bluuebunny/crossref_metadata_2025 huggingface dataset:
Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features
Authors: Celis Raquel , Planell Núria , Fernández-Sueiro José L , Sanmartí Raimon , Ramírez Julio , González-Álvaro Isidoro , Pablos José L , Cañete Juan D
Published: April 2012

Introduction

Psoriatic arthritis (PsA) is an autoantibody-negative immune-mediated disease in which synovial lymphoid neogenesis (LN) occurs. We determined whether LN is associated with specific patterns of inflammatory cytokine expression in paired synovial tissue (ST) and fluid (SF) samples and their potential correlation with the clinical characteristics of PsA.

Methods

ST and paired SF samples were obtained from the inflamed knee of PsA patients. ST samples were immunostained with CD3 (T cell), CD20 (B cell), and MECA-79 (high endothelial vessels). Total ST mRNA was extracted, and the gene expression of 21 T-cell-derived and proinflammatory cytokines were measured with quantitative real-time PCR. SF concentrations of Th1, Th2, Th17, and proinflammatory cytokines were determined with the Quantibody Human Th17 Array. Clinical and biologic data were collected at inclusion and after a median of 27 months of follow-up.

Results

Twenty (43.5%) of 46 patients had LN. Only two genes showed differences (Wilcoxon test, P < 0.06) in ST between LN-positive and LN-negative patients: interleukin-23A (IL-23A) (P = 0.058) and transforming growth factor-beta (TGF-β1) (P = 0.050). IL-23A expression was higher, and TGF-β1 expression was lower in LN-positive patients. ST IL-15 mRNA showed a nonsignificant trend toward higher expression in LN-positive patients, and SF IL-15 protein levels were significantly higher in LN-positive patients (P = 0.002). In all PsA patients, IL-23A mRNA expression correlated with C-reactive protein (CRP) (r = 0.471; P = 0.001) and swollen-joint count (SJC) (r = 0.350; P = 0.018), whereas SF levels of IL-6 and CC chemokine-ligand 20 (CCL-20) correlated with CRP levels (r = 0.377; P = 0.014 and r = 0.501; P < 0.0001, respectively).

Conclusions

These findings suggest differences in the cytokine profile of PsA patients with LN, with a higher expression of IL-23A and IL-15 and a lower expression of TGF-β1. In the entire group of patients, IL-23 ST expression and CCL20 SF levels strongly correlated with markers of disease activity. This cytokine pattern was not accompanied by gross clinical or biologic differences between LN-positive and -negative patients. Taken together, these results suggest a role of the IL-17/IL-23 cytokine axis in synovial LN in PsA.
The interferon type I signature towards prediction of non-response to rituximab in rheumatoid arthritis patients
Authors: Raterman Hennie G , Vosslamber Saskia , de Ridder Sander , Nurmohamed Michael T , Lems Willem F , Boers Maarten , van de Wiel Mark , Dijkmans Ben AC , Verweij Cornelis L , Voskuyl Alexandre E
Published: April 2012

Introduction

B cell depletion therapy is efficacious in rheumatoid arthritis (RA) patients failing on tumor necrosis factor (TNF) blocking agents. However, approximately 40% to 50% of rituximab (RTX) treated RA patients have a poor response. We investigated whether baseline gene expression levels can discriminate between clinical non-responders and responders to RTX.

Methods

In 14 consecutive RA patients starting on RTX (test cohort), gene expression profiling on whole peripheral blood RNA was performed by Illumina® HumanHT beadchip microarrays. Supervised cluster analysis was used to identify genes expressed differentially at baseline between responders and non-responders based on both a difference in 28 joints disease activity score (ΔDAS28 < 1.2) and European League against Rheumatism (EULAR) response criteria after six months RTX. Genes of interest were measured by quantitative real-time PCR and tested for their predictive value using receiver operating characteristics (ROC) curves in an independent validation cohort (n = 26).

Results

Genome-wide microarray analysis revealed a marked variation in the peripheral blood cells between RA patients before the start of RTX treatment. Here, we demonstrated that only a cluster consisting of interferon (IFN) type I network genes, represented by a set of IFN type I response genes (IRGs), that is, LY6E, HERC5, IFI44L, ISG15, MxA, MxB, EPSTI1 and RSAD2, was associated with ΔDAS28 and EULAR response outcome (P = 0.0074 and P = 0.0599, respectively). Based on the eight IRGs an IFN-score was calculated that reached an area under the curve (AUC) of 0.82 to separate non-responders from responders in an independent validation cohort of 26 patients using Receiver Operator Characteristics (ROC) curves analysis according to ΔDAS28 < 1.2 criteria. Advanced classifier analysis yielded a three IRG-set that reached an AUC of 87%. Comparable findings applied to EULAR non-response criteria.

Conclusions

This study demonstrates clinical utility for the use of baseline IRG expression levels as a predictive biomarker for non-response to RTX in RA.
Role of common mental and physical disorders in partial
disability around the world
Authors: Bruffaerts Ronny , Vilagut Gemma , Demyttenaere Koen , Alonso Jordi , AlHamzawi Ali , Andrade Laura Helena , Benjet Corina , Bromet Evelyn , Bunting Brendan , de Girolamo Giovanni , Florescu Silvia , Gureje Oye , Haro Josep Maria , He Yanling , Hinkov Hristo , Hu Chiyi , Karam Elie G. , Lepine Jean-Pierre , Levinson Daphna , Matschinger Herbert , Nakane Yoshibumi , Ormel Johan , Posada-Villa Jose , Scott Kate M. , Varghese Matthew , Williams David R. , Xavier Miguel , Kessler Ronald C.
Published: April 2012

Background

Mental and physical disorders are associated with total disability, but
their effects on days with partial disability (i.e. the ability to
perform some, but not full-role, functioning in daily life) are not well
understood.

Aims

To estimate individual (i.e. the consequences for an individual with a
disorder) and societal effects (i.e. the avoidable partial disability in
the society due to disorders) of mental and physical disorders on days
with partial disability around the world.

Method

Respondents from 26 nationally representative samples (n
= 61 259, age 18+) were interviewed regarding mental and physical
disorders, and day-to-day functioning. The Composite International
Diagnostic Interview, version 3.0 (CIDI 3.0) was used to assess mental
disorders; partial disability (expressed in full day equivalents) was
assessed with the World Health Organization Disability Assessment
Schedule in the CIDI 3.0.

Results

Respondents with disorders reported about 1.58 additional disability days
per month compared with respondents without disorders. At the individual
level, mental disorders (especially post-traumatic stress disorder,
depression and bipolar disorder) yielded a higher number of days with
disability than physical disorders. At the societal level, the population
attributable risk proportion due to physical and mental disorders was 49%
and 15% respectively.

Conclusions

Mental and physical disorders have a considerable impact on partial
disability, at both the individual and at the societal level. Physical
disorders yielded higher effects on partial disability than mental
disorders.
Cognitive–behavioural group treatment for a range of functional somatic syndromes: Randomised trial
Authors: Schröder Andreas , Rehfeld Emma , Ørnbøl Eva , Sharpe Michael , Licht Rasmus W. , Fink Per
Published: April 2012

Background

Many specialty-specific functional somatic syndrome diagnoses exist to describe people who are experiencing so-called medically unexplained symptoms. Although cognitive–behavioural therapy can be effective in the management of such syndromes, it is rarely available. A cognitive–behavioural therapy suitable for group treatment of people with different functional somatic syndromes could address this problem.

Aims

To test the efficacy of a cognitive–behavioural therapy (Specialised Treatment for Severe Bodily Distress Syndromes, STreSS) designed for patients with a range of severe functional somatic syndromes.

Method

A randomised controlled trial (clinicaltrials.gov, NCT00132197) compared STreSS (nine 3.5 h sessions over 4 months,n= 54) with enhanced usual care (management by primary care physician or medical specialist,n= 66). The primary outcome was improvement in aggregate score on subscales of the 36-item Short Form Health Survey (physical functioning, bodily pain and vitality) at 16 months.

Results

Participants receiving STreSS had a greater improvement on the primary outcome (adjusted mean difference 4.0, 95% CI 1.4–6.6,P= 0.002) and on most secondary outcomes.

Conclusions

In the management of functional somatic syndromes, a cognitive–behavioural group treatment was more effective than enhanced usual care.
Effects of emotion perception training on mood in undergraduate students: randomised controlled trial
Authors: Penton-Voak Ian S. , Bate Helen , Lewis Glyn , Munafò Marcus R.
Published: April 2012

We investigated the effects of emotion perception training on depressive symptoms and mood in young adults reporting high levels of depressive symptoms (trial registration: ISRCTN02532638). Participants were randomised to an intervention procedure designed to increase the perception of happiness over sadness in ambiguous facial expressions or a control procedure, and completed self-report measures of depressive symptoms and mood. Those in the intervention condition had lower depressive symptoms and negative mood at 2-week follow-up, but there was no statistical evidence for a difference. There was some evidence for increased positive mood. Modification of emotional perception may lead to an increase in positive affect.
PTTG-Binding Factor (PBF) Is a Novel Regulator of the Thyroid Hormone Transporter MCT8
Authors: Smith V. E. , Read M. L. , Turnell A. S. , Sharma N. , Lewy G. D. , Fong J. C. W. , Seed R. I. , Kwan P. , Ryan G. , Mehanna H. , Chan S. Y. , Darras V. M. , Boelaert K. , Franklyn J. A. , McCabe C. J.
Published: April 2012

Within the basolateral membrane of thyroid follicular epithelial cells, two transporter proteins are central to thyroid hormone (TH) biosynthesis and secretion. The sodium iodide symporter (NIS) delivers iodide from the bloodstream into the thyroid, and after TH biosynthesis, monocarboxylate transporter 8 (MCT8) mediates TH secretion from the thyroid gland. Pituitary tumor-transforming gene-binding factor (PBF; PTTG1IP) is a protooncogene that is up-regulated in thyroid cancer and that binds NIS and modulates its subcellular localization and function. We now show that PBF binds MCT8 in vitro, eliciting a marked shift in MCT8 subcellular localization and resulting in a significant reduction in the amount of MCT8 at the plasma membrane as determined by cell surface biotinylation assays. Colocalization and interaction between PBF and Mct8 was also observed in vivo in a mouse model of thyroid-specific PBF overexpression driven by a bovine thyroglobulin (Tg) promoter (PBF-Tg). Thyroidal Mct8 mRNA and protein expression levels were similar to wild-type mice. Critically, however, PBF-Tg mice demonstrated significantly enhanced thyroidal TH accumulation and reduced TH secretion upon TSH stimulation. Importantly, Mct8-knockout mice share this phenotype. These data show that PBF binds and alters the subcellular localization of MCT8 in vitro, with PBF overexpression leading to an accumulation of TH within the thyroid in vivo. Overall, these studies identify PBF as the first protein to interact with the critical TH transporter MCT8 and modulate its function in vivo. Furthermore, alongside NIS repression, PBF may thus represent a new regulator of TH biosynthesis and secretion.
Ghrelin Prevents Incidence of Malignant Arrhythmia after Acute Myocardial Infarction through Vagal Afferent Nerves
Authors: Mao Yuanjie , Tokudome Takeshi , Otani Kentaro , Kishimoto Ichiro , Nakanishi Michio , Hosoda Hiroshi , Miyazato Mikiya , Kangawa Kenji
Published: April 2012

Ghrelin is a GH-releasing peptide mainly excreted from the stomach. Ghrelin administration has been shown to inhibit cardiac sympathetic nerve activity (CSNA), reduce malignant arrhythmia, and improve prognosis after acute myocardial infarction (MI). We therefore investigated the effects and potential mechanisms of the action of endogenous ghrelin on survival rate and CSNA after MI by using ghrelin-knockout (KO) mice. MI was induced by left coronary artery ligation in 46 KO mice and 41 wild-type mice. On the first day, malignant arrhythmia-induced mortality was observed within 30 min of the ligation and had an incidence of 2.4% in wild-type and 17.4% in KO mice (P < 0.05). We next evaluated CSNA by spectral analysis of heart rate variability. CSNA, represented by the low frequency/high frequency ratio, was higher in KO mice at baseline (2.18 ± 0.43 vs. 0.98 ± 0.09; P < 0.05), and especially after MI (25.5 ± 11.8 vs. 1.4 ± 0.3; P < 0.05), than in wild-type mice. Ghrelin (150 μg/kg, sc) 15 min before ligation suppressed the activation of CSNA and reduced mortality in KO mice. Further, this effect of ghrelin was inhibited by methylatropine bromide (1 mg/kg, ip) or by perineural treatment of both cervical vagal trunks with capsaicin (a specific afferent neurotoxin). Our data demonstrated that both exogenous and endogenous ghrelin suppressed CSNA, prevented the incidence of malignant arrhythmia, and improved the prognosis after acute MI. These effects are likely to be via the vagal afferent nerves.
CPAP is required for cilia formation in neuronal cells
Authors: Wu Kuo-Sheng , Tang Tang K.
Published: April 2012

The primary cilium is a microtubule-based structure protruded from the basal body analogous to the centriole. CPAP (centrosomal P4.1-associated protein) has previously been reported to be a cell cycle-regulated protein that controls centriole length. Mutations in CPAP cause primary microcephaly (MCPH) in humans. Here, using a cell-based system that we established to monitor cilia formation in neuronal CAD (Cath.a-differentiated) cells and hippocampal neurons, we found that CPAP is required for cilia biogenesis. Overexpression of wild-type CPAP promoted cilia formation and induced longer cilia. In contrast, an exogenously expressed CPAP-377EE mutant that lacks tubulin-dimer binding significantly inhibited cilia formation and caused cilia shortening. Furthermore, depletion of CPAP inhibited ciliogenesis and such effect was effectively rescued by expression of wild-type CPAP, but not by the CPAP-377EE mutant. Taken together, our results suggest that CPAP is a positive regulator of ciliogenesis whose intrinsic tubulin-dimer binding activity is required for cilia formation in neuronal cells.
Interactions between Type III receptor tyrosine phosphatases and growth factor receptor tyrosine kinases regulate tracheal tube formation in Drosophila
Authors: Jeon Mili , Scott Matthew P. , Zinn Kai
Published: April 2012

The respiratory (tracheal) system of the Drosophila melanogaster larva is an intricate branched network of air-filled tubes. Its developmental logic is similar in some ways to that of the vertebrate vascular system. We previously described a unique embryonic tracheal tubulogenesis phenotype caused by loss of both of the Type III receptor tyrosine phosphatases (RPTPs), Ptp4E and Ptp10D. In Ptp4E Ptp10D double mutants, the linear tubes in unicellular and terminal tracheal branches are converted into bubble-like cysts that incorporate apical cell surface markers. This tube geometry phenotype is modulated by changes in the activity or expression of the epidermal growth factor receptor (Egfr) tyrosine kinase (TK). Ptp10D physically interacts with Egfr. Here we demonstrate that the Ptp4E Ptp10D phenotype is the consequence of the loss of negative regulation by the RPTPs of three growth factor receptor TKs: Egfr, Breathless and Pvr. Reducing the activity of any of the three kinases by tracheal expression of dominant-negative mutants suppresses cyst formation. By competing dominant-negative and constitutively active kinase mutants against each other, we show that the three RTKs have partially interchangeable activities, so that increasing the activity of one kinase can compensate for the effects of reducing the activity of another. This implies that SH2-domain downstream effectors that are required for the phenotype are likely to be able to interact with phosphotyrosine sites on all three receptor TKs. We also show that the phenotype involves increases in signaling through the MAP kinase and Rho GTPase pathways.
Funding health and social services for older people – a qualitative study of care recipients in the last year of life
Authors: Hanratty Barbara , Lowson Elizabeth , Holmes Louise , Grande Gunn , Addington-Hall Julia , Payne Sheila , Seymour Jane
Published: April 2012

Objectives

This study explores the views of older adults who are receiving health and social care at the end of their lives, on how services should be funded, and describes their health-related expenditure.

Design

Qualitative interview study

Setting

North West England

Participants

30 people aged 69–93 years, diagnosed with lung cancer, heart failure or stroke and judged by health professionals to be in their last year of life. Sixteen participants lived in disadvantaged areas.

Main outcome measures

Views of older adults on funding of services.

Results

Participants expressed a belief in an earned entitlement to services funded from taxation, based on a broad sense of being a good citizen. Irrespective of social background, older people felt that those who could afford to pay for social care, should do so. Sale of assets and use of children's inheritance to fund care was widely perceived as an injustice. The costs of living with illness are a burden, and families are filling many of the gaps left by welfare provision. People who had worked in low-wage occupations were most concerned to justify their current acceptance of services, and distance themselves from what they described as welfare ‘spongers’ or ‘layabouts.’

Conclusions

There is a gap between the health and social care system that older adults expect and what may be provided by a reformed welfare state at a time of financial stringencies. The values that underpinned the views expressed – mutuality, care for the most needy, and the importance of working to contribute to society – are an important contribution to the debate on welfare funding.
Metal-ion rescue revisited: Biochemical detection of site-bound metal ions important for RNA folding
Authors: Frederiksen John K. , Li Nan-Sheng , Das Rhiju , Herschlag Daniel , Piccirilli Joseph A.
Published: April 2012

Within the three-dimensional architectures of RNA molecules, divalent metal ions populate specific locations, shedding their water molecules to form chelates. These interactions help the RNA adopt and maintain specific conformations and frequently make essential contributions to function. Defining the locations of these site-bound metal ions remains challenging despite the growing database of RNA structures. Metal-ion rescue experiments have provided a powerful approach to identify and distinguish catalytic metal ions within RNA active sites, but the ability of such experiments to identify metal ions that contribute to tertiary structure acquisition and structural stability is less developed and has been challenged. Herein, we use the well-defined P4–P6 RNA domain of theTetrahymenagroup I intron to reevaluate prior evidence against the discriminatory power of metal-ion rescue experiments and to advance thermodynamic descriptions necessary for interpreting these experiments. The approach successfully identifies ligands within the RNA that occupy the inner coordination sphere of divalent metal ions and distinguishes them from ligands that occupy the outer coordination sphere. Our results underscore the importance of obtaining complete folding isotherms and establishing and evaluating thermodynamic models in order to draw conclusions from metal-ion rescue experiments. These results establish metal-ion rescue as a rigorous tool for identifying and dissecting energetically important metal-ion interactions in RNAs that are noncatalytic but critical for RNA tertiary structure.
Development of a siRNA and shRNA screening system based on a kinase fusion protein
Authors: Pieraets Sofie , Cox Luk , Gielen Olga , Cools Jan
Published: April 2012

RNA interference (RNAi) is one of the processes in the cell that regulates mRNA expression levels. RNAi can be exploited to experimentally knockdown the expression of one or more genes in cell lines or even in cells in vivo and also became an interesting tool to develop new therapeutic approaches. One of the major challenges of using RNAi is selecting effective shRNAs or siRNAs that sufficiently down-regulate the expression of the target gene. Here, we describe a system to select functional shRNAs or siRNAs that makes use of the leukemia cell line Ba/F3 that is dependent on the expression of a mutant form of the PDGFRα kinase for its proliferation and survival. The basis of this system is the generation of an expression construct, where part of the open reading frame of the gene of interest is linked to the mutant PDGFRα. Thus, shRNAs or siRNAs that effectively target the gene of interest also result in a reduction of the expression of the mutant PDGFRα protein, which can be detected by a reduction of the proliferation of the cells. We demonstrate that this validation system can be used for the selection of effective siRNAs as well as shRNAs. Unlike other systems, the system described here is not dependent on obtaining high-transduction efficiencies, and nonspecific effects of the siRNAs or shRNAs can be detected by comparing the effects in the presence or absence of the growth factor interleukin-3.
RNA secondary structure mediates alternative 3′ss selection in Saccharomyces cerevisiae
Authors: Plass Mireya , Codony-Servat Carles , Ferreira Pedro Gabriel , Vilardell Josep , Eyras Eduardo
Published: April 2012

Alternative splicing is the mechanism by which different combinations of exons in the pre-mRNA give rise to distinct mature mRNAs. This process is mediated by splicing factors that bind the pre-mRNA and affect the recognition of its splicing signals. Saccharomyces species lack many of the regulatory factors present in metazoans. Accordingly, it is generally assumed that the amount of alternative splicing is limited. However, there is recent compelling evidence that yeast have functional alternative splicing, mainly in response to environmental conditions. We have previously shown that sequence and structure properties of the pre-mRNA could explain the selection of 3′ splice sites (ss) in Saccharomyces cerevisiae. In this work, we extend our previous observations to build a computational classifier that explains most of the annotated 3′ss in the CDS and 5′ UTR of this organism. Moreover, we show that the same rules can explain the selection of alternative 3′ss. Experimental validation of a number of predicted alternative 3′ss shows that their usage is low compared to annotated 3′ss. The majority of these alternative 3′ss introduce premature termination codons (PTCs), suggesting a role in expression regulation. Furthermore, a genome-wide analysis of the effect of temperature, followed by experimental validation, yields only a small number of changes, indicating that this type of regulation is not widespread. Our results are consistent with the presence of alternative 3′ss selection in yeast mediated by the pre-mRNA structure, which can be responsive to external cues, like temperature, and is possibly related to the control of gene expression.
Determination of ribonuclease sequence-specificity using Pentaprobes and mass spectrometry
Authors: McKenzie Joanna L. , Duyvestyn Johanna M. , Smith Tony , Bendak Katerina , MacKay Joel , Cursons Ray , Cook Gregory M. , Arcus Vickery L.
Published: April 2012

The VapBC toxin-antitoxin (TA) family is the largest of nine identified TA families. The toxin, VapC, is a metal-dependent ribonuclease that is inhibited by its cognate antitoxin, VapB. Although the VapBCs are the largest TA family, little is known about their biological roles. Here we describe a new general method for the overexpression and purification of toxic VapC proteins and subsequent determination of their RNase sequence-specificity. Functional VapC was isolated by expression of the nontoxic VapBC complex, followed by removal of the labile antitoxin (VapB) using limited trypsin digestion. We have then developed a sensitive and robust method for determining VapC ribonuclease sequence-specificity. This technique employs the use of Pentaprobes as substrates for VapC. These are RNA sequences encoding every combination of five bases. We combine the RNase reaction with MALDI-TOF MS to detect and analyze the cleavage products and thus determine the RNA cut sites. Successful MALDI-TOF MS analysis of RNA fragments is acutely dependent on sample preparation methods. The sequence-specificity of four VapC proteins from two different organisms (VapCPAE0151 and VapCPAE2754 from Pyrobaculum aerophilum, and VapCRv0065 and VapCRv0617 from Mycobacterium tuberculosis) was successfully determined using the described strategy. This rapid and sensitive method can be applied to determine the sequence-specificity of VapC ribonucleases along with other RNA interferases (such as MazF) from a range of organisms.
Structure and folding of a rare, natural kink turn in RNA with an A•A pair at the 2b•2n position
Authors: Schroeder Kersten T. , Daldrop Peter , McPhee Scott A. , Lilley David M.J.
Published: April 2012

The kink turn (k-turn) is a frequently occurring motif, comprising a bulge followed by G•A and A•G pairs that introduces a sharp axial bend in duplex RNA. Natural k-turn sequences exhibit significant departures from the consensus, including the A•G pairs that form critical interactions stabilizing the core of the structure. Kt-23 found in the small ribosomal subunit differs from the consensus in many organisms, particularly in the second A•G pair distal to the bulge (2b•2n). Analysis of many Kt-23 sequences shows that the frequency of occurrence at the 2n position (i.e., on the nonbulged strand, normally G in standard k-turns) is U>C>G>A. Less than 1% of sequences have A at the 2n position, but one such example occurs in Thelohania solenopsae Kt-23. This sequence folds only weakly in the presence of Mg2+ ions but is induced to fold normally by the binding of L7Ae protein. Introduction of this sequence into the SAM-I riboswitch resulted in normal binding of SAM ligand, indicating that tertiary RNA contacts have resulted in k-turn folding. X-ray crystallography shows that the T. solenopsae Kt-23 adopts a standard k-turn geometry, making the key, conserved hydrogen bonds in the core and orienting the 1n (of the bulge-proximal A•G pair) and 2b adenine nucleobases in position facing the opposing minor groove. The 2b and 2n adenine nucleobases are not directly hydrogen bonded, but each makes hydrogen bonds to their opposing strands.
Synthesis of myxobacteria metabolites
Authors: Birkett Stephen L. , Loits Darran A. , Wimala Samantha , Rizzacasa Mark A.
Published: April 2012

Myxobacteria are an excellent source of novel secondary metabolites with a range of biological activities. This review details the synthesis of several examples of these natural products. The total synthesis of all the members of the crocacin family is presented where the stereochemistry of the stereotetrad was set via a tin-mediated syn-aldol reaction followed by selective anti-reduction. The other key step in the route to crocacins A, B, and D was the introduction of the enamide functionality by acylation of an enecarbamate. A formal synthesis of apicularen A is also discussed, which involved a base-induced macrolactonization reaction and a transannular oxy-Michael cyclization to secure the tetrahydropyran ring. Finally, the total synthesis of deshydroxyajudazol B is summarized. This route details a modified approach to the 2,4-disubstituted oxazole, and a Diels–Alder reaction followed by aromatization was utilized to form the isochromanone moiety. A highly efficient Sonogashira coupling followed by partial reduction then gave deshydroxyajudazol B.
Influence without Organizations: State-Business Relations and their Impact on Business Environments in Contemporary Africa
Authors: Taylor Scott D.
Published: April 2012

Formal institutions such as business chambers have been assumed to be a key indicator of the health of state-business relations (SBR). Yet in Africa these organizations have seldom risen to the level of access and influence enjoyed by some of their counterparts elsewhere in the developing world. A number of recent studies of SBR in Africa continue to overstate the importance of business associations (BAs). Yet despite the widespread marginality of BAs in Africa, the receptiveness of African states to leading firms and business interests has increased markedly. While this poses certain risks of increased corruption, collusion and monopoly, the institutional and political environment for doing business has also improved, thereby fostering new opportunities for further business-related growth and business sector development among bona fide firms. Drawing on evidence from Zambia and elsewhere, this paper finds that the benefits provided to individual firms who enjoy state access can, paradoxically, contribute to an improved environment for other private sector actors whose interests are directly represented only in moribund formal associations. Even without strong BAs, when aided by the state, individual firms, and/or international actors, Africa's improved business environment has a salutary impact on growth.
Dual specificity phosphatase 6 as a predictor of invasiveness in papillary thyroid cancer
Authors: Lee Jung Uee , Huang Songmei , Lee Min Hee , Lee Seong Eun , Ryu Min Jeong , Kim Soung Jung , Kim Yong Kyung , Kim Seul Young , Joung Kyong Hye , Kim Jin Man , Shong Minho , Jo Young Suk
Published: April 2012

Objective

The genetic mutations causing the constitutive activation of MEK/ERK have been regarded as an initiating factor in papillary thyroid carcinoma (PTC). The ERK-specific dual specificity phosphatase 6 (DUSP6) is part of the ERK-dependent transcriptional output. Therefore, the coordinated regulation of the activities of ERK kinases and DUSP6 may need to be reestablished to make new balances in PTC.

Methods

To investigate the role of DUSP6 in the regulation of ERK1/2 (MAPK3/1)-dependent transcription, 42 benign neoplasms and 167 PTCs were retrospectively analyzed by immunohistochemistry with dideoxy sequencing to detectBRAFV600Emutation.

Results

The expressions of totalERK1/2,DUSP6,c-Fos(FOS),c-Myc(MYC), cyclin D1, andPCNAwere markedly increased in PTC compared with those in benign neoplasms. However, phospho-ERK1/2 was detected in only eight (4.8%) cases out of 167 PTC samples. Unexpectedly, the staining intensity and nuclear localization of ERK1/2 were not affected by the presence or absence of theBRAFV600Emutation. However, the expressions ofc-FosandPCNAwere elevated inBRAFV600E-positive PTC compared with those inBRAFV600E-negative PTC. Interestingly, the higher staining intensities of DUSP6 were associated with the level of totalERK1/2expression (P=0.04) and with high-risk biological features such as age (P=0.05), tumor size (P=0.01), and extrathyroidal extension (linear by linear association,P=0.02). In addition, DUSP6 silencing significantly decreased the cell viability and migration rate of FRO cells.

Conclusions

The coordinated upregulation of total ERK1/2 and its phosphatase, DUSP6, is related to bare detection of phospho-ERK1/2 in PTC regardless ofBRAFV600Emutation status. A link betweenDUSP6expression and high-risk features of PTC suggested thatDUSP6is an important independent factor affecting the signaling pathways in established PTC.
Resources & Herrmann research
Authors: Wrobel Bill
Published: April 2012

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Lessons from Ives
Authors: Waxman Jonathan
Published: April 2012

Although Charles Ives is rarely considered a major influence on movie scoring, the composer Bernard Herrmann, in both his film scores and his symphonic compositions, drew on Ives’s techniques and his broader aesthetic. However, Herrmann did so sparingly incorporating only one or two of Ives’s techniques in a symphonic work or film score. The result is a fusion of Ivesian modernism with Herrmann’s own neo-Romantic idiom; a contribution to film music that has been almost completely overlooked. This paper focuses on Herrmann’s cantata Moby Dick, dedicated to Ives, and his film scores, The Devil and Daniel Webster and Hangover Square in order to explore the impact of the older composer. The ‘psychological’ hallmarks of Herrmann’s film scores, shocking orchestral colors, unresolved chromaticisms, and ostinatos, are also significant characteristics of Ives’s music. Herrmann’s use of these practices, refined in his later, more famous scores as well, profoundly influenced future film composers and thus the development of music for cinema.
Bernard Herrmann
Authors: Green Edward
Published: April 2012

Introducing a special issue of Popular Music History honoring, on his centenary, the great American film composer Bernard Herrmann, this essay explores the complex and conflicted relation Herrmann had to the world of ‘popular’ music—his great interest in its history, yet the distance he kept from contemporary popular styles. Among matters discussed are: his partnership with Alfred Hitchcock and its breakup over Hitchcock’s insistence on the inclusion of a ‘pop song’ for the 1966 film Torn Curtain; the scores to The Wrong Man and North by Northwest; and Herrmann’s attempts to write Broadway musicals. In the process, comparison is made to music by Henry Mancini and Max Steiner—among others. The essay suggests that Eli Siegel’s philosophy of Aesthetic Realism can shed crucial light on both the music and life of Herrmann; in particular it can make sense of the anguish Herrmann had on the question of whether his artistic self-expression could include contemporary vernacular styles of music, or needed to exclude them. The essay concludes with a brief discussion of the term ‘classic’, and also of current methodology in the field of ‘popular music studies’.
Traditional jazz and the mainstreaming of authenticity
Authors: Ekins Richard
Published: April 2012

This article sets forth a grounded theory of ‘mainstreaming’ with reference to traditional jazz, the mainstreaming of authenticity, and the relevant popular music studies literature. It considers ‘British traddy pop’ (the ‘trad fad’)—a major force in British popular music between 1959 and 1963—in terms of a phased trajectory of mainstreaming. Mainstreaming is considered as a generic social process which subsumes a number of Janus-faced major sub-processes: those of ‘sourcing’, ‘selecting’, ‘adopting/adapting’, ‘commodifying’, and ‘progressing’. The dimensions of each sub-process are examined in terms of musical style, instrumentation, personnel, and repertoire, and their various properties. It is suggested that the conceptual framework detailed in the article might provide the foundations for a comprehensive theory of mainstreaming in popular music studies, more generally.
Skin deep
Authors: Stratton Jon
Published: April 2012

This article tracks the history of ska in Britain in terms of its relationship with the mainstream white population. The article tracks a brief history from The Equals, through the impact of reggae during the punk era, to the use of ska by the Two Tone, and similar, groups. One of the article’s most important concerns is with the relationship between the reception of ska and the ways that issues related to race were played out in Britain. The article argues that, while Jerry Dammers, the instigator of The Specials and founder of the Two Tone ska/punk sound, claimed that the reworking of ska by punk-influenced groups comprised of both black and white members was an assertion of racial equality, in reality the resurrection of ska marked a retrograde step full of nostalgia for an earlier time when black migrants were clearly positioned as subordinate to the white, British population.
Ideology and the performance of Chineseness
Authors: Gorfinkel Lauren
Published: April 2012

This article examines the construction of Chinese nationalism through song performances on China’s national network, China Central Television (CCTV), with a particular focus on the accommodation of Hong Kong singers. It contributes to the body of knowledge on televised musical performances in Asia, a subject on which there is limited research. I examine two performances by Hong Kong singers on CCTV’s travelling programme The Same Song in 2007, the year China celebrated ten years since the end of British sovereignty over Hong Kong. I argue that singers who are identified as hailing from Hong Kong perform different but overlapping ideological roles for Party-state television. They appear to offer audiences a sense of freshness and modernity, and therefore help the Party-state project an image of open-mindedness and inclusivity. In addition, their songs serve to ease audiences into paying attention to the more overt ideological messages presented through the programme’s dialogue segments.
Soundscapes in Vedic metal
Authors: Dairianathan Eugene
Published: April 2012

Local death metal group Rudra’s presence and practice has posed prospects and problems for studies concerning musicians who compose, perform and generate forms of extreme metal. Their relative in/significance in written accounts is as revealing as their seventeen-year existence; a revelation of the complexity of the author-functions—South Indian, Hindu, Youth, Singaporean, South Asian and extreme metal musicians—as a consequence of legal, psychological, social, moral and aesthetic layers in operation. Rudra’s lived and living practices resonate with Appadurai’s five -scape articulation of the problems of social reproduction and integration in the face of multiple trajectories of globalization which potentially obfuscate any meaningful contemporary discourse on nationalism. While Appadurai’s -scapes are not constituent of global flows but disjunct trajectories along which im/materiality may be seen to be moving across multiple boundaries, it is the porosity of sounds that permeate these trajectories; soundscapes. Soundscapes emergent from Rudra’s practice (through interviews, privately held material, newspaper articles and local as well as international interviews posted on the group’s website) provide opportunities of negotiating meaning by deep listening and invite an informed perspective of and about their musical practice and their situatedness in Singapore.
Bond stress–slip behaviour of two common GFRP rebar types with pullout failure
Authors: Lee Jung Yoon , Yi Chong Ku , Cheong Yeon Gul , Kim Byung Il
Published: April 2012

Numerous studies on fibre reinforced plastic (FRP) rebar–concrete bond behaviour have been carried out by many researchers. However, most of the reported works have focused on the ascending part of bond–slip behaviour, especially the maximum bond stress and corresponding slip values. Fewer efforts have been made to explore the post-peak bond–slip behaviour of FRP rebars in concrete. In this study, a series of pullout tests was performed to investigate the bond stress–slip behaviour of glass fibre reinforced plastic (GFRP) bars in concrete failed by pullout under monotonic load. The test specimens were prepared using two common types of GFRP rebars (helically wrapped and sand coated) with three different concrete strengths (25, 40 and 70 MPa). The results showed quite different pre- and post-peak bond–slip behaviours for the two GFRP types. Based on an analysis of the experimental data from this study and additional data from a literature review, simple model equations to predict the bond stress–slip behaviour for the two GFRP rebar types are suggested. The predicted bond–slip curves showed good agreement with the test results.
Total phenolic content, antioxidant and antimicrobial activity of Equisetum arvense L.
Authors: Kukric Zoran , Topalic-Trivunovic Ljiljana , Pavicic Svetlana , Zabic Mirjana , Matos Snjezana , Davidovic Asima
Published: April 2012

The antioxidant and antimicrobial activity of Equisetum arvense L. harvested
in a polluted urban area were investigated. The total phenolic content
determined by a modified Folin-Ciocalteu method was 335.8 mg of GEA/g of the
dried ethanol extract. Antioxidant activity determined by FRAP method was
28.7 mM Fe(II)/g of extract, whereas antioxidant activity index for stable
DPPH free radicals was 3.86. The results were compared with control
antioxidants (gallic acid, vitamin C, BHA and BHT). Antimicrobial activity
was tested by monitoring the impact of different extract concentrations
through measuring the change in optical density of bacterial suspension over
time and by determining MIC and MBC using macrodilution method. E. arvense
extract has been effective on the tested microorganisms depending on the
concentration and exposure time. The extract had the strongest antibacterial
activity on Staphylococcus aureus, with MIC and MBC of 11.14 mg/mL and 22.28
mg/mL respectively, and the weakest effect on Bacillus cereus, with MIC of
89.10 mg/mL.
The effect of copper ions, aluminium ions and their mixtures on separation of pectin from the sugar beet juice
Authors: Kuljanin Tatjana , Misljenovic Nevena , Koprivica Gordana , Jevric Lidija , Grbic Jasna
Published: April 2012

In sugar industry there is a problem of the presence of undesirable
macromolecules compounds such as pectin in sugar beet juice. The affinity of
calcium ions commonly used in the sugar industry for the removal of pectin
from the sugar beet juice is relatively small. Coagulation and precipitation
of pectin can be performed by process of discharging that is chemically
induced. Compounds with di- and trivalent cations such as pure CuSO4,
Al2(SO4)3 or their mixtures can be applied for clarification of pectin
colloidal systems. According to data from the order of pectin selectivity to
divalent metal ions, Cu2+ ions are the first order of ion binding. Also,
aluminum sulfate is commonly used in the waste water treatment. Two model
solutions of pectin whose concentration corresponds to the concentration of
these macromolecules in sugar beet juice (0.1% w/w) are investigated. Using a
method of measuring zeta potential, it was proven for both investigated
pectin that fewer quantities of Cu2+ ions compared to the values of Al3+ ions
are needed to reach zero zeta potential. In all the investigated coagulants
and their mixtures, zeta potential has changed the sign. In experiments with
mixtures has been shown that pure salts showed better coagulation properties.
The reduced strength of binding of cations in the case of most of the applied
mixture of Cu2+ and Al3+ ions, can be explained by the mutual competition of
these ions for the adsorption site (COO- groups) on the surface of
macromolecules. Mixture with approximately equal shares of ions Cu2+ and Al3+
had the most unfavorable coagulation ability (ion antagonism). Mechanism of
discharge as well as the model of double electric layer surrounding pectin
macromolecules in the presence of mixtures of Cu2+ and Al3+ ions are
suggested. However, due to possible undesirable effects of CuSO4 on food
processing, Al2(SO4)3 is proposed instead of traditional coagulant CaO, not
only because of lower consumptions of coagulants but owing to protection of
the environment.
The influence of the morphometric parameters of the intercondylar notch on rupture of the anterior cruciate ligament
Authors: Stijak Lazar , Malis Milos , Maksimovic Ruzica , Aksic Milan , Filipovic Branislav
Published: April 2012

Background/Aim. Morpohometric parameters of the intercondylar notch of femur
present one of the substantial risk factors for rupture of the anterior
cruciate ligament (ACL). In morphometric studies of the knee the most often
referred indexes are notch width index and notch shape index. The aim of this
study was to identificate the morphometric parameters of the intercondylar
notch as risk factors for ACL rupture. Methods. This study included 99
patients divided into two groups: the study group (n = 57) composed of
patients with chronic instability of the knee because of previos rupture of
the ACL, and the control group (n = 42) composed of patients with lesion of
the knee, but without rupture of the ACL. Measuring the width and height of
intercondylar notch and epicondylar width was observed on a horizontal MR
section. According to these values notch width and notch shape indexes were
calculated. Results. The study group had statistically significantly higher
(p < 0.05) intercondylar notch and lesser notch shape index than the control
group (p < 0.05). The difference was highly statistically significant (p <
0.01) only in males, but not in females (p > 0.05). Absolute dimensions of
the morphometric parameters of the distal part of the femur had highly
statatistically significant larger values (p < 0.01) in males than females,
exept in case of the intercondilar height in the control group (p > 0.05).
Conclusion. Enhanced height of the intercondylar notch as well as lesser
value of the notch shape index are associated with rupture of the ACL in
males but not in females.
The position of the Chinese massage (Tuina) in clinical medicine
Authors: Ilic Dejan , Djurovic Aleksandar , Brdareski Zorica , Vukomanovic Aleksandra , Pejovic Vesna , Grajic Мirko
Published: April 2012

nema
Incresed inflammatory response in patients with the first myocardial infarction and nonsignificant stenosis of infarct-related artery
Authors: Ratkovic Nenad , Dincic Dragan , Gligic Branko , Vukotic Snjezana , Jovelic Aleksandra , Obradovic Slobodan
Published: April 2012

Introduction/Aim. Atherosclerosis presents a serial of highly specific
cellular and molecular responses, and could be described as inflammatory
diseases. Accordingly, for development of acute myocardial infarction (AMI),
structure and vulnerability of atherosclerotic plaque are more important than
the extent of stenosis of infarct-related artery. Consequently, inflammation
and atherosclerosis and its complications are in good correlation. C-reactive
protein (CRP) as nonspecific inflammatory marker, has prognostic significance
in coronary artery diseases. The aim of this study was to establish the
correlation between inflammatory response expressed as levels of CRP and
fibrinogen in serum and extent of coronary artery stenosis. Methods. Study
included 35 patients with acute myocardial infarction, as the first
manifestation of coronary artery disease, which were treated with
thrombolytic therapy according to the guidelines. All the patient had a
reperfusion. The patients with acute or chronic inflammatory diseases, an
increased value of sedimentation, fibrinogen, CK ?190 U/L, early and late
complications of AMI were excluded. CRP was measured on admission, after 24,
48 and 72 hrs, and 21 days latter, while fibriogen only on admission.
Results. All the patients underwent coronary angiography, and were divided
into two groups: the group 1 (23 patients), with significant stenosis of
infarct-related artery (stenosis ? 75%), and the group 2 (13 patients)
without significant stenosis (< 75%). Mean value of CRP serum level on
admission in the group 1 was 4.4 mg/L, and in the group 2 7.2 mg/L (p <
0.001). The mean value of fibrinogen on admission in the group 1 was 2.7 g/L,
and in the group 2 3.0 g/L (p < 0.001). The mean CRP value after 48 hrs in
the group 1 was 21.7 mg/L, and in the group 2 42.4 mg/L. (p < 0.001). After
three weeks, the mean CRP value was 4 mg/L in the group 1 and 5.5 mg/L in the
group 2 (p < 0.001). There was no significant difference between the groups 1
and 2 related to gender, age, localization of AMI, CK, EF value, and risk
factors for coronary artery disease. Conclusion. The patients with
nonsignificant stenosis of infarct-related artery had increased inflammtory
responses according to the CRP value, as a result of inflammatory process in
atherosclerotic plaque and/or enhanced individual reactivity.