bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of cardiac structure and function in patients without and with peripheral oedema during rosiglitazone treatment
Authors: Narang Nikhil , Armstead Sumiko I , Stream Amanda , Abdullah Shuaib M , See Raphael , Snell Peter G , McGavock Jonathan , Ayers Colby R , Gore M Odette , Khera Amit , de Lemos James A , McGuire Darren K
Published: May 2011

Background: Thiazolidinediones cause peripheral oedema, the aetiology of which remains poorly understood.

Methods: In a sub-study of a 6-month trial comparing rosiglitazone (Rsg) versus placebo, we compared those with versus without oedema among the 74 subjects treated with Rsg with respect to peak oxygen consumption indexed to fat-free mass (VO2peak-FFM ), cardiac MRI and markers of plasma volume expansion.

Results: Almost half (49%) of the Rsg-treated patients developed oedema. Baseline VO 2peak-FFM was not different between those with versus without oedema (25.8 versus 28.2 ml/kg/min; p = 0.22) and declined 5% in the oedema group (Δ -1.3 ml/min/kg; p = 0.005) with no change in those without oedema. Stroke volume increased in both groups (Δ 8.7 and 8.8 ml; p < 0.001 for each); end-diastolic volume increased only in those with oedema (+13.1 ml; p = 0.001). No other cardiac function changes were observed. In both groups, weight increased (3.6 and 2.2 kg) and haematocrit decreased (-3.2% and -2.1%; p < 0.001 for each). In those with oedema, albumin decreased (-0.2 g/dl) and brain natriuretic peptide increased (11.9 pg/ml; p < 0.03 for each).

Conclusions: Oedema was associated with a small decline in VO2peak FFM, no adverse effects on cardiac function, and changes in selected measures suggesting that volume expansion underpins Rsg oedema.
The predictive value of inflammatory activity and markers of the adipo-insular axis on restenosis in patients with type 2 diabetes
Authors: Hage Camilla , Grip Lars , Malmberg Klas , Rydén Lars , Wallander Märit , Saleh Nawsad
Published: May 2011

Aims: Patients with type 2 diabetes (T2DM) have a high restenosis rate after percutaneous coronary intervention (PCI). This study investigated whether markers of inflammation and the adipo-insular axis associated with T2DM and poor metabolic control were able to predict restenosis after PCI in T2DM patients.

Methods and results: The predictive value of traditional and non-traditional risk markers, including IL-1β, IL-6, TNF-α, hsCRP, interferon gamma, leptin, IGF-I, insulin, proinsulin and NT-proBNP, was investigated in 82 patients with T2DM. A re-angiography 6 months after the index percutaneous coronary intervention (PCI) revealed that 43% of the patients had a restenosis. In a multiple regression analysis, the only independent predictors of restenosis were fasting glucose before the PCI and previous myocardial infarction (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.07—1.92; p = 0.015 and OR 8.00, 95% CI 2.49—25.67; p ≤ 0.001, respectively). None of the other markers remained as significant predictors.

Conclusion: Fasting glucose prior to the PCI was an independent predictor of restenosis in patients with T2DM while analyses of a variety of markers related to inflammation and the adipo-insular axis did not add any further information.
A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE-/- mouse model
Authors: Gaspari Tracey , HongBin Liu  , Welungoda Iresha , Yunshan Hu  , Widdop Robert E , Knudsen Lotte B , Simpson Richard W , Dear Anthony E
Published: May 2011

The glucagon like peptide-1 receptor (GLP-1R) agonist liraglutide attenuates induction of plasminogen activator inhibitor type-1 (PAI-1) and vascular adhesion molecule (VAM) expression in human vascular endothelial cells (hVECs) in vitro and may afford protection against endothelial cell dysfunction (ECD), an early abnormality in diabetic vascular disease. Our study aimed to establish the dependence of the in vitro effects of liraglutide on the GLP-1R and characterise its in vivo effects in a mouse model of ECD. In vitro studies utilised the human vascular endothelial cell line C11-STH and enzyme-linked immunosorbent assays (ELISA) for determination of PAI-1 and VAM expression. In vivo studies of vascular reactivity and immunohistochemical analysis were performed in the ApoE-/- mouse model. In vitro studies demonstrated GLP-1R-dependent liraglutide-mediated inhibition of stimulated PAI-1 and VAM expression. In vivo studies demonstrated significant improvement in endothelial function in liraglutide treated mice, a GLP-1R dependent effect. Liraglutide treatment also increased endothelial nitric oxide synthase (eNOS) and reduced intercellular adhesion molecule-1 (ICAM-1) expression in aortic endothelium, an effect again dependent on the GLP-1R. Together these studies identify in vivo protection, by the GLP-1R agonist liraglutide, against ECD and provide a potential molecular mechanism responsible for these effects.
Safety and efficacy of saxagliptin added to thiazolidinedione over 76 weeks in patients with type 2 diabetes mellitus
Authors: Hollander Priscilla L , Jia Li  , Frederich Robert , Allen Elsie , Chen Roland ,   CV181013 Investigators
Published: May 2011

To assess the long-term efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus inadequately controlled with thiazolidinedione monotherapy, 565 patients were randomised to saxagliptin (2.5 mg or 5 mg) or placebo added to thiazolidinedione over 76 weeks (24-week short-term + 52-week long-term extension period) in this phase 3, double-blind, placebo-controlled trial; 360 patients completed the study. At 76 weeks, adjusted mean changes from baseline HbA1C (repeated measures model; 95% CI) for saxagliptin 2.5 mg, 5 mg, and placebo were -0.59% (-0.75, -0.43), -1.09% (-1.26, -0.93), and -0.20% (-0.39, -0.01), respectively ( post hoc and nominal p=0.0019 and p<0.0001 for saxagliptin 2.5 mg and 5 mg vs. placebo, respectively). Adverse event frequency was similar between groups. Confirmed hypoglycaemic events were 1.0% and 0% vs. 0.5% for saxagliptin 2.5 mg and 5 mg vs. placebo, respectively. Results should be interpreted with caution given the proportion of patients who discontinued or required glycaemic rescue therapy during the 76-week course of study. Saxagliptin added to thiazolidinedione provided sustained incremental efficacy vs. placebo with little hypoglycaemia for up to 76 weeks and was generally well tolerated.
Impaired compensatory response to hypovolaemic circulatory stress in type 1 diabetes mellitus
Authors: Lindenberger Marcus , Olsen Henrik , Lanne Toste
Published: May 2011

Diabetes mellitus is associated with decreased haemodynamic stability and reduced tolerance to hypovolaemia. Compensatory haemodynamic responses during experimental hypovolaemia in type 1 diabetes patients with (DMR+) and without (DMR-) retinopathy as well as healthy controls (C) were studied. Lower body negative pressure created hypovolaemic circulatory stress. Volumetric techniques were used to assess the compensatory capacitance response (redistribution of peripheral venous blood to the central circulation) and to assess capillary fluid absorption from tissue to blood. The compensatory capacitance response was 1/3 lower in DMR+ compared with C ( p = 0.002) and DMR- ( p = 0.01). Net capillary fluid absorption was reduced by one-third in DMR- and DMR+ compared with C (each p < 0.05). Type 1 diabetes patients with retinopathy demonstrate reduced mobilisation of peripheral venous blood to the central circulation. Furthermore, type 1 diabetes patients present with impaired capillary fluid absorption, which in combination with potentially decreased sympathetic vasoconstriction impedes cardiovascular homeostasis during acute hypovolaemic stress.
Harnessing Social Media for Health Promotion and Behavior Change
Authors: Korda Holly , Itani Zena
Published: May 2011

Rapid and innovative advances in participative Internet communications, referred to as “social media,” offer opportunities for modifying health behavior. Social media let users choose to be either anonymous or identified. People of all demographics are adopting these technologies whether on their computers or through mobile devices, and they are increasingly using these social media for health-related issues. Although social media have considerable potential as tools for health promotion and education, these media, like traditional health promotion media, require careful application and may not always achieve their desired outcomes. This article summarizes current evidence and understanding of using social media for health promotion. More important, it discusses the need for evaluating the effectiveness of various forms of social media and incorporating outcomes research and theory in the design of health promotion programs for social media.
Policy and politics
Authors: Waters Elizabeth
Published: May 2011

Evidence of new innovations: Investing in evidence synthesis, generation and translation ensures public health innovations improve population health
Feature
Authors: Hunter Dawn
Published: May 2011

With governments across the world facing the prospect of an ageing population, the debate about ‘active ageing’ is entering the mainstream and the European Commission has proposed that next year should be the European Year for Active Ageing
Lean thinking in NHS Blood and Transplant
Authors: Warwick Robert
Published: May 2011

Robert Warwick, from NHS Blood and Transplant, discusses the importance of ongoing conversations in implementing ‘Lean’ programmes.
Innovating to achieve sustainable wellbeing inside the built environment
Authors: Hemingway Ann , Steven Paul
Published: May 2011

Dr Ann Hemingway and Dr Paul Steven from the Centre for Wellbeing and Quality of Life at Bournemouth University look at the importance of creating a supportive environment to encourage people to have the confidence to take risks and move out of their comfort zone.
A new vision for care: Looking beyond the NHS to the whole care ecosystem
Authors: Welbourn David , Fathers Dean , Holbourn Alison
Published: May 2011

Dr David Welbourn, Dean Fathers and Alison Holbourn from the Centre for Better Managed Health and Social Care, London put forward a new vision for healthcare.
Immunogenicity and other problems associated with the use of biopharmaceuticals
Authors: Tovey Michael G. , Lallemand Christophe
Published: May 2011

Biopharmaceuticals are used widely for the treatment of cancer, chronic viral hepatitis, inflammatory, and autoimmune diseases. Biopharmaceuticals such as interferons are well tolerated for the most part with the most common adverse events observed being ‘flu-like’ symptoms that resolve rapidly after initial treatment. Prolonged treatment is associated, however, with more serious adverse events including leucopenia, thrombocytopenia, and neuropsychiatric effects, which may necessitate dose reduction or even cessation of treatment in some patients. Recombinant growth factors, such as erythropoietin (EPO), granulocyte colony-stimulating factor, or granulocyte macrophage colony-stimulating factor, are for the most part well tolerated, although severe complications have been reported in patients with cancer or chronic kidney disease treated with EPO. Similarly, treatment of patients with cancer with high doses of interleukin-2 is associated with significant toxicity. Treatment of chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis, and Crohn’s disease, with antitumor necrosis factor-alpha monoclonal antibodies is associated with an increased risk of granulomatous infections and, in particular, tuberculosis. The monoclonal antibody, natalizumab, that targets alpha4 integrins is effective in the treatment of multiple sclerosis but is associated with the activation of JC virus and development of progressive multifocal leukoencephalopathy. Repeated administration of recombinant proteins can cause a break in immune tolerance in some patients resulting in the production of a polyclonal antibody response that can adversely affect pharmacokinetics and clinical response. In addition, neutralizing antibodies that cross react with nonredundant essential proteins such as EPO can cause severe autoimmune reactions.
No association of maternal vitamin E intake with higher risk of cardiovascular malformations in children: a population-based case–control study
Authors: Szilasi Mária , Bártfai Liza , Bártfai Zoltán , Bánhidy Ferenc , Czeizel Andrew E.
Published: May 2011

Objective:

In Hungary, vitamin E is frequently used to prevent repeated or threatened abortion. A previous study showed a higher risk of cardiovascular malformations in the children of pregnant women who had a high vitamin E intake either in their diet or by taking supplements. The objective was to examine this association.

Methods:

The Hungarian Case–Control Surveillance System of Congenital Abnormalities, 1980–1996, is a large, population-based dataset including 22,843 cases with congenital abnormalities, 38,151 healthy controls matched to the cases, and 834 patient controls with Down syndrome. Vitamin E treatment was compared in the mothers of these children.

Results:

The mothers of 1418 cases with congenital abnormalities (6.2%), 2267 controls (6.0%) and 43 patient controls (5.2%) had vitamin E treatment during pregnancy. A preliminary comparison of cases and controls showed a higher risk for four congenital abnormality groups, including cardiovascular malformations. However, if only prospectively and medically recorded vitamin E treatments in the prenatal maternity logbook were evaluated during the critical period of different congenital abnormalities, the higher risk for these congenital abnormalities was not found.

Conclusions:

The results of this study were based on relatively high-dose vitamin E intake in pregnant women and were not able to confirm the previously reported teratogenic effect of vitamin E.
Inferring functional modules of protein families with probabilistic topic models
Authors: Konietzny Sebastian GA , Dietz Laura , McHardy Alice C
Published: May 2011

Background

Genome and metagenome studies have identified thousands of protein families whose functions are poorly understood and for which techniques for functional characterization provide only partial information. For such proteins, the genome context can give further information about their functional context.

Results

We describe a Bayesian method, based on a probabilistic topic model, which directly identifies functional modules of protein families. The method explores the co-occurrence patterns of protein families across a collection of sequence samples to infer a probabilistic model of arbitrarily-sized functional modules.

Conclusions

We show that our method identifies protein modules - some of which correspond to well-known biological processes - that are tightly interconnected with known functional interactions and are different from the interactions identified by pairwise co-occurrence. The modules are not specific to any given organism and may combine different realizations of a protein complex or pathway within different taxa.
Myomegalin is a novel A-kinase anchoring protein involved in the phosphorylation of cardiac myosin binding protein C
Authors: Uys Gerrida M , Ramburan Amsha , Loos Benjamin , Kinnear Craig J , Korkie Lundi J , Mouton Jomien , Riedemann Johann , Moolman-Smook Johanna C
Published: May 2011

Background

Cardiac contractility is regulated by dynamic phosphorylation of sarcomeric proteins by kinases such as cAMP-activated protein kinase A (PKA). Efficient phosphorylation requires that PKA be anchored close to its targets by A-kinase anchoring proteins (AKAPs). Cardiac Myosin Binding Protein-C (cMyBPC) and cardiac troponin I (cTNI) are hypertrophic cardiomyopathy (HCM)-causing sarcomeric proteins which regulate contractility in response to PKA phosphorylation.

Results

During a yeast 2-hybrid (Y2H) library screen using a trisphosphorylation mimic of the C1-C2 region of cMyBPC, we identified isoform 4 of myomegalin (MMGL) as an interactor of this N-terminal cMyBPC region. As MMGL has previously been shown to interact with phosphodiesterase 4D, we speculated that it may be a PKA-anchoring protein (AKAP).

To investigate this possibility, we assessed the ability of MMGL isoform 4 to interact with PKA regulatory subunits R1A and R2A using Y2H-based direct protein-protein interaction assays. Additionally, to further elucidate the function of MMGL, we used it as bait to screen a cardiac cDNA library. Other PKA targets, viz. CARP, COMMD4, ENO1, ENO3 and cTNI were identified as putative interactors, with cTNI being the most frequent interactor.

We further assessed and confirmed these interactions by fluorescent 3D-co-localization in differentiated H9C2 cells as well as byin vivoco-immunoprecipitation. We also showed that quantitatively more interaction occurs between MMGL and cTNI under β-adrenergic stress. Moreover, siRNA-mediated knockdown of MMGL leads to reduction of cMyBPC levels under conditions of adrenergic stress, indicating that MMGL-assisted phosphorylation is requisite for protection of cMyBPC against proteolytic cleavage.

Conclusions

This study ascribes a novel function to MMGL isoform 4: it meets all criteria for classification as an AKAP, and we show that is involved in the phosphorylation of cMyBPC as well as cTNI, hence MMGL is an important regulator of cardiac contractility. This has further implications for understanding the patho-aetiology of HCM-causing mutations in the genes encoding cMyBPC and cTNI, and raises the question of whether MMGL might itself be considered a candidate HCM-causing or modifying factor.
Physical mapping and BAC-end sequence analysis provide initial insights into the flax (Linum usitatissimum L.) genome
Authors: Ragupathy Raja , Rathinavelu Rajkumar , Cloutier Sylvie
Published: May 2011

Background

Flax (Linum usitatissimumL.) is an important source of oil rich in omega-3 fatty acids, which have proven health benefits and utility as an industrial raw material. Flax seeds also contain lignans which are associated with reducing the risk of certain types of cancer. Its bast fibres have broad industrial applications. However, genomic tools needed for molecular breeding were non existent. Hence a project, Total Utilization Flax GENomics (TUFGEN) was initiated. We report here the first genome-wide physical map of flax and the generation and analysis of BAC-end sequences (BES) from 43,776 clones, providing initial insights into the genome.

Results

The physical map consists of 416 contigs spanning ~368 Mb, assembled from 32,025 fingerprints, representing roughly 54.5% to 99.4% of the estimated haploid genome (370-675 Mb). The N50 size of the contigs was estimated to be ~1,494 kb. The longest contig was ~5,562 kb comprising 437 clones. There were 96 contigs containing more than 100 clones. Approximately 54.6 Mb representing 8-14.8% of the genome was obtained from 80,337 BES. Annotation revealed that a large part of the genome consists of ribosomal DNA (~13.8%), followed by known transposable elements at 6.1%. Furthermore, ~7.4% of sequence was identified to harbour novel repeat elements. Homology searches against flax-ESTs and NCBI-ESTs suggested that ~5.6% of the transcriptome is unique to flax. A total of 4064 putative genomic SSRs were identified and are being developed as novel markers for their use in molecular breeding.

Conclusion

The first genome-wide physical map of flax constructed with BAC clones provides a framework for accessing target loci with economic importance for marker development and positional cloning. Analysis of the BES has provided insights into the uniqueness of the flax genome. Compared to other plant genomes, the proportion of rDNA was found to be very high whereas the proportion of known transposable elements was low. The SSRs identified from BES will be valuable in saturating existing linkage maps and for anchoring physical and genetic maps. The physical map and paired-end reads from BAC clones will also serve as scaffolds to build and validate the whole genome shotgun assembly.
The impact of oxygen on the transcriptome of recombinant S. cerevisiae and P. pastoris - a comparative analysis
Authors: Baumann Kristin , Dato Laura , Graf Alexandra B , Frascotti Gianni , Dragosits Martin , Porro Danilo , Mattanovich Diethard , Ferrer Pau , Branduardi Paola
Published: May 2011

Background

Saccharomyces cerevisiae and Pichia pastoris are two of the most relevant microbial eukaryotic platforms for the production of recombinant proteins. Their known genome sequences enabled several transcriptomic profiling studies under many different environmental conditions, thus mimicking not only perturbations and adaptations which occur in their natural surroundings, but also in industrial processes. Notably, the majority of such transcriptome analyses were performed using non-engineered strains.

In this comparative study, the gene expression profiles of S. cerevisiae and P. pastoris, a Crabtree positive and Crabtree negative yeast, respectively, were analyzed for three different oxygenation conditions (normoxic, oxygen-limited and hypoxic) under recombinant protein producing conditions in chemostat cultivations.

Results

The major differences in the transcriptomes of S. cerevisiae and P. pastoris were observed between hypoxic and normoxic conditions, where the availability of oxygen strongly affected ergosterol biosynthesis, central carbon metabolism and stress responses, particularly the unfolded protein response. Steady state conditions under low oxygen set-points seemed to perturb the transcriptome of S. cerevisiae to a much lesser extent than the one of P. pastoris, reflecting the major tolerance of the baker's yeast towards oxygen limitation, and a higher fermentative capacity. Further important differences were related to Fab production, which was not significantly affected by oxygen availability in S. cerevisiae, while a clear productivity increase had been previously reported for hypoxically grown P. pastoris.

Conclusions

The effect of three different levels of oxygen availability on the physiology of P. pastoris and S. cerevisiae revealed a very distinct remodelling of the transcriptional program, leading to novel insights into the different adaptive responses of Crabtree negative and positive yeasts to oxygen availability. Moreover, the application of such comparative genomic studies to recombinant hosts grown in different environments might lead to the identification of key factors for efficient protein production.
Probing genomic diversity and evolution of Streptococcus suis serotype 2 by NimbleGen tiling arrays
Authors: Wu Zuowei , Li Ming , Wang Changjun , Li Jing , Lu Na , Zhang Ruifen , Jiang Yongqiang , Yang Ruifu , Liu Cuihua , Liao Hui , Gao George F , Tang Jiaqi , Zhu Baoli
Published: May 2011

Background

Our previous studies revealed that a new disease form of streptococcal toxic shock syndrome (STSS) is associated with specific Streptococcus suis serotype 2 (SS2) strains. To achieve a better understanding of the pathogenicity and evolution of SS2 at the whole-genome level, comparative genomic analysis of 18 SS2 strains, selected on the basis of virulence and geographic origin, was performed using NimbleGen tiling arrays.

Results

Our results demonstrate that SS2 isolates have highly divergent genomes. The 89K pathogenicity island (PAI), which has been previously recognized as unique to the Chinese epidemic strains causing STSS, was partially included in some other virulent and avirulent strains. The ABC-type transport systems, encoded by 89K, were hypothesized to greatly contribute to the catastrophic features of STSS. Moreover, we identified many polymorphisms in genes encoding candidate or known virulence factors, such as PlcR, lipase, sortases, the pilus-associated proteins, and the response regulator RevS and CtsR. On the basis of analysis of regions of differences (RDs) across the entire genome for the 18 selected SS2 strains, a model of microevolution for these strains is proposed, which provides clues into Streptococcus pathogenicity and evolution.

Conclusions

Our deep comparative genomic analysis of the 89K PAI present in the genome of SS2 strains revealed details into how some virulent strains acquired genes that may contribute to STSS, which may lead to better environmental monitoring of epidemic SS2 strains.
Transcriptional profiling of fetal hypothalamic TRH neurons
Authors: Guerra-Crespo Magdalena , Pérez-Monter Carlos , Janga Sarath Chandra , Castillo-Ramírez Santiago , Gutiérrez-Rios Rosa María , Joseph-Bravo Patricia , Pérez-Martínez Leonor , Charli Jean-Louis
Published: May 2011

Background

During murine hypothalamic development, different neuroendocrine cell phenotypes are generated in overlapping periods; this suggests that cell-type specific developmental programs operate to achieve complete maturation. A balance between programs that include cell proliferation, cell cycle withdrawal as well as epigenetic regulation of gene expression characterizes neurogenesis. Thyrotropin releasing hormone (TRH) is a peptide that regulates energy homeostasis and autonomic responses. To better understand the molecular mechanisms underlying TRH neuron development, we performed a genome wide study of its transcriptome during fetal hypothalamic development.

Results

In primary cultures, TRH cells constitute 2% of the total fetal hypothalamic cell population. To purify these cells, we took advantage of the fact that the segment spanning -774 to +84 bp of the Trh gene regulatory region confers specific expression of the green fluorescent protein (GFP) in the TRH cells. Transfected TRH cells were purified by fluorescence activated cell sorting, various cell preparations pooled, and their transcriptome compared to that of GFP- hypothalamic cells. TRH cells undergoing the terminal phase of differentiation, expressed genes implicated in protein biosynthesis, intracellular signaling and transcriptional control. Among the transcription-associated transcripts, we identified the transcription factors Klf4, Klf10 and Atf3, which were previously uncharacterized within the hypothalamus.

Conclusion

To our knowledge, this is one of the first reports identifying transcripts with a potentially important role during the development of a specific hypothalamic neuronal phenotype. This genome-scale study forms a rational foundation for identifying genes that might participate in the development and function of hypothalamic TRH neurons.
Phenotypic characteristics of isolates of Aspergillus section Fumigatifrom different geographic origins and their relationships with genotypic characteristics
Authors: Frías-De León María Guadalupe , Zavala-Ramírez Monserrat , Córdoba Susana , Zúñiga Gerardo , Duarte-Escalante Esperanza , Pérez-Torres Armando , Zepeda-Rodríguez Armando , López-Martínez Irma , Buitrago María José , del Rocío Reyes-Montes María
Published: May 2011

Background

Epidemiological studies worldwide have shown that A. fumigatus exhibits important phenotypic and genotypic diversity, and these findings have been of great importance in improving the diagnosis and treatment of diseases caused by this fungus. However, few studies have been carried out related to the epidemiology of this fungus in Latin America. This study´s aim is to report on the epidemiology of the fungus by analyzing the phenotypic variability of Aspergillus section Fumigati isolates from different Latin American countries and the relationship between this variability, the geographical origin and genotypic characteristics.

Methods

We analyzed the phenotypic characteristics (macro- and micromorphology, conidial size, vesicles size, antifungal susceptibility and thermotolerance at 28, 37 and 48°C) of A. section Fumigati isolates from Mexico (MX), Argentina (AR), Peru (PE) and France (FR). The results were analyzed using analysis of variance (ANOVA) and Tukey's multiple comparison test to detect significant differences. Two dendrograms among isolates were obtained with UPGMA using the Euclidean distance index. One was drawn for phenotypic data, and the other for phenotypic and genotypic data. A PCoA was done for shown isolates in a space of reduced dimensionality. In order to determine the degree of association between the phenotypic and genotypic characteristics AFLP, we calculated the correlation between parwise Euclidean distance matrices of both data sets with the nonparametric Mantel test.

Results

No variability was found in the macromorphology of the studied isolates; however, the micromorphology and growth rate showed that the PE isolates grew at a faster rate and exhibited the widest vesicles in comparison to the isolates from MX, AR and FR. The dendrogram constructed with phenotypic data showed three distinct groups. The group I and II were formed with isolates from PE and FR, respectively, while group III was formed with isolates from MX and AR. The dendrogram with phenotypic and genotypic data showed the same cluster, except for an isolate from FR that formed a separate cluster. This cluster was confirmed using PCoA. The correlation between the phenotypic and genotypic data of the isolates revealed a statistically significant association between these characteristics.

Conclusions

The PE isolates showed specific phenotypic characteristics that clearly differentiate them from the rest of the isolates, which matches the genotypic data. The correlation between the phenotypic and genotypic characteristics showed a statistically significant association. In conclusion, phenotypic and genotypic methods together increase the power of correlation between isolates.
The prognostic effect of ethnicity for gastric and esophageal cancer: the population-based experience in British Columbia, Canada
Authors: Bashash Morteza , Hislop T Greg , Shah Amil M , Le Nhu , Brooks-Wilson Angela , Bajdik Chris D
Published: May 2011

Background

Gastric and esophageal cancers are among the most lethal human malignancies. Their epidemiology is geographically diverse. This study compares the survival of gastric and esophageal cancer patients among several ethnic groups including Chinese, South Asians, Iranians and Others in British Columbia (BC), Canada.

Methods

Data were obtained from the population-based BC Cancer Registry for patients diagnosed with invasive esophageal and gastric cancer between 1984 and 2006. The ethnicity of patients was estimated according to their names and categorized as Chinese, South Asian, Iranian or Other. Cox proportional hazards regression analysis was used to estimate the effect of ethnicity adjusted for patient sex and age, disease histology, tumor location, disease stage and treatment.

Results

The survival of gastric cancer patients was significantly different among ethnic groups. Chinese patients showed better survival compared to others in univariate and multivariate analysis. The survival of esophageal cancer patients was significantly different among ethnic groups when the data was analyzed by a univariate test (p = 0.029), but not in the Cox multivariate model adjusted for other patient and prognostic factors.

Conclusions

Ethnicity may represent underlying genetic factors. Such factors could influence host-tumor interactions by altering the tumor's etiology and therefore its chance of spreading. Alternatively, genetic factors may determine response to treatments. Finally, ethnicity may represent non-genetic factors that affect survival. Differences in survival by ethnicity support the importance of ethnicity as a prognostic factor, and may provide clues for the future identification of genetic or lifestyle factors that underlie these observations.
Selection of drug resistant mutants from random library of Plasmodium falciparum dihydrofolate reductase in Plasmodium berghei model
Authors: Tipsuwan Wachiraporn , Srichairatanakool Somdet , Kamchonwongpaisan Sumalee , Yuthavong Yongyuth , Uthaipibull Chairat
Published: May 2011

Background

The prevalence of drug resistance amongst the human malaria Plasmodium species has most commonly been associated with genomic mutation within the parasites. This phenomenon necessitates evolutionary predictive studies of possible resistance mutations, which may occur when a new drug is introduced. Therefore, identification of possible new Plasmodium falciparum dihydrofolate reductase (Pf DHFR) mutants that confer resistance to antifolate drugs is essential in the process of antifolate anti-malarial drug development.

Methods

A system to identify mutations in Pfdhfr gene that confer antifolate drug resistance using an animal Plasmodium parasite model was developed. By using error-prone PCR and Plasmodium transfection technologies, libraries of Pfdhfr mutant were generated and then episomally transfected to Plasmodium berghei parasites, from which pyrimethamine-resistant Pf DHFR mutants were selected.

Results

The principal mutation found from this experiment was S108N, coincident with the first pyrimethamine-resistance mutation isolated from the field. A transgenic P. berghei, in which endogenous Pbdhfr allele was replaced with the mutant Pfdhfr

S108N
, was generated and confirmed to have normal growth rate comparing to parental non-transgenic parasite and also confer resistance to pyrimethamine.

Conclusion

This study demonstrated the power of the transgenic P. berghei system to predict drug-resistant Pfdhfr mutations in an in vivo parasite/host setting. The system could be utilized for identification of possible novel drug-resistant mutants that could arise against new antifolate compounds and for prediction the evolution of resistance mutations.
Expression of mutant alpha-synuclein modulates microglial phenotype in vitro
Authors: Rojanathammanee Lalida , Murphy Eric J , Combs Colin K
Published: May 2011

Background

Increased reactive microglia are a histological characteristic of Parkinson's disease (PD) brains, positively correlating with levels of deposited α-synuclein protein. This suggests that microglial-mediated inflammatory events may contribute to disease pathophysiology. Mutations in the gene coding for α-synuclein lead to a familial form of PD. Based upon our prior findings that α-synuclein expression regulates microglial phenotype we hypothesized that expression of mutant forms of the protein may contribute to the reactive microgliosis characteristic of PD brains.

Methods

To quantify the effects of wild type and mutant α-synuclein over-expression on microglial phenotype a murine microglial cell line, BV2, was transiently transfected to express human wild type (WT), and mutant α-synuclein (A30P and A53T) proteins. Transfected cells were used to assess changes in microglia phenotype via Western blot analysis, ELISA, phagocytosis, and neurotoxicity assays.

Results

As expected, over-expression of α-synuclein induced a reactive phenotype in the transfected cells. Expression of α-synuclein increased protein levels of cycloxygenase-2 (Cox-2). Transfected cells demonstrated increased secretion of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as increased nitric oxide production. Transfected cells also had impaired phagocytic ability correlating with decreased protein levels of lysosomal-associated membrane protein 1 (LAMP-1). In spite of the increased cytokine secretion profile, the transfected cells did not exhibit increased neurotoxic ability above control non-transfected BV2 cells in neuron-microglia co-cultures.

Conclusions

These data demonstrated that over-expression of α-synuclein drives microglial cells into a form of reactive phenotype characterized by elevated levels of arachidonic acid metabolizing enzymes, cytokine secretion, and reactive nitrogen species secretion all superimposed upon impaired phagocytic potential.
Regulation of Toll-like receptor 1 and -2 in neonatal mice brains after hypoxia-ischemia
Authors: Stridh Linnea , Smith Peter LP , Naylor Andrew S , Wang Xiaoyang , Mallard Carina
Published: May 2011

Background

Hypoxic-ischemic (HI) brain injury remains a major problem in newborns, resulting in increased risk of neurological disorders. Neonatal HI triggers a broad inflammatory reaction in the brain, including activation of the innate immune system. Toll-like receptors (TLRs), which are key components of the innate immune system, are believed to play a role in adult cerebral ischemic injury. The expression of TLRs in the neonatal brain and their regulation after HI is unknown.

Methods

Wild type C57BL/6, TLR 1 knockout (KO) and TLR 2 KO mice were subjected to HI at postnatal day 9 and sacrificed 30 min, 6 h, 24 h or 5 days after HI. TLR mRNA expression was determined by RT-qPCR and protein and cell type localisation by immunohistochemistry (IHC). To evaluate brain injury, infarct volume was measured in the injured hemisphere.

Results

mRNA expression was detected for all investigated TLRs (TLR1-9), both in normal and HI exposed brains. After HI, TLR-1 was down-regulated at 30 min and up-regulated at 6 h and 24 h. TLR-2 was up-regulated at 6 h and 24 h, and TLR-7 at 24 h. Both TLR-5 and TLR-8 were down-regulated at 24 h and 30 min respectively. IHC showed an increase of TLR-1 in neurons in the ipsilateral hemisphere after HI. TLR-2 was constitutively expressed in astrocytes and in a population of neurons in the paraventricular nucleus in the hypothalamus. No changes in expression were detected following HI. Following HI, TLR-2 KO mice, but not TLR-1 KO, showed a decreased infarct volume compared to wild type (p = 0.0051).

Conclusions

This study demonstrates that TLRs are regulated after HI in the neonatal brain. TLR-1 protein was up-regulated in injured areas of the brain but TLR-1 KO animals were not protected from HI. In contrast, TLR-2 was constitutively expressed in the brain and TLR-2 deficiency reduced HI injury. These data suggest that TLR-2, but not TLR-1, plays a role in neonatal HI brain injury.
Induction of immune responses in ducks with a DNA vaccine encoding duck plague virus glycoprotein C
Authors: Lian Bei , Cheng Anchun , Wang Mingshu , Zhu Dekang , Luo Qihui , Jia Renyong , Liu Fei , Han Xinfeng , Chen Xiaoyue
Published: May 2011

Background

A DNA vaccine expressing glycoprotein C (gC) of duck plague virus (DPV) was evaluated for inducing immunity in ducks. The plasmid encoding gC of DPV was administered via intramuscular (IM) injection and gene gun bombardment.

Results

After immunization by both routes virus-specific serum antibody and T-cell responses developed. Vaccination of ducks by IM injection induced a stronger humoral, but weaker cell-mediated immune response. In contrast, a better cell-mediated immune response was achieved by using a gene gun to deliver DNA-coated gold beads to the epidermis with as little as 6 μg of DNA.

Conclusions

This demonstrated that both routes of DNA inoculation can be used for eliciting virus-specific immune responses. Although DNA vaccine containing DPV gC is effective in both intramuscular injection and gene gun bombardment, the latter could induce significantly higher cell-mediated responses against DPV.
Traditions and plant use during pregnancy, childbirth and postpartum recovery by the Kry ethnic group in Lao PDR
Authors: Lamxay Vichith , de Boer Hugo J , Björk Lars
Published: May 2011

Background

Activities and diet during the postpartum period are culturally dictated in many Southeast Asian cultures, and a period of confinement is observed. Plants play an important role in recovery during the postpartum period in diet and traditional medicine. Little is known of the Kry, a small ethnic group whose language was recently described, concerning its traditions and use of plants during pregnancy, parturition, postpartum recovery and infant healthcare. This research aims to study those traditions and identify medicinal plant use.

Methods

Data were collected in the 3 different Kry villages in Khammouane province, Lao PDR, through group and individual interviews with women by female interviewers.

Results

A total of 49 different plant species are used in women's healthcare. Plant use is culturally different from the neighboring Brou and Saek ethnic groups. Menstruation, delivery and postpartum recovery take place in separate, purpose-built, huts and a complex system of spatial restrictions is observed.

Conclusions

Traditions surrounding childbirth are diverse and have been strictly observed, but are undergoing a shift towards those from neighboring ethnic groups, the Brou and Saek. Medicinal plant use to facilitate childbirth, alleviate menstruation problems, assist recovery after miscarriage, mitigate postpartum haemorrhage, aid postpartum recovery, and for use in infant care, is more common than previously reported (49 species instead of 14). The wealth of novel insights into plant use and preparation will help to understand culturally important practices such as traditional delivery, spatial taboos, confinement and dietary restrictions, and their potential in modern healthcare.
En1 and Wnt signaling in midbrain dopaminergic neuronal development
Authors: Alves dos Santos Maria TM , Smidt Marten P
Published: May 2011

Dopaminergic neurons of the ventral mesodiencephalon are affected in significant health disorders such as Parkinson's disease, schizophrenia, and addiction. The ultimate goal of current research endeavors is to improve the clinical treatment of such disorders, such as providing a protocol for cell replacement therapy in Parkinson's disease that will successfully promote the specific differentiation of a stem cell into a dopaminergic neuronal phenotype. Decades of research on the developmental mechanisms of the mesodiencephalic dopaminergic (mdDA) system have led to the identification of many signaling pathways and transcription factors critical in its development. The unraveling of these pathways will help fill in the pieces of the puzzle that today dominates neurodevelopment research: how to make and maintain a mdDA neuron. In the present review, we provide an overview of the mdDA system, the processes and signaling molecules involved in its genesis, with a focus on the transcription factor En1 and the canonical Wnt pathway, highlighting recent findings on their relevance - and interplay - in the development and maintenance of the mdDA system.
Coordinated trafficking of synaptic vesicle and active zone proteins prior to synapse formation
Authors: Bury Luke AD , Sabo Shasta L
Published: May 2011

Background

The proteins required for synaptic transmission are rapidly assembled at nascent synapses, but the mechanisms through which these proteins are delivered to developing presynaptic terminals are not understood. Prior to synapse formation, active zone proteins and synaptic vesicle proteins are transported along axons in distinct organelles referred to as piccolo-bassoon transport vesicles (PTVs) and synaptic vesicle protein transport vesicles (STVs), respectively. Although both PTVs and STVs are recruited to the same site in the axon, often within minutes of axo-dendritic contact, it is not known whether or how PTV and STV trafficking is coordinated before synapse formation.

Results

Here, using time-lapse confocal imaging of the dynamics of PTVs and STVs in the same axon, we show that vesicle trafficking is coordinated through at least two mechanisms. First, a significant proportion of STVs and PTVs are transported together before forming a stable terminal. Second, individual PTVs and STVs share pause sites within the axon. Importantly, for both STVs and PTVs, encountering the other type of vesicle increases their propensity to pause. To determine if PTV-STV interactions are important for pausing, PTV density was reduced in axons by expression of a dominant negative construct corresponding to the syntaxin binding domain of syntabulin, which links PTVs with their KIF5B motor. This reduction in PTVs had a minimal effect on STV pausing and movement, suggesting that an interaction between STVs and PTVs is not responsible for enhancing STV pausing.

Conclusions

Our results indicate that trafficking of STVs and PTVs is coordinated even prior to synapse development. This novel coordination of transport and pausing might provide mechanisms through which all of the components of a presynaptic terminal can be rapidly accumulated at sites of synapse formation.
Clinical and animal research findings in pycnodysostosis and gene mutations of cathepsin K from 1996 to 2011
Authors: Xue Yang , Cai Tao , Shi Songtao , Wang Weiguang , Zhang Yanli , Mao Tianqiu , Duan Xiaohong
Published: May 2011

Cathepsin K (CTSK) is a member of the papain-like cysteine protease family. Mutations in the CTSK gene cause a rare autosomal recessive bone disorder called pycnodysostosis (OMIM 265800). In order to follow the advances in the research about CTSK and pycnodysostosis, we performed a literature retrospective study of 159 pycnodysostosis patients reported since 1996 and focused on the genetic characteristics of CTSK mutations and/or the clinical phenotypes of pycnodysostosis. Thirty three different CTSK mutations have been found in 59 unrelated pycnodysostosis families. Of the 59 families, 37.29% are from Europe and 30.51% are from Asia. A total of 69.70% of the mutations were identified in the mature domain of CTSK, 24.24% in the proregion, and 6.06% in the preregion. The hot mutation spots are found in exons 6 and 7. CTSK mutations result in total loss or inactivity of the CTSK protein, which causes abnormal degradation of bone matrix proteins such as type I collagen. Skeletal abnormalities, including short stature, an increase in bone density with pathologic fractures, and open fontanels and sutures, are the typical phenotypes of pycnodysostosis. Research on Ctsk
-/- mouse models was also reviewed here to elucidate the biological function of Ctsk and the mechanism of pycnodysostosis. New evidence suggests that Ctsk plays an important role in the immune system and may serve as a valid therapeutic target in the future treatment of pycnodysostosis.
Rapid change of strategy is necessary for development of dromedary camel pastoralism in the Cholistan desert of Pakistan
Authors: Raziq Abdul , de Verdier Kerstin , Younas Muhammad
Published: May 2011

The Cholistan desert is part of the ancient Hakra River civilization, one of the oldest of the Aryan settlers in the Indian subcontinent. It is one of the largest deserts in Pakistan, inhabited by around 1.2 million Rohi pastoral people practicing mobile livestock husbandry. This production system is extremely important for food security and conservation of livestock and landscape. The camel is one of the important animal genetic resources and about 80,000 are found in the desert. The main tribe with camel herds is Marrecha. The desert pastoralists also raise goats, sheep and cattle breeds. The major camel breed is Marrecha following by Brela. The precious camel genetic resources are under threat due to commercial agricultural practices, land grabbing and faulty development projects. The policies come from the top and pastoral peoples do not participate in formulating strategies for development. Hence the projects are not supported by local livestock keepers and always result in failure. There is an urgent need to save this pastoral livestock system, especially the camel breeds. It is suggested that niche marketing, value addition, ecotourism and participation of pastoral people in development policies may help achieve this goal. Organization of the livestock keepers in the region can be an efficient tool to halt land grabbing