bluuebunny/crossref_metadata_2025 huggingface dataset:
Dramatizing proximity: Cultural and social discourses in soap operas from production to reception
Authors: Castelló Enric
Published: April 2010

The idea that audiences prefer television fiction that is culturally proximate is well developed in studies on soap operas and telenovelas. This article shows how attempts to apply this cultural proximity are made from the production level down, how audiovisual texts are represented and, finally, how this is interpreted by the audience. This study is based on the Catalan television context, applying a close reading of two soap operas, in-depth interviews with producers and focus groups with viewers. The author argues that the discourses on society and culture proposed at production level are received as being ‘proximate’, but that this perception is not just national, cultural or linguistic. Cultural proximity also incorporates educative, cognitive and emotional elements and aspects related to the audience’s immediate surroundings. The work proposes a revision of the concept of cultural proximity applied to fiction, accepting the geographic or cultural meaning of the term, but also accentuating the relationship with the discursive formations that arise from audiovisual texts.
The economy of live music in the digital age
Authors: Holt Fabian
Published: April 2010

Popular music culture has changed significantly with the diffusion of networked digital media in the late 1990s. The present article theorizes the concept of live music in light of those changes and develops the idea of a new economy of live music. The perception of concerts as live music is central, so this is explored conceptually and historically before outlining the main elements of the new economy. Two immediate elements are the new economic centrality of live music and the categorical change in concert ticket prices. Two other elements are the rise of new and renewed event genres and the broader dynamics of the digital information society. The article integrates perspectives of cultural and performance studies.
‘I didn’t realize how attached I am’: On the environmental experiences of trans-European migrants
Authors: Moores Shaun , Metykova Monika
Published: April 2010

This article presents findings from a qualitative research project on the environmental experiences of trans-European migrants, drawing on conversational interviews with young people who have moved to Britain over recent years from the new European Union Member States in Eastern Europe. It explores these migrants’ practical and emotional relationships with physical (and media) environments, also drawing on the literature of phenomenological geography, in which there is a helpful concern with environmental experiences and associated senses of place. Such experiences and perceptions are not usually objects of reflection in day-to-day social circumstances, precisely because of their routine, familiar and taken-for-granted character. However, transnational migration can bring a profound disturbance of lifeworlds, throwing senses of place into sharp relief. Therefore, a major theme of this article is the close connection between matters of migration and those of place-making in daily living.
Lifestyle television programmes and the construction of the expert host
Authors: Smith Angela
Published: April 2010

This article will seek to explore the role of the host presenter in television lifestyle programmes. In the general context of consumer culture, the apparently mundane interactions between the host of lifestyle programmes and the members of the public serve to circulate discourses about preferred lifestyles, aesthetic tastes and cultural activity. The most common format of many of the lifestyle programmes features a host who is constructed as ‘expert’ in their field, offering guidance to members of the public. A case study of the British television programme Property Ladder, where the host offers advice and guidance to amateur property developers, will draw on the work of Davies to develop an analytical structure that explores the frames of friendship and credibility informed by theories of politeness. These frames will be explored in relation to double audience structure.
Online news consumption research: An assessment of past work and an agenda for the future
Authors: Mitchelstein Eugenia , Boczkowski Pablo J.
Published: April 2010

This article assesses the main findings and dominant modes of inquiry in recent scholarship on online news consumption. The findings suggest that the consumption of news on the internet has not yet differed drastically from the consumption of news in traditional media. The assessment shows that the dominant modes of inquiry have also been characterized by stability rather than change (because research has usually drawn on traditional theoretical and methodological approaches). In addition, these modes of inquiry exhibit three systematic limitations: the assumption of a division between print, broadcast, and online media; the notion that the analysis should treat media features and social practices separately; and the inclination to focus on ordinary or extraordinary patterns of phenomena but not on both at the same time. On the basis of this assessment, this article proposes an integrative research agenda that builds on this scholarship but also contributes to solve some of its main limitations.
The Clinical Use of Human Culture–Expanded Autologous Bone Marrow Mesenchymal Stem Cells Transplanted on Platelet-Rich Fibrin Glue in the Treatment of Articular Cartilage Defects
Authors: Haleem Amgad M. , Singergy Abdel Aziz El , Sabry Dina , Atta Hazem M. , Rashed Laila A. , Chu Constance R. , Shewy Mohammed T. El , Azzam Akram , Aziz Mohammed T. Abdel
Published: April 2010

Objective:

To test the hypothesis that platelet-rich fibrin glue (PR-FG) can be used clinically as a scaffold to deliver autologous culture-expanded bone marrow mesenchymal stem cells (BM-MSCs) for cartilage repair and to report clinical results 1 y after implantation of MSCs PR-FG.

Patients and Methods:

Autologous BM-MSCs were culture expanded, placed on PR-FG intraoperatively, and then transplanted into 5 full-thickness cartilage defects of femoral condyles of 5 patients and covered with an autologous periosteal flap. Patients were evaluated clinically at 6 and 12 mo by the Lysholm and Revised Hospital for Special Surgery Knee (RHSSK) scores and radiographically by x-rays and magnetic resonance imaging (MRI) at the same time points. Repair tissue in 2 patients was rated arthroscopically after 12 mo using the International Cartilage Repair Society (ICRS) Arthroscopic Score.

Study Design:

Case series; level of evidence 4.

Results:

All patients’ symptoms improved over the follow-up period of 12 mo. Average Lysholm and RHSSK scores for all patients showed statistically significant improvement at 6 and 12 mo postoperatively ( P < 0.05). There was no statistically significant difference between the 6 and 12 mo postoperative clinical scores ( P = 0.18). ICRS arthroscopic scores were 8/12 and 11/12 (nearly normal) for the 2 patients who consented to arthroscopy. MRI of 3 patients at 12 mo postoperatively revealed complete defect fill and complete surface congruity with native cartilage, whereas that of 2 patients showed incomplete congruity.

Conclusion:

Autologous BM-MSC transplantation on PR-FG as a cell scaffold may be an effective approach to promote the repair of articular cartilage defects of the knee in human patients.
Shepherd Hook Anomaly of Ductus Arteriosus With Sudden Intrapartum Fetal Demise: Two Case Reports
Authors: Mavroudis Constantine D. , Fitchev Philip , Plunkett Beth A. , Crawford Susan E.
Published: April 2010

Patency of the ductus arteriosus is critical in maintaining fetal circulation, and premature closure is associated with fetal and early neonatal death. We present 2 cases of sudden demise in the delivery room associated with atypical ductal anatomy with obstruction due to kinking and intraluminal intimal ridges. Shepherd hook anomaly of the ductus arteriosus may represent a new congenital heart lesion associated with poor fetal outcome.
Individualized Approach to Repair of Complete Atrioventricular Canal: Selective Use of the Traditional Single-Patch Technique Versus the Australian Technique
Authors: Jonas Richard A. , Mora Bassem
Published: April 2010

The traditional single-patch technique for repair of complete atrioventricular (AV) canal requires surgical division of the superior and inferior common leaflets. In the neonate and young infant, subsequent resuspension of very delicate AV valve tissue on the pericardial patch can be problematic. Selective application of the modified single-patch technique as described by Nunn (Australian technique) minimizes manipulation of the AV valve leaflet tissue. Previous reports have documented that since the late 1980s, the traditional single-patch approach with leaflet resuspension is possible with a mortality of 3% or less. A review of the initial 33 patients managed with the Australian technique was undertaken. The ventricular septal defect was moderate or large in 29 patients (88%). In the balanced canal subgroup, there was no early mortality; 1 patient underwent reoperative mitral repair for cleft dehiscence 1 year postoperatively, and 1 patient with heterotaxy required pacemaker implantation. In the unbalanced canal subgroup, 2 patients died perioperatively (22%). There have been no late deaths or new left ventricular outflow tract obstruction in either subgroup. Selective application of the single-patch technique currently allows excellent results for surgical repair in the neonatal period or early infancy. Even during the learning phase of the Australian technique, satisfactory results were achieved.
Rationale and Use of Perfusion Variables in the 2010 Update of the Society of Thoracic Surgeons Congenital Heart Surgery Database
Authors: Shann Kenneth G. , Giacomuzzi Carmen R. , Jacobs Jeffrey P. , Myers Gerard J. , Paugh Theron A. , Mellas Nicholas , Puis Luc , Ojito Jorge W. , Gomez Daniel , Olshove Vincent , Fitzgerald David C. , Itoh Hideshi , Brabant Christopher , Thuys Clarke A. , Charette Kevin , Calaritis Christos , Parpard Michael , Chancy Tom , Baker Robert A. , Pourmoghadam Kamal K. , Likosky Donald S.
Published: April 2010

Patients undergoing congenital heart surgery are at risk of morbidity and mortality. The reasons underlying this risk are complex. To identify opportunities to reduce adverse sequelae, the cardiovascular perfusion community was invited to amend existing perfusion-related fields as well as add new ones to the current version of the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD). The International Consortium for Evidence-Based Perfusion (ICEBP) was invited by the STS-CHSD Task Force to identify and resolve ambiguities related to definitions among the 3 current perfusion-related fields as well as to propose new variables (and definitions) for inclusion in the 2010 update of the STS-CHSD. The ICEBP used teleconferences, wiki-based communication software, and e-mail to discuss current definitions and create new fields with definitions. The ICEBP created modified definitions to existing fields related to cardiovascular perfusion and also developed and defined new fields that focus on (1) techniques of circulatory arrest and cerebral perfusion, (2) strategies of myocardial protection, and (3) techniques to minimize hemodilution and allogeneic blood transfusions. Three fields in the STS-CHSD related to perfusion were redefined, and 23 new variables and definitions were selected for inclusion. Identifying and defining fields specific to the practice of perfusion are requisite for assessing and subsequently improving the care provided to patients undergoing congenital heart surgery. The article describes the methods and justification for adjudicating extant and new perfusion-related fields added to the 2010 update of the STS-CHSD.
Preliminary Experience With Cardiac Reconstruction Using Decellularized Porcine Extracellular Matrix Scaffold: Human Applications in Congenital Heart Disease
Authors: Scholl Frank G. , Boucek Mark M. , Chan Kak-Chen , Valdes-Cruz Lilliam , Perryman Richard
Published: April 2010

An ideal material for repair of congenitally malformed hearts would encourage tissue regeneration with growth potential. Decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) promotes tissue regeneration in animal models and noncardiac human applications. This retrospective review evaluates SIS-ECM for reconstruction of congenital heart defects. From June 2007 to May 2009, SIS-ECM patches were used in 43 operations on 40 patients aged 2 days to 13 years. In 16 cases, the SIS-ECM was used for pericardial closure. The SIS-ECM was used for cardiac or great vessel repair in 37 cases: atrial septal defect repair in 11, pulmonary arterioplasty in 10, right ventricular outflow tract patch in 6, pulmonary monocusp valve creation in 5, superior vena cava patch in 2 and aortoplasty in 2, valve leaflet augmentation in 2, and repair of unroofed coronary sinus in 1. Follow-up was complete. There were 5 deaths, all unrelated to the SIS-ECM. Mean follow-up was 7.85 months (0.5-24 months). No pericardial effusions or intracardiac or intravascular thromboses occurred related to the SIS-ECM. The patches did not shrink or calcify. Four of 5 monocusp valves were competent and none were stenotic. One patient who underwent tricuspid valve anterior leaflet augmentation with SIS-ECM required tricuspid valve replacement 4 months later for severe regurgitation following a catheter-based procedure. Explanted tissue showed resorption of the SIS-ECM, replacement with organized collagen, and re-endothelialization. Repair of congenital heart defects using SIS-ECM is feasible and safe. In valve reconstruction, this procedure shows potential for replacement by autologous tissue. Longer-term follow-up is required to assess the potential for growth.
Repair of Atrioventricular Canal With Double-Outlet Right Ventricle, Transposition, or Truncus Arteriosus
Authors: Tchervenkov Christo I. , Bernier Pierre-Luc , Duca Danny Del , Hill Samantha , Ota Noritaka , Samoukovic Gordan , Al-Habib Hamad , Korkola Stephen
Published: April 2010

Atrioventricular canal and conotruncal anomalies are a heterogeneous group of lesions presenting unique challenges for surgical repair. These are the establishment of unobstructed pathways from left ventricle (LV) to aorta and from right ventricle (RV) to pulmonary artery, closure of the inlet ventricular septal defect (VSD) and atrial septal defect (ASD) ostium primum, and the avoidance of significant left and right atrioventricular valve (AV) regurgitation. Repair of complete atrioventricular canal (CAVC) with tetralogy of Fallot (TOF) has been most commonly achieved, either using a single-patch or a 2-patch technique. In patients with CAVC with double-outlet right ventricle (DORV) with subaortic VSD extension, the 2-patch repair is not unlike that of CAVC with TOF. However, biventricular repair is most challenging in patients with CAVC and complete origin of the aorta from the RV, as in CAVC with DORV and noncommitted VSD and those with CAVC with transposition of the great arteries (TGA) and LVOTO. The technique of VSD translocation allows anatomic biventricular repair for these particularly challenging patients. The arterial switch operation with CAVC repair can be used for patients with CAVC with DORV with subpulmonary VSD extension and CAVC with TGA without left ventricular outflow tract obstruction. Biventricular repair is achievable in most patients with balanced complete atrioventricular canal and conotruncal anomaly. The extreme heterogeneity of CAVC with conotruncal anomalies requires a highly individual approach that is tailored to the specific constellation of lesions in each patient.
Lentiviral gene therapy of murine hematopoietic stem cells ameliorates the Pompe disease phenotype
Authors: van Til Niek P. , Stok Merel , Aerts Kaya Fatima S. F. , de Waard Monique C. , Farahbakhshian Elnaz , Visser Trudi P. , Kroos Marian A. , Jacobs Edwin H. , Willart Monique A. , van der Wegen Pascal , Scholte Bob J. , Lambrecht Bart N. , Duncker Dirk J. , van der Ploeg Ans T. , Reuser Arnold J. J. , Verstegen Monique M. , Wagemaker Gerard
Published: April 2010

Pompe disease (acid α-glucosidase deficiency) is a lysosomal glycogen storage disorder characterized in its most severe early-onset form by rapidly progressive muscle weakness and mortality within the first year of life due to cardiac and respiratory failure. Enzyme replacement therapy prolongs the life of affected infants and supports the condition of older children and adults but entails lifelong treatment and can be counteracted by immune responses to the recombinant enzyme. We have explored the potential of lentiviral vector–mediated expression of human acid α-glucosidase in hematopoietic stem cells (HSCs) in a Pompe mouse model. After mild conditioning, transplantation of genetically engineered HSCs resulted in stable chimerism of approximately 35% hematopoietic cells that overexpress acid α-glucosidase and in major clearance of glycogen in heart, diaphragm, spleen, and liver. Cardiac remodeling was reversed, and respiratory function, skeletal muscle strength, and motor performance improved. Overexpression of acid α-glucosidase did not affect overall hematopoietic cell function and led to immune tolerance as shown by challenge with the human recombinant protein. On the basis of the prominent and sustained therapeutic efficacy without adverse events in mice we conclude that ex vivo HSC gene therapy is a treatment option worthwhile to pursue.
Human leukocyte antigen class I and II alleles in non-Hodgkin lymphoma etiology
Authors: Wang Sophia S. , Abdou Amr M. , Morton Lindsay M. , Thomas Rasmi , Cerhan James R. , Gao Xiaojiang , Cozen Wendy , Rothman Nathaniel , Davis Scott , Severson Richard K. , Bernstein Leslie , Hartge Patricia , Carrington Mary
Published: April 2010

Genome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes.
Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1
Authors: Meltzer Mirjam E. , Lisman Ton , de Groot Philip G. , Meijers Joost C. M. , le Cessie Saskia , Doggen Carine J. M. , Rosendaal Frits R.
Published: April 2010

Elevated plasma clot lysis time (CLT) increases risk of venous and arterial thrombosis. It is unclear which fibrinolytic factors contribute to thrombosis risk. In 743 healthy control subjects we investigated determinants of CLT. By comparison with 770 thrombosis patients, we assessed plasma levels of fibrinolytic proteins as risk factors for a first thrombosis. Plasminogen activator inhibitor-1 (PAI-1) levels were the main determinants of CLT, followed by plasminogen, thrombin-activatable fibrinolysis inhibitor (TAFI), prothrombin, and α2-antiplasmin. Fibrinogen, factor VII, X, and XI contributed minimally. These proteins explained 77% of variation in CLT. Levels of the fibrinolytic factors were associated with thrombosis risk (odds ratios, highest quartile vs lowest, adjusted for age, sex, and body mass index: 1.6 for plasminogen, 1.2 for α2-antiplasmin, 1.6 for TAFI, 1.6 for PAI-1, and 1.8 for tissue plasminogen activator [t-PA]). Adjusting for acute-phase proteins attenuated the risk associated with elevated plasminogen levels. The risk associated with increased t-PA nearly disappeared after adjusting for acute-phase proteins and endothelial activation. TAFI and PAI-1 remained associated with thrombosis after extensive adjustment. In conclusion, CLT reflects levels of all fibrinolytic factors except t-PA. Plasminogen, TAFI, PAI-1, and t-PA are associated with venous thrombosis. However, plasminogen and t-PA levels may reflect underlying risk factors.
Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma
Authors: Richardson Paul G. , Weller Edie , Lonial Sagar , Jakubowiak Andrzej J. , Jagannath Sundar , Raje Noopur S. , Avigan David E. , Xie Wanling , Ghobrial Irene M. , Schlossman Robert L. , Mazumder Amitabha , Munshi Nikhil C. , Vesole David H. , Joyce Robin , Kaufman Jonathan L. , Doss Deborah , Warren Diane L. , Lunde Laura E. , Kaster Sarah , DeLaney Carol , Hideshima Teru , Mitsiades Constantine S. , Knight Robert , Esseltine Dixie-Lee , Anderson Kenneth C.
Published: April 2010

This phase 1/2 study is the first prospective evaluation of lenalidomide-bortezomib-dexamethasone in front-line myeloma. Patients (N = 66) received 3-week cycles (n = 8) of bortezomib 1.0 or 1.3 mg/m2 (days 1, 4, 8, 11), lenalidomide 15 to 25 mg (days 1-14), and dexamethasone 40 or 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12). Responding patients proceeded to maintenance or transplantation. Phase 2 dosing was determined to be bortezomib 1.3 mg/m2, lenalidomide 25 mg, and dexamethasone 20 mg. Most common toxicities included sensory neuropathy (80%) and fatigue (64%), with only 27%/2% and 32%/3% grade 2/3, respectively. In addition, 32% reported neuropathic pain (11%/3%, grade 2/3). Grade 3/4 hematologic toxicities included lymphopenia (14%), neutropenia (9%), and thrombocytopenia (6%). Thrombosis was rare (6% overall), and no treatment-related mortality was observed. Rate of partial response was 100% in both the phase 2 population and overall, with 74% and 67% each achieving very good partial response or better. Twenty-eight patients (42%) proceeded to undergo transplantation. With median follow-up of 21 months, estimated 18-month progression-free and overall survival for the combination treatment with/without transplantation were 75% and 97%, respectively. Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma. This study is registered at http://clinicaltrials.gov as NCT00378105.
Artificial and natural duplicates in pyrosequencing reads of metagenomic data
Authors: Niu Beifang , Fu Limin , Sun Shulei , Li Weizhong
Published: April 2010

Background

Artificial duplicates from pyrosequencing reads may lead to incorrect interpretation of the abundance of species and genes in metagenomic studies. Duplicated reads were filtered out in many metagenomic projects. However, since the duplicated reads observed in a pyrosequencing run also include natural (non-artificial) duplicates, simply removing all duplicates may also cause underestimation of abundance associated with natural duplicates.

Results

We implemented a method for identification of exact and nearly identical duplicates from pyrosequencing reads. This method performs an all-against-all sequence comparison and clusters the duplicates into groups using an algorithm modified from our previous sequence clustering method cd-hit. This method can process a typical dataset in ~10 minutes; it also provides a consensus sequence for each group of duplicates. We applied this method to the underlying raw reads of 39 genomic projects and 10 metagenomic projects that utilized pyrosequencing technique. We compared the occurrences of the duplicates identified by our method and the natural duplicates made by independent simulations. We observed that the duplicates, including both artificial and natural duplicates, make up 4-44% of reads. The number of natural duplicates highly correlates with the samples' read density (number of reads divided by genome size). For high-complexity metagenomic samples lacking dominant species, natural duplicates only make up <1% of all duplicates. But for some other samples like transcriptomic samples, majority of the observed duplicates might be natural duplicates.

Conclusions

Our method is available from http://cd-hit.org as a downloadable program and a web server. It is important not only to identify the duplicates from metagenomic datasets but also to distinguish whether they are artificial or natural duplicates. We provide a tool to estimate the number of natural duplicates according to user-defined sample types, so users can decide whether to retain or remove duplicates in their projects.
Third chromosome candidate genes for conspecific sperm precedence between D. simulans and D. mauritiana
Authors: Levesque Lisa , Brouwers Barb , Sundararajan Vignesh , Civetta Alberto
Published: April 2010

Background

Male - female incompatibilities can be critical in keeping species as separate and discrete units. Premating incompatibilities and postzygotic hybrid sterility/inviability have been widely studied as isolating barriers between species. In recent years, a number of studies have brought attention to postmating prezygotic barriers arising from male - male competition and male - female interactions. Yet little is known about the genetic basis of postmating prezygotic isolation barriers between species.

Results

Using D. simulans lines with mapped introgressions of D. mauritiana into their third chromosome, we find at least two D. mauritiana introgressions causing male breakdown in competitive paternity success. Eighty one genes within the mapped introgressed regions were identified as broad-sense candidates on the basis of male reproductive tract expression and male-related function. The list of candidates was narrowed down to five genes based on differences in male reproductive tract expression between D. simulans and D. mauritiana. Another ten genes were confirmed as candidates using evidence of adaptive gene coding sequence diversification in the D. simulans and/or D. mauritiana lineage. Our results show a complex genetic basis for conspecific sperm precedence, with evidence of gene interactions between at least two third chromosome loci. Pleiotropy is also evident from correlation between conspecific sperm precedence and female induced fecundity and the identification of candidate genes that might exert an effect through genetic conflict and immunity.

Conclusions

We identified at least two loci responsible for conspecific sperm precedence. A third of candidate genes within these two loci are located in the 89B cytogenetic position, highlighting a possible major role for this chromosome position during the evolution of species specific adaptations to postmating prezygotic reproductive challenges.
Thioredoxin and glutathione systems differ in parasitic and free-living platyhelminths
Authors: Otero Lucía , Bonilla Mariana , Protasio Anna V , Fernández Cecilia , Gladyshev Vadim N , Salinas Gustavo
Published: April 2010

Background

The thioredoxin and/or glutathione pathways occur in all organisms. They provide electrons for deoxyribonucleotide synthesis, function as antioxidant defenses, in detoxification, Fe/S biogenesis and participate in a variety of cellular processes. In contrast to their mammalian hosts, platyhelminth (flatworm) parasites studied so far, lack conventional thioredoxin and glutathione systems. Instead, they possess a linked thioredoxin-glutathione system with the selenocysteine-containing enzyme thioredoxin glutathione reductase (TGR) as the single redox hub that controls the overall redox homeostasis. TGR has been recently validated as a drug target for schistosomiasis and new drug leads targeting TGR have recently been identified for these platyhelminth infections that affect more than 200 million people and for which a single drug is currently available. Little is known regarding the genomic structure of flatworm TGRs, the expression of TGR variants and whether the absence of conventional thioredoxin and glutathione systems is a signature of the entire platyhelminth phylum.

Results

We examine platyhelminth genomes and transcriptomes and find that all platyhelminth parasites (from classes Cestoda and Trematoda) conform to a biochemical scenario involving, exclusively, a selenium-dependent linked thioredoxin-glutathione system having TGR as a central redox hub. In contrast, the free-living platyhelminth Schmidtea mediterranea (Class Turbellaria) possesses conventional and linked thioredoxin and glutathione systems. We identify TGR variants in Schistosoma spp. derived from a single gene, and demonstrate their expression. We also provide experimental evidence that alternative initiation of transcription and alternative transcript processing contribute to the generation of TGR variants in platyhelminth parasites.

Conclusions

Our results indicate that thioredoxin and glutathione pathways differ in parasitic and free-living flatworms and that canonical enzymes were specifically lost in the parasitic lineage. Platyhelminth parasites possess a unique and simplified redox system for diverse essential processes, and thus TGR is an excellent drug target for platyhelminth infections. Inhibition of the central redox wire hub would lead to overall disruption of redox homeostasis and disable DNA synthesis.
Phloem small RNAs, nutrient stress responses, and systemic mobility
Authors: Buhtz Anja , Pieritz Janin , Springer Franziska , Kehr Julia
Published: April 2010

Background

Nutrient availabilities and needs have to be tightly coordinated between organs to ensure a balance between uptake and consumption for metabolism, growth, and defense reactions. Since plants often have to grow in environments with sub-optimal nutrient availability, a fine tuning is vital. To achieve this, information has to flow cell-to-cell and over long-distance via xylem and phloem. Recently, specific miRNAs emerged as a new type of regulating molecules during stress and nutrient deficiency responses, and miR399 was suggested to be a phloem-mobile long-distance signal involved in the phosphate starvation response.

Results

We used miRNA microarrays containing all known plant miRNAs and a set of unknown small (s) RNAs earlier cloned from Brassica phloem sap [1], to comprehensively analyze the phloem response to nutrient deficiency by removing sulfate, copper or iron, respectively, from the growth medium. We show that phloem sap contains a specific set of sRNAs that is distinct from leaves and roots, and that the phloem also responds specifically to stress. Upon S and Cu deficiencies phloem sap reacts with an increase of the same miRNAs that were earlier characterized in other tissues, while no clear positive response to -Fe was observed. However, -Fe led to a reduction of Cu- and P-responsive miRNAs. We further demonstrate that under nutrient starvation miR399 and miR395 can be translocated through graft unions from wild type scions to rootstocks of the miRNA processing hen1-1 mutant. In contrast, miR171 was not transported. Translocation of miR395 led to a down-regulation of one of its targets in rootstocks, suggesting that this transport is of functional relevance, and that miR395, in addition to the well characterized miR399, could potentially act as a long-distance information transmitter.

Conclusions

Phloem sap contains a specific set of sRNAs, of which some specifically accumulate in response to nutrient deprivation. From the observation that miR395 and miR399 are phloem-mobile in grafting experiments we conclude that translocatable miRNAs might be candidates for information-transmitting molecules, but that grafting experiments alone are not sufficient to convincingly assign a signaling function.
The realistic performance achievable with mycobacterial automated culture systems in high and low prevalence settings
Authors: van Kampen Sanne C , Anthony Richard M , Klatser Paul R
Published: April 2010

Background

Diagnostic tests are generally used in situations with similar pre-test probability of disease to where they were developed. When these tests are applied in situations with very different pre-test probabilities of disease, it is informative to model the likely implications of known characteristics of test performance in the new situation. This is the case for automated Mycobacterium tuberculosis (MTB) liquid culture systems for tuberculosis case detection which were developed and are widely used in low burden settings but are only beginning to be applied on a large scale in high burden settings.

Methods

Here we model the performance of MTB liquid culture systems in high and low tuberculosis (TB) prevalence settings using detailed published data concentrating on the likely frequency of cross-contamination events.

Results

Our model predicts that as the TB prevalence in the suspect population increases there is an exponential increase in the risk of MTB cross-contamination events expected in otherwise negative samples, even with equivalent technical performance of the laboratories. Quality control and strict cross-contamination measures become increasingly critical as the burden of MTB infection among TB suspects increases. Even under optimal conditions the realistically achievable specificity of these systems in high burden settings will likely be significantly below that obtained in low TB burden laboratories.

Conclusions

Liquid culture systems can play a valuable role in TB case detection in laboratories in high burden settings, but laboratory workers, policy makers and clinicians should be aware of the increased risks, independent of laboratory proficiency, of cross-contamination events in high burden settings.
Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer
Authors: Sánchez-Muñoz Alfonso , Gallego Elena , de Luque Vanessa , Pérez-Rivas Luís G , Vicioso Luís , Ribelles Nuria , Lozano José , Alba Emilio
Published: April 2010

Background

Mutational analysis of the KRAS gene has recently been established as a complementary in vitro diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of KRAS might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although KRAS is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of KRAS in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies.

Methods

Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. KRAS mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type KRAS or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp.

Results

We found no evidence of KRAS oncogenic mutations in all analyzed tumors.

Conclusions

This study indicates that KRAS mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases.
p16

INK4a
hypermethylation and p53, p16 and MDM2 protein expression in Esophageal Squamous Cell Carcinoma
Authors: Taghavi Noushin , Biramijamal Firouzeh , Sotoudeh Masoud , Khademi Hooman , Malekzadeh Reza , Moaven Omeed , Memar Bahram , A'rabi Azadeh , Abbaszadegan Mohammad Reza
Published: April 2010

Background

Tumor suppressor genes p53 and p16
INK4a and the proto-oncogene MDM2 are considered to be essential G1 cell cycle regulatory genes whose loss of function is associated with ESCC carcinogenesis. We assessed the aberrant methylation of the p16 gene and its impact on p16

INK4a
protein expression and correlations with p53 and MDM2 protein expressions in patients with ESCC in the Golestan province of northeastern Iran in which ESCC has the highest incidence of cancer, well above the world average.

Methods

Cancerous tissues and the adjacent normal tissue obtained from 50 ESCC patients were assessed with Methylation-Specific-PCR to examine the methylation status of p16. The expression of p16, p53 and MDM2 proteins was detected by immunohistochemical staining.

Results

Abnormal expression of p16 and p53, but not MDM2, was significantly higher in the tumoral tissue. p53 was concomitantly accumulated in ESCC tumor along with MDM2 overexpression and p16 negative expression. Aberrant methylation of the p16

INK4a
gene was detected in 31/50 (62%) of esophageal tumor samples, while two of the adjacent normal mucosa were methylated (P < 0.001). p16

INK4a
aberrant methylation was significantly associated with decreased p16 protein expression (P = 0.033), as well as the overexpression of p53 (P = 0.020).

Conclusions

p16 hypermethylation is the principal mechanism of p16 protein underexpression and plays an important role in ESCC development. It is associated with p53 protein overexpression and may influence the accumulation of abnormally expressed proteins in p53-MDM2 and p16-Rb pathways, suggesting a possible cross-talk of the involved pathways in ESCC development.
Blood pressure, body mass index and risk of cardiovascular disease in Chinese men and women
Authors: Wang Hongwei , Cao Jie , Li Jianxin , Chen Jichun , Wu Xigui , Duan Xiufang , Huang Jianfeng , Gu Dongfeng
Published: April 2010

Background

It is still uncertain whether increased blood pressure (BP) has a stronger effect on the risk of cardiovascular disease (CVD) in lean persons than in obese persons. We tested it using a data set collected from a large cohort of Chinese adults.

Methods

Systolic and diastolic BP, body mass index (BMI) and other variables were measured in 169,871 Chinese men and women ≥ 40 years of age in 1991 using standard protocols. Follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4%. Data were analyzed with Cox proportional hazards models.

Results

After adjusted for age, sex, cigarette smoking, alcohol consumption, high school education, physical inactivity, geographic region, and urbanization, we found that the effects of systolic or diastolic BP on risk of CVD generally increased with the increasing BMI levels (underweight, normal, overweight, and obese). For example, hazard ratios (HRs) and 95% confidence interval (CI) per 1- standard deviation (SD) increase in systolic BP within corresponding BMI levels were 1.27(1.21-1.33), 1.45(1.41-1.48), 1.52 (1.45-1.59) and 1.63 (1.51-1.76), respectively. Statistically significant interactions (P < 0.0001) were observed between systolic BP, diastolic BP and BMI in relation to CVD. In baseline hypertensive participants we found both obese men and women had higher risk of CVD than normal-weight persons. The multivariate-adjusted HRs(95%CI) were 1.23(1.03-1.47) and 1.20(1.02-1.40), respectively.

Conclusion

Our study suggests that the magnitude of the association between BP and CVD generally increase with increasing BMI. Hypertension should not be regarded as a less serious risk factor in obese than in lean or normal-weight persons in Chinese adults.
Validity of self-reported weight, height and resultant body mass index in Chinese adolescents and factors associated with errors in self-reports
Authors: Zhou Xiaoyan , Dibley Michael J , Cheng Yue , Ouyang Xue , Yan Hong
Published: April 2010

Background

Validity of self-reported height and weight has not been adequately evaluated in diverse adolescent populations. In fact there are no reported validity studies conducted in Asian children and adolescents. This study aims to examine the accuracy of self-reported weight, height, and resultant BMI values in Chinese adolescents, and of the adolescents' subsequent classification into overweight categories.

Methods

Weight and height were self-reported and measured in 1761 adolescents aged 12-16 years in a cross-sectional survey in Xi'an city, China. BMI was calculated from both reported values and measured values. Bland-Altman plots with 95% limits of agreement, Pearson's correlation and Kappa statistics were calculated to assess the agreement.

Results

The 95% limits of agreement were -11.16 and 6.46 kg for weight, -4.73 and 7.45 cm for height, and -4.93 and 2.47 kg/m2for BMI. Pearson correlation between measured and self-reported values was 0.912 for weight, 0.935 for height and 0.809 for BMI. Weighted Kappa was 0.859 for weight, 0.906 for height and 0.754 for BMI. Sensitivity for detecting overweight (includes obese) in adolescents was 56.1%, and specificity was 98.6%. Subjects' area of residence, age and BMI were significant factors associated with the errors in self-reporting weight, height and relative BMI.

Conclusions

Reported weight and height does not have an acceptable agreement with measured data. Therefore, we do not recommend the application of self-reported weight and height to screen for overweight adolescents in China. Alternatively, self-reported data could be considered for use, with caution, in surveillance systems and epidemiology studies.
Perception of epidemic's related anxiety in the General French Population: a cross-sectional study in the Rhône-Alpes region
Authors: Saadatian-Elahi Mitra , Facy Françoise , Del Signore Corinne , Vanhems Philippe
Published: April 2010

Background

To efficiently plan appropriate public health interventions during possible epidemics, governments must take into consideration the following factors about the general population: their knowledge of epidemics, their fears of and psychological responses to them, their level of compliance with government measures and their communities' trusted sources of information. However, such surveys among the French general population are rare.

Methods

A cross-sectional study was conducted in 2006 in a representative sample of 600 subjects living in the Rhône-Alpes region (south-east France) to investigate self-reported knowledge about infectious diseases and anxiety generated by epidemic risk with particular reference to avian influenza. Data on reactions to potentially new epidemics and the confidence level in various sources of information were also collected.

Results

Respondents were most knowledgeable about AIDS, followed by avian influenza. Overall, 75% of respondents had adequate knowledge of avian influenza. The percentage was even higher (88%) among inhabitants of the Ain district, where an avian influenza epidemic had previously been reported. However, 39% expressed anxiety about this disease. In total, 20% of respondents with knowledge about avian influenza stated that they had changed their behaviours during the epizooty. Epidemics were perceived as a real threat by 27% of respondents. In the event of a highly contagious outbreak, the majority of respondents said they would follow the advice given by authorities. The study population expressed a high level of confidence in physicians and scientists, but had strong reservations about politicians, deputies and the media.

Conclusions

Although the survey was conducted only four months after the avian influenza outbreak, epidemics were not perceived as a major threat by the study population. The results showed that in the event of a highly infectious disease, the population would comply with advice given by public authorities.
Use of the piggyBac transposon to create HIV-1 gag transgenic insect cell lines for continuous VLP production
Authors: Lynch Alisson G , Tanzer Fiona , Fraser Malcolm J , Shephard Enid G , Williamson Anna-Lise , Rybicki Edward P
Published: April 2010

Background

Insect baculovirus-produced Human immunodeficiency virus type 1 (HIV-1) Gag virus-like-particles (VLPs) stimulate good humoral and cell-mediated immune responses in animals and are thought to be suitable as a vaccine candidate. Drawbacks to this production system include contamination of VLP preparations with baculovirus and the necessity for routine maintenance of infectious baculovirus stock. We used piggyBac transposition as a novel method to create transgenic insect cell lines for continuous VLP production as an alternative to the baculovirus system.

Results

Transgenic cell lines maintained stable gag transgene integration and expression up to 100 cell passages, and although the level of VLPs produced was low compared to baculovirus-produced VLPs, they appeared similar in size and morphology to baculovirus-expressed VLPs. In a murine immunogenicity study, whereas baculovirus-produced VLPs elicited good CD4 immune responses in mice when used to boost a prime with a DNA vaccine, no boost response was elicited by transgenically produced VLPs.

Conclusion

Transgenic insect cells are stable and can produce HIV Pr55 Gag VLPs for over 100 passages: this novel result may simplify strategies aimed at making protein subunit vaccines for HIV. Immunogenicity of the Gag VLPs in mice was less than that of baculovirus-produced VLPs, which may be due to lack of baculovirus glycoprotein incorporation in the transgenic cell VLPs. Improved yield and immunogenicity of transgenic cell-produced VLPs may be achieved with the addition of further genetic elements into the piggyBac integron.
Epitope mapping of PfCP-2.9, an asexual blood-stage vaccine candidate of Plasmodium falciparum
Authors: Li Changling , Wang Rui , Wu Yuan , Zhang Dongmei , He Zhicheng , Pan Weiqing
Published: April 2010

Background

Apical membrane antigen 1 (AMA-1) and merozoite surface protein 1 (MSP1) of Plasmodium falciparum are two leading blood-stage malaria vaccine candidates. A P. falciparum chimeric protein 2.9 (PfCP-2.9) has been constructed as a vaccine candidate, by fusing AMA-1 domain III (AMA-1 (III)) with a C-terminal 19 kDa fragment of MSP1 (MSP1-19) via a 28-mer peptide hinge. PfCP-2.9 was highly immunogenic in animal studies, and antibodies elicited by the PfCP-2.9 highly inhibited parasite growth in vitro. This study focused on locating the distribution of epitopes on PfCP-2.9.

Methods

A panel of anti-PfCP-2.9 monoclonal antibodies (mAbs) were produced and their properties were examined by Western blot as well as in vitro growth inhibition assay (GIA). In addition, a series of PfCP-2.9 mutants containing single amino acid substitution were produced in Pichia pastoris. Interaction of the mAbs with the PfCP-2.9 mutants was measured by both Western blot and enzyme-linked immunosorbent assay (ELISA).

Results

Twelve mAbs recognizing PfCP-2.9 chimeric protein were produced. Of them, eight mAbs recognized conformational epitopes and six mAbs showed various levels of inhibitory activities on parasite growth in vitro. In addition, seventeen PfCP-2.9 mutants with single amino acid substitution were produced in Pichia pastoris for interaction with mAbs. Reduced binding of an inhibitory mAb (mAb7G), was observed in three mutants including M62 (Phe491→Ala), M82 (Glu511→Gln) and M84 (Arg513→Lys), suggesting that these amino acid substitutions are critical to the epitope corresponding to mAb7G. The binding of two non-inhibitory mAbs (mAbG11.12 and mAbW9.10) was also reduced in the mutants of either M62 or M82. The substitution of Leu31 to Arg resulted in completely abolishing the binding of mAb1E1 (a blocking antibody) to M176 mutant, suggesting that the Leu residue at this position plays a crucial role in the formation of the epitope. In addition, the Asn15 residue may also play an important role in the global folding of PfCP-2.9, as its substitution by Arg lead to reduced binding of most mAbs and abolishing the binding of mAb6G and mAbP5-W12.

Conclusions

This study provided valuable information on epitopes of PfCP-2.9 vaccine candidate through generation of a panel of mAbs and a series of PfCP-2.9 mutants. The information may prove to be useful for designing more effective malaria vaccines against blood-stage parasites.