bluuebunny/crossref_metadata_2025 huggingface dataset:
How much democracy does journalism need?
Authors: Josephi Beate
Published: October 2012

In posing the question ‘How much democracy does journalism need?’, much depends on the definition of journalism. This article suggests that journalism should be viewed not in terms of media systems but instead using journalism practice as the main frame of reference, as this allows for an appreciation of journalism beyond the confines of western democratic countries. The analysis of historical and current examples shows that journalism offering accurate and verified information resting on independent news judgement also happens in places that are deemed semi- or non-democratic. This article argues that it is not the political form of democracy that is essential to journalism but the freedom of expression and relative journalistic autonomy afforded to media workers. Democracies, as compellingly shown in recent years, may offer the legal framework for freedom of speech but they do not offer protection for journalistic services which have to be largely financed privately. The dependency on media owners is no less in many democratic nations than it is in non-democratic countries. Most importantly, journalism needs supporters who see value in independent information provision and credible news judgement.
Hierarchical linear modeling: Applications to social work research
Authors: Putnam-Hornstein Emily
Published: October 2012

Using examples and nomenclature familiar to social workers, this article provides a brief, nontechnical introduction to hierarchically structured data and multilevel modeling.

Findings

Data structured hierarchically consist of units clustered within higher-level groups, such as individuals nested within families and families nested within counties. Longitudinal observations can also be thought of as having a hierarchical structure, with repeated measures clustered within a given individual. Because lower-level units within a group tend to be systematically more similar to one another than to units from another group, there is often a need to make statistical adjustments for within-group dependence. Hierarchical or multilevel modeling provides a method for researchers to account for possible within-group correlations while also explicitly modeling group-level attributes and membership, acknowledging the potential importance of contextual effects on lower-level outcomes.

Applications

Although hierarchical or multilevel modeling has been discussed (and used) extensively by researchers in other disciplines and fields, it has been more recently adopted as a modeling tool by social work researchers. Because hierarchical modeling is now a commonly employed technique, it is important that those in the field have a basic understanding of these models so that they remain informed consumers of research. This article offers a conceptual overview of hierarchical linear models written for social work practitioners, policy-makers, and other consumers of social welfare research.
The Relationship Between Work Engagement and Performance
Authors: Kim Woocheol , Kolb Judith A. , Kim Taesung
Published: October 2012

Engagement has been defined in a variety of ways. Engagement in the workplace generally is viewed as a positive, fulfilling, affective-motivational state of work-related well-being. Due to its structural relationship between antecedents (e.g., job resources and personal resources) and consequences (e.g., performance and turnover intention), work engagement has been receiving considerable attention from both scholars and practitioners in the fields of human resource development (HRD), organization development (OD), psychology, and business. In spite of this popularity, there is a scarcity of empirical research on work engagement in the academic literature. The relationship between work engagement and performance, in particular, is deserving of attention given our field’s focus on performance improvement. In this article, we review and analyze relevant research and then propose a research agenda to guide future research on this topic. Conclusions and implications for HRD and OD are discussed.
Violent Video Games, Delinquency, and Youth Violence
Authors: DeLisi Matt , Vaughn Michael G. , Gentile Douglas A. , Anderson Craig A. , Shook Jeffrey J.
Published: October 2012

Violent video game playing is correlated with aggression, but its relation to antisocial behavior in correctional and juvenile justice samples is largely unknown. Based on a data from a sample of institutionalized juvenile delinquents, behavioral and attitudinal measures relating to violent video game playing were associated with a composite measure of delinquency and a more specific measure of violent delinquency after controlling for the effects of screen time, years playing video games, age, sex, race, delinquency history, and psychopathic personality traits. Violent video games are associated with antisociality even in a clinical sample, and these effects withstand the robust influences of multiple correlates of juvenile delinquency and youth violence most notably psychopathy.
A genome-wide survey for prion-regulated miRNAs associated with cholesterol homeostasis
Authors: Montag Judith , Brameier Markus , Schmädicke Ann-Christin , Gilch Sabine , Schätzl Hermann M , Motzkus Dirk
Published: October 2012

Background

Prion diseases are neurodegenerative diseases that are characterized by the conversion of the cellular prion protein (PrPc) into a pathogenic isoform (PrPSc). It is known that neurodegeneration is often accompanied by the disturbance of cholesterol homeostasis. We have recently identified a set of genes that were upregulated after prion infection of N2a neuronal cells (Bach et al., 2009).

Results

We have now used ultra-deep sequencing technology to profile all microRNAs (miRNA) that could be associated with this effect in these N2a cells. Using stringent filters and normalization strategies we identified a small set of miRNAs that were up- or downregulated upon prion infection. Using bioinformatic tools we predicted whether the downregulated miRNAs could target mRNAs that have been previously identified to enhance cholesterol synthesis in these cells. Application of this joint profiling approach revealed that nine miRNAs potentially target cholesterol-related genes. Four of those miRNAs are localized in a miRNA-dense cluster on the mouse X-chromosome. Among these, twofold downregulation of mmu-miR-351 and mmu-miR-542-5p was confirmed by qRT-PCR. The same miRNAs were predicted as putative regulators of the sterol regulatory element-binding factor 2 (Srebf2), the low-density lipoprotein receptor (Ldlr) or the IPP isomerase.

Conclusions

The results demonstrate that joined profiling by ultra-deep sequencing is highly valuable to identify candidate miRNAs involved in prion-induced dysregulation of cholesterol homeostasis.
Alternative mRNA fates identified in microRNA-associated transcriptome analysis
Authors: Carroll Adam P , Tran Nham , Tooney Paul A , Cairns Murray J
Published: October 2012

Background

MicroRNA (miRNA) are small non-coding RNA molecules which function as nucleic acid-based specificity factors in the universal RNA binding complex known as the RNA induced silencing complex (RISC). In the canonical gene-silencing pathway, these activated RISC particles are associated with RNA decay and gene suppression, however, there is evidence to suggest that in some circumstances they may also stabilise their target RNA and even enhance translation. To further explore the role of miRNA in this context, we performed a genome-wide expression analysis to investigate the molecular consequences of bidirectional modulation of the disease-associated miRNAs miR-181b and miR-107 in multiple human cell lines.

Results

This data was subjected to pathways analysis and correlated against miRNA targets predicted through seed region homology. This revealed a large number of both conserved and non-conserved miRNA target genes, a selection of which were functionally validated through reporter gene assays. Contrary to expectation we also identified a significant proportion of predicted target genes with both conserved and non-conserved recognition elements that were positively correlated with the modulated miRNA. Finally, a large proportion of miR-181b associated genes devoid of the corresponding miRNA recognition element, were enriched with binding motifs for the E2F1 transcription factor, which is encoded by a miR-181b target gene.

Conclusions

These findings suggest that miRNA regulate target genes directly through interactions with both conserved and non-conserved target recognition elements, and can lead to both a decrease and increase in transcript abundance. They also multiply their influence through interaction with transcription factor genes exemplified by the observed miR-181b/E2F1 relationship.
Comparison of methanogen diversity of yak (Bos grunniens) and cattle (Bos taurus) from the Qinghai-Tibetan plateau, China
Authors: Huang Xiao Dan , Tan Hui Yin , Long Ruijun , Liang Juan Boo , Wright André-Denis G
Published: October 2012

Background

Methane emissions by methanogen from livestock ruminants have significantly contributed to the agricultural greenhouse gas effect. It is worthwhile to compare methanogen from “energy-saving” animal (yak) and normal animal (cattle) in order to investigate the link between methanogen structure and low methane production.

Results

Diversity of methanogens from the yak and cattle rumen was investigated by analysis of 16S rRNA gene sequences from rumen digesta samples from four yaks (209 clones) and four cattle (205 clones) from the Qinghai-Tibetan Plateau area (QTP). Overall, a total of 414 clones (i.e. sequences) were examined and assigned to 95 operational taxonomic units (OTUs) using MOTHUR, based upon a 98% species-level identity criterion. Forty-six OTUs were unique to the yak clone library and 34 OTUs were unique to the cattle clone library, while 15 OTUs were found in both libraries. Of the 95 OTUs, 93 putative new species were identified. Sequences belonging to the Thermoplasmatales-affiliated Linage C (TALC) were found to dominate in both libraries, accounting for 80.9% and 62.9% of the sequences from the yak and cattle clone libraries, respectively. Sequences belonging to the Methanobacteriales represented the second largest clade in both libraries. However, Methanobrevibacter wolinii (QTPC 110) was only found in the cattle library. The number of clones from the order Methanomicrobiales was greater in cattle than in the yak clone library. Although the Shannon index value indicated similar diversity between the two libraries, the Libshuff analysis indicated that the methanogen community structure of the yak was significantly different than those from cattle.

Conclusion

This study revealed for the first time the molecular diversity of methanogen community in yaks and cattle in Qinghai-Tibetan Plateau area in China. From the analysis, we conclude that yaks have a unique rumen microbial ecosystem that is significantly different from that of cattle, this may also help to explain why yak produce less methane than cattle.
Cloning, ligand-binding, and temporal expression of ecdysteroid receptors in the diamondback moth, Plutella xylostella
Authors: Tang Baozhen , Dong Wei , Liang Pei , Zhou Xuguo , Gao Xiwu
Published: October 2012

Background

The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), is a devastating pest of cruciferous crops worldwide, and has developed resistance to a wide range of insecticides, including diacylhydrazine-based ecdysone agonists, a highly selective group of molt-accelerating biopesticides targeting the ecdysone receptors.

Result

In this study, we cloned and characterized the ecdysone receptors from P. xylostella, including the two isoforms of EcR and a USP. Sequence comparison and phylogenetic analysis showed striking conservations among insect ecdysone receptors, especially between P. xylostella and other lepidopterans. The binding affinity of ecdysteroids to in vitro- translated receptor proteins indicated that PxEcRB isoform bound specifically to ponasterone A, and the binding affinity was enhanced by co-incubation with PxUSP (K
d =3.0±1.7 nM). In contrast, PxEcRA did not bind to ponasterone A, even in the presence of PxUSP. The expression of PxEcRB were consistently higher than that of PxEcRA across each and every developmental stage, while the pattern of PxUSP expression is more or less ubiquitous.

Conclusions

Target site insensitivity, in which the altered binding of insecticides (ecdysone agonists) to their targets (ecdysone receptors) leads to an adaptive response (resistance), is one of the underlying mechanisms of diacylhydrazine resistance. Given the distinct differences at expression level and the ligand-binding capacity, we hypothesis that PxEcRB is the ecdysone receptor that controls the remodeling events during metamorphosis. More importantly, PxEcRB is the potential target site which is modified in the ecdysone agonist-resistant P. xylostella.
The spatial epidemiology of tuberculosis in Linyi City, China, 2005–2010
Authors: Wang Tao , Xue Fuzhong , Chen Yongjin , Ma Yunbo , Liu Yanxun
Published: October 2012

Background

Tuberculosis (TB) remains a major public health burden in many developing countries. China alone accounted for an estimated 12% of all incident TB cases worldwide in 2010. Several studies showed that the spatial distribution of TB was nonrandom and clustered. Thus, a spatial analysis was conducted with the aim to explore the spatial epidemiology of TB in Linyi City, which can provide guidance for formulating regional prevention and control strategies.

Methods

The study was based on the reported cases of TB, between 2005 and 2010. 35,308 TB cases were geo-coded at the town level (n = 180). The spatial empirical Bayes smoothing, spatial autocorrelation and space-time scan statistic were used in this analysis.

Results

Spatial distribution of TB in Linyi City from 2005 to 2010 was mapped at town level in the aspects of crude incidence, excess hazard and spatial smoothed incidence. The spatial distribution of TB was nonrandom and clustered with the significant Moran’s I for each year. Local G

i

* detected five significant spatial clusters for high incidence of TB. The space-time analysis identified one most likely cluster and nine secondary clusters for high incidence of TB.

Conclusions

There is evidence for the existence of statistically significant TB clusters in Linyi City, China. The result of this study may assist health departments to develop a better preventive strategy and increase the public health intervention’s effectiveness.
Association between bisphenol A exposure and body mass index in Chinese school children: a cross-sectional study
Authors: Wang He-xing , Zhou Ying , Tang Chuan-xi , Wu Jin-gui , Chen Yue , Jiang Qing-wu
Published: October 2012

Background

There is increasing evidence suggesting that Bisphenol A (BPA), one of the highest volume chemicals produced worldwide, can interfere with the body’s natural weight control mechanisms to promote obesity. However, epidemiological studies for this are limited, especially for children.

Methods

A cross-sectional study was conducted to investigate the association between BPA exposure and body mass index (BMI) in school children. Three primary and three middle schools were randomly selected from 26 primary and 30 middle candidate schools in Changning District of Shanghai City in China. According to the BMI-based criteria by age and sex for screening of overweight or obese children, we randomly chose 20 obese, 10 overweight, and 30 normal weight children aged 8-15 years of age from each selected school. First morning urine was collected and total urine BPA concentrations were determined by ultra-performance liquid chromatography tandem mass spectrometry. Multiple linear regression analysis was conducted to examine the association of urine BPA concentrations and daily intake estimates with BMI.

Results

BPA was detected in 84.9% of urine samples with a geometric mean of 0.45 ng/mL. The daily intake estimates ranged from 0.03 μg/day to 1.96 μg/day with a geometric mean of 0.37 μg/day. The average urine BPA concentrations and daily intake estimates were similar for boys and girls, but significantly higher in older children than younger ones, and showed an increasing trend with BMI. Multiple linear regression analyses showed that urine BPA concentrations were significantly associated with increasing BMI values in all subjects after adjustment for age and sex and the results were similar before and after corrected by urine specific gravity. When stratified by age or sex, the associations remained significant in females and in those 8-11 years of age before corrected by specific gravity. Similar results were shown for the association between BMI and daily intake estimates.

Conclusions

There is a possibility that BPA exposure increases BMI in school children. Given the cross-sectional nature of this study, longitudinal studies are warranted to confirm BPA exposure as a contributor to increased BMI in children.
Muscle cells challenged with saturated fatty acids mount an autonomous inflammatory response that activates macrophages
Authors: Pillon Nicolas J , Arane Karen , Bilan Philip J , Chiu Tim T , Klip Amira
Published: October 2012

Obesity is associated with chronic low-grade inflammation. Within adipose tissue of mice fed a high fat diet, resident and infiltrating macrophages assume a pro-inflammatory phenotype characterized by the production of cytokines which in turn impact on the surrounding tissue. However, inflammation is not restricted to adipose tissue and high fat-feeding is responsible for a significant increase in pro-inflammatory cytokine expression in muscle. Although skeletal muscle is the major disposer of dietary glucose and a major determinant of glycemia, the origin and consequence of muscle inflammation in the development of insulin resistance are poorly understood.

We used a cell culture approach to investigate the vectorial crosstalk between muscle cells and macrophages upon exposure to physiological, low levels of saturated and unsaturated fatty acids. Inflammatory pathway activation and cytokine expression were analyzed in L6 muscle cells expressing myc-tagged GLUT4 (L6GLUT4myc) exposed to 0.2 mM palmitate or palmitoleate. Conditioned media thereof, free of fatty acids, were then tested for their ability to activate RAW264.7 macrophages.

Palmitate -but not palmitoleate- induced IL-6, TNFα and CCL2 expression in muscle cells, through activation of the NF-κB pathway. Palmitate (0.2 mM) alone did not induce insulin resistance in muscle cells, yet conditioned media from palmitate-challenged muscle cells selectively activated macrophages towards a pro-inflammatory phenotype.

These results demonstrate that low concentrations of palmitate activate autonomous inflammation in muscle cells to release factors that turn macrophages pro-inflammatory. We hypothesize that saturated fat-induced, low-grade muscle cell inflammation may trigger resident skeletal muscle macrophage polarization, possibly contributing to insulin resistancein vivo.
Gene expression analysis of matched ovarian primary tumors and peritoneal metastasis
Authors: Malek Joel A , Martinez Alejandra , Mery Eliane , Ferron Gwenael , Huang Ruby , Raynaud Christophe , Jouve Eva , Thiery Jean-Paul , Querleu Denis , Rafii Arash
Published: October 2012

Background

Ovarian cancer is the most deadly gynecological cancer due to late diagnosis at advanced stage with major peritoneal involvement. To date most research has focused on primary tumor. However the prognosis is directly related to residual disease at the end of the treatment. Therefore it is mandatory to focus and study the biology of meatastatic disease that is most frequently localized to the peritoneal caivty in ovarian cancer.

Methods

We used high-density gene expression arrays to investigate gene expression changes between matched primary and metastatic (peritoneal) lesions.

Results

Here we show that gene expression profiles in peritoneal metastasis are significantly different than their matched primary tumor and these changes are affected by underlying copy number variation differences among other causes. We show that differentially expressed genes are enriched in specific pathways including JAK/STAT pathway, cytokine signaling and other immune related pathways. We show that underlying copy number variations significantly affect gene expression. Indeed patients with important differences in copy number variation displayed greater gene expression differences between their primary and matched metastatic lesions.

Conclusions

Our analysis shows a very specific targeting at both the genomic and transcriptomic level to upregulate certain pathways in the peritoneal metastasis of ovarian cancer. Moreover, while primary tumors use certain pathways we identify distinct differences with metastatic lesions. The variation between primary and metastatic lesions should be considered in personalized treatment of ovarian cancer.
Electrospray tandem mass spectrometric analysis of a dimeric conjugate, salvialeriafone and related compounds
Authors: Ghulam Musharraf Syed , Goher Madiha , Hussain Amjad , Choudhary M Iqbal
Published: October 2012

Background

Electrospray tandem mass spectrometry approach is widely used for the rapid characterization of natural products. This paper describes the gas-phased ESI-MS/MS fragmentation of abietane-type diterpenoids and their novel dimeric conjugate, salvialeriafone (1) using both positive and negative ion electrospray ionization quadropole time-of-flight mass spectrometry (ESI-QqTOF-MS/MS) hybrid instrument. Diterpenoids are widely distributed throughout the plant kingdom and posses interesting biological activities.

Results

ESI-QqTOF-MS (positive ion mode) of diterpenoids 1–6 under collision-induced dissociation tandem mass spectrometric analysis (CID-MS/MS) showed the characteristic losses of water, carbonmonoxide and propene molecules, while analysis in negative ion mode showed the characteristic losses of water, carbon monoxide, methane molecules and methyl radical. Results demonstrated the differences in the product ions and base peaks due to the differences in the skeleton. A novel dimeric conjugate, salvialeriafone (1) showed characteristic fragmentation pattern and was found to be more prone to form radical ions, as compared to monomeric diterpenoids. The fragmentation pathways of characteristic fragments were proposed with the aid of HRESIMS.

Conclusions

Extensive tandem mass spectrometric studies of salvialeriafone (1) and related diterpenoids 2–6 were conducted and their characteristic fragments were identified. The knowledge of the fragmentation pattern of these diterpenoids will be useful for the characterization of new dimers of this class of compounds.
Identification of inhibitors of ovarian cancer stem-like cells by high-throughput screening
Authors: Mezencev Roman , Wang Lijuan , McDonald John F
Published: October 2012

Background

Ovarian cancer stem cells are characterized by self-renewal capacity, ability to differentiate into distinct lineages, as well as higher invasiveness and resistance to many anticancer agents. Since they may be responsible for the recurrence of ovarian cancer after initial response to chemotherapy, development of new therapies targeting this special cellular subpopulation embedded within bulk ovarian cancers is warranted.

Methods

A high-throughput screening (HTS) campaign was performed with 825 compounds from the Mechanistic Set chemical library [Developmental Therapeutics Program (DTP)/National Cancer Institute (NCI)] against ovarian cancer stem-like cells (CSC) using a resazurin-based cell cytotoxicity assay. Identified sets of active compounds were projected onto self-organizing maps to identify their putative cellular response groups.

Results

From 793 screening compounds with evaluable data, 158 were found to have significant inhibitory effects on ovarian CSC. Computational analysis indicates that the majority of these compounds are associated with mitotic cellular responses.

Conclusions

Our HTS has uncovered a number of candidate compounds that may, after further testing, prove effective in targeting both ovarian CSC and their more differentiated progeny.
Evaluation of parenteral nutritional support in the surgical and medical wards of a referral teaching hospital
Authors: Bairami Samaneh , Elyasi Sepideh , Khalili Hossein , Jamali-Moghadam Saeed Reza
Published: October 2012

Background and purpose

Malnutrition is a common problem in patients who are hospitalized in surgical and medical wards. Surgical patients, geriatric populations and individuals with severe illness are more vulnerable to malnutrition during their hospitalization course.

The purpose of this study was evaluation of parenteral nutrition services in a referral teaching hospital, Tehran, Iran.

Method

Medical records of 72 patients who received parenteral nutrition during one year period in different surgical and medical wards of Imam Khomeini hospital were reviewed retrospectively by clinical pharmacists. Criteria for initiation of parenteral nutrition, selection of appropriate formulation and monitoring parameters were assessed based on the American Society of Parenteral and Enteral Nutrition recommendations.

Results

Based on the patients' anthropometric parameters and serum albumin levels, 4.2%, 75% and 20.8% of the patients were well-nourished, moderately malnourished and severely malnourished respectively at the hospital admission and before nutritional support. Adequate calorie, protein, carbohydrate and lipid supports were achieved in 21.1%, 32.4%, 23.7% and 10.5% of the patients respectively. About 91% of the patients experienced at least one complication of the nutritional support.

Conclusion

In this evaluation, several errors in assessment, establishing goals, and monitoring of parenteral nutrition regimens have been detected. Approximately all of the patients did not receive to the trace elements supports goals.
The German ban on GM maize MON810: scientifically justified or unjustified?
Authors: Bøhn Thomas , Primicerio Raul , Traavik Terje
Published: October 2012

The ongoing controversies over genetically modified organisms (GMOs) in Europe remain intense. Assessing the risks associated with new technologies is crucial, and becomes particularly important for self-replicating GMOs used in open ecosystems. In general, scientific disagreement and debate is at the core of knowledge generation. However, in the GMO debate, it seems that pre-conceived conclusions can in some cases overshadow real data and factual results of investigations. In this article, we describe how the German ban on the cultivation of MON810 Bt-transgenic maize plant has been criticized for not having a sound scientific justification and provide arguments for why we disagree with this perspective. We do this by demonstrating in detail how arguments put forward by Agnes Ricroch and colleagues in an article from Transgenic Research are based on i) serious scientific flaws, such as omitting core results and misrepresenting others; ii) inconsistency in how laboratory studies that show negative effects of GM plant exposure should be followed up; and iii) a systematic selection of particular results and/or studies that match their own arguments. We conclude that Ricroch et al. misrepresent and selectively scrutinize certain data only. The effect of this double standard is that those only reading or referring to Ricroch et al. will be seriously misinformed about our study as well as in the discussion on the 2009 German ban of the MON810 GM maize. However, we do not claim that the ban was finally and irreversibly justified by the science referred to, including our own studies within the field. The German ban on MON810 was, and must be, a political decision, guided by valid scientific evidence.
Osteogenesis and osteoclast inhibition in rheumatoid arthritis patients treated with bisphosphonates alone or in combination with pitavastatin over an 18-month follow-up after more than 4 years of treatment with bisphosphonates
Authors: Nagashima Masakazu , Takahashi Hiroshi , Shimane Kenichi , Nagase Yuichi , Wauke Koichi
Published: October 2012

Introduction

To investigate the effects of bisphosphonates (Bis) (etidronate, alendronate, and risedronate), alone and in combination with statin, on the BMD (bone mineral density) and bone metabolism of rheumatoid arthritis (RA) patients.

Methods

Seventy-seven RA patients who had been receiving prednisolone (PSL) and Bis for over 4 years were divided into two groups: Bis and Bis + statin (n = 42 and 35; average age, 66.4 and 65.3 years; average disease duration, 24.9 and 20.8 years; average PSL dose, 2.4 and 2.7 mg, respectively). Serum levels of NTX (N-terminal telopeptide of type I collagen), TRACP-5b (tartrate-resistant acid phosphate-5b), PICP (C-terminal propeptide of type I procollagen), and RANKL (receptor activator of NF-κB ligand) were measured over an 18-month period of treatment and follow-up. The BMD levels of the two groups at the radius, lumbar spine, and femoral neck were compared using DXA (dual-energy x-ray absorptiometry).

Results

A significant increase was only observed in the BMD of the lumbar spine at 18-months, but the BMDs of the radius and femoral neck decreased during the follow-up period in the Bis group. Meanwhile, a significant increase was observed in the BMD of the lumbar spine in the Bis + statin group during administration and the BMDs of the radius and femoral neck stayed at baseline. Among the markers of bone metabolism, serum NTX was up-regulated after 6 months in the Bis + statin group. Serum TRACP-5b was significantly increased during the follow-up period in the Bis + statin group, but only at 18 months in the Bis group. Serum PICP recovered to base line in the Bis + statin group, whereas that in the Bis group did not observably recover during the post-administration follow-up, but rather decreased.

Conclusion

Our findings suggest that both bone resorption and bone formation were inhibited by long-term administration of Bis alone, whereas combination therapy with Bis + statin may be associated with a less marked inhibition of bone metabolism. Cardiovascular disease is highly prevalent in RA patients and some patients are prescribed statins and bisphosphonate. Bis + statin may confer more benefit to the bone metabolism of these patients compared to Bis alone.
Synovial DKK1 expression is regulated by local glucocorticoid metabolism in inflammatory arthritis
Authors: Hardy Rowan , Juarez Maria , Naylor Amy , Tu Jinwen , Rabbitt Elizabeth H , Filer Andrew , Stewart Paul M , Buckley Christopher D , Raza Karim , Cooper Mark S
Published: October 2012

Introduction

Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Local glucocorticoid production is also significantly increased during joint inflammation. Therefore, we investigated how locally derived glucocorticoids and inflammatory cytokines regulate DKK1 synthesis in synovial fibroblasts during inflammatory arthritis.

Methods

We examined expression and regulation of DKK1 in primary cultures of human synovial fibroblasts isolated from patients with inflammatory arthritis. The effect of TNFα, IL-1β and glucocorticoids on DKK1 mRNA and protein expression was examined by real-time PCR and ELISA. The ability of inflammatory cytokine-induced expression of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to sensitise fibroblasts to endogenous glucocorticoids was explored. Global expression of Wnt signalling and target genes in response to TNFα and glucocorticoids was assessed using a custom array.

Results

DKK1 expression in human synovial fibroblasts was directly regulated by glucocorticoids but not proinflammatory cytokines. Glucocorticoids, but not TNFα, regulated expression of multiple Wnt agonists and antagonists in favour of inhibition of Wnt signalling. However, TNFα and IL-1β indirectly stimulated DKK1 production through increased expression of 11β-HSD1.

Conclusions

These results demonstrate that in rheumatoid arthritis synovial fibroblasts, DKK1 expression is directly regulated by glucocorticoids rather than TNFα. Consequently, the links between synovial inflammation, altered Wnt signalling and bone remodelling are not direct but are dependent on local activation of endogenous glucocorticoids.
Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis
Authors: Wang Fang , Xu Lingxiao , Feng Xiaoke , Guo Dunming , Tan Wenfeng , Zhang Miaojia
Published: October 2012

Introduction

The immunoregulatory function of interleukin (IL)-29 has recently been recognized. However, little is known about the involvement of IL-29 in the pathogenesis of rheumatoid arthritis (RA). This study aimed to examine the expression profiles of IL-29 in blood, synovial fluid (SF) and synovium in RA patients and investigate the effect of IL-29 on cytokines production in RA synovial fibroblasts.

Methods

The transcript levels of IL-29 and its specific receptor IL-28Rα in peripheral blood mononuclear cells (PBMC) and synovium were determined by real-time reverse transcription-polymerase chain reaction (real-time PCR). The concentrations of IL-29 in serum and synovial fluid (SF) were quantified by enzyme-linked immunoassay (ELISA), and the correlation of serum IL-29 levels with disease activity in RA patients was investigated. Furthermore, the expression of IL-29 in RA synovium was examined by immunohistochemistry and double immunofluorescence analysis. Finally, the expression of IL-6, IL-8, IL-10, IL-17 and matrix metalloproteinase-3 (MMP-3) in synovial fibroblasts upon IL-29 stimulation was determined by real-time PCR.

Results

IL-29 and IL-28Rα mRNA expression in PBMC was significantly increased in patients with RA compared with healthy controls (HC). The serum levels of circulating IL-29 were higher in RA than those in HC. Increased IL-29 levels were detected in RA SF when compared with osteoarthritis (OA) SF. However, serum IL-29 levels showed no significant correlation with RA disease activity. IL-29 was mostly expressed in the lining region of RA synovium. Moreover, IL-29 was expressed predominately in synovial macrophages and fibroblasts. RA synovial fibroblasts exposed to IL-29 specifically upregulated IL-6, -8 and MMP-3 but downregulated IL-10.

Conclusions

The findings in the present study indicate, for the first time, that IL-29 is dysregulated in patients with RA, which may contribute to the RA pathogenesis via inducing the production of proinflammatory cytokines, chemokines or matrix metalloproteinases in synovial fibroblasts.
Long-term quality of life in patients with acute respiratory distress syndrome requiring extracorporeal membrane oxygenation for refractory hypoxaemia
Authors: Hodgson Carol L , Hayes Kate , Everard Tori , Nichol Alistair , Davies Andrew R , Bailey Michael J , Tuxen David V , Cooper David J , Pellegrino Vin
Published: October 2012

Introduction

The purpose of the study was to assess the long term outcome and quality of life of patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia.

Methods

A retrospective observational study with prospective health related quality of life (HRQoL) assessment was conducted in ARDS patients who had ECMO as a rescue therapy for reversible refractory hypoxemia from January 2009 until April 2011 in a tertiary Australian centre. Survival and long-term quality of life assessment, using the Short-Form 36 (SF-36) and the EuroQol health related quality of life questionnaire (EQ5D) were assessed and compared to international data from other research groups.

Results

Twenty-one patients (mean age 36.3 years) with ARDS receiving ECMO for refractory hypoxemia were studied. Eighteen (86%) patients were retrieved from external intensive care units (ICUs) by a dedicated ECMO retrieval team. Eleven (55%) had H1N1 influenza A-associated pneumonitis. Eighteen (86%) patients survived to hospital discharge. Of the 18 survivors, ten (56%) were discharged to other hospitals and 8 (44%) were discharged directly home. Sequelae and health related quality of life were evaluated for 15 of the 18 (71%) long-term survivors (assessment at median 8 months). Mean SF-36 scores were significantly lower across all domains compared to age and sex matched Australian norms. Mean SF-36 scores were lower (minimum important difference at least 5 points) than previously described ARDS survivors in the domains of general health, mental health, vitality and social function. One patient had long-term disability as a result of ICU acquired weakness. Only 26% of survivors had returned to previous work levels at the time of follow-up.

Conclusions

This ARDS cohort had a high survival rate (86%) after use of ECMO support for reversible refractory hypoxemia. Long term survivors had similar physical health but decreased mental health, general health, vitality and social function compared to other ARDS survivors and an unexpectedly poor return to work.
Characterization of bone marrow derived mesenchymal stem cells in suspension
Authors: Akiyama Kentaro , You Yong-Ouk , Yamaza Takayoshi , Chen Chider , Tang Liang , Jin Yan , Chen Xiao-Dong , Gronthos Stan , Shi Songtao
Published: October 2012

Introduction

Bone marrow mesenchymal stem cells (BMMSCs) are a heterogeneous population of postnatal precursor cells with the capacity of adhering to culture dishes generating colony-forming unit-fibroblasts (CFU-F). Here we identify a new subset of BMMSCs that fail to adhere to plastic culture dishes and remain in culture suspension (S-BMMSCs).

Methods

To catch S-BMMSCs, we used BMMSCs-produced extracellular cell matrix (ECM)-coated dishes. Isolated S-BMMSCs were analyzed by in vitro stem cell analysis approaches, including flow cytometry, inductive multiple differentiation, western blot and in vivo implantation to assess the bone regeneration ability of S-BMMSCs. Furthermore, we performed systemic S-BMMSCs transplantation to treat systemic lupus erythematosus (SLE)-like MRL/lpr mice.

Results

S-BMMSCs are capable of adhering to ECM-coated dishes and showing mesenchymal stem cell characteristics with distinction from hematopoietic cells as evidenced by co-expression of CD73 or Oct-4 with CD34, forming a single colony cluster on ECM, and failure to differentiate into hematopoietic cell lineage. Moreover, we found that culture-expanded S-BMMSCs exhibited significantly increased immunomodulatory capacities in vitro and an efficacious treatment for SLE-like MRL/lpr mice by rebalancing regulatory T cells (Tregs) and T helper 17 cells (Th17) through high NO production.

Conclusions

These data suggest that it is feasible to improve immunotherapy by identifying a new subset BMMSCs.
Estrogen Receptors Are Found in Glia and at Extranuclear Neuronal Sites in the Dorsal Striatum of Female Rats: Evidence for Cholinergic But Not Dopaminergic Colocalization
Authors: Almey Anne , Filardo Edward J. , Milner Teresa A. , Brake Wayne G.
Published: October 2012

Estrogens rapidly affect dopamine (DA) neurotransmission in the dorsal striatum (dSTR) and DA-related diseases, such as Parkinson's disease and schizophrenia. How estrogens influence DA function remains unclear, in part, because the ultrastructural localization of estrogen receptors (ER) in the dSTR is not known. Light microscopic studies of the dSTR have suggested the presence of ER. This experiment used electron microscopy to determine whether these ER are at extranuclear sites in the dSTR, providing evidence for a mechanism through which estrogen could rapidly affect DA transmission. The dSTR was labeled with antibodies for ERα, ERβ, and G protein-coupled ER 1 (GPER-1) to confirm whether these ER were present in this brain area. After this, the dSTR was dual labeled with antibodies for ERα or GPER-1 and tyrosine hydroxylase or vesicular acetylcholine transporter to determine whether ER are localized to dopaminergic and/or cholinergic processes, respectively. Ultrastructural analysis revealed immunoreactivity (IR) for ERα, ERβ, and GPER-1 exclusively at extranuclear sites throughout the dSTR. ERα-, ERβ-, and GPER-1-IR are mostly frequently observed in axons and glial profiles but are also localized to other neuronal profiles. Dual labeling revealed that ERα- and GPER-1-IR is not associated with DA axons and terminals but is sometimes associated with cholinergic neurons. Because these receptors are exclusively extranuclear in the dSTR, binding at these receptors likely affects neurotransmission via nongenomic mechanisms.
Adverse Cardiovascular Outcomes of Corticosteroid Excess
Authors: Pimenta Eduardo , Wolley Martin , Stowasser Michael
Published: October 2012

Corticosteroid excess is associated with adverse cardiovascular outcomes. Patients with Cushings's syndrome, either caused by endogenous or exogenous glucocorticoid excess, and patients with primary aldosteronism have increased cardiovascular risk. The increase in risk is mediated partly by traditional cardiovascular risk factors including hypertension and metabolic syndrome but also by other, less well-characterized mechanisms. Experimental and human studies have shown that target organ deterioration induced by aldosterone depends on concomitant high dietary salt intake. Key ongoing research questions that warrant further study by both clinical and experimental approaches include the following: 1) beyond inducing the metabolic syndrome, what are the mechanisms by which glucocorticoids are associated with excess cardiovascular risk, 2) what are the cellular pathways by which excessive mineralocorticoid receptor activation brings about cardiovascular and renal damage, and 3) why is salt critical in this process?
Quantum Dot Motion on Microtubules
Authors: Sikora Aurélien , Oliveira Daniel , Kim Kyongwan , Liao Andrew L , Umetsu Mitsuo , Kumagai Izumi , Adschiri Tadafumi , Hwang Wonmuk , Teizer Winfried
Published: October 2012

Kinesin is one of the numerous motor proteins present in the cell. Its function is to transport cargo along microtubules, which serve as tracks, by efficiently making use of chemical energy. Here, we have studied the translocation of quantum dots by kinesin. Kinesin was bacterially expressed and conjugated to quantum dots, thus allowing observation of the motion of the quantum dots along the microtubules by fluorescence microscopy. The velocity was determined by a kymograph, and was in agreement with expectations.
Model Surfaces Produced by Atomic Layer Deposition
Authors: Walsh Rick B , Howard Shaun C , Nelson Andrew , Skinner William M , Liu Guangming , Craig Vincent S J
Published: October 2012

Atomic layer deposition is used with the aim of producing new model surfaces suitable for fundamental wet surface science investigations. Alumina surfaces are found to dissolve in aqueous solutions, although they can be passivated against dissolution by adsorption. Highly useful thick titania films can be produced by employing low temperatures during formation, whereas hafnia and zirconia films have a tendency to produce films that crystallize, and this increases the roughness of the films.
Calculation of van der Waals Interaction Energy in Free Liquid Films Accounting for Many-body Contributions
Authors: Emelyanenko Kirill A , Emelyanenko Alexandre M , Boinovich Ludmila
Published: October 2012

In our work, we have adopted a coupled fluctuating dipoles method based on a microscopic approach that accounts for many-body interactions to compute the van der Waals forces in free liquid films. We have analyzed the peculiarities of the surface forces in films with thicknesses of a few molecular diameters, where the macroscopic theory is not applicable. The problem addressed in our study is related to the influence of the nanobubble size on the energy of the liquid film formed when two nanobubbles approach each other. It is shown that the decrease in lateral size of the liquid film results in the diminution of the van der Waals specific attraction, a change in the contribution of many-body interactions to the total energy, and variation of the thickness dependence of the free excess energy of the liquid film.
Structure Determination of Hydrogen-bonding Network of Water in Hydrophobic Nanospace by Neutron and X-ray Diffractions
Authors: Iiyama Taku , Fujisaki Fumika , Futamura Ryusuke , Hamasaki Atom , Ozeki Sumio , Hoshikawa Akinori , Ishigaki Toru
Published: October 2012

The structure of the hydrogen-bonding network of water in carbon micropores was investigated by X-ray diffraction (XRD) and neutron diffraction (ND). ND provided positional information about both oxygen and hydrogen. A reverse Monte Carlo simulation was performed to combine the XRD and ND data. The results of ND from the adsorbed water showed that the hydrogen-bonding structure resembled that of bulk water when the pore width was 1 nm but was distorted at the 2nd nearest-neighbor distance.
Study of Water Adsorption on Hydrophobic Na-ZSM-5 and H-ZSM-5 by Directly Measuring Adsorption Isobars and Isotherms
Authors: Ito Hiromitsu , Iiyama Taku , Hamasaki Atom , Ozeki Sumio , Yamazaki Satoshi
Published: October 2012

The effects of different cation species on water adsorption on hydrophobic ZSM-5 zeolite are investigated through adsorption isotherm and isobar measurements. The adsorption isobars clearly show that sodium cations behave as stronger water adsorption sites than do protons. Furthermore, the adsorption isotherms of Na- and H-zeolites show such differences at part of the hysteresis loop. This suggests that the cation species in ZSM-5 affect the formation of the first, second, and third hydration shells in the hydrophobic space.
Gold Mesh Structures with Controlled Aperture Ratios Fabricated by Reactive-monolayer-assisted Thermal Nanoimprint Lithography
Authors: Kubo Shoichi , Nagase Koichi , Nakagawa Masaru
Published: October 2012

Fabrication of Au mesh structures by reactive-monolayer-assisted thermal nanoimprint lithography was demonstrated. A fluorescent dye-doped polystyrene thin film on a Au-plated substrate modified with a photoreactive monolayer was transformed using a mold with a lattice pattern. Au mesh patterns were obtained by removal of the residual layers and subsequent wet etching. The aperture ratio could be tuned by controlled side-etching. Au mesh structures with a Au line width of approximately 1 µm are promising for transparent conductive substrates.
Nanostructured Silica–Lipid Hybrid Microparticles: A Supersaturating Carrier for Water- and Lipid-resistant Compounds
Authors: Tan Angel , Prestidge Clive
Published: October 2012

Nanostructured silica–lipid hybrid (SLH) microparticles, which are fabricated based on Pickering emulsion templates, are reported to enhance the encapsulation efficiency of a weak base anthelmintic, albendazole (ABZ). ABZ exhibits poor solubility in aqueous solutions and in commonly used pharmaceutical surfactants and oils. The encapsulation of ABZ–SLH in a supersaturated but noncrystalline form was shown to enhance its dissolution kinetics (up to tenfold) in simulated gastric fluids, regardless of the presence of sink conditions that were representative of the influence of food intake.
Photoelectrochemical Responses from Polymer-coated Plasmonic Copper Nanoparticles on TiO2
Authors: Yamaguchi Taishi , Kazuma Emiko , Sakai Nobuyuki , Tatsuma Tetsu
Published: October 2012

Plasmonic Cu nanoparticles photocatalytically deposited on a TiO2 electrode show photocorrosion under visible light. The electrode protected with poly(vinyl alcohol) exhibits photopotential and photocurrent responses due to localized surface plasmon resonance, suggesting that it could be applied to cost-effective plasmonic devices.