bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells
Authors: Collins Hilary M , Abdelghany Magdy K , Messmer Marie , Yue Baigong , Deeves Sian E , Kindle Karin B , Mantelingu Kempegowda , Aslam Akhmed , Winkler G Sebastiaan , Kundu Tapas K , Heery David M 
Published: January 2013

AbstractBackgroundPost-translational modifications (PTMs) of histones and other proteins are perturbed in tumours. For example, reduced levels of acetylated H4K16 and trimethylated H4K20 are associated with high tumour grade and poor survival in breast cancer. Drug-like molecules that can reprogram selected histone PTMs in tumour cells are therefore of interest as potential cancer chemopreventive agents. In this study we assessed the effects of the phytocompounds garcinol and curcumin on histone and p53 modification in cancer cells, focussing on the breast tumour cell line MCF7.MethodsCell viability/proliferation assays, cell cycle analysis by flow cytometry, immunodetection of specific histone and p53 acetylation marks, western blotting, siRNA and RT-qPCR.ResultsAlthough treatment with curcumin, garcinol or the garcinol derivative LTK-14 hampered MCF7 cell proliferation, differential effects of these compounds on histone modifications were observed. Garcinol treatment resulted in a strong reduction in H3K18 acetylation, which is required for S phase progression. Similar effects of garcinol on H3K18 acetylation were observed in the osteosarcoma cells lines U2OS and SaOS2. In contrast, global levels of acetylated H4K16 and trimethylated H4K20 in MCF7 cells were elevated after garcinol treatment. This was accompanied by upregulation of DNA damage signalling markers such as γH2A.X, H3K56Ac, p53 and TIP60. In contrast, exposure of MCF7 cells to curcumin resulted in increased global levels of acetylated H3K18 and H4K16, and was less effective in inducing DNA damage markers. In addition to its effects on histone modifications, garcinol was found to block CBP/p300-mediated acetylation of the C-terminal activation domain of p53, but resulted in enhanced acetylation of p53K120, and accumulation of p53 in the cytoplasmic compartment. Finally, we show that the elevation of H4K20Me3 levels by garcinol correlated with increased expression of SUV420H2, and was prevented by siRNA targeting of SUV420H2.ConclusionIn summary, although garcinol and curcumin can both inhibit histone acetyltransferase activities, our results show that these compounds have differential effects on cancer cells in culture. Garcinol treatment alters expression of chromatin modifying enzymes in MCF7 cells, resulting in reprogramming of key histone and p53 PTMs and growth arrest, underscoring its potential as a cancer chemopreventive agent.
Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis
Authors: Zhu Jun , Li Te , Wang Xiaohui , Ye Ming , Cai Jian , Xu Yuejuan , Wu Bin 
Published: January 2013

Abstract

Background
Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear.

Methods
A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP) was evaluated.

Results
After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP). The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate) without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results.

Conclusions
These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option.
How has the flu virus infected the Web? 2010 influenza and vaccine information available on the Internet
Authors: Covolo Loredana , Mascaretti Silvia , Caruana Anna , Orizio Grazia , Caimi Luigi , Gelatti Umberto 
Published: January 2013

Abstract

Background
The 2009–10 influenza pandemic was a major public health concern. Vaccination was recommended by the health authorities, but compliance was not optimal and perception of the presumed associated risks was high among the public. The Internet is increasingly being used as a source of health information and advice. The aim of the study was to investigate the characteristics of websites providing information about flu vaccine and the quality of the information provided.

Methods
Website selection was performed in autumn 2010 by entering eight keywords in two of the most commonly used search engines (Google.com and Yahoo.com). The first three result pages were analysed for each search, giving a total of 480 occurrences. Page rank was evaluated to assess visibility. Websites based on Web 2.0 philosophy, websites merely displaying popular news/articles and single files were excluded from the subsequent analysis. We analysed the selected websites (using WHO criteria) as well as the information provided, using a codebook for pro/neutral websites and a qualitative approach for the adverse ones.

Results
Of the 89 websites selected, 54 dealt with seasonal vaccination, three with anti-H1N1 vaccination and 32 with both. Rank analysis showed that only classic websites (ones not falling in any other category) and one social network were provided on the first pages by Yahoo; 21 classic websites, six displaying popular news/articles and one blog by Google. Analysis of the selected websites revealed that the majority of them (88.8%) had a positive/neutral attitude to flu vaccination. Pro/neutral websites distinguished themselves from the adverse ones by some revealing features like greater transparency, credibility and privacy protection.

Conclusions
We found that the majority of the websites providing information on flu vaccination were pro/neutral and gave sufficient information. We suggest that antivaccinationist information may have been spread by a different route, such as via Web 2.0 tools, which may be more prone to the dissemination of “viral” information. The page ranking analysis revealed the crucial role of search engines regarding access to information on the Internet.
Ultrasonic evaluation of the abductor hallucis muscle in hallux valgus: a cross-sectional observational study
Authors: Stewart Sarah , Ellis Richard , Heath Mike , Rome Keith 
Published: January 2013

AbstractBackgroundThe aim of the study was to investigate the abductor hallucis muscle characteristics, defined as dorso-plantar (DP) thickness, medio-lateral (ML) width, and cross-sectional area (CSA) in relation to the severity of hallux valgus using musculoskeletal ultrasound. One hundred and two feet, mean (SD) age of 60.3 (20.54) years old, displaying varying severities of hallux valgus were stratified into four groups representing the four grades of the Manchester Scale (grade 0: no deformity, grade 1: mild deformity, grade 2: moderate deformity and grade 3: severe deformity).MethodsThe abductor hallucis muscle was imaged in each foot using a portable ultrasound system. The mean (SD) DP thickness, ML width, and CSA measurements were compared across the four Manchester Scale grades using a one-way ANOVA.ResultsSignificant differences in DP thickness were found between feet with no hallux valgus (grade 0) and feet with hallux valgus grade 2 (p = 0.001) and 3 (p < 0.001). Significant differences were also found in ML width between feet with no hallux valgus (grade 0) and feet with grade 2 hallux valgus (p = 0.010). Significant differences in CSA were found between feet with no hallux valgus (grade 0) and feet with grade 2 (p < 0.001) and grade 3 (p < 0.001) hallux valgus. No significant differences in these three muscle characteristics were found between grades 1, 2 and 3 (p > 0.0125).ConclusionsWe speculate that morphological changes to the abductor hallucis muscle occur early in the development of the deformity.
An exploration of student experiences of using biology podcasts in nursing training
Authors: Mostyn Alison , Jenkinson Claire M , McCormick Damion , Meade Oonagh , Lymn Joanne S 
Published: January 2013

AbstractBackgroundStudents regard biological science as one of the most difficult components of the nursing curriculum. However, a good understanding of this area is essential for effective nursing practice. The aim of this study was to explore nursing students’ perceptions of the usefulness of supplementary biology podcasts for their learning.MethodsBiological science podcasts (n = 9) were made available to first-year nursing students (n = 189) as supplementary learning tools. On completion of their first year, students were asked to complete a survey which investigated the frequency of their podcast use, reasons for use and their perception of the usefulness of podcasts as a learning tool. 153 of these students participated in the survey study (80.9%). Two focus groups were conducted with students (n = 6) to gain a detailed understanding of student experiences of the usefulness of the podcasts for their learning.ResultsSurvey data demonstrated that most students (71%) accessed at least one podcast. The majority of students who reported accessing podcasts agreed that they were useful as learning tools (83%), revision aids (83%) and that they helped promote understanding of course materials (72%). Focus group participants discussed how they found podcasts especially useful in terms of revision. Students valued being able to repeatedly access the lecture materials, and appreciated having access to podcasts from a range of lecturers. Focus group members discussed the benefits of live recordings, in terms of valuing the information gleaned from questions asked during the lecture sessions, although there were concerns about the level of background noise in live recordings. Lack of awareness of the availability of podcasts was an issue raised by participants in both the survey component and the focus groups and this negatively impacted on podcast use.ConclusionsNursing students found the availability of biology podcasts helpful for their learning. Successful implementation of these tools to support learning requires teaching staff to understand and promote the importance of these tools.
Changes in red blood cell membrane structure in type 2 diabetes: a scanning electron and atomic force microscopy study
Authors: Buys Antoinette V , Van Rooy Mia-Jean , Soma Prashilla , Van Papendorp Dirk , Lipinski Boguslaw , Pretorius Etheresia 
Published: January 2013

Abstract
Red blood cells (RBCs) are highly deformable and possess a robust membrane that can withstand shear force. Previous research showed that in diabetic patients, there is a changed RBC ultrastructure, where these cells are elongated and twist around spontaneously formed fibrin fibers. These changes may impact erythrocyte function. Ultrastructural analysis of RBCs in inflammatory and degenerative diseases can no longer be ignored and should form a fundamental research tool in clinical studies. Consequently, we investigated the membrane roughness and ultrastructural changes in type 2 diabetes. Atomic force microscopy (AFM) was used to study membrane roughness and we correlate this with scanning electron microscopy (SEM) to compare results of both the techniques with the RBCs of healthy individuals. We show that the combined AFM and SEM analyses of RBCs give valuable information about the disease status of patients with diabetes. Effectiveness of treatment regimes on the integrity, cell shape and roughness of RBCs may be tracked, as this cell’s health status is crucial to the overall wellness of the diabetic patient.
Fibronectin coating of oxygenator membranes enhances endothelial cell attachment
Authors: Cornelissen Christian G , Dietrich Maren , Gromann Kai , Frese Julia , Krueger Stefan , Sachweh Jörg S , Jockenhoevel Stefan 
Published: January 2013

AbstractBackgroundExtracorporeal membrane oxygenation (ECMO) can replace the lungs’ gas exchange capacity in refractory lung failure. However, its limited hemocompatibility, the activation of the coagulation and complement system as well as plasma leakage and protein deposition hamper mid- to long-term use and have constrained the development of an implantable lung assist device. In a tissue engineering approach, lining the blood contact surfaces of the ECMO device with endothelial cells might overcome these limitations. As a first step towards this aim, we hypothesized that coating the oxygenator’s gas exchange membrane with proteins might positively influence the attachment and proliferation of arterial endothelial cells.MethodsSheets of polypropylene (PP), polyoxymethylpentene (TPX) and polydimethylsiloxane (PDMS), typical material used for oxygenator gas exchange membranes, were coated with collagen, fibrinogen, gelatin or fibronectin. Tissue culture treated well plates served as controls. Endothelial cell attachment and proliferation were analyzed for a period of 4 days by microscopic examination and computer assisted cell counting.ResultsEndothelial cell seeding efficiency is within range of tissue culture treated controls for fibronectin treated surfaces only. Uncoated membranes as well as all other coatings lead to lower cell attachment. A confluent endothelial cell layer develops on fibronectin coated PDMS and the control surface only.ConclusionsFibronectin increases endothelial cells’ seeding efficiency on different oxygenator membrane material. PDMS coated with fibronectin shows sustained cell attachment for a period of four days in static culture conditions.
The effects of deprivation and relative deprivation on self-reported morbidity in England: an area-level ecological study
Authors: Zhang Xin , Cook Penny A , Lisboa Paulo J , Jarman Ian H , Bellis Mark A 
Published: January 2013

Abstract

Background
Socioeconomic status gradients in health outcomes are well recognised and may operate in part through the psychological effect of observing disparities in affluence. At an area-level, we explored whether the deprivation differential between neighbouring areas influenced self-reported morbidity over and above the known effect of the deprivation of the area itself.

Methods
Deprivation differentials between small areas (population size approximately 1,500) and their immediate neighbours were derived (from the Index of Multiple Deprivation (IMD)) for Lower Super Output Area (LSOA) in the whole of England (n=32482). Outcome variables were self-reported from the 2001 UK Census: the proportion of the population suffering Limiting Long-Term Illness (LLTI) and ‘not good health’. Linear regression was used to identify the effect of the deprivation differential on morbidity in different segments of the population, controlling for the absolute deprivation. The population was segmented using IMD tertiles and P2 People and Places geodemographic classification. P2 is a commercial market segmentation tool, which classifies small areas according to the characteristics of the population. The classifications range in deprivation, with the most affluent type being ‘Mature Oaks’ and the least being ‘Urban Challenge’.

Results
Areas that were deprived compared to their immediate neighbours suffered higher rates of ‘not good health’ (β=0.312, p<0.001) and LLTI (β=0.278, p<0.001), after controlling for the deprivation of the area itself (‘not good health’—ß=0.655, p<0.001; LLTI—ß=0.548, p<0.001). The effect of the deprivation differential relative to the effect of deprivation was strongest in least deprived segments (e.g., for ‘not good health’, P2 segments ‘Mature Oaks’—β=0.638; ‘Rooted Households’—β=0.555).

Conclusions
Living in an area that is surrounded by areas of greater affluence has a negative impact on health in England. A possible explanation for this phenomenon is that negative social comparisons between areas cause ill-health. This ‘psychosocial effect’ is greater still in least deprived segments of the population, supporting the notion that psychosocial effects become more important when material (absolute) deprivation is less relevant.
High efficacy of CpG-ODN, Cetuximab and Cisplatin combination for very advanced ovarian xenograft tumors
Authors: Sommariva Michele , de Cesare Michelandrea , Meini Alessandra , Cataldo Alessandra , Zaffaroni Nadia , Tagliabue Elda , Balsari Andrea 
Published: January 2013

Abstract

Background
To mimic clinical treatment situations in advanced human ovarian disease, we tested the efficacy of CpG-oligodeoxynucleotides (CpG-ODN), synthetic DNA sequences recognized by Toll-like receptor 9 and able to induce innate/adaptive immune responses, in combination with other possible therapeutic reagents in ovarian carcinoma ascites-bearing athymic mice.

Methods
Mice injected i.p. with IGROV-1 ovarian cancer cells were treated at different stages of ascites progression for 4 weeks with CpG-ODN, alone or in combination with Bevacizumab, Polyinosinic:Polycytidylic acid (Poly(I):Poly(C)), Gefitinib, Cetuximab and Cisplatin. Median survival time (MST) was calculated for each group. IGROV-1 cells treated or not with Cetuximab were assayed for antibody-dependent cellular cytotoxicity by 51Cr-release assay, and for macrophage antibody-dependent cell-mediated phagocytosis by flow cytometry.

Results
In mice treated when ascitic fluid began to accumulate, CpG-ODN combined with Bevacizumab, Poly(I):Poly(C) or Gefitinib did not significantly increase MST as compared with that using CpG-ODN alone, whereas MST in mice treated with CpG-ODN plus Cetuximab was significantly increased (>103 days for combination vs 62 days for CpG alone; P = 0.0008), with 4/8 mice alive at the end of the experiment. In experiments in mice showing increased abdominal volume and body weight (27.9 ± 0.8 g after vs 23 ± 1.1 g before tumor cell injection), treatment with Cisplatin in addition to CpG-ODN/Cetuximab led to significantly increased MST (105.5 days; P = 0.001), with all mice still alive at 85 days, over that using CpG-ODN/Cetuximab (66 days), Cetuximab/Cisplatin (18.5 days), Cisplatin (23 days) or saline (16 days). At a very advanced stage of disease (body weight: 31.4 ± 0.9 g), when more than half of control mice had to be sacrificed 6 days after starting treatments, the triple-combination therapy still increased MST (45 days; P = 0.0089) vs controls.

Conclusions
CpG-ODN combination therapies that enhance the immune response in the tumor microenvironment and concomitantly target tumor cells are highly efficacious even in experimental advanced malignancies. Although differences in the distribution of TLR9 in mice and humans and the enrichment of this receptor on innate immune cells of athymic mice must be considered, our results indicate a promising strategy to treat ovarian cancer patients with bulky ascites.
Lineage shift in Indian strains of Dengue virus serotype-3 (Genotype III), evidenced by detection of lineage IV strains in clinical cases from Kerala
Authors: Manakkadan Anoop , Joseph Iype , Prasanna Raji Rajendran , kunju Riaz Ismail , Kailas Lalitha , Sreekumar Easwaran 
Published: January 2013

Abstract

Background
Local epidemiology of Dengue is defined by the genetic diversity of the circulating Dengue virus (DENV) strains. This important information is not available for the virus strains from most parts of the Indian subcontinent. The present study focused on the genetic diversity of the serotype 3 DENV strains (DENV-3) from India.

Results
A total of 22 DENV-3 strains identified by reverse-transcription PCR analysis of serum samples from 709 patients were studied. These samples were collected over a period of 4 years (2008–2011) from dengue fever suspected patients from Kerala, a dengue endemic state in South India. Comparison of a 1740bp nucleotide sequence of the viral Capsid-Pre-membrane-Envelope coding region of our strains and previously reported DENV-3 strains from India, South Asia and South America revealed non-synonymous substitutions that were genotype III-specific as well as sporadic. Evidence of positive selection was detected in the I81 amino acid residue of the envelope protein. Out of the 22 samples, three had I81A and 18 had I81V substitutions. In the phylogenetic analysis by maximum likelihood method the strains from Kerala clustered in two different lineages (lineage III and IV) within genotype III clade of DENV-3 strains. The ten strains that belonged to lineage IV had a signature amino acid substitution T219A in the envelope protein. Interestingly, all these strains were found to be closely related to a Singapore strain GU370053 isolated in 2007.

Conclusions
Our study identifies for the first time the presence of lineage IV strains in the Indian subcontinent. Results indicate the possibility of a recent exotic introduction and also a shift from the existing lineage III strains to lineage IV. Lineage shifts in DENV-3 strains have been attributed to dramatic increase in disease severity in many parts of the world. Hence the present observation could be significant in terms of the clinical severity of future dengue cases in the region.
Effect of overexpressing nhaA and nhaR on sodium tolerance and lactate production in Escherichia coli
Authors: Wu Xianghao , Altman Ronni , Eiteman Mark A , Altman Elliot 
Published: January 2013

Abstract

Background
Like other bacteria, Escherichia coli must carefully regulate the intracellular concentration of sodium ion (Na+). During the bacterial production of any organic acid, cations like Na+ invariably accumulate during a process which must maintain a near neutral pH. In this study, the E. coli nhaA gene encoding the Na+/H+ antiporter membrane protein and the nhaR gene encoding the NhaA regulatory protein were overexpressed in wild-type E. coli MG1655 and in MG1655 pflB (ALS1317) which lacks pyruvate formate lyase activity and thus accumulates lactate under anaerobic conditions.

Results
Expression of either the nhaA or nhaR gene on the high copy inducible expression vector pTrc99A caused a significant reduction in the growth rate of MG1655. No change in growth rate was observed for MG1655 or ALS1317 for Na+ concentrations of 0.75–0.90 M when the medium copy pBR322 plasmid was used to overexpress the two genes. In a fed-batch process to produce the model acid lactate with NaOH addition for pH control, lactate accumulation ceased in MG1655, MG1655/pBR322, MG1655/pBR322-nhaR and MG1655/pBR322-nhaA when the concentration reached 55–58 g/L. In an identical process lactate accumulation in MG1655/pBR322-nhaAR did not terminate until the concentration reached over 70 g/L.

Conclusions
Although overexpression the genes did not improve growth rate at high Na+ concentrations, the overexpression of nhaA and nhaR together led to a 25% increase in lactate production. Thus, the observed (absence of) impact that these genetic modifications had on growth rate is a poor indicator of their effect on acid accumulation. The overexpression of nhaAR did not cause faster lactate production, but permitted the culture to continue accumulating lactate at 10% greater Na+ concentration.