bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuity of Public Insurance Coverage
Authors: Guevara James P. , Moon Jeanhee , Hines Elizabeth M. , Fremont Ettya , Wong Angie , Forrest Christopher B. , Silber Jeffrey H. , Pati Susmita
Published: November 2013

Publicly financed insurance programs are tasked with maintaining coverage for eligible children, but published measures to assess coverage have not been evaluated. Therefore, we sought to identify and categorize measures of health insurance continuity for children and adolescents. We conducted a systematic review of Medline and HealthStar databases, review of reference lists of eligible articles, and contact with experts. We categorized measures into 8 domains based on a conceptual framework. We identified 147 measures from 84 eligible articles. Most measures evaluated the following domains: always insured (41%), repeatedly uninsured (36%), and transition out of coverage (29%), while fewer assessed single gap in coverage, always uninsured, transition into coverage, change in coverage, and eligibility. Only 18% of measures assessed associations between continuity of coverage and child and adolescent health outcomes. These results suggest that a number of measures of continuity of coverage exist, but few measures have assessed impact on outcomes.
A Case Study of a Team-Based, Quality-Focused Compensation Model for Primary Care Providers
Authors: Greene Jessica , Hibbard Judith H. , Overton Valerie
Published: November 2013

In 2011, Fairview Health Services began replacing their fee-for-service compensation model for primary care providers (PCPs), which included an annual pay-for-performance bonus, with a team-based model designed to improve quality of care, patient experience, and (eventually) cost containment. In-depth interviews and an online survey of PCPs early after implementation of the new model suggest that it quickly changed the way many PCPs practiced. Most PCPs reported a shift in orientation toward quality of care, working more collaboratively with their colleagues and focusing on their full panel of patients. The majority reported that their quality of care had improved because of the model and that their colleagues’ quality had to. The comprehensive change did, however, result in lower fee-for-service billing and reductions in PCP satisfaction. While Fairview’s compensation model is still a work in progress, their early experiences can provide lessons for other delivery systems seeking to reform PCP compensation.
Teaching Teamwork Through Coteaching in the Business Classroom
Authors: Kliegl Julie A. , Weaver Kari D.
Published: November 2013

Business educators recognize the importance of developing teamwork as an employability skill. However, current methods used to teach teamwork have been met with mixed results from both students and educators. This article integrates research on the importance of teamwork, team development processes, and coteaching through examining a case study wherein coteaching was used as a means of conveying teamwork concepts to students. Coteaching is an alternate approach to teaching teamwork skills. In this case, the core competencies of shared values, complementary expertise, and the willingness to experiment were critical to forming and developing a functional teaching partnership.
The 2009 Victorian Bushfires
Authors: Linnenluecke Martina K. , Griffiths Andrew
Published: November 2013

One of the expected consequences of climate change is an increase in the frequency and intensity of weather extremes such as heat waves, droughts, and large-scale bushfires. The possible escalation in the frequency and magnitude of resulting impacts has led to arguments that future strategies for emergency management should be based on achieving organizational and community resilience. However, relatively little is known about the limits to conventional emergency management approaches and factors leading to resilience. Drawing on the 2009 Victorian Bushfires as an analogue for a “more-severe-than-expected” event likely under a future, changed climate, this article analyzes the limits to emergency management approaches under unfamiliar conditions. Our assessment focuses on three organizations involved in the Victorian Bushfires emergency response. Results show how events that occur with unprecedented severity are well beyond the routine emergency management capacities of emergency organizations. We discuss how the long-term promotion of organizational and societal resilience could be achieved and outline implications for research and practice.
Using the cyborg to re-think young people’s uses of Facebook
Authors: Waite Catherine , Bourke Lisa
Published: November 2013

The use of information technologies by young people is commonly understood to be a separate, often risky, activity and a distinct form of sociality. Challenging the dominant understanding, this article applies Haraway’s cyborg theory to explore how Facebook-mediated relationships are interconnected with material relationships and daily social life. Young people’s perspectives are privileged through 40 face-to-face interviews in two rural Victorian towns. The cyborg metaphor highlights the fluid melding of various conceptual dualisms altered in the overlap between the virtual environs of Facebook and the material, everyday lives of the young participants, analysed here using the cyborg metaphor. In this sense, Facebook can be best understood as an individualised extension of young people’s broader social lives, part of a larger suite of information technologies, social media and other mediated sociality that is interconnected with materially based, face-to-face interactions.
Optimization of formability parameters of alpha–beta-processed titanium alloy at elevated temperature
Authors: Shukla Anoop Kumar , Raghu T , Rajesham S , Balasunder I
Published: November 2013

A material’s inherent ability of strain distribution decides forming limits and affects the overall formability. In the present work, aero space grade titanium alloy – Titan 31 developed by MIDHANI India is selected. The material is hot rolled under alpha–beta-rolling process and heat treated at different temperatures and subjected to various cooling rates in the alpha plus beta regime to obtain a fine equiaxed alpha–beta microstructure that ensures high formability . Taguchi’s design of experiments approach is used to optimize the processing parameters (temperature, crosshead speed and angle-to-rolling direction specimen tested) to maximize formability depending on intrinsic material properties. Percentage contributions of these parameters towards maximizing the formability are also determined using analysis of variance. The optimal combination of parameters is evaluated as a temperature of 998 K, a crosshead speed of 1.25 × 10−5m/sec and an angle of testing the specimen from rolling direction 45°, among all the parameters selected in the study.
Bonded bimaterial ring under compressive load
Authors: Budzik Michal K , Jensen Henrik Myhre
Published: November 2013

A bonded ring test is proposed to study crack onset under pure and mixed mode conditions. In the existing centre-cracked Brazilian disc configuration, introduction of a central crack may be arbitrary and can easily lead to initial asymmetric crack configuration. Moreover, the crack front geometry is, in general, unknown which may result in serious consequences on crack onset and fracture parameters. In the present work, a bonded ring loaded in compression was investigated numerically and experimentally. Two bimaterial singular points were introduced between the half discs and the adhesive providing privileged crack onset location – controllable during specimen fabrication. Three types of specimens were analysed using digital image correlation and finite element techniques: homogenous poly(methyl methacrylate), bonded poly(methyl methacrylate) and bonded poly(methyl methacrylate) to stainless steel rings. A satisfying agreement between experimental and numerical approaches was found enabling more complex analysis in future. Such test configuration can be of interest for crack onset studies and estimation of fracture parameters under mixed mode I/II loading conditions.
What does sexualisation mean?
Authors: Duschinsky Robbie
Published: November 2013

‘Sexualisation’ has been dismissed by some as no more than yet another moral panic about youth and sex. However, it is striking that the term appears to have helped galvanise feminist activism, speaking in some way to the experiences of young people. Building from a history and analysis of the term, I propose that ‘sexualisation’ has served as an interpretive theory of contradictory gender norms, using the figure of the ‘girl’ to gesture towards an intensifying contradiction between the demands that young women display both desirability and innocence. In addressing sexist dimensions of gender norms through the figure of the ‘girl’, a minor, discourses on sexualisation can help circumvent liberal objections about free choice. However, I also express concern that the term has facilitated a focus in media and policy texts which attends less to gender inequity than to sexuality as a contaminant of young femininity.
The mystique of the young girl
Authors: Driscoll Catherine
Published: November 2013

The collective Tiqqun’s 2001 tract, Raw Materials for a Theory of the YoungGirl, in which they stress the way modern girl culture represents the triumph of capitalism, has recently drawn fresh attention. Here I consider the argument about girls made in this text and its perhaps surprising relevance to contemporary feminist accounts of girlhood and girl culture.
(Post)Feminist development fables: The Girl Effect and the production of sexual subjects
Authors: Switzer Heather
Published: November 2013

The Nike Foundation’s flagship corporate social responsibility campaign, ‘The Girl Effect’, has generated support for targeted investments in adolescent girls as the ‘key’ economic development in the global south. As a representational regime, the campaign is an example of an increasingly hegemonic discourse of global girl power via formal education. In an era of ‘sexualisation moral panic’ regarding representations of contemporary young female sexual subjectivities in the global north, this article considers ideological figurings of adolescent female sexual embodiment in the global south through a discursive analysis of the campaign’s three most popular viral videos.
News sourcing and gender on Twitter
Authors: Artwick Claudette G
Published: November 2013

Traditional news sourcing practices that favor official, male voices have been widely documented over time and across media. But do these patterns persist in today’s social media environment, where women outnumber and spend more time than men? This study explores news sourcing and gender on Twitter by analyzing more than 2700 tweets from reporters at 51 US newspapers. Guided by hegemony and set within the framework of social networking technology, the research examines quoting practices and interaction with sources by gender, beat, newspaper size, and live coverage. The analyzed tweets show a severe underrepresentation of women in quotes, indicating perpetuation of the status quo. The data also suggest a conformity mechanism may be at work in larger newspapers, where female reporters quoted fewer women than their counterparts in smaller news organizations. But at the same time, the research offers evidence that both male and female reporters are using the technology to engage with a more diverse community via @mentions and to share conversations by retweeting those messages to their networks.
Destination loyalty: Effects of wine tourists’ experiences, memories, and satisfaction on intentions
Authors: Quadri-Felitti Donna L , Fiore Ann Marie
Published: November 2013

The present study analyzed survey data from 970 tourists to evaluate their Lake Erie wine region experience. Using structural equation modeling, an adapted scale of the experience economy’s 4Es (i.e. educational, esthetic, entertainment, and escapist experiences) proved reliable and valid for measuring rural wine tourism. This study contributes new information to research examining the 4Es applied to tourism venues by showing the 4Es’ impact on tourist response to loyalty for an entire destination. Structural modeling demonstrated the dominance of the esthetic experience in predicting positive memories and destination loyalty in the wine tourism context. Education played a significant but lesser role in creating memories and satisfaction but not in destination loyalty. Although the esthetic experience’s preeminence was consistent with other findings, these results contradict Pine and Gilmore’s assertion that simultaneous incorporation of the 4Es is necessary.
Imperfect informed consent for prenatal screening: Lessons from the Quad screen
Authors: Constantine ML , Allyse M , Wall M , Vries R De , Rockwood TH
Published: November 2013

Objective

The study evaluated patient informed consent (IC) for the Quad screen and examined differences in IC between test acceptors and test refusers. A multidimensional model of IC was used.

Methods

Women seeking prenatal care at nine obstetrics clinics in a large Midwestern city completed surveys between February and December 2006. Surveys contained measures for three dimensions of IC: intention, understanding and controlling influence.

Results

56.2% of women did not meet criteria for all three of our dimensions of IC and therefore failed to give it. The failure rate was higher among women who choose to screen (72.6%) than women who choose not screen (50%) (p < 0.001). Women who met all criteria for IC were over three times less likley to choose to screen (or = 0.32, CI 0.17–0.62 ( p < 0.01)) than women who did not meet criteria for IC.

Conclusion

The decision to screen for fetal anomalies is less of a deliberated action than the decision not to screen. Women who lack a fundamental understanding of the purpose and nature of the screen may be operating on the belief that the screen is part of standard care and presents no need to deliberate.
Reverse Fox Test for Detecting Visuospatial Dysfunction Corresponding to Parietal Hypoperfusion in Mild Alzheimer’s Disease
Authors: Tabuchi Hajime , Konishi Mika , Saito Nao , Kato Motoichiro , Mimura Masaru
Published: November 2013

Background/Aim:

We developed a novel visuospatial clinical task to detect parietal dysfunction in mild Alzheimer’s disease (AD).

Methods:

A total of 65 outpatients, including 47 with mild AD and 18 cognitively and neuroradiologically normal individuals with subjective memory impairment (NL), performed the “Reverse Fox” test and underwent brain single photon emission tomography. Patients with AD were divided into subgroups according to the results of the Reverse Fox test (successful vs unsuccessful).

Results:

Success in the Reverse Fox test was achieved by 31.9% of patients with AD and 94.4% of NL. The unsuccessful AD subgroup had reduced perfusion of the medial parietal and bilateral temporoparietal regions compared with the successful AD subgroup.

Conclusions:

Failure in the Reverse Fox test was related to parietal hypoperfusion in patients with mild AD. Our findings suggest that the Reverse Fox test may be one of the useful supporting tools for detecting mild AD at outpatient clinic.
Detection of spontaneous tumorigenic transformation during culture expansion of human mesenchymal stromal cells
Authors: Pan Qiuwei , Fouraschen Suomi MG , de Ruiter Petra E , Dinjens Winand NM , Kwekkeboom Jaap , Tilanus Hugo W , van der Laan Luc JW
Published: November 2013

Human mesenchymal stem/stromal cells (MSCs) have been explored in a number of clinical trials as a possible method of treating various diseases. However, the effect of long-term cell expansion in vitro on physiological function and genetic stability is still poorly understood. In this study, MSC cultures derived from bone marrow and liver were evaluated for the presence of aberrant cells following long-term expansion. In 46 independent cultures, four batches of transformed MSCs (TMCs) were found, which were all beyond the culture period of five weeks. These aberrant cells were first identified based on the appearance of abnormal cytology and the acquirement of growth advantage. Despite common MSC markers being diminished or absent, TMCs remain highly susceptible to lysis by allogenic natural killer (NK) cells. When transplanted into immunodeficient mice, TMCs formed sarcoma-like tumors, whereas parental MSCs did not form tumors in mice. Using a combination of high-resolution genome-wide DNA array and short-tandem repeat profiling, we confirmed the origin of TMCs and excluded the possibility of human cell line contamination. Additional genomic duplication and deletions were observed in TMCs, which may be associated with the transformation event. Using gene and microRNA expression arrays, a number of genes were identified that were differentially expressed between TMCs and their normal parental counterparts, which may potentially serve as biomarkers to screen cultures for evidence of early transformation events. In conclusion, the spontaneous transformation of MSCs resulting in tumorigenesis is rare and occurs after relatively long-term (beyond five weeks) culture. However, as an added safety measure, cultures of MSCs can potentially be screened based on a novel gene expression signature.
Inflammatory Abdominal Aortic Aneurysm
Authors: Ketha Siva S. , Warrington Kenneth J. , McPhail Ian R.
Published: November 2013

We report a case of an abdominal aortic aneurysm (AAA) that underwent inflammatory transformation which we treated medically with corticosteroids. Medical therapy resulted in resolution of presenting symptoms and observed inflammatory changes. We review the clinical features, associated pathology, diagnostic, and therapeutic options in the management of inflammatory AAA.
Endovascular Management of Venous Ulcer in a Patient With Occluded Duplicated Inferior Vena Cava and Review of Inferior Vena Cava Development
Authors: Verma Himanshu , Hiremath Niranjan , George Robbie K. , Tripathi Ramesh K.
Published: November 2013

Duplication of inferior vena cava (IVC) is the most common IVC anomaly. We report a successful iliac vein and collateral stenting for venous decompression in a patient with an occluded right femorocaval graft with a duplicated IVC. We also review the literature of embryological development of IVC.
Exploring Jakobson’s ‘phatic function’ in instant messaging interactions
Authors: Kulkarni Dipti
Published: November 2013

This research investigates the nature of phatic communion in instant messaging interactions. It adopts and expands Jakobson’s much-quoted definition according to which ‘phatic’ is the language in an interaction whose primary purpose is to maintain contact between the speakers. Adapting conversation analysis for the study of textual interactions, the research observes the linguistic means used by interlocutors to signal attention, interest, and agreement – these being identified as important constituents of contact. The corpus comprises 60 chats, collected from 20 participants who chat in a mixture of English and Indian languages such as Marathi and Hindi. Openings, middles, and closings of these interactions are analyzed to study the ways in which participants establish, maintain, and terminate contact. The use of various linguistic means in these interactions such as back-channels, evaluations, expressives, and questions draws attention to a significant amount of interactional work done by interlocutors towards maintaining contact.
Augmentation of LPS-induced vascular endothelial cell growth factor production in macrophages by transforming growth factor-β1
Authors: Koide Naoki , Odkhuu Erdenezaya , Naiki Yoshikazu , Tsolmongyn Bilegtsaikhan , Ito Kiyoaki , Komatsu Takayuki , Yoshida Tomoaki , Yokochi Takashi
Published: November 2013

The effect of LPS on the production of vascular endothelial growth factor (VEGF) was examined using RAW 264.7 macrophage cells. LPS induced VEGF production in RAW 264.7 cells and mouse peritoneal cells. LPS induced VEGF production via the expression of hypoxia inducible factor-1α and LPS-induced VEGF production was dependent on the activation of p38 MAPK and NF-κB activation· Transforming growth factor (TGF)-β1 augmented LPS-induced VEGF production, although TGF-β1 alone did not induce VEGF production. The augmentation of LPS-induced VEGF production by TGF-β1 was inhibited by a p38 MAPK inhibitor and was correlated with the phosphorylation of Smad3. The enhancing effect of TGF-β1 on LPS-induced VEGF production was observed in vivo in the skin lesions of mice receiving a subcutaneous injection of LPS. Taken together, it is suggested that LPS induced the VEGF production in macrophages and that it was augmented by TGF-β1 in vitro and in vivo.
Assessing member expertise in groups
Authors: Barton Michelle A. , Bunderson J. Stuart
Published: November 2013

In contemporary organizations, the knowledge needed to perform work is frequently housed within groups. In order to effectively leverage this knowledge, however, groups must identify relative member expertise. Unfortunately, assessments of expertise in groups can be error-prone, given the human tendency to rely on efficient but noisy schemas and heuristics. The purpose of this paper is to consider the factors that lead to more mindful and, ultimately, more useful expertise attributions in task groups. We begin with the observation that mindful expertise attribution can be modeled as a motivation problem using expectancy theory. In order for group members to move beyond superficial expertise attributions, they must see value in doing so (valence) and they must feel that exerting that effort will be both possible (expectancy) and beneficial (instrumentality). We build on this basic observation to propose an “expertise dependence theory” of mindful attributions in task groups.
Effect of early stages of thermomechanical processing on inclusions in high carbon steel
Authors: Faraji M. , Wilcox D. P. , Thackray R. P. , Todd I. , Howe A. A. , Tsakiropoulos P.
Published: November 2013

The effect of heat treatment and thermomechanical processing on size, size distribution, distribution and chemistry of non-metallic inclusions in a continuously cast high carbon steel was investigated using a Gleeble hot compression simulator at temperatures of 1050 and 1150°C and strains of 0·3 and 0·7 at strain rate 1 s−1. The results showed that the total number of inclusions classified into three main types, namely, sulphide, oxide and duplex, was reduced after the deformation at high temperature. Inclusions of different size and chemistry were found being present in different locations of the bloom, which was related with microsegregation in the as cast bloom. This suggested that inclusions were influenced by solidification conditions and subsolidus homogenisation. Furthermore, the observed changes of chemistry of inclusions during heat treatment and thermomechanical processing at high temperature (∼1100°C) are discussed. These changes were substantiated by evidence of devitrification of oxide inclusions including different manganese silicates.
Rational design of small molecules targeting the C2 domain of coagulation factor VIII
Authors: Nicolaes Gerry A. F. , Kulharia Mahesh , Voorberg Jan , Kaijen Paul H. , Wroblewska Aleksandra , Wielders Simone , Schrijver Roy , Sperandio Olivier , Villoutreix Bruno O.
Published: November 2013

Key Points

Novel small molecules have been identified that specifically target FVIII. These small molecules are able to reduce in vitro thrombin formation in full blood.
Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A
Authors: Mahlangu Johnny , Powell Jerry S. , Ragni Margaret V. , Chowdary Pratima , Josephson Neil C. , Pabinger Ingrid , Hanabusa Hideji , Gupta Naresh , Kulkarni Roshni , Fogarty Patrick , Perry David , Shapiro Amy , Pasi K. John , Apte Shashikant , Nestorov Ivan , Jiang Haiyan , Li Shuanglian , Neelakantan Srividya , Cristiano Lynda M. , Goyal Jaya , Sommer Jurg M. , Dumont Jennifer A. , Dodd Nigel , Nugent Karen , Vigliani Gloria , Luk Alvin , Brennan Aoife , Pierce Glenn F.
Published: November 2013

Key Points

A novel recombinant factor VIII with prolonged half-life, rFVIIIFc, was developed to reduce prophylactic injection frequency. rFVIIIFc was well-tolerated in patients with severe hemophilia A, and resulted in low bleeding rates when dosed 1 to 2 times per week.
Characterization of a chemostable serine alkaline protease from Periplaneta americana
Authors: Sanatan Prashant T , Lomate Purushottam R , Giri Ashok P , Hivrale Vandana K
Published: November 2013

Background

Proteases are important enzymes involved in numerous essential physiological processes and hold a strong potential for industrial applications. The proteolytic activity of insects’ gut is endowed by many isoforms with diverse properties and specificities. Thus, insect proteases can act as a tool in industrial processes.

Results

In the present study, purification and properties of a serine alkaline protease from Periplaneta americana and its potential application as an additive in various bio-formulations are reported. The enzyme was purified near to homogeneity by using acetone precipitation and Sephadex G-100 gel filtration chromatography. Enzyme activity was increased up to 4.2 fold after gel filtration chromatography. The purified enzyme appeared as single protein-band with a molecular mass of ~ 27.8 kDa in SDS-PAGE. The optimum pH and temperature for the proteolytic activity for purified protein were found around pH 8.0 and 60°C respectively. Complete inhibition of the purified enzyme by phenylmethylsulfonyl fluoride confirmed that the protease was of serine-type. The purified enzyme revealed high stability and compatibility towards detergents, oxidizing, reducing, and bleaching agents. In addition, enzyme also showed stability towards organic solvents and commercial detergents.

Conclusion

Several important properties of a serine protease from P. Americana were revealed. Moreover, insects can serve as excellent and alternative source of industrially important proteases with unique properties, which can be utilized as additives in detergents, stain removers and other bio-formulations. Properties of the P. americana protease accounted in the present investigation can be exploited further in various industrial processes. As an industrial prospective, identification of enzymes with varying essential properties from different insect species might be good approach and bioresource.
3DScapeCS: application of three dimensional, parallel, dynamic network visualization in Cytoscape
Authors: Wang Qi , Tang Biao , Song Lifu , Ren Biao , Liang Qun , Xie Feng , Zhuo Ying , Liu Xueting , Zhang Lixin
Published: November 2013

Background

The exponential growth of gigantic biological data from various sources, such as protein-protein interaction (PPI), genome sequences scaffolding, Mass spectrometry (MS) molecular networking and metabolic flux, demands an efficient way for better visualization and interpretation beyond the conventional, two-dimensional visualization tools.

Results

We developed a 3D Cytoscape Client/Server (3DScapeCS) plugin, which adopted Cytoscape in interpreting different types of data, and UbiGraph for three-dimensional visualization. The extra dimension is useful in accommodating, visualizing, and distinguishing large-scale networks with multiple crossed connections in five case studies.

Conclusions

Evaluation on several experimental data using 3DScapeCS and its special features, including multilevel graph layout, time-course data animation, and parallel visualization has proven its usefulness in visualizing complex data and help to make insightful conclusions.
The Gut Microbiotassay: a high-throughput qPCR approach combinable with next generation sequencing to study gut microbial diversity
Authors: Hermann-Bank Marie Louise , Skovgaard Kerstin , Stockmarr Anders , Larsen Niels , Mølbak Lars
Published: November 2013

Background

The intestinal microbiota is a complex and diverse ecosystem that plays a significant role in maintaining the health and well-being of the mammalian host. During the last decade focus has increased on the importance of intestinal bacteria. Several molecular methods can be applied to describe the composition of the microbiota. This study used a new approach, the Gut Microbiotassay: an assembly of 24 primer sets targeting the main phyla and taxonomically related subgroups of the intestinal microbiota, to be used with the high-throughput qPCR chip ‘Access Array 48.48′, AA48.48, (Fluidigm®) followed by next generation sequencing. Primers were designed if necessary and all primer sets were screened against DNA extracted from pure cultures of 15 representative bacterial species. Subsequently the setup was tested on DNA extracted from small and large intestinal content from piglets with and without diarrhoea. The PCR amplicons from the 2304 reaction chambers were harvested from the AA48.48, purified, and sequenced using 454-technology.

Results

The Gut Microbiotassay was able to detect significant differences in the quantity and composition of the microbiota according to gut sections and diarrhoeic status. 454-sequencing confirmed the specificity of the primer sets. Diarrhoea was associated with a reduced number of members from the genus Streptococcus, and in particular S. alactolyticus.

Conclusion

The Gut Microbiotassay provides fast and affordable high-throughput quantification of the bacterial composition in many samples and enables further descriptive taxonomic information if combined with 454-sequencing.
The role of arginine and arginine-metabolizing enzymes during Giardia – host cell interactions in vitro
Authors: Stadelmann Britta , Hanevik Kurt , Andersson Mattias K , Bruserud Oystein , Svärd Staffan G
Published: November 2013

Background

Arginine is a conditionally essential amino acid important in growing individuals and under non-homeostatic conditions/disease. Many pathogens interfere with arginine-utilization in host cells, especially nitric oxide (NO) production, by changing the expression of host enzymes involved in arginine metabolism. Here we used human intestinal epithelial cells (IEC) and three different isolates of the protozoan parasite Giardia intestinalis to investigate the role of arginine and arginine-metabolizing enzymes during intestinal protozoan infections.

Results

RNA expression analyses of major arginine-metabolizing enzymes revealed the arginine-utilizing pathways in human IECs (differentiated Caco-2 cells) grown in vitro. Most genes were constant or down-regulated (e.g. arginase 1 and 2) upon interaction with Giardia, whereas inducible NO synthase (iNOS) and ornithine decarboxylase (ODC) were up-regulated within 6 h of infection. Giardia was shown to suppress cytokine-induced iNOS expression, thus the parasite has both iNOS inducing and suppressive activities. Giardial arginine consumption suppresses NO production and the NO-degrading parasite protein flavohemoglobin is up-regulated in response to host NO. In addition, the secreted, arginine-consuming giardial enzyme arginine deiminase (GiADI) actively reduces T-cell proliferation in vitro. Interestingly, the effects on NO production and T cell proliferation could be reversed by addition of external arginine or citrulline.

Conclusions

Giardia affects the host’s arginine metabolism on many different levels. Many of the effects can be reversed by addition of arginine or citrulline, which could be a beneficial supplement in oral rehydration therapy.
Multivariable analysis of the association between fathers’ and youths’ physical activity in the United States
Authors: Isgor Zeynep , Powell Lisa M , Wang Youfa
Published: November 2013

Background

Although the benefits of physical activity have been well-established, a significant number of children and adolescents in the U.S. do not meet the recommended levels of daily physical activity. Parental influences such as parents’ physical activity participation may play an important role in affecting youths’ physical activity.

Methods

This study used the Child Development Supplement of the Panel Study of Income Dynamics to examine the associations between fathers’ vigorous physical activity (VPA) and VPA participation (>0 day(s)/week) and frequency (days/week) of 887 youths aged 10 through 18 based on a nationally representative sample of families in the US. Logistic and negative binomial regression analyses were used to examine the association between past frequency (times/week) and an indicator of recommended (≥3 times/week) frequency of father’s VPA and youth’s VPA participation and youths’ VPA frequency, respectively. We examined the sensitivity to the inclusion of various youth, family, mother’s VPA, and contextual control measures. Analyses also were undertaken by gender.

Results

Father’s past VPA frequency was positively associated with both youths’ VPA participation and with youths’ VPA frequency for the full and female samples of youths, even after the inclusion of demographic, socio-economic, and local area characteristics. Father’s past recommended VPA frequency was positively associated with youths’ VPA participation in the full sample only and with youths’ VPA frequency in the female sub-sample only. Simulation results showed that an increase in father’s past weekly VPA frequency from zero to the minimum recommended level (three times per week) was associated with an increased predicted probability of youths’ weekly VPA participation from approximately 67% to 74% for the full sample (61% to 73% for females and 74% to 77% for males).

Conclusion

The results from this study suggest that environmental and/or family based interventions that increase fathers’ VPA may help improve youths’ VPA.
Experimental evidence and isotopomer analysis of mixotrophic glucose metabolism in the marine diatom Phaeodactylum tricornutum
Authors: Zheng Yuting , Quinn Andrew H , Sriram Ganesh
Published: November 2013

Background

Heterotrophic fermentation using simple sugars such as glucose is an established and cost-effective method for synthesizing bioproducts from bacteria, yeast and algae. Organisms incapable of metabolizing glucose have limited applications as cell factories, often despite many other advantageous characteristics. Therefore, there is a clear need to investigate glucose metabolism in potential cell factories. One such organism, with a unique metabolic network and a propensity to synthesize highly reduced compounds as a large fraction of its biomass, is the marine diatom Phaeodactylum tricornutum (Pt). Although Pt has been engineered to metabolize glucose, conflicting lines of evidence leave it unresolved whether Pt can natively consume glucose.

Results

Isotope labeling experiments in which Pt was mixotrophically grown under light on 100% U-13C glucose and naturally abundant (~99% 12C) dissolved inorganic carbon resulted in proteinogenic amino acids with an average 13C-enrichment of 88%, thus providing convincing evidence of glucose uptake and metabolism. The dissolved inorganic carbon was largely incorporated through anaplerotic rather than photosynthetic fixation. Furthermore, an isotope labeling experiment utilizing 1-13C glucose and subsequent metabolic pathway analysis indicated that (i) the alternative Entner-Doudoroff and Phosphoketolase glycolytic pathways are active during glucose metabolism, and (ii) during mixotrophic growth, serine and glycine are largely synthesized from glyoxylate through photorespiratory reactions rather than from 3-phosphoglycerate. We validated the latter result for mixotrophic growth on glycerol by performing a 2-13C glycerol isotope labeling experiment. Additionally, gene expression assays showed that known, native glucose transporters in Pt are largely insensitive to glucose or light, whereas the gene encoding cytosolic fructose bisphosphate aldolase 3, an important glycolytic enzyme, is overexpressed in light but insensitive to glucose.

Conclusion

We have shown that Pt can use glucose as a primary carbon source when grown in light, but cannot use glucose to sustain growth in the dark. We further analyzed the metabolic mechanisms underlying the mixotrophic metabolism of glucose and found isotopic evidence for unusual pathways active in Pt. These insights expand the envelope of Pt cultivation methods using organic substrates. We anticipate that they will guide further engineering of Pt towards sustainable production of fuels, pharmaceuticals, and platform chemicals.
PftetQ and pfmdt copy numbers as predictive molecular markers of decreased ex vivo doxycycline susceptibility in imported Plasmodium falciparum malaria
Authors: Gaillard Tiphaine , Briolant Sébastien , Houzé Sandrine , Baragatti Meïli , Wurtz Nathalie , Hubert Véronique , Lavina Morgane , Pascual Aurélie , Travaillé Christelle , Le Bras Jacques , Pradines Bruno ,   The French National Reference Centre for Imported Malaria Study Group
Published: November 2013

Background

The objective of this study was to evaluate the distribution of a series of independent doxycycline inhibitory concentration 50% (IC50) values to validate the trimodal distribution previously described and to validate the use of thepftetQandpfmdtgenes as molecular markers of decreasedin vitrodoxycycline susceptibility inPlasmodium falciparummalaria.

Methods

Doxycycline IC50values, from 484 isolates obtained at the French National Reference Centre for Imported Malaria (Paris) between January 2006 and December 2010, were analysed for the first time by a Bayesian mixture modelling approach to distinguish the differentin vitrophenotypic groups by their IC50values. Quantitative real-time polymerase chain reaction was used to evaluate thepftetQandpfmdtcopy numbers of 89 AfricanP. falciparumisolates that were randomly chosen from the phenotypic groups.

Results

The existence of at least three doxycycline phenotypes was demonstrated. The mean doxycycline IC50was significantly higher in the group with apftetQcopy number >1 compared to the group with apftetQcopy number = 1 (33.17 μMversus17.23 μM) and the group with apfmdtcopy number >1 (28.28 μMversus16.11 μM). There was a significant difference between the combined low and medium doxycycline IC50group and the high IC50group in terms of the per cent of isolates with one or more copy numbers of thepftetQgene (0%versus20.69%) orpfmdtgene (8.33%versus37.93%). In the logistic regression model, thepfmdtandpftetQcopy numbers >1 (odds ratio = 4.65 and 11.47) were independently associated with the high IC50group.

Conclusions

Copy numbers ofpftetQandpfmdtare potential predictive molecular markers of decreased susceptibility to doxycycline.
Cheek cell fatty acids reflect n-3 PUFA in blood fractions during linseed oil supplementation: a controlled human intervention study
Authors: Grindel Annemarie , Staps Frank , Kuhnt Katrin
Published: November 2013

Background

Adequate biomarkers for the dietary supply of fatty acids (FA) are FA of adipose tissue and blood fractions. In human studies, invasive sample collection is unpleasant for subjects. In contrast, cheek cell sampling can be considered as a non-invasive alternative to investigate FA status.

The aim of this study was to analyze whether cheek cell FA composition reflect the supplementation of alpha-linolenic acid (ALA) using a linseed oil mixture compared to olive oil supplementation. Additionally, it was investigated if cheek cell FA composition correlates with the FA composition of plasma, red blood cells (RBC) and peripheral blood mononuclear cells (PBMC) before and during both interventions.

Methods

During a 10-week randomized, controlled, double-blind human intervention study, 38 subjects provided cheek cell and blood samples. After a two-week run-in period, the test group (n = 23) received 17 g/d of an ALA-rich linseed oil mixture, while the control group (n = 15) received 17 g/d of an omega-3 (n-3) polyunsaturated FA (PUFA)-free olive oil. Cheek cells and blood were collected on days 0, 7 and 56 of the 8-week intervention period.

Results

Compared to olive oil, the linseed oil intervention increased ALA and also the endogenously converted long-chain n-3 metabolites eicosatetraenoic-, eicosapentaenoic- and docosapentaenoic acid in cheek cells (P ≤ 0.05). Docosahexaenoic acid remained unchanged. Reflecting the treatment, the n-6/n- 3 ratio decreased in the test group. In general, cheek cell FA reflected the changes of FA in blood fractions. Independent of treatment, significant correlations (P ≤ 0.05) of n-6 PUFA and n- 3 PUFA between cheek cells and plasma, RBC and PBMC were found, except for linoleic acid and ALA.

Conclusions

The changes in FA composition of cheek cells confirmed that ALA from linseed oil increased endogenously derived n- 3 PUFA in cheek cell lipids. These changes in cheek cells and their correlation to the respective FA in blood fractions indicate the cheek cell FA profile as an adequate non-invasive biomarker for short-term n-3 PUFA intake and metabolism. Therefore, cheek cell FA can be used in human intervention studies or large-scale epidemiological studies, especially for assessment of the n-3 PUFA status.

Trial registration

ClinicalTrials.gov, IDNCT01317290
Effects of selenoprotein S on oxidative injury in human endothelial cells
Authors: Zhao Yin , Li Hua , Men Li-li , Huang Rong-chong , Zhou Hai-cheng , Xing Qian , Yao Jun-jie , Shi Chun-hong , Du Jian-ling
Published: November 2013

Background

Selenoprotein S (SelS) is an important endoplasmic reticulum and plasma membrane-located selenoprotein implicated in inflammatory responses and insulin resistance. However, the effects of SelS on endothelial cells (ECs) have not been reported. In the present study, the role of SelS in oxidative stress and the underlying mechanism were investigated in human ECs.

Methods

A SelS over-expression plasmid (pc-SelS) and a SelS-siRNA plasmid were transfected into human umbilical vein endothelial cells (American Type Culture Collection, USA). The cells were divided into four groups: control, SelS over-expression (transfected with pc-SelS), vector control, and SelS knockdown (transfected with siRNA-SelS). After treating the cells with H2O2, the effects of oxidative stress and the expression of caveolin-1 (Cav-1) and protein kinase Cα (PKCα) were investigated.

Results

Following treatment with H2O2, over-expression of SelS significantly increased cell viability and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) production and Cav-1 gene and protein expression. However, no effects on PKCα were observed. In contrast, knockdown of SelS significantly decreased cell viability, SOD activity, and PKCα gene and protein expression, and increased MDA production and Cav-1 gene and protein expression.

Conclusions

SelS protects ECs from oxidative stress by inhibiting the expression of Cav-1 and PKCα.
Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen
Authors: Trible Ronald P , Narute Purushottam , Emert-Sedlak Lori A , Alvarado John Jeff , Atkins Katelyn , Thomas Laurel , Kodama Toshiaki , Yanamala Naveena , Korotchenko Vasiliy , Day Billy W , Thomas Gary , Smithgall Thomas E
Published: November 2013

Background

HIV-1 Nef is a viral accessory protein critical for AIDS progression. Nef lacks intrinsic catalytic activity and binds multiple host cell signaling proteins, including Hck and other Src-family tyrosine kinases. Nef binding induces constitutive Hck activation that may contribute to HIV pathogenesis by promoting viral infectivity, replication and downregulation of cell-surface MHC-I molecules. In this study, we developed a yeast-based phenotypic screen to identify small molecules that inhibit the Nef-Hck complex.

Results

Nef-Hck interaction was faithfully reconstituted in yeast cells, resulting in kinase activation and growth arrest. Yeast cells expressing the Nef-Hck complex were used to screen a library of small heterocyclic compounds for their ability to rescue growth inhibition. The screen identified a dihydrobenzo-1,4-dioxin-substituted analog of 2-quinoxalinyl-3-aminobenzene-sulfonamide (DQBS) as a potent inhibitor of Nef-dependent HIV-1 replication and MHC-I downregulation in T-cells. Docking studies predicted direct binding of DQBS to Nef which was confirmed in differential scanning fluorimetry assays with recombinant purified Nef protein. DQBS also potently inhibited the replication of HIV-1 NL4-3 chimeras expressing Nef alleles representative of all M-group HIV-1 clades.

Conclusions

Our findings demonstrate the utility of a yeast-based growth reversion assay for the identification of small molecule Nef antagonists. Inhibitors of Nef function discovered with this assay, such as DQBS, may complement the activity of current antiretroviral therapies by enabling immune recognition of HIV-infected cells through the rescue of cell surface MHC-I.
In vitro inhibition of mumps virus by retinoids
Authors: Soye Kaitlin J , Trottier Claire , Di Lenardo Thomas Z , Restori Katherine H , Reichman Lee , Miller Wilson H , Ward Brian J
Published: November 2013

Background

Mumps virus (MuV) is a highly infectious paramyxovirus closely related to measles virus (MeV). Despite the availability of a mumps vaccine, outbreaks continue to occur and no treatment options are available. Vitamin A and other naturally occurring retinoids inhibit the replication of MeVin vitro.

Methods

Anti-viral effects of retinoids were observed in cell culture using the myelomonocytic U937, NB4/R4, and Huh7/7.5 cells. Observations of anti-viral effect were quantified using TCID50 analysis. Molecular properties of the antiviral effect were analysed using quantitative RT-PCR and western blot.

Results

The current work demonstrates that retinoids inhibit MuVin vitrodue to up-regulation of type I interferon (IFN) and IFN stimulated genes. This effect is mediated by nuclear retinoid receptor signalling and RIG-I is required. The antiviral retinoid-induced state makes cells less permissive to viral replication from subsequent challenge with either MuV or MeV for less than 12 hours.

Conclusions

These results demonstrate that retinoids inhibit MuV replication in uninfected bystander cells through a retinoid inducible gene I (RIG-I), retinoic acid receptor (RAR) and IFN dependent manner making them refractory to subsequent rounds of viral replication. These observations raise the possibility that pharmacological doses of retinoids might have clinical benefit in MuV infection.
Interventions for increasing ankle joint dorsiflexion: a systematic review and meta‐analysis
Authors: Young Rebekah , Nix Sheree , Wholohan Aaron , Bradhurst Rachael , Reed Lloyd
Published: November 2013

Background

Ankle joint equinus, or restricted dorsiflexion range of motion (ROM), has been linked to a range of pathologies of relevance to clinical practitioners. This systematic review and meta‐analysis investigated the effects of conservative interventions on ankle joint ROM in healthy individuals and athletic populations.

Methods

Keyword searches of Embase, Medline, Cochrane and CINAHL databases were performed with the final search being run in August 2013. Studies were eligible for inclusion if they assessed the effect of a non‐surgical intervention on ankle joint dorsiflexion in healthy populations. Studies were quality rated using a standard quality assessment scale. Standardised mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and results were pooled where study methods were homogenous.

Results

Twenty‐three studies met eligibility criteria, with a total of 734 study participants. Results suggest that there is some evidence to support the efficacy of static stretching alone (SMDs: range 0.70 to 1.69) and static stretching in combination with ultrasound (SMDs: range 0.91 to 0.95), diathermy (SMD 1.12), diathermy and ice (SMD 1.16), heel raise exercises (SMDs: range 0.70 to 0.77), superficial moist heat (SMDs: range 0.65 to 0.84) and warm up (SMD 0.87) in improving ankle joint dorsiflexion ROM.

Conclusions

Some evidence exists to support the efficacy of stretching alone and stretching in combination with other therapies in increasing ankle joint ROM in healthy individuals. There is a paucity of quality evidence to support the efficacy of other non‐surgical interventions, thus further research in this area is warranted.