bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparisons of resistance of CF and Non-CF pathogens to Hydrogen Peroxide and Hypochlorous Acid Oxidants In Vitro
Authors: Bonvillain Ryan W , Painter Richard G , Ledet Elisa M , Wang Guoshun 
Published: May 2011

Abstract

Background
Cystic fibrosis (CF) lung disease has a unique profile of pathogens predominated by Pseudomonas aeruginosa (PsA) and Staphylococcus aureus (SA). These microorganisms must overcome host immune defense to colonize the CF lungs. Polymorphonuclear neutrophils are a major component of the host defense against bacterial infection. A crucial microbicidal mechanism is the production of oxidants including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) by neutrophils to achieve efficient bacterial killing. To determine to what degrees various CF pathogens resist the oxidants relative to non-CF pathogens, we compared the susceptibility of PsA, SA, Burkholderia cepacia (BC), Klebsiella pneumoniae (KP), and Escherichia coli (EC) to various concentrations of H2O2 or HOCl, in vitro. The comparative oxidant-resistant profiles were established. Oxidant-induced damage to ATP production and cell membrane integrity of the microbes were quantitatively assessed. Correlation of membrane permeability and ATP levels with bacterial viability was statistically evaluated.

Results
PsA was relatively resistant to both H2O2 (LD50 = 1.5 mM) and HOCl (LD50 = 0.035 mM). SA was susceptible to H2O2 (LD50 = 0.1 mM) but resistant to HOCl (LD50 = 0.035 mM). Interestingly, KP was extremely resistant to high doses of H2O2 (LD50 = 2.5-5.0 mM) but was very sensitive to low doses of HOCl (LD50 = 0.015 mM). BC was intermediate to resist both oxidants: H2O2 (LD50 = 0.3-0.4 mM) and HOCl (LD50 = 0.025 mM). EC displayed the least resistance to H2O2 (LD50 = 0.2-0.3 mM) and HOCl (LD50 = 0.015 mM). The identified profile of H2O2-resistance was KP > PsA > BC > EC > SA and the profile of HOCl-resistance PsA > SA > BC > EC > KP. Moreover, both oxidants affected ATP production and membrane integrity of the cells. However, the effects varied among the tested organisms and, the oxidant-mediated damage correlated differentially with the bacterial viability.

Conclusions
The order of HOCl-resistance identified herein best fits the clinical profile of CF infections. Even though oxidants are able to disrupt ATP production and cell membrane integrity, the degrees of damage vary among the organisms and correlate differentially with their viability.
An evolutionary conserved region (ECR) in the human dopamine receptor D4 gene supports reporter gene expression in primary cultures derived from the rat cortex
Authors: Paredes Ursula M , Bubb Vivien J , Haddley Kate , Macho Gabriele A , Quinn John P 
Published: May 2011

Abstract

Background
Detecting functional variants contributing to diversity of behaviour is crucial for dissecting genetics of complex behaviours. At a molecular level, characterisation of variation in exons has been studied as they are easily identified in the current genome annotation although the functional consequences are less well understood; however, it has been difficult to prioritise regions of non-coding DNA in which genetic variation could also have significant functional consequences. Comparison of multiple vertebrate genomes has allowed the identification of non-coding evolutionary conserved regions (ECRs), in which the degree of conservation can be comparable with exonic regions suggesting functional significance.

Results
We identified ECRs at the dopamine receptor D4 gene locus, an important gene for human behaviours. The most conserved non-coding ECR (D4ECR1) supported high reporter gene expression in primary cultures derived from neonate rat frontal cortex. Computer aided analysis of the sequence of the D4ECR1 indicated the potential transcription factors that could modulate its function. D4ECR1 contained multiple consensus sequences for binding the transcription factor Sp1, a factor previously implicated in DRD4 expression. Co-transfection experiments demonstrated that overexpression of Sp1 significantly decreased the activity of the D4ECR1 in vitro.

Conclusion
Bioinformatic analysis complemented by functional analysis of the DRD4 gene locus has identified a) a strong enhancer that functions in neurons and b) a transcription factor that may modulate the function of that enhancer.
Assessing the contribution of alternative splicing to proteome diversity in Arabidopsis thalianausing proteomics data
Authors: Severing Edouard I , van Dijk Aalt DJ , van Ham Roeland CHJ 
Published: May 2011

Abstract

Background
Large-scale analyses of genomics and transcriptomics data have revealed that alternative splicing (AS) substantially increases the complexity of the transcriptome in higher eukaryotes. However, the extent to which this complexity is reflected at the level of the proteome remains unclear. On the basis of a lack of conservation of AS between species, we previously concluded that AS does not frequently serve as a mechanism that enables the production of multiple functional proteins from a single gene. Following this conclusion, we hypothesized that the extent to which AS events contribute to the proteome diversity in Arabidopsis thaliana would be lower than expected on the basis of transcriptomics data. Here, we test this hypothesis by analyzing two large-scale proteomics datasets from Arabidopsis thaliana.

Results
A total of only 60 AS events could be confirmed using the proteomics data. However, for about 60% of the loci that, based on transcriptomics data, were predicted to produce multiple protein isoforms through AS, no isoform-specific peptides were found. We therefore performed in silico AS detection experiments to assess how well AS events were represented in the experimental datasets. The results of these in silico experiments indicated that the low number of confirmed AS events was the consequence of a limited sampling depth rather than in vivo under-representation of AS events in these datasets.

Conclusion
Although the impact of AS on the functional properties of the proteome remains to be uncovered, the results of this study indicate that AS-induced diversity at the transcriptome level is also expressed at the proteome level.
Ethylene is involved in pistil fate by modulating the onset of ovule senescence and the GA-mediated fruit set in Arabidopsis
Authors: Carbonell-Bejerano Pablo , Urbez Cristina , Granell Antonio , Carbonell Juan , Perez-Amador Miguel A 
Published: May 2011

AbstractBackgroundOvule lifespan is an important factor in determining the ability to set fruits and produce seeds. Once ovule senescence is established, fruit set capacity in response to gibberellins (GAs) is lost. We aimed to elucidate whether ethylene plays a role in controlling ovule senescence and the fruit set response inArabidopsis.ResultsEthylene response inhibitors, silver thiosulphate (STS) and 1-methylcyclopropene (1-MCP), were able to delay the loss of pistil response to GA3. In addition, ethylene insensitive mutantsein2-5andein3-1showed delayed loss of pistil response, as in plants treated with STS and 1-MCP, while constitutive mutantctr1-1displayed premature loss of response. The analysis of the expression of ethylene biosynthesis genes suggests that ethylene is synthesised in ovules at the onset of ovule senescence, while a transcriptional meta-analysis also supports an activated ethylene-dependent senescence upon the establishment of ovule senescence. Finally, aSAG12:GUSreporter line proved useful to monitor ovule senescence and to directly demonstrate that ethylene specifically modulates ovule senescence.ConclusionsWe have shown that ethylene is involved in both the control of the ovule lifespan and the determination of the pistil/fruit fate. Our data support a role of the ovule in modulating the GA response during fruit set inArabidopsis. A possible mechanism that links the ethylene modulation of the ovule senescence and the GA3-induced fruit set response is discussed.
Quantitative metric profiles capture three-dimensional temporospatial architecture to discriminate cellular functional states
Authors: McKeen-Polizzotti Lindsey , Henderson Kira M , Oztan Basak , Bilgin C Cagatay , Yener Bülent , Plopper George E 
Published: May 2011

Abstract

Background
Computational analysis of tissue structure reveals sub-visual differences in tissue functional states by extracting quantitative signature features that establish a diagnostic profile. Incomplete and/or inaccurate profiles contribute to misdiagnosis.

Methods
In order to create more complete tissue structure profiles, we adapted our cell-graph method for extracting quantitative features from histopathology images to now capture temporospatial traits of three-dimensional collagen hydrogel cell cultures. Cell-graphs were proposed to characterize the spatial organization between the cells in tissues by exploiting graph theory wherein the nuclei of the cells constitute the nodes and the approximate adjacency of cells are represented with edges. We chose 11 different cell types representing non-tumorigenic, pre-cancerous, and malignant states from multiple tissue origins.

Results
We built cell-graphs from the cellular hydrogel images and computed a large set of features describing the structural characteristics captured by the graphs over time. Using three-mode tensor analysis, we identified the five most significant features (metrics) that capture the compactness, clustering, and spatial uniformity of the 3D architectural changes for each cell type throughout the time course. Importantly, four of these metrics are also the discriminative features for our histopathology data from our previous studies.

Conclusions
Together, these descriptive metrics provide rigorous quantitative representations of image information that other image analysis methods do not. Examining the changes in these five metrics allowed us to easily discriminate between all 11 cell types, whereas differences from visual examination of the images are not as apparent. These results demonstrate that application of the cell-graph technique to 3D image data yields discriminative metrics that have the potential to improve the accuracy of image-based tissue profiles, and thus improve the detection and diagnosis of disease.
9/11-Related Experiences and Tasks of Landfill and Barge Workers: Qualitative Analysis from the World Trade Center Health Registry
Authors: Ekenga Christine C , Scheu Katherine E , Cone James E , Stellman Steven D , Farfel Mark R 
Published: May 2011

Abstract

Background
Few studies have documented the experiences of individuals who participated in the recovery and cleanup efforts at the World Trade Center Recovery Operation at Fresh Kills Landfill, on debris loading piers, and on transport barges after the September 11, 2001 terrorist attack.

Methods
Semi-structured telephone interviews were conducted with a purposive sample of workers and volunteers from the World Trade Center Health Registry. Qualitative methods were used to analyze the narratives.

Results
Twenty workers and volunteers were interviewed. They described the transport of debris to the Landfill via barges, the tasks and responsibilities associated with their post-9/11 work at the Landfill, and their reflections on their post-9/11 experiences. Tasks included sorting through debris, recovering human remains, searching for evidence from the terrorist attacks, and providing food and counseling services. Exposures mentioned included dust, fumes, and odors. Eight years after the World Trade Center disaster, workers expressed frustration about poor risk communication during recovery and cleanup work. Though proud of their contributions in the months after 9/11, some participants were concerned about long-term health outcomes.

Conclusions
This qualitative study provided unique insight into the experiences, exposures, and concerns of understudied groups of 9/11 recovery and cleanup workers. The findings are being used to inform the development of subsequent World Trade Center Health Registry exposure and health assessments.
Hong Kong Chinese school children with elevated urine melamine levels: A prospective follow up study
Authors: Kong Alice PS , Choi Kai-Chow , Ho Chung Shun , Chan Michael HM , Wong Chun Kwok , Liu Eric KH , Chu Winnie CW , Chow Viola CY , Lau Joseph TF , Chan Juliana CN 
Published: May 2011

Abstract

Background
In 2008, the outbreak of kidney stones in children fed by melamine-tainted milk products in Mainland China has caused major public concern of food safety. We identified Hong Kong school children with elevated urine melamine level from a community-based school survey in 2007-08 and reviewed their clinical status in 2009.

Methods
In 2007-08, 2119 school children participated in a primary and secondary school survey in Hong Kong using a cluster sampling method. Urine aliquots from 502 subjects were assayed for melamine level. High urine melamine level was defined as urine melamine/creatinine ratio >7.1 μg/mmol. Subjects with high urine melamine level were invited for clinical evaluation in 2009 including urinalysis and ultrasound imaging of the urinary system.

Results
The age range of this subcohort was 6 - 20 years with 67% girls (335 female and 167 male subjects). The spot urine melamine/creatinine ratio of the 502 urine aliquots ranged from undetectable to 1467 μg/mmol (median 0.8 μg/mmol). Of these, 213 subjects had undetectable level (42%). We invited 47 (9%) subjects with high urine melamine level for re-evaluation and one subject declined. The median duration of follow-up was 23.5 months (interquartile range: 19.8 - 30.6 months). None of the 46 subjects (28% boys, mean age 13.9 ± 2.9 years) had any abnormality detected on ultrasound study of the urinary system. All subjects had stable renal function with a median urine albumin-creatinine ratio of 0.70 mg/mmol (interquartile range: 0.00 - 2.55 mg/mmol).

Conclusions
Hong Kong Chinese school children with high urine melamine levels appeared to have benign clinical course in the short term although a long term follow-up study is advisable in those with persistently high urine melamine level.
Determination of some significant batch culture conditions affecting acetyl-xylan esterase production by Penicillium notatum NRRL-1249
Authors: Atta S , Ali S , Akhtar MN , Haq I 
Published: May 2011

Abstract

Background
Acetyl-xylan esterase (AXE, EC 3.1.1.72) hydrolyses acetate group from the linear chain of xylopyranose residues bound by β-1,4-linkage. The enzyme finds commercial applications in bio-bleaching of wood pulp, treating animal feed to increase digestibility, processing food to increase clarification and converting lignocellulosics to feedstock and fuel. In the present study, we report on the production of an extracellular AXE from Penicillium notatum NRRL-1249 by solid state fermentation (SSF).

Results
Wheat bran at a level of 10 g (with 4 cm bed height) was optimized as the basal substrate for AXE production. An increase in enzyme activity was observed when 7.5 ml of mineral salt solution (MSS) containing 0.1% KH2PO4, 0.05% KCl, 0.05% MgSO4.7H2O, 0.3% NaNO3, 0.001% FeSO4.2H2O and 0.1% (v/w) Tween-80 as an initial moisture content was used. Various nitrogen sources including ammonium sulphate, urea, peptone and yeast extract were compared for enzyme production. Maximal enzyme activity of 760 U/g was accomplished which was found to be highly significant (p ≤ 0.05). A noticeable enhancement in enzyme activity was observed when the process parameters including incubation period (48 h), initial pH (5), 0.2% (w/w) urea as nitrogen source and 0.5% (v/w) Tween-80 as a stimulator were further optimized using a 2-factorial Plackett-Burman design.

Conclusion
From the results it is clear that an overall improvement of more than 35% in terms of net enzyme activity was achieved compared to previously reported studies. This is perhaps the first report dealing with the use of P. notatum for AXE production under batch culture SSF. The Plackett-Burman model terms were found highly significant (HS), suggesting the potential commercial utility of the culture used (df = 3, LSD = 0.126).
The structural impact of cancer-associated missense mutations in oncogenes and tumor suppressors
Authors: Stehr Henning , Jang Seon-Hi J , Duarte José M , Wierling Christoph , Lehrach Hans , Lappe Michael , Lange Bodo MH 
Published: May 2011

Abstract

Background
Current large-scale cancer sequencing projects have identified large numbers of somatic mutations covering an increasing number of different cancer tissues and patients. However, the characterization of these mutations at the structural and functional level remains a challenge.

Results
We present results from an analysis of the structural impact of frequent missense cancer mutations using an automated method. We find that inactivation of tumor suppressors in cancer correlates frequently with destabilizing mutations preferably in the core of the protein, while enhanced activity of oncogenes is often linked to specific mutations at functional sites. Furthermore, our results show that this alteration of oncogenic activity is often associated with mutations at ATP or GTP binding sites.

Conclusions
With our findings we can confirm and statistically validate the hypotheses for the gain-of-function and loss-of-function mechanisms of oncogenes and tumor suppressors, respectively. We show that the distinct mutational patterns can potentially be used to pre-classify newly identified cancer-associated genes with yet unknown function.
Tailored, iterative, printed dietary feedback is as effective as group education in improving dietary behaviours: results from a randomised control trial in middle-aged adults with cardiovascular risk factors
Authors: Wright Janine L , Sherriff Jillian L , Dhaliwal Satvinder S , Mamo John CL 
Published: May 2011

Abstract

Background
Tailored nutrition interventions have been shown to be more effective than non-tailored materials in changing dietary behaviours, particularly fat intake and fruit and vegetable intake. But further research examining efficacy of tailored nutrition education in comparison to other nutrition education methods and across a wider range of dietary behaviours is needed. The Stages to Healthy Eating Patterns Study (STEPs) was an intervention study, in middle-aged adults with cardiovascular risk factors, to examine the effectiveness of printed, tailored, iterative dietary feedback delivered by mail in improving short-term dietary behaviour in the areas of saturated fat, fruit, vegetable and grain and cereal intake.

Methods
STEPs was a 3-month randomised controlled trial with a pre and post-test design. There were three experimental conditions: 1) tailored, iterative, printed dietary feedback (TF) with three instalments mail-delivered over a 3-month period that were re-tailored to most recent assessment of dietary intake, intention to change and assessment of self-adequacy of dietary intake. Tailoring for dietary intake was performed on data from a validated 63-item combination FFQ designed for the purpose 2) small group nutrition education sessions (GE): consisting of two 90-minute dietitian-led small group nutrition education sessions and 3) and a wait-listed control (C) group who completed the dietary measures and socio-demographic questionnaires at baseline and 3-months later. Dietary outcome measures in the areas of saturated fat intake (g), and the intake of fruit (serves), vegetables (serves), grain and cereals as total and wholegrain (serves) were collected using 7-day estimated dietary records. Descriptive statistics, paired t-tests and general linear models adjusted for baseline dietary intake, age and gender were used to examine the effectiveness of different nutrition interventions.

Results
The TF group reported a significantly greater increase in fruit intake (0.3 serves/d P = 0.031) in comparison to GE and the C group. All three intervention groups showed a reduction in total saturated fat intake. GE also had a within-group increase in mean vegetable intake after 3 months, but this increase was not different from changes in the other groups.

Conclusions
In this study, printed, tailored, iterative dietary feedback was more effective than small group nutrition education in improving the short-term fruit intake behaviour, and as effective in improving saturated fat intake of middle-aged adults with cardiovascular risk factors. This showed that a low-level dietary intervention could achieve modest dietary behaviour changes that are of public health significance.
Value of large scale expansion of tumor infiltrating lymphocytes in a compartmentalised gas-permeable bag: interests for adoptive immunotherapy
Authors: Zuliani Thomas , David Julien , Bercegeay Sylvain , Pandolfino Marie-Christine , Rodde-Astier Isabelle , Khammari Amir , Coissac Cécile , Delorme Bruno , Saïagh Soraya , Dréno Brigitte 
Published: May 2011

Abstract

Background
Adoptive cell therapy (ACT) has emerged as an effective treatment for patients with metastatic melanoma. However, there are several logistical and safety concerns associated with large-scale ex vivo expansion of tumour-specific T lymphocytes for widespread availability of ACT for cancer patients. To address these problems we developed a specific compartmentalised bag allowing efficient expansion of tumour-specific T lymphocytes in an easy handling, closed system.

Methods
Starting from lymph nodes from eight melanoma patients, we performed a side-by-side comparison of Tumour-Infiltrating Lymphocytes (TIL) produced after expansion in the compartmentalised bag versus TIL produced using the standard process in plates. Proliferation yield, viability, phenotype and IFNγ secretion were comparatively studied.

Results
We found no differences in proliferation yield and cell viability between both TIL production systems. Moreover, each of the cell products complied with our defined release criteria before being administered to the patient. The phenotype analysis indicated that the compartmentalised bag favours the expansion of CD8+ cells. Finally, we found that TIL stimulated in bags were enriched in reactive CD8+ T cells when co-cultured with the autologous melanoma cell line.

Conclusions
The stimulation of TIL with feeder cells in the specifically designed compartmentalised bag can advantageously replace the conventional protocol using plates. In particular, the higher expansion rate of reactive CD8+ T cells could have a significant impact for ACT.