kendellτstatistic and binary logistic regression (BLR).FindingsQualification for the Gold Cup tournament and all human resources were positively and statistically associated (officials (0.493,p<0.01), amateurs (0.464,p<0.01) and professionals (0.624,p<0.01)), and BLR model (NegelkerkeR2) explained 55.8 percent of the variance of human resources.Research limitations/implicationsThe research focused exclusively on football-specific human capital and not alternative sources of CA such as economy power, political stability and/or national football popularity amongst others.Practical implicationsHuman resources are a valuable source of CA which requires long-term strategy geared toward training, development and promotion of talent. Superior football team performance is directly proportional to talented players.Originality/valueThe study was unique in two ways. First, it made clear the positive significance of human resources as a source of CA. Second, it highlighted the distinction between professional and amateur footballers – a factor uncommon in similar studies.
Bayesian-based conflict conversion path discovery for waste management policy implementation in China
Authors: Yang Qing , He Ling , Liu Xingxing , Cheng Mengying 
Published: May 2018

Purpose
This study aims to analyze reform path for waste management policy implementation. With reference to the Bayesian theory, this study provides a dynamic policy conversion method through various context settings. Furthermore, this study attempts to present an empirical research paradigm.

Design/methodology/approach
Matland’s “ambiguity-conflict model” is applied to explain the problems and reform paths of China’s waste management policy implementation. Integrating structure discovery and bibliometrics into qualitative analysis, this study used search data from literature search engine with specific themes to achieve structure learning of Bayesian network with key factors refined in waste management policy.

Findings
The results show that China’s waste management policy implementation belongs to symbolic implementation with high ambiguity and high conflict. Four basic conversion paths for the waste management policy are proposed, which are classified by length and stability. Then, it is possible to locate the factors, paths and types of policy implementation through involvement analysis with features of each path and each district of policy implementation. Public education holds direct but unstable impact on waste management. Economic incentives hold continuous but gradually diminishing impact. Perceived policy effectiveness plays the crucial role like a central bridge. Resident conditions have a positive impact, which could be enhanced through economic development of China. The impact of subjective norm on waste management is not significant. But subjective norm has the potential breakthrough for solving stagnation of waste classification policy. However, the impacts from each factor may change along with economy growth and technology innovation.

Originality/value
This study uses the “ambiguity-conflict model” to position China’s waste classification policy and suggests that structure discovery methods help understand feasible reform paths for reform policy. The integration of theoretical analysis and quantitative simulation can achieve a comprehensive analysis of problems and solutions in waste management policy implementation of China. Promotion and education, economic incentives, perceived value, behavior control, subjective norm, perceived policy effectiveness, informal waste recycling system and residential conditions are explored as key factors for waste classification policy implementation as a representative in waste management policy. The role of each key factor and features of each conversion paths are integrated to position reform paths in the ambiguity-conflict model. This work helps to explain the stagnation of waste management policy implementation from the perspective of dynamic structure evolution, and some specific suggestions to get out of stagnation are proposed.
The path to mall patronage intentions is paved with 4E-based experiential value for Indian consumers
Authors: Sadachar Amrut , Fiore Ann Marie 
Published: May 2018

Purpose
The purpose of this paper is to examine whether experiential offerings from two types of retailers play a significant role in consumer responses toward Indian malls. Specifically, this study examined the relationships between consumer perceptions of experience economy 4E constructs (i.e. educational, entertainment, escapist, and esthetic experiences) and experiential value associated with merchandise retailers and service retailers in Indian shopping malls, and between perceived experiential value and mall patronage intention.

Design/methodology/approach
A mall intercept survey conducted in two shopping malls in India resulted in 552 useable responses. Structural equation modeling was used to test the hypothesized relationships.

Findings
Experience economy constructs (i.e. entertainment, escapist, and esthetic experiences) contributed to the experiential value associated with merchandise retailers and/or service retailers in the mall. Experiential value associated with both merchandise retailers and service retailers in the mall positively influenced mall patronage intention.

Practical implications
The results have practical implications for mall retailers, mall managers, and mall developers; particular experiential strategies for both merchandise retailers and service retailers may improve patronage intentions toward the mall, which includes a measure of purchase intentions.

Originality/value
Although academic articles support the idea that retailers can obtain benefits by offering experiences to consumers, this is the first study to empirically validate the role of specific consumer experiences, the 4Es, resulting from both merchandise retailers and service retailers, in a non-Western mall context on value creation for shoppers and the consequent influence on patronage intentions.
The German source market perceptions: how risky is Turkey to travel to?
Authors: Isaac Rami K. , Velden Vanessa 
Published: May 2018

Purpose
The purpose of this paper is to get a better understanding of the influence of terrorism on risk perception and attitudes of the German travel behavior toward Turkey as a destination in crisis, which has been considered one of the biggest losers for 2016.

Design/methodology/approach
The research process involved an online self-administered method created with one of the leading research and web-based survey tools called Qualtrics. This tool has been considered useful to reach a wider target, the questionnaire filled in by 305 respondents.

Findings
The findings revealed a strong tendency of a low safety perception among the sample toward Turkey. Furthermore, a large proportion indicated a strong unlikelihood of traveling to the country within the upcoming 12 months independently of a past travel experience. In addition, Turkey and Egypt were the countries perceived as most unsafe among the mentioned destinations.

Research limitations/implications
The majority of the respondents of the study were aged between 50 and 59 years and were employed as commercial employee, office or administration workers. The outcomes might be different for a higher sample size with a tendency of various demographic characteristic such as age and profession. Furthermore, the study should be repeated while focusing on respondents with accompanied children on holidays, which only made up a minority for the present research study.

Originality/value
To the best of the knowledge, this is the first study to examine the influence of terrorism on risk perception and attitudes of the German travel behavior toward Turkey and their risk reduction strategies/preventive measures.
A study of crowd-collaborative learning: an empirical study
Authors: Lin Wen-Shan , Wang Yi-Ju , Chen Hong-Ren 
Published: May 2018

Purpose
Information technology is widely applied for completing group tasks and enhancing learning in computer-supported collaborative learning (CSCL) environment. Group members not only complete tasks but also learn ideas from other members of the group. These ideas can be better than what individual could come up with. As these ideas are referred as an upward comparison in the perspective of social comparison theory. However, there are limited studies that provide evidence in investigating how social comparison orientation (SCO) perceived by individual learner impacts on learning and group performance. The paper aims to discuss these issues.

Design/methodology/approach
This study experimentally tackles this problem at both individual and group level. An experimental study was applied in this study. Structural equation modeling and hierarchical linear modeling approaches are used to validate the data.

Findings
Results of 168 subjects reveal that SCO does have associations with group performance and learning performance respectively. Discussions and implications for literature and practice are given at the end of the paper.

Originality/value
This study confirms that the social genesis occurs more effectively through social interactions in CSCL. It also extends our understandings about the impacts of SCO. Results reveal that the higher level of SCO adopted by group members, the higher level of social interactions at group level can be triggered. As a result, the group performance can be enhanced. On one hand, these findings bridge the research gap in terms of investigating the notion of SCT on CSCL. On the other hand, it provides a possible solution in alleviating the problem of social loafing as commonly observed in CSCL. Therefore, these findings fulfilled the two research objectives.
Value innovation and how to successfully incubate “blue ocean” initiatives
Authors: Leavy Brian 
Published: May 2018

Purpose
This masterclass examines the blue ocean value innovation process, how it works in practice and how it has evolved since the publication of Blue Ocean Strategy (2005) by W. Chan Kim and Renee Mauborgne as explored in their new book their new book Blue Ocean Shift (2017).

Design/methodology/approach
The main focus is the value innovation methodology that underlies blue ocean strategy.

Findings
Blue ocean strategy is a process of value innovation that uncovers new aggregations of demand by redefining the offering category.

Practical implications
Blue ocean strategy tends to focus on value innovation that uncovers new aggregations of demand by redefining the category while disruptive innovation tends to concentrate on new demand-creation that expands the current served market.

Originality/value
Blue ocean strategy sets out to reconfigure value propositions in compelling new ways that can deliver a quantum leap beyond the current red ocean value-cost frontier through raising buyer value and lowering company costs simultaneously. The emphasis on both value and innovation is essential to the creation of new “blue ocean” market spaces.
Customized reconstruction with modified keystone flaps
Authors: Lee Jang Won , Kim Chan Woo , Park Tae Hwan 
Published: May 2018

AbstractThe reconstruction of soft tissue defects with a similar type of tissue and minimizing morbidities are important. Herein, we describe our surgical experience using customized reconstruction with a series of modified keystone flaps. We retrospectively reviewed data of 48 consecutive soft tissue reconstructions using modified keystone flaps between March and December 2017. Soft tissue reconstruction was performed and there was no major complication in the follow‐up period. The dimensions of the wound defect ranged from 1 × 1 cm2 to 20 × 18 cm2 with a mean size of 4.7 × 3.5 cm2, while the dimensions of the customized keystone design flap ranged from 2 × 1 cm2 to 23 × 19 cm2 with a mean size of 7.9 × 5.4 cm2. Minor dehiscence in three cases (6%) and partial flap loss in one case (2%) were noticed. Two cases healed spontaneously and other two cases were surgically recovered. Due to its simplicity, reliability, versatility and minimal morbidity, our modified keystone flaps could be excellent surgical options in various soft tissue reconstructions.
Modelling the wave phenomena in acoustic and elastic media with sharp variations of physical properties using the grid‐characteristic method
Authors: Favorskaya Alena V. , Zhdanov Michael S. , Khokhlov Nikolay I. , Petrov Igor B. 
Published: May 2018

ABSTRACTThis paper introduces a novel method of modelling acoustic and elastic wave propagation in inhomogeneous media with sharp variations of physical properties based on the recently developed grid‐characteristic method which considers different types of waves generated in inhomogeneous linear‐elastic media (e.g., longitudinal, transverse, Stoneley, Rayleigh, scattered PP‐, SS‐waves, and converted PS‐ and SP‐waves). In the framework of this method, the problem of solving acoustic or elastic wave equations is reduced to the interpolation of the solutions, determined at earlier time, thus avoiding a direct solution of the large systems of linear equations required by the FD or FE methods. We apply the grid‐characteristic method to compare wave phenomena computed using the acoustic and elastic wave equations in geological medium containing a hydrocarbon reservoir or a fracture zone. The results of this study demonstrate that the developed algorithm can be used as an effective technique for modelling wave phenomena in the models containing hydrocarbon reservoir and/or the fracture zones, which are important targets of seismic exploration.
Metformin directly targets the H3K27me3 demethylase KDM6A/UTX
Authors: Cuyàs Elisabet , Verdura Sara , Llorach‐Pares Laura , Fernández‐Arroyo Salvador , Luciano‐Mateo Fedra , Cabré Noemí , Stursa Jan , Werner Lukas , Martin‐Castillo Begoña , Viollet Benoit , Neuzil Jiri , Joven Jorge , Nonell‐Canals Alfons , Sanchez‐Martinez Melchor , Menendez Javier A. 
Published: May 2018

SummaryMetformin, the first drug chosen to be tested in a clinical trial aimed to target the biology of aging per se, has been clinically exploited for decades in the absence of a complete understanding of its therapeutic targets or chemical determinants. We here outline a systematic chemoinformatics approach to computationally predict biomolecular targets of metformin. Using several structure‐ and ligand‐based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3‐specific demethylase subfamily, KDM6A/UTX. AlphaScreen and AlphaLISA assays confirmed the ability of metformin to inhibit the demethylation activity of purified KDM6A/UTX enzyme. Structural studies revealed that metformin might occupy the same set of residues involved in H3K27me3 binding and demethylation within the catalytic pocket of KDM6A/UTX. Millimolar metformin augmented global levels of H3K27me3 in cultured cells, including reversion of global loss of H3K27me3 occurring in premature aging syndromes, irrespective of mitochondrial complex I or AMPK. Pharmacological doses of metformin in drinking water or intraperitoneal injection significantly elevated the global levels of H3K27me3 in the hepatic tissue of low‐density lipoprotein receptor‐deficient mice and in the tumor tissues of highly aggressive breast cancer xenograft‐bearing mice. Moreover, nondiabetic breast cancer patients receiving oral metformin in addition to standard therapy presented an elevated level of circulating H3K27me3. Our biocomputational approach coupled to experimental validation reveals that metformin might directly regulate the biological machinery of aging by targeting core chromatin modifiers of the epigenome.