bluuebunny/crossref_metadata_2025 huggingface dataset:
The culture of liberalism and the virtue of ‘balance’
Authors: Gregory James
Published: April 2013

This article argues for a virtue-based account of the value and legitimacy of liberalism in increasingly multicultural societies. In contrast to the recent trend to seek consensus and stability through an overlapping ‘political’ consensus, this article argues for a more ‘comprehensive’ view of the attraction of liberalism in a culturally diverse world. This attraction resides in a particular view of the properly constituted ‘self’, able to appreciate and navigate a range of competing ethical demands, coming from a wide range of cultural sources. In support of this virtue-based picture of liberalism, this article seeks to draw out the tacit importance of such an account in two ostensibly different liberal theorists, John Rawls and Michael Walzer, both of whom rely on the virtue of psychological and moral ‘balance’. The article then argues that this sense of virtue as balance is more attractive to non-liberal cultures than a narrow conception of ‘political’ liberalism, and that it therefore offers a more promising basis for cultural cohesion than a more basic appeal to ‘political’ liberalism.
Dual Effects of Body-Weight Supported Treadmill Training on Cardiovascular Fitness and Walking Ability Early After Stroke
Authors: MacKay-Lyons Marilyn , McDonald Alison , Matheson Jane , Eskes Gail , Klus Mary-Anne
Published: April 2013

Background. Body-weight-supported treadmill training (BWSTT) to train both fitness and ambulation has not been investigated. Objective. To compare the effectiveness of BWSTT to dose-equivalent usual care (UC) in improving cardiovascular fitness and walking early after stroke. Methods. Participants were randomly assigned to 1 of 2 interventions: BWSTT + UC or UC. All individuals participated in 60-minute physiotherapy sessions 5 times weekly as inpatients for 6 weeks and 3 times weekly as outpatients for another 6 weeks. Baseline, posttraining, 6-, and 12-month follow-up outcome measures were as follows: primary, fitness (peak oxygen consumption, VO2peak) and walking ability (6-Minute Walk Test [6MWT] and 10-m walk); secondary, Berg Balance Scale (BBS) and motor impairment (Chedoke-McMaster Stages of Recovery [CMSR] Leg and Foot). Results. In all, 50 individuals (mean age, 60 ± 14 years; mean event-to-randomization, 23 ± 5 days; 29 men) participated. No adverse events occurred. BWSTT improved VO2peak by 30%, which was significantly greater than the 8% improvement observed for UC ( P = .004 between groups). Similarly, there were significant Time × Group interactions for 6MWT and CMSR Foot, with BWSTT outperforming UC for gains in distance ( P = .15; 48% vs 19%, respectively) and stage ( P = .01; 1.0 vs 0.3, respectively). No group effect was seen for 10-m walk speed, BBS, or CMSR Leg, with both groups demonstrating significant gains. In general, gains observed were preserved for 12 months. Conclusions. BWSTT elicits greater improvements in cardiovascular fitness and walking endurance than UC in the subacute poststroke period. These gains are largely sustained for 1 year.
A Multilevel Framework
Authors: Searle Travis P. , Barbuto John E.
Published: April 2013

This article reviews the literature on the micro (i.e., individual level) and macro levels (i.e., organizational level) of positive behavior to propose a framework that includes seven levels of positive behaviors—individual, dyadic, team/group, organizational, community, societal, and environmental levels. The micro level of positive organizational behavior is extended from the individual level to include the dyadic and team/group levels. The macro level of positive organizational scholarship is extended from the organizational level to include the community, societal, and environmental levels. The role of leadership as antecedents to positive behaviors is also developed. Three positive forms of leadership (i.e., transformational leadership, servant leadership, and authentic leadership) are used as antecedents, and the potential multilevel outcomes associated with positive behavior are explored. This article provides testable propositions and sets the stage for future empirical research.
Emotion Regulation and Its Implications for Leadership
Authors: Haver Annie , Akerjordet Kristin , Furunes Trude
Published: April 2013

This integrative review synthesizes research on emotion regulation and its implications for leadership, from both leaders’ and followers’ perspectives. Regulating one’s emotions is considered an area of key competence associated with effective and good leadership. Three themes emerged from the preliminary synthesis: (a) emotion regulation strategies as facilitators of health, (b) emotion regulation strategies as facilitators of job outcome, and (c) emotion regulation as barriers to health and job outcomes. Findings revealed that leaders’ emotion competencies, cultural understanding, and coaching ability and the quality of leader–member relationships seem particularly important for the efficiency of emotion regulation. Methodological shortcomings and future research are discussed.
The US influence in shaping Iraq’s sectarian media
Authors: Al-Rawi Ahmed K
Published: April 2013

After the Anglo-American invasion, the US neo-conservative administration established the Iraqi Governing Council in July 2003, which included 25 members selected for their ethnic and religious origins; it was the most obvious sign of the US political separatist strategy. As a result of the new political reality, the Iraqi media was divided into ethno-sectarian lines, resulting from previous policies followed by the US administration. This article argues that the US media policy prior and after the US invasion of Iraq played a part in enhancing and encouraging the sectarian divisions in the Iraqi society. This was mainly done by sending biased media messages through the state-run Iraqi Media Network (IMN) and other US-aligned channels and allowing militant voices from different Iraqi sides to wage wars of words without interfering. In fact, the only time US officials interfered is when they were criticized by Iraqi media outlets. This study cites different US government reports, accounts from media practitioners who worked for IMN and other journalists that monitored the Iraqi media.
The gates of op-ed diplomacy
Authors: Golan Guy J
Published: April 2013

The op-ed section of the newspaper is unique in that it allows experts to articulate their opinions regarding salient issues without editorial interference. The current study builds upon previous research on the op-ed through the analysis of the op-ed articles that were published in two European newspapers during the Egyptian revolution of 2011. The content analysis focused on the identity of the op-ed contributors, their use of sources, and their selection of frames as highlighted in their opinion articles. The results of the study indicate that the majority of contributors were American newspaper columnists and that the op-eds in the two newspapers focused on similar issue frames but discussed them from different perspectives.
Al-Jazeera and Al-Arabiya framing of the Israel–Palestine conflict during war and calm periods
Authors: Elmasry Mohamad Hamas , Shamy Alaa El , Manning Peter , Mills Andrew , Auter Philip J
Published: April 2013

This framing study compares Al-Jazeera and Al-Arabiya coverage of the Israel–Palestine conflict during the 2008/2009 Gaza conflict and one year later, during a period of calm. Findings suggest that both networks used framing mechanisms to highlight Palestinian perspectives over Israeli ones and frame Palestinians as victims of Israeli aggression. The networks regularly described Palestinian casualties and showed images of Palestinian grief, provided more voice to Palestinian sources, and personalized Palestinian deaths.
Reproducibility of radiographic classification of scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) wrist
Authors: Vishwanathan K. , Hearnden A. , Talwalkar S. , Hayton M. , Murali S. R. , Trail I. A.
Published: April 2013

The aim of this study was to measure inter- and intra-observer agreement on the radiographic classification of scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) wrist. Radiographs of 41 patients with SLAC wrist and 47 patients with SNAC wrist were graded on two separate occasions by four orthopaedic consultants specializing in hand and wrist surgery. Inter-observer agreement was evaluated using the multi-rater kappa value. Landis and Koch criteria were used to assess the level of agreement. Intra-observer agreement was tested by re-grading the radiographs after an interval of 2 to 4 weeks and calculating the weighted kappa value. For SLAC wrist, the inter-observer agreement was moderate (kappa value = 0.59) and intra-observer agreement substantial (kappa value = 0.65). For SNAC wrist, the inter-observer agreement was slight (kappa value = 0.20) and intra-observer agreement was fair (kappa value = 0.29). Radiographic classification of SLAC wrist has moderate reliability and reproducibility, whereas classification of SNAC wrist has limited reliability.
Malnutrition in Congenital Heart Disease
Authors: Hubschman Lilly Erna
Published: April 2013

Advanced corrective and palliative cardiovascular surgical procedures have significantly reduced mortality related to congenital heart disease. However, in infants with congenital heart disease, inadequate nutrient intake, insufficient nutrient absorption, and increased energy needs limit the ability to grow and develop. Infants with congenital heart disease have a high prevalence of malnutrition. Nutrition provides an opportunity to optimize growth, development, and quality of life in an era of increased survival. Early intervention and identification of at-risk patients has the potential to decrease morbidity and mortality related to malnutrition in infants with congenital heart disease. Currently, a paucity of research prohibits practitioners from providing comprehensive evidence-based care and compromises the care of the growing population of patients with congenital heart disease who survive infancy. The purpose of this article is to examine existing evidence that could contribute to guidelines for improving outcomes and data gaps that can be filled. This article establishes a malnutrition prevention/growth promotion protocol using risk assessments, estimation of resting energy expenditure, calorie and protein administration recommendations, growth charts, discharge planning, and follow-up care.
Can a pain management programme approach reduce healthcare use? Stopping the revolving door
Authors: Clare Ajay , Andiappan Manoharan , MacNeil Sarah , Bunton Tamzin , Jarrett Stephanie
Published: April 2013

Patients with chronic musculoskeletal pain are frequent users of healthcare. Whilst evidence suggests that a multidisciplinary pain management programme (PMP) approach is effective in reducing patients’ levels of distress and disability, there is little research examining the cost-effectiveness of such an approach. The present study sought to address this by examining the impact a PMP had on patients’ pain-related secondary care healthcare use. A 90.5% reduction in healthcare use was found 12 months after the PMP, compared with 12 months before the PMP. The cost of the pain-related healthcare use 12 months before the PMP was £35,700. Twelve months after the PMP, the cost of healthcare use had reduced to £3879. The findings suggest that a PMP approach could reduce pain-related healthcare use.
Desmond and Moore’s Darwin’s Sacred Cause
Authors: Esterson Allen
Published: April 2013

In their book Darwin’s Sacred Cause (2009) Adrian Desmond and James Moore purport to demonstrate that they have provided an original explanation for the inspiration behind Darwin’s determined pursuit of an explanatory theory for the transformation of species of which he became convinced as a result of his experiences during the Beagle voyage of 1831 to 1836. This, they argue, was the “moral passion” that was evoked by his encountering the horrors of slavery during the periods he was able to disembark to explore areas of South America in the years 1832 to 1835. In short, they provide what they describe as “the untold story of how Darwin’s abhorrence of slavery led to our modern understanding of evolution.” This article explores the means by which the authors seek to persuade readers of the validity of their thesis, and concludes that far from providing compelling evidence, by providing a mass of historically interesting material relating to slavery that is actually tangential to their case, they obscure the fact that they fail to accomplish their aim. There is nothing in their account of events that provides a reason for preferring their explanation for Darwin’s devotion to understanding the processes involved in the transformation of species to the known historical facts of Darwin’s early zeal for natural science, exhibited in his childhood exploits with beetles and his more organized scientific activities when he was a student at Cambridge, enabled to come to fruition by his scientific activities during the voyage of the Beagle.
War Zone Stress Interacts With the 5-HTTLPR Polymorphism to Predict the Development of Sustained Attention for Negative Emotion Stimuli in Soldiers Returning From Iraq
Authors: Disner Seth G. , Beevers Christopher G. , Lee Han-Joo , Ferrell Robert E. , Hariri Ahmad R. , Telch Michael J.
Published: April 2013

Biased attention toward negative stimuli is a known vulnerability for affective psychopathology. However, factors that contribute to the development of this cognitive bias are largely unknown. Variation within the serotonin transporter gene (i.e., 5-HTTLPR) is associated with increased susceptibility to environmental influence and biased processing of negative stimuli. Using a passive viewing eye-tracking paradigm, this study examined gaze fixation for emotion stimuli in 91 U.S. Army soldiers before and after deployment to Iraq. In addition, participants underwent genetic assay and provided in situ measures of war zone stress exposure. 5-HTTLPR short allele homozygotes were more likely than other genotype groups to develop a gaze bias toward negative stimuli as a function of increasing war zone stress, even when controlling for postdeployment posttraumatic stress disorder and depression severity. Short allele homozygotes appear especially sensitive to environmental influence, which likely contributes to the development of cognitive vulnerability to anxiety and mood disorders.
The Effect of Physical Cleaning on Threatened Morality in Individuals With Obsessive-Compulsive Disorder
Authors: Reuven Orna , Liberman Nira , Dar Reuven
Published: April 2013

The association between morality and physical cleansing has been demonstrated in a series of studies by Zhong and Liljenquist. We predicted that this association would be especially prominent in people with obsessive-compulsive disorder (OCD). Participants with OCD and matched control participants wrote about an immoral deed they had committed, after which half of the participants in each group cleaned their hands with a wipe. All participants were then offered an opportunity to help a fictitious graduate student by taking part in her experiment. Replicating previous findings, physical cleaning reduced the willingness to help and relieved moral emotions. As predicted, this effect was particularly prominent among participants with OCD. We discuss two processes that may account for the association between morality and cleanliness in general and particularly in the context of OCD: embodiment of morality in terms of physical cleanliness and assigning abstract meaning to the physical actions of cleaning.
Neglected evidence in idiopathic pulmonary fibrosis: from history to earlier diagnosis
Authors: Cordier Jean-François , Cottin Vincent
Published: April 2013

This perspective highlights some evidence that has hitherto been neglected, especially because it may not have been sufficiently explicated in the clinical respiratory medicine literature. Idiopathic pulmonary fibrosis (IPF) has appeared only in the second half of the 20th century and, like lung cancer and chronic obstructive pulmonary disease, may be a direct consequence of the cigarette smoking epidemic. It is a disease of lung ageing, with most affected patients being >70 years of age. The relationship between lung ageing and pulmonary fibrosis is further illustrated in the bleomycin mouse model, in which older males develop more fibrosis than young female mice.

Earlier diagnosis of IPF is a prerequisite for significant progress to be made in the long-term outcome and prognosis. We consider that only two different yet complementary and realistic approaches could lead to earlier diagnosis of IPF and possibly to allowing more efficient disease management: 1) investigating any patients with early Velcro crackles at lung auscultation through proactive education of, and commitment from, primary care physicians; and 2) using current large-scale lung cancer screening strategies with low-dose high-resolution computed tomography in smokers for the detection of subclinical interstitial lung disease and especially early IPF.
The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study
Authors: Hoefsloot Wouter , van Ingen Jakko , Andrejak Claire , Ängeby Kristian , Bauriaud Rosine , Bemer Pascale , Beylis Natalie , Boeree Martin J. , Cacho Juana , Chihota Violet , Chimara Erica , Churchyard Gavin , Cias Raquel , Daza Rosa , Daley Charles L. , Dekhuijzen P.N. Richard , Domingo Diego , Drobniewski Francis , Esteban Jaime , Fauville-Dufaux Maryse , Folkvardsen Dorte Bek , Gibbons Noel , Gómez-Mampaso Enrique , Gonzalez Rosa , Hoffmann Harald , Hsueh Po-Ren , Indra Alexander , Jagielski Tomasz , Jamieson Frances , Jankovic Mateja , Jong Eefje , Keane Joseph , Koh Wo-Jung , Lange Berit , Leao Sylvia , Macedo Rita , Mannsåker Turid , Marras Theodore K. , Maugein Jeannette , Milburn Heather J. , Mlinkó Tamas , Morcillo Nora , Morimoto Kozo , Papaventsis Dimitrios , Palenque Elia , Paez-Peña Mar , Piersimoni Claudio , Polanová Monika , Rastogi Nalin , Richter Elvira , Ruiz-Serrano Maria Jesus , Silva Anabela , da Silva M. Pedro , Simsek Hulya , van Soolingen Dick , Szabó Nora , Thomson Rachel , Tórtola Fernandez Teresa , Tortoli Enrico , Totten Sarah E. , Tyrrell Greg , Vasankari Tuula , Villar Miguel , Walkiewicz Renata , Winthrop Kevin L. , Wagner Dirk
Published: April 2013

A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide.

To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials Group (NET) framework (www.ntm-net.org), a branch of the Tuberculosis Network European Trials Group (TB-NET), provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualised the relative distribution of the different NTM found per continent and per country.

We received species identification data for 20 182 patients, from 62 laboratories in 30 countries across six continents. 91 different NTM species were isolated.Mycobacterium aviumcomplex (MAC) bacteria predominated in most countries, followed byM. gordonaeandM. xenopi. Important differences in geographical distribution of MAC species as well asM. xenopi, M. kansasiiand rapid-growing mycobacteria were observed.

This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differed by country within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location.
Aetiology of paediatric pneumonia after the introduction of pneumococcal conjugate vaccine
Authors: Elemraid Mohamed A. , Sails Andrew D. , Eltringham Gary J.A. , Perry John D. , Rushton Stephen P. , Spencer David A. , Thomas Matthew F. , Eastham Katherine M. , Hampton Fiona , Gennery Andrew R. , Clark Julia E.
Published: April 2013

We describe the aetiology of community-acquired pneumonia in children before and after the introduction of the pneumococcal conjugate vaccination (PCV) programme in 2006.

Prospective studies were conducted in 2001–2002 (pre-vaccine) and 2009–2011 (post-vaccine) of children aged 0–16 years with radiologically confirmed pneumonia seen in hospital. Investigations included culture, serology, immunofluorescence antibody and urine antigen testing, with an increased use of PCR assays and expanded panels of pathogens in the post-vaccine study.

241 and 160 children were enrolled in the pre- and post-vaccine studies, respectively (73% aged <5 years). Identification of a causative pathogen was higher post-vaccination (61%) than pre-vaccination (48.5%) (p=0.019). Rates of bacterial infections were not different between post- and pre-vaccine studies (17.5%versus24%, p=0.258). Viral (31%) and mixed (12.5%) infections were found more often post-vaccination (19.5%, p=0.021) than pre-vaccination (5%, p=0.015). Rates of identified pneumococcal infections were comparable between pre- and post-vaccine studies (14.7%versus17.4%, p=0.557). Diagnosis of pneumococcal infection post-vaccination improved when PCR was used compared to culture (21.6%versus6%, p=0.0004). Serotypes included in PCV13 but not PCV7 were identified in 75% (18 out of 24) post-vaccination.

Infection with nonvaccine pneumococcal serotypes continues to be a significant cause of pneumonia in children in the UK.
Hermite-Hadamard-type inequalities for "Equation missing" -convex dominated functions
Authors: Özdemir Muhamet Emin , Gürbüz Mustafa , Kavurmacı Havva
Published: April 2013

In this paper, we introduce the notion of

(
g
,

φ
h

)

-convex dominated function and present some properties of them. Finally, we present a version of Hermite-Hadamard-type inequalities for

(
g
,

φ
h

)

-convex dominated functions. Our results generalize the Hermite-Hadamard-type inequalities in Dragomir et al. (Tamsui Oxford Univ. J. Math. Sci. 18(2):161-173, 2002), Kavurmacı et al. (New Definitions and Theorems via Different Kinds of Convex Dominated Functions, 2012) and Özdemir et al. (Two new different kinds of convex dominated functions and inequalities via Hermite-Hadamard type, 2012).

MSC:26D15, 26D10, 05C38.
Convergent evolution of [D-Leucine1] microcystin-LR in taxonomically disparate cyanobacteria
Authors: Shishido Tânia Keiko , Kaasalainen Ulla , Fewer David P , Rouhiainen Leo , Jokela Jouni , Wahlsten Matti , Fiore Marli Fátima , Yunes João Sarkis , Rikkinen Jouko , Sivonen Kaarina
Published: April 2013

Background

Many important toxins and antibiotics are produced by non-ribosomal biosynthetic pathways. Microcystins are a chemically diverse family of potent peptide toxins and the end-products of a hybrid NRPS and PKS secondary metabolic pathway. They are produced by a variety of cyanobacteria and are responsible for the poisoning of humans as well as the deaths of wild and domestic animals around the world. The chemical diversity of the microcystin family is attributed to a number of genetic events that have resulted in the diversification of the pathway for microcystin assembly.

Results

Here, we show that independent evolutionary events affecting the substrate specificity of the microcystin biosynthetic pathway have resulted in convergence on a rare [D-Leu1] microcystin-LR chemical variant. We detected this rare microcystin variant from strains of the distantly related genera Microcystis, Nostoc, and Phormidium. Phylogenetic analysis performed using sequences of the catalytic domains within the mcy gene cluster demonstrated a clear recombination pattern in the adenylation domain phylogenetic tree. We found evidence for conversion of the gene encoding the McyA2 adenylation domain in strains of the genera Nostoc and Phormidium. However, point mutations affecting the substrate-binding sequence motifs of the McyA2 adenylation domain were associated with the change in substrate specificity in two strains of Microcystis. In addition to the main [D-Leu1] microcystin-LR variant, these two strains produced a new microcystin that was identified as [Met1] microcystin-LR.

Conclusions

Phylogenetic analysis demonstrated that both point mutations and gene conversion result in functional mcy gene clusters that produce the same rare [D-Leu1] variant of microcystin in strains of the genera Microcystis, Nostoc, and Phormidium. Engineering pathways to produce recombinant non-ribosomal peptides could provide new natural products or increase the activity of known compounds. Our results suggest that the replacement of entire adenylation domains could be a more successful strategy to obtain higher specificity in the modification of the non-ribosomal peptides than point mutations.
Evolution and variability of Solanum RanGAP2, a cofactor in the incompatible interaction between the resistance protein GPA2 and the Globodera pallida effector Gp-RBP-1
Authors: Carpentier Jean , Grenier Eric , Esquibet Magalie , Hamel Louis-Philippe , Moffett Peter , Manzanares-Dauleux Maria J , Kerlan Marie-Claire
Published: April 2013

Background

The Ran GTPase Activating Protein 2 (RanGAP2) was first described as a regulator of mitosis and nucleocytoplasmic trafficking. It was then found to interact with the Coiled-Coil domain of the Rx and GPA2 resistance proteins, which confer resistance to Potato Virus X (PVX) and potato cyst nematode Globodera pallida, respectively. RanGAP2 is thought to mediate recognition of the avirulence protein GP-RBP-1 by GPA2. However, the Gpa2-induced hypersensitive response appears to be relatively weak and Gpa2 is limited in terms of spectrum of efficiency as it is effective against only two nematode populations. While functional and evolutionary analyses of Gp-Rbp-1 and Gpa2 identified key residues in both the resistance and avirulence proteins that are involved in recognition determination, whether variation in RanGAP2 also plays a role in pathogen recognition has not been investigated.

Results

We amplified a total of 147 RanGAP2 sequences from 55 accessions belonging to 18 different di-and tetraploid Solanum species from the section Petota. Among the newly identified sequences, 133 haplotypes were obtained and 19.1% of the nucleotide sites were found to be polymorphic. The observed intra-specific nucleotide diversity ranges from 0.1 to 1.3%. Analysis of the selection pressures acting on RanGAP2 suggests that this gene evolved mainly under purifying selection. Nonetheless, we identified polymorphic positions in the protein sequence at the intra-specific level, which could modulate the activity of RanGAP2. Two polymorphic sites and a three amino-acid deletion in RanGAP2 were found to affect the timing and intensity of the Gpa2-induced hypersensitive response to avirulent GP-RBP-1 variants even though they did not confer any gain of recognition of virulent GP-RBP-1 variants.

Conclusions

Our results highlight how a resistance gene co-factor can manage in terms of evolution both an established role as a cell housekeeping gene and an implication in plant parasite interactions. StRanGAP2 gene appears to evolve under purifying selection. Its variability does not seem to influence the specificity of GPA2 recognition but is able to modulate this activity by enhancing the defence response. It seems therefore that the interaction with the plant resistance protein GPA2 (and/or Rx) rather than with the nematode effector was the major force in the evolution of the RanGAP2 locus in potato. From a mechanistic point of view these results are in accordance with a physical interaction of RanGAP2 with GPA2 and suggest that RBP-1 would rather bind the RanGAP2-GPA2 complex than the RanGAP2 protein alone.
Bone formation in rabbit cancellous bone explant culture model is enhanced by mechanical load
Authors: Zong ming Wan , Jian yu Li , Rui xin Li , Hao Li , Yong Guo , Lu Liu , Xin chang Zhang , Xi zheng Zhang
Published: April 2013

Background

When studying and designing an artificial bone in vitro with similar features and functionality of natural bone by tissue engineering technology, the culturing environment, especially the mechanical environment is supposed to be an important factor, because a suitable mechanical environment in vitro may improve the adaptability of the planted-in tissue engineering bone in the body. Unfortunately, up to now, the relationship between mechanical stimuli and natural bone growth has not yet been precisely determined, and it is so imperative for a prior study on effect of mechanical loading on growth of the natural bone cultured in vitro.

Methods

Under sterile conditions, explant models of rabbit cancellous bone with 3 mm in thickness and 8 mm in diameter were prepared and cultured in a dynamic loading and circulating perfusion bioreactor system. By Micro-CT scanning, a 3D model for finite element (FEM) analysis was achieved. According to the results of FEM analysis and physiological load bearing capacity of the natural bone, these models were firstly subjected to mechanical load with 1Hz frequency causing average apparent strain of 1000 μϵ, 2000 μϵ, 3000 μϵ and 4000 μϵ respectively for 30 min every day, activities of alkaline phosphatase (AKP) were detected on the 5th and the 14th loading day and on the 14th and the 21st day, mechanical properties, tissue mineral density (TMD) of the bone explant models were investigated and Von-kossa staining and fluorescence double labeling assays were conducted to evaluate whether there were fresh osteoid in the bone explant models. In addition, Western blot, Elisa and Real-time PCR were employed to analyze expression of Collagen-I (COL-1), bone morphogenetic protein-2 (BMP-2) and osteoprotegerin (OPG) protein and RNA.

Results

The explant models of rabbit cancellous bone prepared under sterile conditions grew well in the bioreactor system. With the increasing culturing time and load levels, bone explant models in groups with 1000 μϵ and 2000 μϵ average apparent strain experienced improving mechanical properties and TMD (P<0.05), and results of Von-kossa staining and fluorescence double labeling also showed apparent fresh osteoid formation. Under the same loading conditions, a up-regulations in protein and RNA of COL-1, BMP-2 and OPG were detected, especially, relative genes notably expressed after 21 days.

Conclusion

Our study demonstrated that mechanical load could improve function and activity of osteoblasts in explant models of cancellous bone. Through regulations of COL-1, OPG and BMP-2 secreted by osteoblasts, the mechanical load could improve the tissue structural density and stiffness due to formation of fresh osteoid.
PAG/Cbp suppression reveals a contribution of CTLA-4 to setting the activation threshold in T cells
Authors: Smida Michal , Cammann Clemens , Gurbiel Slavyana , Kerstin Nadja , Lingel Holger , Lindquist Sabine , Simeoni Luca , Brunner-Weinzierl Monika C , Suchanek Miloslav , Schraven Burkhart , Lindquist Jonathan A
Published: April 2013

Background

PAG/Cbp represents a ubiquitous mechanism for regulating Src family kinases by recruiting Csk to the plasma membrane, thereby controlling cellular activation. Since Src kinases are known oncogenes, we used RNA interference in primary human T cells to test whether the loss of PAG resulted in lymphocyte transformation.

Results

PAG-depletion enhanced Src kinase activity and augmented proximal T-cell receptor signaling; exactly the phenotype expected for loss of this negative regulator. Surprisingly, rather than becoming hyper-proliferative, PAG-suppressed T cells became unresponsive. This was mediated by a Fyn-dependent hyper-phosphorylation of the inhibitory receptor CTLA-4, which recruited the protein tyrosine phosphatase Shp-1 to lipid rafts. Co-suppression of CTLA-4 abrogates this inhibition and restores proliferation to T cells.

Conclusion

We have identified a fail-safe mechanism as well as a novel contribution of CTLA-4 to setting the activation threshold in T cells.
Bio-fabrication of gold nanoparticles using aqueous extract of red tomato and its use as a colorimetric sensor
Authors: Barman Gadadhar , Maiti Swarnali , Laha Jayasree Konar
Published: April 2013

In this work, we report a green method for the synthesis of gold nanoparticles (GNP) using the aqueous extract of red tomato (Lycopersicon esculentum). We believe that citric acid and ascorbic acid present in tomato juice are responsible for the reduction of gold ions. This biosynthesized GNP in the presence of sodium dodecyl sulfate has been used as a colorimetric sensor to detect and estimate the pesticide, methyl parathion. The GNP in the presence of methyl parathion shows a new peak at 400 nm due to the formation of 4-nitrophenolate ion by catalytic hydrolysis of methyl parathion in alkaline medium. A calibration curve between the absorption coefficients of the 400-nm peak versus the concentration of the pesticide allows the quantitative estimation of the 4-nitrophenolate ion, thereby enabling indirect estimation of methyl parathion present in the system.
Mixed protein-templated luminescent metal clusters (Au and Pt) for H2O2 sensing
Authors: Li Min , Yang Da-Peng , Wang Xiansong , Lu Jianxin , Cui Daxiang
Published: April 2013

A simple and cost-effective method to synthesize the luminescent noble metal clusters (Au and Pt) in chicken egg white aqueous solution at room temperature is reported. The red-emitting Au cluster is used as fluorescent probe for sensitive detection of H2O2.
miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs
Authors: Riaz Muhammad , van Jaarsveld Marijn TM , Hollestelle Antoinette , Prager-van der Smissen Wendy JC , Heine Anouk AJ , Boersma Antonius WM , Liu Jingjing , Helmijr Jean , Ozturk Bahar , Smid Marcel , Wiemer Erik A , Foekens John A , Martens John WM
Published: April 2013

Introduction

Breast cancer is a genetically and phenotypically complex disease. To understand the role of miRNAs in this molecular complexity, we performed miRNA expression analysis in a cohort of molecularly well-characterized human breast cancer cell lines to identify miRNAs associated with the most common molecular subtypes and the most frequent genetic aberrations.

Methods

Using a microarray carrying LNA™ modified oligonucleotide capture probes), expression levels of 725 human miRNAs were measured in 51 breast cancer cell lines. Differential miRNA expression was explored by unsupervised cluster analysis and was then associated with the molecular subtypes and genetic aberrations commonly present in breast cancer.

Results

Unsupervised cluster analysis using the most variably expressed miRNAs divided the 51 breast cancer cell lines into a major and a minor cluster predominantly mirroring the luminal and basal intrinsic subdivision of breast cancer cell lines. One hundred and thirteen miRNAs were differentially expressed between these two main clusters. Forty miRNAs were differentially expressed between basal-like and normal-like/claudin-low cell lines. Within the luminal-group, 39 miRNAs were associated with ERBB2 overexpression and 24 with E-cadherin gene mutations, which are frequent in this subtype of breast cancer cell lines. In contrast, 31 miRNAs were associated with E-cadherin promoter hypermethylation, which, contrary to E-cadherin mutation, is exclusively observed in breast cancer cell lines that are not of luminal origin. Thirty miRNAs were associated with p16
INK4
status while only a few miRNAs were associated with BRCA1, PIK3CA/PTEN and TP53 mutation status. Twelve miRNAs were associated with DNA copy number variation of the respective locus.

Conclusion

Luminal-basal and epithelial-mesenchymal associated miRNAs determine the subdivision of miRNA transcriptome of breast cancer cell lines. Specific sets of miRNAs were associated with ERBB2 overexpression, p16
INK4a
or E-cadherin mutation or E-cadherin methylation status, which implies that these miRNAs may contribute to the driver role of these genetic aberrations. Additionally, miRNAs, which are located in a genomic region showing recurrent genetic aberrations, may themselves play a driver role in breast carcinogenesis or contribute to a driver gene in their vicinity. In short, our study provides detailed molecular miRNA portraits of breast cancer cell lines, which can be exploited for functional studies of clinically important miRNAs.
A comparative study of varying doses of enoxaparin for thromboprophylaxis in critically ill patients: a double-blinded, randomised controlled trial
Authors: Robinson Sian , Zincuk Aleksander , Larsen Ulla Lei , Ekstrøm Claus , Nybo Mads , Rasmussen Bjarne , Toft Palle
Published: April 2013

Introduction

Critically ill patients are predisposed to venous thromboembolism. We hypothesized that higher doses of enoxaparin would improve thromboprophylaxis without increasing the risk of bleeding. Peak anti-factor Xa (anti-Xa) levels of 0.1 to 0.4 IU/ml reflect adequate thromboprophylaxis for general ward patients. Studies conducted in orthopaedic patients demonstrated a statistically significant relationship between anti-Xa levels and wound haematoma and thrombosis. Corresponding levels for critically ill patients may well be higher, but have never been validated in large studies.

Methods

Eighty critically ill patients weighing 50 to 90 kilograms were randomised in a double-blinded study to receive subcutaneous (sc) enoxaparin: 40 mg once daily (QD), 30 mg twice daily (BID), 40 mg BID, or 1 mg/kg QD, each administered for three days. Anti-Xa activity was measured at baseline, and daily at 4, 12, 16 and 24 hours post administration. Antithrombin, fibrinogen, and platelets were measured at baseline and twice daily thereafter.

Results

Two patients were transferred prior to participation. On day 1, doses of 40 mg QD (n = 20) and 40 mg BID (n = 19) yielded mean peak anti-Xa of 0.20 IU/ml and 0.17 IU/ml respectively. A dose of 30 mg BID (n = 20) resulted in much lower levels (0.08 IU/ml). Patients receiving 1 mg/kg QD (n = 19) achieved near steady-state mean peak anti-Xa levels from day 1 (0.34 IU/ml). At steady state (day 3), mean peak anti-Xa levels of 0.13 IU/ml and 0.15 IU/ml were achieved with doses of 40 mg QD and 30 mg BID respectively. This increased significantly to 0.33 IU/ml and 0.40 IU/ml for doses of 40 mg BID and 1 mg/kg QD respectively. Thus anti-Xa response profiles differed significantly over the three days between enoxaparin treatment groups (P <0.0001). Doses of 40 mg BID and1 mg/kg QD enoxaparin yielded target anti-Xa levels for over 80% of the study period. There were no adverse effects.

Conclusions

Doses of 40 mg QD enoxaparin (Europe) or 30 mg BID (North America) yield levels of anti-Xa which may be inadequate for critically ill patients. A weight-based dose yielded the best anti-Xa levels without bioaccumulation, and allowed the establishment of near steady-state levels from the first day of enoxaparin administration.

Trial registration

Current Controlled Trials ISRCTN91570009.
Increased survival of cirrhotic patients with septic shock
Authors: Sauneuf Bertrand , Champigneulle Benoit , Soummer Alexis , Mongardon Nicolas , Charpentier Julien , Cariou Alain , Chiche Jean-Daniel , Mallet Vincent , Mira Jean-Paul , Pène Frédéric
Published: April 2013

Introduction

The overall outcome of septic shock has been recently improved. We sought to determine whether this survival gain extends to the high-risk subgroup of patients with cirrhosis.

Methods

Cirrhotic patients with septic shock admitted to a medical intensive care unit (ICU) during two consecutive periods (1997-2004 and 2005-2010) were retrospectively studied.

Results

Forty-seven and 42 cirrhotic patients presented with septic shock in 1997-2004 and 2005-2010, respectively. The recent period differed from the previous one by implementation of adjuvant treatments of septic shock including albumin infusion as fluid volume therapy, low-dose glucocorticoids, and intensive insulin therapy. ICU and hospital survival markedly improved over time (40% in 2005-2010 vs. 17% in 1997-2004, P = 0.02 and 29% in 2005-2010 vs. 6% in 1997-2004, P = 0.009, respectively). Furthermore, this survival gain in the latter period was sustained for 6 months (survival rate 24% in 2005-2010 vs. 6% in 1997-2004, P = 0.06). After adjustment with age, the liver disease stage (Child-Pugh score), and the critical illness severity score (SOFA score), ICU admission between 2005 and 2010 remained an independent favorable prognostic factor (odds ratio (OR) 0.09, 95% confidence interval (CI) 0.02-0.4, P = 0.004). The stage of the underlying liver disease was also independently associated with hospital mortality (Child-Pugh score: OR 1.42 per point, 95% CI 1.06-1.9, P = 0.018).

Conclusions

In the light of advances in management of both cirrhosis and septic shock, survival of such patients substantially increased over recent years. The stage of the underlying liver disease and the related therapeutic options should be included in the decision-making process for ICU admission.
Pbx and Prdm1a transcription factors differentially regulate subsets of the fast skeletal muscle program in zebrafish
Authors: Yao Zizhen , Farr, Gist H. , Tapscott Stephen J. , Maves Lisa
Published: April 2013

The basic helix–loop–helix factor Myod initiates skeletal muscle differentiation by directly and sequentially activating sets of muscle differentiation genes, including those encoding muscle contractile proteins. We hypothesize that Pbx homeodomain proteins direct Myod to a subset of its transcriptional targets, in particular fast-twitch muscle differentiation genes, thereby regulating the competence of muscle precursor cells to differentiate. We have previously shown that Pbx proteins bind with Myod on the promoter of the zebrafish fast muscle gene mylpfa and that Pbx proteins are required for Myod to activate mylpfa expression and the fast-twitch muscle-specific differentiation program in zebrafish embryos. Here we have investigated the interactions of Pbx with another muscle fiber-type regulator, Prdm1a, a SET-domain DNA-binding factor that directly represses mylpfa expression and fast muscle differentiation. The prdm1a mutant phenotype, early and increased fast muscle differentiation, is the opposite of the Pbx-null phenotype, delayed and reduced fast muscle differentiation. To determine whether Pbx and Prdm1a have opposing activities on a common set of genes, we used RNA-seq analysis to globally assess gene expression in zebrafish embryos with single- and double-losses-of-function for Pbx and Prdm1a. We find that the levels of expression of certain fast muscle genes are increased or approximately wild type in pbx2/4-MO;prdm1a−/− embryos, suggesting that Pbx activity normally counters the repressive action of Prdm1a for a subset of the fast muscle program. However, other fast muscle genes require Pbx but are not regulated by Prdm1a. Thus, our findings reveal that subsets of the fast muscle program are differentially regulated by Pbx and Prdm1a. Our findings provide an example of how Pbx homeodomain proteins act in a balance with other transcription factors to regulate subsets of a cellular differentiation program.
The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2
Authors: Van Rijssel Jos , Timmerman Ilse , Van Alphen Floris P. J. , Hoogenboezem Mark , Korchynskyi Olexandr , Geerts Dirk , Geissler Judy , Reedquist Kris A. , Niessen Hans W. M. , Van Buul Jaap D.
Published: April 2013

Inflammation is characterized by endothelium that highly expresses numerous adhesion molecules to trigger leukocyte extravasation. Central to this event is increased gene transcription. Small Rho-GTPases not only control the actin cytoskeleton, but are also implicated in gene regulation. However, in inflammation, it is not clear how this is regulated. Here, we show that the guanine-nucleotide exchange factor Trio expression is increased upon inflammatory stimuli in endothelium. Additionally, increased Trio expression was found in the vessel wall of rheumatoid arthritis patients. Trio silencing impaired VCAM-1 expression. Finally, we excluded that Trio-controlled VCAM-1 expression used the classical NFκB or MAP-kinase pathways, but rather acts on the transcriptional level by increasing phosphorylation and nuclear translocalization of Ets2. These data implicate Trio in regulating inflammation and provide novel targets for therapeutic purposes to treat inflammatory diseases such as rheumatoid arthritis.
Evidence against a germ plasm in the milkweed bugOncopeltus fasciatus, a hemimetabolous insect
Authors: Ewen-Campen Ben , Jones Tamsin E. M. , Extavour Cassandra G.
Published: April 2013

Primordial germ cell (PGC) formation in holometabolous insects like Drosophila melanogaster relies on maternally synthesised germ cell determinants that are asymmetrically localised to the oocyte posterior cortex. Embryonic nuclei that inherit this “germ plasm” acquire PGC fate. In contrast, historical studies of basally branching insects (Hemimetabola) suggest that a maternal requirement for germ line genes in PGC specification may be a derived character confined principally to Holometabola. However, there have been remarkably few investigations of germ line gene expression and function in hemimetabolous insects. Here we characterise PGC formation in the milkweed bug Oncopeltus fasciatus, a member of the sister group to Holometabola, thus providing an important evolutionary comparison to members of this clade. We examine the transcript distribution of orthologues of 19 Drosophila germ cell and/or germ plasm marker genes, and show that none of them localise asymmetrically within Oncopeltus oocytes or early embryos. Using multiple molecular and cytological criteria, we provide evidence that PGCs form after cellularisation at the site of gastrulation. Functional studies of vasa and tudor reveal that these genes are not required for germ cell formation, but that vasa is required in adult males for spermatogenesis. Taken together, our results provide evidence that Oncopeltus germ cells may form in the absence of germ plasm, consistent with the hypothesis that germ plasm is a derived strategy of germ cell specification in insects.
Annulation of 2H-Pyran onto 1-Oxa- or 1-Azacyclohexane-2,4-diones and Their Analogues via Sequential Condensation with α-Substituted Enals and 6π-Electrocyclization
Authors: Hossain Md Imran , Shaban Elkhabiry , Ikemi Taku , Peng Wei , Kawafuchi Hiroyuki , Inokuchi Tsutomu
Published: April 2013

2H-Pyrans are constructed on a 1-oxa- or 1-azacyclohexane-2,4-dione core via Knoevenagel condensation with enals followed by 6π-electrocyclization, which are readily catalyzed with ethylenediammonium diacetate. This formal [3 + 3] strategy constitutes C–O and C–C bond making and the diastereomer formation is circumvented using 6,6-disubstitution with the same aryl group in the 1-oxacyclohexane-2,4-diones. This facile methodology significantly advances the access to polysubstituted bicyclic 2H-pyrans with a versatile substrate choice and improved stability of the product.