bluuebunny/crossref_metadata_2025 huggingface dataset:
Fgd5 identifies hematopoietic stem cells in the murine bone marrow
Authors: Gazit Roi , Mandal Pankaj K. , Ebina Wataru , Ben-Zvi Ayal , Nombela-Arrieta César , Silberstein Leslie E. , Rossi Derrick J.
Published: June 2014

Hematopoietic stem cells (HSCs) are the best-characterized tissue-specific stem cells, yet experimental study of HSCs remains challenging, as they are exceedingly rare and methods to purify them are cumbersome. Moreover, genetic tools for specifically investigating HSC biology are lacking. To address this we sought to identify genes uniquely expressed in HSCs within the hematopoietic system and to develop a reporter strain that specifically labels them. Using microarray profiling we identified several genes with HSC-restricted expression. Generation of mice with targeted reporter knock-in/knock-out alleles of one such gene, Fgd5, revealed that though Fgd5 was required for embryonic development, it was not required for definitive hematopoiesis or HSC function. Fgd5 reporter expression near exclusively labeled cells that expressed markers consistent with HSCs. Bone marrow cells isolated based solely on Fgd5 reporter signal showed potent HSC activity that was comparable to stringently purified HSCs. The labeled fraction of the Fgd5 reporter mice contained all HSC activity, and HSC-specific labeling was retained after transplantation. Derivation of next generation mice bearing an Fgd5-CreERT2 allele allowed tamoxifen-inducible deletion of a conditional allele specifically in HSCs. In summary, reporter expression from the Fgd5 locus permits identification and purification of HSCs based on single-color fluorescence.
What Elements of Successful Scientific Theories Are the Correct Targets for “Selective” Scientific Realism?
Authors: Peters Dean
Published: June 2014

Selective scientific realists disagree on which theoretical posits should be regarded as essential to the empirical success of a scientific theory. A satisfactory account of essentialness will show that the (approximate) truth of the selected posits adequately explains the success of the theory. Therefore, (a) the essential elements must be discernible prospectively; (b) there cannot be a priori criteria regarding which type of posit is essential; and (c) the overall success of a theory, or ‘cluster’ of propositions, not only individual derivations, should be explicable. Given these desiderata, I propose a “unification criterion” for identifying essential elements.
Cost Analysis of Strategies to Reduce Blood Culture Contamination in the Emergency Department: Sterile Collection Kits and Phlebotomy Teams
Authors: Self Wesley H. , Talbot Thomas R. , Paul Barbara R. , Collins Sean P. , Ward Michael J.
Published: June 2014

Objective

Blood culture collection practices that reduce contamination, such as sterile blood culture collection kits and phlebotomy teams, increase up-front costs for collecting cultures but may lead to net savings by eliminating downstream costs associated with contamination. The study objective was to compare overall hospital costs associated with 3 collection strategies: usual care, sterile kits, and phlebotomy teams.

Design

Cost analysis.

Setting

This analysis was conducted from the perspective of a hospital leadership team selecting a blood culture collection strategy for an adult emergency department (ED) with 8,000 cultures drawn annually.

Methods

Total hospital costs associated with 3 strategies were compared: (1) usual care, with nurses collecting cultures without a standardized protocol; (2) sterile kits, with nurses using a dedicated sterile collection kit; and (3) phlebotomy teams, with cultures collected by laboratory-based phlebotomists. In the base case, contamination rates associated with usual care, sterile kits, and phlebotomy teams were assumed to be 4.34%, 1.68%, and 1.10%, respectively. Total hospital costs included costs of collecting cultures and hospitalization costs according to culture results (negative, true positive, and contaminated).

Results

Compared with usual care, annual net savings using the sterile kit and phlebotomy team strategies were $483,219 and $288,980, respectively. Both strategies remained less costly than usual care across a broad range of sensitivity analyses.

Conclusions

EDs with high blood culture contamination rates should strongly consider evidence-based strategies to reduce contamination. In addition to improving quality, implementing a sterile collection kit or phlebotomy team strategy is likely to result in net cost savings.
Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America
Authors: Stevens Dennis L. , Bisno Alan L. , Chambers Henry F. , Dellinger E. Patchen , Goldstein Ellie J. C. , Gorbach Sherwood L. , Hirschmann Jan V. , Kaplan Sheldon L. , Montoya Jose G. , Wade James C.
Published: June 2014

A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.
The New Epidemiology of Celiac Disease
Authors: Catassi Carlo , Gatti Simona , Fasano Alessio
Published: June 2014

The prevalence of celiac disease (CD) varies greatly, but several reports have shown that CD is increasing in frequency in different geographic areas. The increase in prevalence can be partially attributed to the improvement in diagnostic techniques and disease awareness; however the equally well documented rise in incidence in the last 30–40 years cannot be so easily explained. The new epidemiology of CD is now characterized by an increase of new cases in the historical CD areas (northern Europe and the United States) and more interestingly in a spread of the disease in new regions (Asian countries). A significant change in diet habits, particularly in gluten consumption as well as in infant feeding patterns are probably the main factors that can account for these new trends in CD epidemiology.
Autoantibodies and CD
Authors: Korponay‐Szabó Ilma R.
Published: June 2014

Celiac disease (CD) is triggered by the consumption of gluten‐containing cereals to which patients mount a T‐lymphocyte and antibody response in both immunoglobulin A and immunoglobulin G classes coupled with autoantibody production against self‐proteins, predominantly type‐2 (tissue) transglutaminase (TG2). TG2 autoantibodies are biologically active and bind to their target protein in the patients' tissues, including the gut and extraintestinal tissues. This peculiar systemic anti‐TG2 reaction is dependent on the presence of dietary gluten and stops after its elimination. As both anti‐TG2 and anti‐gliadin antibodies are activity markers, their detection is valuable for the disease recognition and therapy monitoring. High concentrations of serum anti‐TG2 antibody positivity supported by highly specific positivity for endomysial antibodies became the critical component of celiac disease diagnosis, although serum antibodies as indirect markers have limitations and are not able to replace histology analysis in all cases. Studies focusing on tissue‐bound antibodies may further improve our understanding of their role.
Diagnosis of Celiac Disease
Authors: Zevit Noam , Shamir Raanan
Published: June 2014

The diagnostic criteria for celiac disease (CD) have undergone significant change during the past several decades following a better understanding of the pathogenesis of the disease and the identification of sensitive and specific serum markers. In 2012, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published new diagnostic algorithms, which for the first time questioned the need for histological evaluation in all patients, and identified specific requirements for omitting intestinal biopsies from diagnosis requirements. Here, we briefly review the evolution of the diagnostic algorithms, emerging data which may be integrated into the diagnosis algorithm in the future and suggest key points which should be considered while we continue to develop and refine the diagnostic criteria for CD in an age of personalized medicine.
Celiac Disease Treatment
Authors: Mäki Markku
Published: June 2014

The basis for celiac disease (CD) treatment is a strict lifelong gluten‐free diet. On the diet, the small intestinal mucosal injury heals and gluten‐induced symptoms and signs disappear. The mucosal healing is a prerequisite for sustaining health and is also obtained with a diet containing oats and trace amounts of gluten, industrially purified wheat starch‐based gluten‐free products. The small intestinal mucosa does not heal in noncompliant people, nor when a patient is inadvertently ingesting gluten. Development of adjunctive or alternative therapies is on its way. There are several novel treatment pipelines within academy and industry. Examples are the ideas of using glutenases as a drug to degrade the ingested gluten, polymers to bind and sequester the gluten to the feces, and also vaccine development for an immunotherapy to induce tolerance towards gluten. Clinical drug trials are to be foreseen in CD, soon also in children.
Early Nutrition
Authors: Schaart Maaike W. , Mearin Maria L.
Published: June 2014

Celiac disease (CD) is an autoimmune disorder caused by ingestion of gluten in genetically predisposed individuals. It is a chronic, multiorgan disease in which small‐intestinal mucosal damage may lead to malabsorption of nutrients. In the last years, several studies suggested a protective role of breast‐feeding and/or the timing and quantity of gluten introduction in the subsequent development of CD. Especially, prolonged breast feeding during the introduction of gluten‐containing feeding has been associated with a reduced risk of developing CD in infancy. The focus of this review was to present the actual knowledge of the possible preventive influence of early nutrition on the risk to develop CD.
Randomized Phase II Study of the X-linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
Authors: Lee Francis A.S. , Zee Benny Chung-Ying , Cheung Foon Yiu , Kwong Philip , Chiang Chi Leung , Leung Kwong Chuen , Siu Steven W.K. , Lee Conrad , Lai Maria , Kwok Chloe , Chong Marc , Jolivet Jacques , Tung Steward
Published: June 2014

Objectives:

This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone.

Methods:

Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone. The primary endpoint was progression-free survival (PFS). Other endpoints include overall survival (OS), objective response rates (ORR), and safety profile.

Results:

A total of 51 patients were enrolled; of them, 48 were evaluable. At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm. The ORR based on Choi and RECIST criteria were 16.1% and 9.7% in combination arm, respectively. The ORR was 0 in control arm. One drug-related serious adverse event of hypersensitivity occurred in the combination arm, whereas 2 gastrointestinal serious adverse events in the sorafenib arm.

Conclusion:

AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated. The benefit on PFS is moderate but more apparent in the dose-reduced subgroups.
Trends in flower symmetry evolution revealed through phylogenetic and developmental genetic advances
Authors: Hileman Lena C.
Published: June 2014

A striking aspect of flowering plant (angiosperm) diversity is variation in flower symmetry. From an ancestral form of radial symmetry (polysymmetry, actinomorphy), multiple evolutionary transitions have contributed to instances of non-radial forms, including bilateral symmetry (monosymmetry, zygomorphy) and asymmetry. Advances in flowering plant molecular phylogenetic research and studies of character evolution as well as detailed flower developmental genetic studies in a few model species (e.g.Antirrhinum majus, snapdragon) have provided a foundation for deep insights into flower symmetry evolution. From phylogenetic studies, we have a better understanding of where during flowering plant diversification transitions from radial to bilateral flower symmetry (and back to radial symmetry) have occurred. From developmental studies, we know that a genetic programme largely dependent on the functional action of theCYCLOIDEAgene is necessary for differentiation along the snapdragon dorsoventral flower axis. Bringing these two lines of inquiry together has provided surprising insights into both the parallel recruitment of aCYC-dependent developmental programme during independent transitions to bilateral flower symmetry, and the modifications to this programme in transitions back to radial flower symmetry, during flowering plant evolution.
Finite-state discrete-time Markov chain models of gene regulatory networks
Authors: Skornyakov V.P. , Skornyakova M.V. , Shurygina A.V. , Skornyakov P.V.
Published: June 2014

In this study Markov chain models of gene regulatory networks (GRN) are developed. These models gives the ability to apply the well known theory and tools of Markov chains to GRN analysis. We introduce a new kind of the finite graph of the interactions called the combinatorial net that formally represent a GRN and the transition graphs constructed from interaction graphs. System dynamics are defined as a random walk on the transition graph that is some Markovian chain. A novel concurrent updating scheme (evolution rule) is developed to determine transitions in a transition graph. Our scheme is based on the firing of a random set of non-steady state vertices of a combinatorial net. We demonstrate that this novel scheme gives an advance in the modeling of the asynchronicity. Also we proof the theorem that the combinatorial nets with this updating scheme can asynchronously compute a maximal independent sets of graphs. As proof of concept, we present here a number of simple combinatorial models: a discrete model of auto-repression, a bi-stable switch, the Elowitz repressilator, a self-activation and show that this models exhibit well known properties.
Estimating cellular pathways from an ensemble of heterogeneous data sources
Authors: Franks Alexander M. , Markowetz Florian , Airoldi Edoardo
Published: June 2014

Building better models of cellular pathways is one of the major challenges of systems biology and functional genomics. There is a need for methods to build on established expert knowledge and reconcile it with results of high-throughput studies. Moreover, the available data sources are heterogeneous and need to be combined in a way specific for the part of the pathway in which they are most informative. Here, we present a compartment specific strategy to integrate edge, node and path data for the refinement of a network hypothesis. Specifically, we use a local-move Gibbs sampler for refining pathway hypotheses from a compendium of heterogeneous data sources, including novel methodology for integrating protein attributes. We demonstrate the utility of this approach in a case study of the pheromone response MAPK pathway in the yeast S. cerevisiae.
(η6-Benzene)(carbonato-κ2O,O′)[dicyclohexyl(naphthalen-1-ylmethyl)phosphane-κP]ruthenium(II) chloroform trisolvate
Authors: Gowrisankar Saravanan , Neumann Helfried , Spannenberg Anke , Beller Matthias
Published: June 2014

The title compound, [Ru(CO3)(η6-C6H6){(C6H11)2P(CH2C10H7)}]·3CHCl3, was synthesized by carbonation of [RuCl2(η6-C6H6){(C6H11)2P(CH2C10H7)}] with NaHCO3in methanol at room temperature. The RuIIatom is surrounded by a benzene ligand, a chelating carbonate group and a phosphane ligand in a piano-stool configuration. The crystal packing is consolidated by C—H...O and C—H...Cl hydrogen-bonding interactions between adjacent metal complexes and between the complexes and the solvent molecules. The asymmetric unit contains one metal complex and three chloroform solvent molecules of which only one was modelled. The estimated diffraction contributions of the other two strongly disordered chloroform solvent molecules were substracted from the observed diffraction data using the SQUEEZE procedure inPLATON[Spek (2009).Acta Cryst.D65, 148–155].
Morphology determination of defect-rich diblock copolymer films with time-of-flight grazing-incidence small-angle neutron scattering
Authors: Müller-Buschbaum Peter , Kaune Gunar , Haese-Seiller Martin , Moulin Jean-Francois
Published: June 2014

The complex nanomorphology of a defect-rich deuterated poly(styrene-block-methyl methacrylate), P(S-b-MMAd), diblock copolymer film is determined with a combination of grazing-incidence small-angle neutron scattering (GISANS) and time-of-flight (TOF) mode. TOF-GISANS enables the simultaneous performance of several GISANS measurements that differ in wavelength. The resulting set of GISANS data covers different ranges of the scattering vector and has different scattering depths. Thus surface-sensitive and bulk-sensitive measurements can be performed simultaneously. The P(S-b-MMAd) film exhibits a lamellar microphase separation structure, which because of the defects is arranged into small, randomly oriented grains, composed of four–five lamellar repetitions. In the near-surface region, the lamellar structure is oriented parallel to the substrate, which explains the smooth surface found with atomic force microscopy.
Does the size of a crystal matter in an X-ray crystal structure analysis of a small molecule?
Authors: Tan Seng Lim , Ng Seik Weng
Published: June 2014

The crystal structures of C7H8FN3, C20H25Br, [Cu(H2O)2(C6H12N4)(C7H3N2O6)2]·2H2O, [SnCl(H2O)(C6H5)3(C10H8N2)]2 and [Pb(NO3)2(C3H9N3S)] refined on numerically absorption-corrected reflections to low R values although the dimensions of the crystals exceeded the diameter of the X-ray beam collimator. The R values for the organic and copper compounds were not significantly different when smaller specimens cut from the large crystals were used. For the tin complex, a large peak persisted in the difference map for all sizes, and for the lead complex, the difference Fourier map was more diffuse the smaller the specimen.
A new two-dimensional manganese(II) coordination polymer based on thiophene-3,4-dicarboxylic acid
Authors: Wang Gui-Xia , Shang Li-Li , Li Zhao-Hao , Zhao Bang-Tun
Published: June 2014

A novel manganese coordination polymer, poly[(μ5-thiophene-3,4-dicarboxylato)manganese(II)], [Mn(C6H2O4S)]n, was synthesized hydrothermally using 3,4-thiophenedicarboxylate (3,4-tdc2−) as the organic linker. The asymmetric unit of the complex contains an Mn2+cation and one half of a deprotonated 3,4-tdc2−anion, both residing on a twofold axis. Each Mn2+centre is six-coordinated by O atoms of bridging/chelating carboxylate groups from five 3,4-tdc2−anions, forming a slightly distorted octahedron. The Mn2+centres are bridged by 3,4-tdc2−anions to give an infinite two-dimensional layer which incorporates one-dimensional Mn–O gridlike chains, and in which the 3,4-tdc2−anion adopts a novel hexadentate chelating and μ5-bridging coordination mode. The fully deprotonated 3,4-tdc2−anion exhibits unexpected efficiency as a ligand towards the Mn2+centres, which it coordinates through all of its carboxylate O atoms to provide the novel coordination mode. The IR spectrum of the complex is also reported.
Institutional distance and international ownership strategies in Russia
Authors: Karhunen Päivi , Kosonen Riitta , Ledyaeva Svetlana
Published: June 2014

Purpose

– The purpose of this paper is to analyse the impact of institutional distance, extended to capture subnational institutional variation, on foreign entry mode choice.

Design/methodology/approach

– As an empirical study, it focuses on manufacturing firms established in Russia by foreign investors from developed countries. The dependent variables, the share of foreign ownership and the entry mode choice binary variable (equal to 1 for full foreign ownership and zero for a joint venture) were obtained from the registry of foreign-owned firms in Russia. The World Bank's regulatory quality (RQ) index on a national level and a respective indicator for the various Russian regions on a subnational level were utilised to measure institutions. Multilevel cross-classified analysis including foreign firms, the various Russian regions and characteristics of the foreign owners’ home countries was applied to for making empirical estimations.

Findings

– The empirical results show, first, that the regionally adjusted institutional distance, i.e. the distance between the home country and the Russian region in question, when measured in terms of RQ, shifts the ownership structure towards shared ownership. However, nation-level institutional distance between the home country and Russia does not show any statistically significant relationship with the modal choice.

Originality/value

– The results indicate that with the exception of industries of strategic importance to the state, the most important “rules of the game” for foreign entry strategies are provided not by the federal government but by the regional governors. The theoretical value of the paper lies in the extension of the institutional distance concept to the subnational level. At the same time, the paper identifies those institutional features that foreign entrants eyeing Russia need to take into account when selecting an entry mode and location within Russia.
Sustainable business models
Authors: M. Høgevold Nils , Svensson Göran , Wagner Beverly , J. Petzer Daniel , Klopper H.B. , Carlos Sosa Varela Juan , Padin Carmen , Ferro Carlos
Published: June 2014

Purpose

– The purpose of this paper is to describe: corporate reasons for, and organizational challenges of sustainable business models; and the evolution of economic effects, social boundaries and environmental actions in sustainable business practices.

Design/methodology/approach

– This study is based on insights gained from eight Norwegian companies in different industries. Purposeful sampling was employed to ensure that the companies had sustainable business models beyond the level of mere compliance, of sustainable business practices in the marketplace and society. A deductive approach to data collection ensured that the companies had sufficient understanding to relate their sustainable business practices to interviewers. The interviews were subsequently transcribed and analyzed systematically by the research team.

Findings

– The empirical findings indicate evolutionary changes as companies move on a continuum from superficial to embedded sustainable business models and the application of sustainable business practices. The planning, implementation and evaluation of sustainable business models evolves over time within companies and their supply chains, as well as in the marketplace and society.

Research limitations/implications

– A limitation of this study is that it is exclusively undertaken in Norwegian companies, although the companies are from different industries with different characteristics. Future research is clearly necessary and will be conducted in other countries in similar industries, so as to explore the empirical findings from this study in other contexts. In addition, the interfaces between environmental actions, economic effects and social boundaries need to be investigated further.

Originality/value

– The study contributes to a growing body of knowledge on corporate reasons for and organizational challenges of sustainable business models, as well as environmental, social and economic aspects of sustainable business practices.
Implementing slack cables in the force density method
Authors: Christou Petros , Michael Antonis , Elliotis Miltiades
Published: June 2014

Purpose

– The purpose of this paper is to present a solution strategy for the analysis of cable networks which includes an extension to the force density method (FDM) in an attempt to support cable elements when they become slack. The ability to handle slack cable elements in the analysis is particularly important especially in cases where the original cable lengths are predefined, i.e. the cable structure has already been constructed, and there is a need for further analysis to account for additional loading such as wind. The solution strategy is implemented in a software application.

Design/methodology/approach

– The development of the software required the implementation of the FDM for the analysis of cable networks and its extension to handle constraints. The implemented constraints included the ability to preserve the length in the stressed or the unstressed state of predefined cable elements. In addition, cable statics are incorporated with the development of the cable equation and its modification to be able to be handled by the FDM .

Findings

– The implementation of the solution strategy is presented through examples using the software which has been developed for these purposes.

Originality/value

– The results suggest that for cable networks spanning large distances or cable elements with considerable self-weight the neglect of the cable slackening effects is not always conservative.
On men, organizations and intersectionality
Authors: Hearn Jeff
Published: June 2014

Purpose

– The purpose of this paper is to reflect, personally, regarding work, politically and theoretically, on 40 years of involvement in organization studies, profeminism and intersectionality.

Design/methodology/approach

– The paper uses autoethnography.

Findings

– The paper shows the need for a broad notion of the field and fieldwork, the development of intersectional thinking, the complexity of men's relations to feminism and intersectionality and the need to both name and deconstruct men in the research field.

Research limitations/implications

– The paper suggests a more explicit naming and deconstruction of men and other intersectional social categories in doing research.

Practical implications

– The paper suggests a more explicit naming and deconstruction of men and other intersectional social categories in equality practice.

Social implications

– The paper suggests a more explicit naming and deconstruction of men and other intersectional social categories in social, political and policy interventions.

Originality/value

– The paper points to recent historical changes in the connections between feminism, gender, profeminism, organizations and intersectionality in relation to equality, diversity and inclusion.
Gamification and the online retail experience
Authors: Insley Victoria , Nunan Daniel
Published: June 2014

Purpose

– As online retailing grows in importance there is increasing interest in the online customer experience. The purpose of this paper is to explore the role of gamification, the use of game mechanics, in enabling consumer engagement with online retailers.

Design/methodology/approach

– The research adopts a qualitative methodology carrying out 19 in-depth interviews with individuals who are frequent online shoppers.

Findings

– Findings support the importance of including game elements to enhance the retail experience. However, data also suggests that without appropriate management customers can subvert gamification strategies to create their own “games” which increases competitive pressure between retailers.

Practical implications

– The paper suggests ways in which retailers might more successfully “gamify” their online retail stores and reduce incidences of undesirable customer behaviour.

Originality/value

– This paper provides empirical support to the current paucity of research into the role of gamification in the context of the online retail experience.
Reinvigorating the mission statement through top management commitment
Authors: I. Williams Jr Ralph , L. Morrell Daniel , V. Mullane John
Published: June 2014

Purpose

– The purpose of this paper is to propose that top management commitment to its organization's mission statement moderates the mission's effect of firm performance. The proposed model combines numerous aspects of top management commitment to give depth to the moderating effect.

Design/methodology/approach

– The paper provides a conceptual overview of the mission statement literature toward a theoretical model.

Findings

– The impact of mission statements on firm performance long has been studied and debated, without consistent results. This paper proposes that this is due to the presence of moderating influences, specifically the commitment of top management, that, if not properly studied, will affect empirical results.

Practical implications

– Practicing managers can unlock the power of the mission statement by involving the entire organization in the mission statement process, clearly and consistently communicating the mission's tenets, setting measurable operational targets from the mission statement, and periodically revising the mission to ensure it is current.

Originality/value

– The concept of a moderator is original in the mission-performance debate. Concepts from several key articles have been combined in a unique manner to develop the model.
Indirect effects of non‐native Spartina alterniflora and its fungal pathogen (Fusarium palustre) on native saltmarsh plants in China
Authors: Li Hui , Zhang Xiameng , Zheng Rushui , Li Xiao , Elmer Wade H. , Wolfe Lorne M. , Li Bo
Published: June 2014

Pathogens can affect their hosts and change community composition and structure. Pathogens may be key determinants of biological invasions. However, few empirical studies exist examining how non‐native plants drive their invasions through indirect effects involved with pathogens. Here, indirect effects refer to how one species alters the effect that another species has on a third.

Fusarium palustre was associated with the dieback of Spartina alterniflora in its native North American saltmarshes. Native plant Phragmites australis was also found to die back in the Dongtan wetland of the Chinese Yangtze River estuary invaded by non‐native Spartina alterniflora. This phenomenon suggests that Spartina might not escape from its pathogen when being introduced from its native North America and has indirectly caused the dieback of Phragmites in China.

To investigate the indirect effect of Spartina involving Fusarium, we sampled plants and soils in dieback patches to isolate the pathogen. Next, we used an artificial inoculation study to determine the virulence of Fusarium to both Phragmites and Spartina. Finally, the spatial distribution of Fusarium was studied through examining its incidence in saltmarshes along the east coast of China.

The endophytic fungus F. palustre was found to be closely associated with Phragmites dieback in the Dongtan wetland and it is likely that it was transported by non‐native Spartina from its native North American saltmarshes to the Chinese saltmarshes. The spillover of F. palustre from non‐native Spartina to native Phragmites might subsequently facilitate Spartina invasion.

Synthesis. Invasive plants do not only directly compete with native plants, but also indirectly cause pathogen infection on the latter, by acting as vectors and reservoirs for pathogens shared with native plants. Our findings highlight the significance of indirect effects involving pathogens in biological invasions. It is necessary to consider these pathogen‐mediated indirect effects of non‐native plant species in multi‐host‐pathogen systems for management and restoration purposes.
The nitrate‐sensing NasST system regulates nitrous oxide reductase and periplasmic nitrate reductase in Bradyrhizobium japonicum
Authors: Sánchez Cristina , Itakura Manabu , Okubo Takashi , Matsumoto Takashi , Yoshikawa Hirofumi , Gotoh Aina , Hidaka Masafumi , Uchida Takafumi , Minamisawa Kiwamu
Published: June 2014

The soybean endosymbiont Bradyrhizobium japonicum is able to scavenge the greenhouse gas N2O through the N2O reductase (Nos). In previous research, N2O emission from soybean rhizosphere was mitigated by B. japonicum Nos++ strains (mutants with increased Nos activity). Here, we report the mechanism underlying the Nos++ phenotype. Comparative analysis of Nos++ mutant genomes showed that mutation of bll4572 resulted in Nos++ phenotype. bll4572 encodes NasS, the nitrate (NO3−)‐sensor of the two‐component NasST regulatory system. Transcriptional analyses of nosZ (encoding Nos) and other genes from the denitrification process in nasS and nasST mutants showed that, in the absence of NO3−, nasS mutation induces nosZ and nap (periplasmic nitrate reductase) via nasT. NO3− addition dissociated the NasS‐NasT complex in vitro, suggesting the release of the activator NasT. Disruption of nasT led to a marked decrease in nosZ and nap transcription in cells incubated in the presence of NO3−. Thus, although NasST is known to regulate the NO3−‐mediated response of NO3− assimilation genes in bacteria, our results show that NasST regulates the NO3−‐mediated response of nosZ and napE genes, from the dissimilatory denitrification pathway, in B. japonicum.
Lyophilized Tea Extracts of Brickellia cavanillesii (Asteraceae): In Vitro Characterization of Biological Activity
Authors: Eshiet Etetor R. , Zhu Jinqiu , Smith Ernest E.
Published: June 2014

Lyophilized Brickellia cavanillesii (LBC) tea extracts and identified chemical compounds of LBC were examined using in vitro human carcinoma liver (HepG2) cells with and without fetal bovine serum (FBS). Cells were incubated for 24 h with varying concentrations of FBS and LBC, respectively; cytotoxicity was determined spectrophotometrically using MTT (Formazan 3‐(4,5‐dimethyl‐thiazol‐2‐yl)‐2, 5‐diphenyl‐tetrazolium bromide) assay. Furthermore, the potential hypoglycemic activity of LBC tea extracts was investigated using glucose transport and metabolism proteins biomarkers. FBS (0% to 10%) increased the viability of HepG2 cells steadily with increasing concentration. Possible therapeutic effects of LBC were concentration dependent with and without FBS. The cytotoxicity of 12 identified compounds from the LBC extract suggests that the individual compounds inhibited the proliferation of HepG2 cells differentially and do not reflect the inhibition of the whole aqueous LBC. Western blot analysis of glucose facilitated transporter protein 2 (GLUT 2) expression of HepG2 cells exposed to 0 mg/mL (Control) and 0.2 mg/mL LBC for 2, 4, 6, and 24 h suggests that GLUT 2 expression was increased. Increase in GLUT 2 expression in the absence of FBS was statistically significant with time of exposure. Significant difference was observed for GLUT 2 expression between 6 and 24 h and also between 4 and 24 h at 0.2 mg/mL LBC. Results obtained indicate that LBC may exhibit antidiabetic activity. However, further studies will be necessary to clearly delineate LBC potential therapeutic benefit and biological activities in animal studies as well as other in vitro models.
Ginsenoside‐Free Molecules from Steam‐Dried Ginseng Berry Promote Ethanol Metabolism: An Alternative Choice for an Alcohol Hangover
Authors: Ik Lee Do , Tae Kim Seung , Hoon Lee Dong , Min Yu Jung , Kil Jang Su , Soo Joo Seong
Published: June 2014

Ethanol metabolism produces harmful compounds that contribute to liver damage and cause an alcohol hangover. The intermediate metabolite acetaldehyde is responsible for alcohol hangover and CYP2E1‐induced reactive oxygen species damage liver tissues. In this study, we examined whether ginsenoside‐free molecules (GFMs) from steam‐dried ginseng berries promote ethanol metabolism and scavenge free radicals by stimulating primary enzymes (alcohol dehydrogenase, aldehyde dehydrogenase, CYP2E1, and catalase) and antioxidant effects using in vitro and in vivo models. The results revealed that GFM effectively scavenged 2,2‐diphenyl‐1‐picrylhydrazyl hydrate radicals and hydroxyl radicals. Notably, GFM significantly enhanced the expression of primary enzymes within 2 h in HepG2 cells. GFM clearly removed the consumed ethanol and significantly reduced the level of acetaldehyde as well as enhancement of primary gene expression in BALB/c mice. Moreover, GFM successfully protected HepG2 cells from ethanol attack. Of the major components identified in GFM, it was believed that linoleic acid was the most active ingredient. Based on these findings, we conclude that GFM holds promise for use as a new candidate for ethanol metabolism and as an antihangover agent.
Silencing of JMJD2B induces cell apoptosis via mitochondria‐mediated and death receptor‐mediated pathway activation in colorectal cancer
Authors: Sun Bei Bei , Fu Lin Na , Wang Yun Qian , Gao Qin Yan , Xu Jie , Cao Zhi Jun , Chen Ying Xuan , Fang Jing Yuan
Published: June 2014

Objective

To investigate the molecular mechanism of colorectal cancer (CRC) cell apoptosis induced by the Jumonji domain containing 2B (JMJD2B) silencing.

Methods

Both HCT116 and LoVo CRC cell lines were used for analyses. Cell apoptosis after JMJD2B silencing was determined by flow cytometry. JC‐1 fluorescence probe was applied to measure the mitochondrial outer membrane permeabilization by flow cytometry and fluorescence microscopy. Immunofluorescence was used to detect cytochrome C translocation from mitochondria to cytosol after JMJD2B silencing. The efficacy of JMJD2B silencing on the protein levels of Bcl‐2 family, caspase proteins, CCAAT/enhancer binding protein homologous protein (CHOP) and glucose‐regulated protein 78 (GRP78) were detected by Western blot.

Results

JMJD2B silencing induced CRC cell apoptosis via a decrease of the anti‐apoptotic gene Bcl‐2 family expression, leading to the translocation of Bak and Bax proteins and the promotion of mitochondrial membrane disruption, resulting in the release of cytochrome C from mitochondria and subsequent caspase‐9 and caspase‐3 cleavage. It also increased the amount of cleaved caspase‐8 involved in the death receptor‐related apoptotic pathway. Bcl‐2 homology 3 interacting‐domain death agonist (Bid), a specific caspase‐8 substrate involved in the Fas signaling pathway, subsequently induced cleavage via caspase‐8 activation. However, levels of CHOP and GRP78 remained unchanged after JMJD2B silencing.

Conclusions

JMJD2B silencing induced CRC cell apoptosis via both mitochondria‐related and death receptor‐related pathways. The cleavage of Bid activated by caspase‐8 might serve as a crosstalk mediator between these two pathways in CRC.
Randomized controlled trial comparing the efficacy of mosapride plus omeprazole combination therapy to omeprazole monotherapy in gastroesophageal reflux disease
Authors: Yamaji Yutaka , Isomura Yoshihiro , Yoshida Shuntaro , Yamada Atsuo , Hirata Yoshihiro , Koike Kazuhiko
Published: June 2014

Objective

We investigated whether the prokinetic activity of mosapride, a 5‐hydroxytryptamine 4 receptor agonist, in combination with proton pump inhibitor (PPI) would ameliorate symptoms of gastroesophageal reflux disease (GERD) in Japanese patients.

Methods

Patients who experienced reflux symptoms more than twice weekly were eligible for this study. In all, 60 patients were randomized to receive mosapride 5 mg thrice daily combined with omeprazole 10 mg once daily (GO group), or omeprazole alone (O group) for 4 weeks. The patients completed the frequency scale for the symptoms of GERD (FSSG) at the beginning and the end of the study. The primary outcome compared changes in the FSSG reflux‐related symptom (RS) score between treatment groups during the study period.

Results

The FSSG RS scores significantly decreased both in the GO group and the O group, with no differences in improvement between the groups (−5.86 for the GO group vs −4.89 for the O group, P = 0.49). In non‐erosive reflux disease (NERD) patients the improvement was significantly lower than that in erosive GERD patients (−4.00 vs −7.67, P = 0.02). However, the addition of mosapride was effective in subgroup analyses of specific symptoms, such as burping.

Conclusions

Combining mosapride with PPI provided no additional amelioration of reflux symptoms compared to PPI alone. Both regimens provided less relief from reflux symptoms in NERD than in erosive GERD patients. The addition of mosapride ameliorated reflux in patients with symptoms like burping.
Heterotrophic bicarbonate assimilation is the main process of de novo organic carbon synthesis in hadal zone of the Hellenic Trench, the deepest part of Mediterranean Sea
Authors: Yakimov Michail M. , La Cono Violetta , Smedile Francesco , Crisafi Francesca , Arcadi Erika , Leonardi Marcella , Decembrini Franco , Catalfamo Maurizio , Bargiela Rafael , Ferrer Manuel , Golyshin Peter N. , Giuliano Laura
Published: June 2014

Ammonium‐oxidizing chemoautotrophic members of Thaumarchaea are proposed to be the key players in the assimilation of bicarbonate in the dark (ABD). However, this process may also involve heterotrophic metabolic pathways, such as fixation of carbon dioxide (CO2) via various anaplerotic reactions. We collected samples from the depth of 4900 m at the Matapan‐Vavilov Deep (MVD) station (Hellenic Trench, Eastern Mediterranean) and used the multiphasic approach to study the ABD mediators in this deep‐sea ecosystem. At this depth, our analysis indicated the occurrence of actively CO2‐fixing heterotrophic microbial assemblages dominated by Gammaproteobacteria with virtually no Thaumarchaea present. [14C]‐bicarbonate incorporation experiments combined with shotgun [14C]‐proteomic analysis identified a series of proteins of gammaproteobacterial origin. More than quarter of them were closely related with Alteromonas macleodii ‘deep ecotype’ AltDE, the predominant organism in the microbial community of MVD. The present study demonstrated that in the aphotic/hadal zone of the Mediterranean Sea, the assimilation of bicarbonate is associated with both chemolithoauto‐ and heterotrophic ABD. In some deep‐sea areas, the latter may predominantly contribute to the de novo synthesis of organic carbon which points at the important and yet underestimated role heterotrophic bacterial populations can play the in global carbon cycle/sink in the ocean interior.
Altered brain functional networks in heavy smokers
Authors: Lin Fuchun , Wu Guangyao , Zhu Ling , Lei Hao
Published: June 2014

Recent neuroimaging studies have demonstrated that cigarette smoking is associated with changed brain structure and function. However, little is known about alterations of the topological organization of brain functional networks in heavy smokers. Thirty‐one heavy smokers and 33 non‐smokers underwent a resting‐state functional magnetic resonance imaging scan. The whole‐brain functional networks were constructed by thresholding the correlation matrices of 90 brain regions and their topological properties were analyzed using graph network analysis. Non‐parametric permutation tests were performed to investigate group differences in network topological measures and multiple regression analysis was conducted to determine the relationships between the network metrics and smoking‐related variables. Both heavy smokers and non‐smokers exhibited small‐world architecture in their brain functional networks. Compared with non‐smokers, however, heavy smokers showed altered topological measurements characterized by lower global efficiency, higher local efficiency and clustering coefficients and greater path length. Furthermore, heavy smokers demonstrated decreased nodal global efficiency mainly in brain regions within the default mode network, whereas increased nodal local efficiency predominated in the visual‐related regions. In addition, heavy smokers exhibited an association between the altered network metrics and the duration of cigarette use or the severity of nicotine dependence. Our results suggest that heavy smokers may have less efficient network architecture in the brain, and chronic cigarette smoking is associated with disruptions in the topological organization of brain networks. Our findings may further the understanding of the effects of chronic cigarette smoking on the brain and the pathophysiological mechanisms underlying nicotine dependence.
Genetic variations in the SPP1 promoter affect gene expression and the level of osteopontin secretion into bovine milk
Authors: Dudemaine P. L. , Thibault C. , Alain K. , Bissonnette N.
Published: June 2014

Osteopontin (OPN) is now recognized as an important cytokine and extracellular integrin‐binding protein at the crossroads of inflammation and homeostasis. In a previous study, we found that OPN gene (SPP1) polymorphisms are associated with milk performance traits and somatic cell score (SCS), a parameter used to estimate the genetic value of udder health in dairy cattle. In this study, we assessed whether the genetic variations had an impact on SPP1 promoter activity, immune response and the level of OPN secreted into milk. The influence of DNA polymorphisms on the promoter activity of SPP1 was confirmed in vitro. To measure the impact of the genetic variations on OPN secretion into milk, we measured OPN levels in both plasma and milk throughout lactation. Cows were grouped by the OPN haplotypes associated with a high (H2 × H3) or low (H1 × H4) SCS. For both H2 × H3 and H1 × H4, the OPN level in plasma remained low throughout lactation, although the concentration in the milk of H1 × H4 cows increased more in late lactation. Moreover, the macrophages of H1 × H4 cows expressed a lower SPP1 and proinflammatory IL6 in response to infection. Regarding the immune cell response, cows with the genetic potential to secrete higher OPN levels during late lactation had macrophages expressing fewer proinflammatory cytokines, a situation that might explain the genetic association with low somatic cells. Although OPN's favorable roles during late lactation remain to be elucidated, the tissue remodeling properties associated with OPN may be beneficial for reducing the incidence of infection during the transition period in lactating cows.