bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microarray identifies ADAM family members as key responders to TGF-β1 in alveolar epithelial cells
Authors: Keating Dominic T , Sadlier Denise M , Patricelli Andrea , Smith Sinead M , Walls Dermot , Egan Jim J , Doran Peter P 
Published: September 2006

Abstract
The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive. Transforming Growth Factor beta 1(TGF-β1) is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549) in response to TGF-β1, IL-4 and IL-13 and Epstein Barr virus.
A549 cells were exposed to 10 ng/ml TGF-β1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM) proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO) databases for baited cluster analysis of ECM associated genes.
Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing) family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity) of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-β1, suggesting a potential role for these molecules in ECM accumulation in IPF.
A joint model of regulatory and metabolic networks
Authors: Yeang Chen-Hsiang , Vingron Martin 
Published: September 2006

Abstract

Background
Gene regulation and metabolic reactions are two primary activities of life. Although many works have been dedicated to study each system, the coupling between them is less well understood. To bridge this gap, we propose a joint model of gene regulation and metabolic reactions.

Results
We integrate regulatory and metabolic networks by adding links specifying the feedback control from the substrates of metabolic reactions to enzyme gene expressions. We adopt two alternative approaches to build those links: inferring the links between metabolites and transcription factors to fit the data or explicitly encoding the general hypotheses of feedback control as links between metabolites and enzyme expressions. A perturbation data is explained by paths in the joint network if the predicted response along the paths is consistent with the observed response. The consistency requirement for explaining the perturbation data imposes constraints on the attributes in the network such as the functions of links and the activities of paths. We build a probabilistic graphical model over the attributes to specify these constraints, and apply an inference algorithm to identify the attribute values which optimally explain the data. The inferred models allow us to 1) identify the feedback links between metabolites and regulators and their functions, 2) identify the active paths responsible for relaying perturbation effects, 3) computationally test the general hypotheses pertaining to the feedback control of enzyme expressions, 4) evaluate the advantage of an integrated model over separate systems.

Conclusion
The modeling results provide insight about the mechanisms of the coupling between the two systems and possible "design rules" pertaining to enzyme gene regulation. The model can be used to investigate the less well-probed systems and generate consistent hypotheses and predictions for further validation.
Analysis of the genome-wide variations among multiple strains of the plant pathogenic bacterium Xylella fastidiosa
Authors: Doddapaneni Harshavardhan , Yao Jiqiang , Lin Hong , Walker M Andrew , Civerolo Edwin L 
Published: September 2006

Abstract

Background
The Gram-negative, xylem-limited phytopathogenic bacterium Xylella fastidiosa is responsible for causing economically important diseases in grapevine, citrus and many other plant species. Despite its economic impact, relatively little is known about the genomic variations among strains isolated from different hosts and their influence on the population genetics of this pathogen. With the availability of genome sequence information for four strains, it is now possible to perform genome-wide analyses to identify and categorize such DNA variations and to understand their influence on strain functional divergence.

Results
There are 1,579 genes and 194 non-coding homologous sequences present in the genomes of all four strains, representing a 76. 2% conservation of the sequenced genome. About 60% of the X. fastidiosa unique sequences exist as tandem gene clusters of 6 or more genes. Multiple alignments identified 12,754 SNPs and 14,449 INDELs in the 1528 common genes and 20,779 SNPs and 10,075 INDELs in the 194 non-coding sequences. The average SNP frequency was 1.08 × 10-2 per base pair of DNA and the average INDEL frequency was 2.06 × 10-2 per base pair of DNA. On an average, 60.33% of the SNPs were synonymous type while 39.67% were non-synonymous type. The mutation frequency, primarily in the form of external INDELs was the main type of sequence variation. The relative similarity between the strains was discussed according to the INDEL and SNP differences. The number of genes unique to each strain were 60 (9a5c), 54 (Dixon), 83 (Ann1) and 9 (Temecula-1). A sub-set of the strain specific genes showed significant differences in terms of their codon usage and GC composition from the native genes suggesting their xenologous origin. Tandem repeat analysis of the genomic sequences of the four strains identified associations of repeat sequences with hypothetical and phage related functions.

Conclusion
INDELs and strain specific genes have been identified as the main source of variations among strains, with individual strains showing different rates of genome evolution. Based on these genome comparisons, it appears that the Pierce's disease strain Temecula-1 genome represents the ancestral genome of the X. fastidiosa. Results of this analysis are publicly available in the form of a web database.
The relationship between quality of research and citation frequency
Authors: Nieminen Pentti , Carpenter James , Rucker Gerta , Schumacher Martin 
Published: September 2006

Abstract

Background
Citation counts are often regarded as a measure of the utilization and contribution of published articles. The objective of this study is to assess whether statistical reporting and statistical errors in the analysis of the primary outcome are associated with the number of citations received.

Methods
We evaluated all original research articles published in 1996 in four psychiatric journals. The statistical and reporting quality of each paper was assessed and the number of citations received up to 2005 was obtained from the Web of Science database. We then examined whether the number of citations was associated with the quality of the statistical analysis and reporting.

Results
A total of 448 research papers were included in the citation analysis. Unclear or inadequate reporting of the research question and primary outcome were not statistically significantly associated with the citation counts. After adjusting for journal, extended description of statistical procedures had a positive effect on the number of citations received. Inappropriate statistical analysis did not affect the number of citations received. Adequate reporting of the primary research question, statistical methods and primary findings were all associated with the journal visibility and prestige.

Conclusion
In this cohort of published research, measures of reporting quality and appropriate statistical analysis were not associated with the number of citations. The journal in which a study is published appears to be as important as the statistical reporting quality in ensuring dissemination of published medical science.
Heparin (GAG-hed) inhibits LCR activity of Human Papillomavirus type 18 by decreasing AP1 binding
Authors: Villanueva Rita , Morales-Peza Néstor , Castelán-Sánchez Irma , García-Villa Enrique , Tapia Rocio , Cid-Arregui Ángel , García-Carrancá Alejandro , López-Bayghen Esther , Gariglio Patricio 
Published: September 2006

AbstractBackgroundHigh risk HPVs are causative agents of anogenital cancers. Viral E6 and E7 genes are continuously expressed and are largely responsible for the oncogenic activity of these viruses. Transcription of the E6 and E7 genes is controlled by the viral Long Control Region (LCR), plus several cellular transcription factors including AP1 and the viral protein E2. Within the LCR, the binding and activity of the transcription factor AP1 represents a key regulatory event in maintaining E6/E7 gene expression and uncontrolled cell proliferation. Glycosaminoglycans (GAGs), such as heparin, can inhibit tumour growth; they have also shown antiviral effects and inhibition of AP1 transcriptional activity. The purpose of this study was to test the heparinoid GAG-hed, as a possible antiviral and antitumoral agent in an HPV18 positive HeLa cell line.MethodsUsingin vivoandin vitroapproaches we tested GAG-hed effects on HeLa tumour cell growth, cell proliferation and on the expression of HPV18 E6/E7 oncogenes. GAG-hed effects on AP1 binding to HPV18-LCR-DNA were tested by EMSA.ResultsWe were able to record the antitumoral effect of GAG-hedin vivoby using as a model tumours induced by injection of HeLa cells into athymic female mice. The antiviral effect of GAG-hed resulted in the inhibition of LCR activity and, consequently, the inhibition of E6 and E7 transcription. A specific diminishing of cell proliferation rates was observed in HeLa but not in HPV-free colorectal adenocarcinoma cells. Treated HeLa cells did not undergo apoptosis but the percentage of cells in G2/M phase of the cell cycle was increased. We also detected that GAG-hed prevents the binding of the transcription factor AP1 to the LCR.ConclusionDirect interaction of GAG-hed with the components of the AP1 complex and subsequent interference with its ability to correctly bind specific sites within the viral LCR may contribute to the inhibition of E6/E7 transcription and cell proliferation. Our data suggest that GAG-hed could have antitumoral and antiviral activity mainly by inhibiting AP1 binding to the HPV18-LCR.
Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity
Authors: Powell Ashley A , Akare Sandeep , Qi Wenqing , Herzer Pascal , Jean-Louis Samira , Feldman Rebecca A , Martinez Jesse D 
Published: September 2006

Abstract

Background
There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA.

Methods
To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis.

Results
We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth.

Conclusion
We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype.
Health status in the ambulance services: a systematic review
Authors: Sterud Tom , Ekeberg Øivind , Hem Erlend 
Published: September 2006

AbstractBackgroundResearchers have become increasingly aware that ambulance personnel may be at risk of developing work-related health problems. This article systematically explores the literature on health problems and work-related and individual health predictors in the ambulance services.MethodsWe identified the relevant empirical literature by searching several electronic databases including Medline, EMBASE, PsychINFO, CINAHL, and ISI Web of Science. Other relevant sources were identified through reference lists and other relevant studies known by the research group.ResultsForty-nine studies are included in this review. Our analysis shows that ambulance workers have a higher standardized mortality rate, higher level of fatal accidents, higher level of accident injuries and a higher standardized early retirement on medical grounds than the general working population and workers in other health occupations. Ambulance workers also seem to have more musculoskeletal problems than the general population. These conclusions are preliminary at present because each is based on a single study. More studies have addressed mental health problems. The prevalence of post-traumatic stress symptom caseness was > 20% in five of seven studies, and similarly high prevalence rates were reported for anxiety and general psychopathology in four of five studies. However, it is unclear whether ambulance personnel suffer from more mental health problems than the general working population.ConclusionSeveral indicators suggest that workers in the ambulance services experience more health problems than the general working population and workers in other health occupations. Several methodological challenges, such as small sample sizes, non-representative samples, and lack of comparisons with normative data limit the interpretation of many studies. More coordinated research and replication are needed to compare data across studies. We discuss some strategies for future research.
The evaluation of the factors that cause aggregation during recombinant expression in E. coli is simplified by the employment of an aggregation-sensitive reporter
Authors: Schultz Tina , Martinez Lucia , de Marco Ario 
Published: September 2006

Abstract

Background
The yields of soluble recombinant proteins expressed in bacteria are often low due to the tendency of the heterologous proteins to form aggregates. Therefore, aggregation reporters have been envisaged to simplify the comparison among different expression conditions and to speed up the identification of suitable protocols that improve the solubility. The probe we used is composed by an Ibp AB promoter specifically activated by protein aggregates fused to a sequence coding the β-galactosidase, the activity of which becomes, therefore, indicative of the aggregation degree.

Results
The collected data show that the probe is reliable in terms of reproducibility inside a range of experimental conditions and faster and more sensitive than the analysis methods based on SDS-PAGE and successive western blot.
The β-galactosidase probe was useful to identify which parameters could influence the aggregation of the model proteins and to set up an optimized expression protocol. The effect of growth temperature, induction modality, co-expression with molecular chaperones and addition of osmolytes on the accumulation of aggregates were evaluated following the β-galactosidase activity. Interestingly, a significant correlation was observed between estimated decreased aggregation and higher yields of soluble protein.
We also compared a set of expression vectors with various regulative features and found that the single characteristics, like promoter, copy number or polymerase, were not relevant for controlling the recombinant protein aggregation whilst the crucial factor resulted being the total expression rate of the system.

Conclusion
The aggregation reporter used in our experiments represents a useful tool to evaluate the different factors that can be modulated to optimize a recombinant expression protocol. Furthermore, the rapid estimation of the aggregation degree enables to discriminate this from other causes responsible for scarce recombinant yields.
Genital tuberculosis in a tamoxifen-treated postmenopausal woman with breast cancer and bloody vaginal discharge
Authors: Neonakis Ioannis , Mantadakis Elpis , Gitti Zoe , Mitrouska Ioanna , Manidakis Louis George , Maraki Sofia , Samonis George 
Published: September 2006

Abstract

Background
Female genital tuberculosis is an uncommon disease that is rarely diagnosed in developed countries.

Case presentation
A 61-year-old postmenopausal woman who had undergone surgery and treated with adjuvant chemotherapy for infiltrating ductal carcinoma of the breast five years ago, presented with bloody vaginal discharge, fatigue, weight loss, and low grade fevers at night for two months. Histological examination of the endometrium, done based on the suspicion of a second primary cancer due to the tamoxifen therapy, revealed a granulomatous reaction. Liquid and solid mycobacterial cultures of the tissues were performed. Although the acid fast staining was negative, the liquid culture was positive for Mycobacterium tuberculosis. Involvement of other systems was not detected. The patient was treated with a three-drug antituberculosis regimen for 9 months and recovered fully.

Conclusion
Female genital tuberculosis is a rare but curable disease that should be included in the differential diagnosis of women with menstrual problems. Early diagnosis is important and may prevent unnecessary invasive procedures for the patient.
Two-dimensional gel proteome reference map of blood monocytes
Authors: Jin Ming , Diaz Philip T , Bourgeois Tran , Eng Charis , Marsh Clay B , Wu Haifeng M 
Published: September 2006

AbstractBackground:Blood monocytes play a central role in regulating host inflammatory processes through chemotaxis, phagocytosis, and cytokine production. However, the molecular details underlying these diverse functions are not completely understood. Understanding the proteomes of blood monocytes will provide new insights into their biological role in health and diseases.Results:In this study, monocytes were isolated from five healthy donors. Whole monocyte lysates from each donor were then analyzed by 2D gel electrophoresis, and proteins were detected using Sypro Ruby fluorescence and then examined for phosphoproteomes using ProQ phospho-protein fluorescence dye. Between 1525 and 1769 protein spots on each 2D gel were matched, analyzed, and quantified. Abundant protein spots were then subjected to analysis by mass spectrometry. This report describes the protein identities of 231 monocyte protein spots, which represent 164 distinct proteins and their respective isoforms or subunits. Some of these proteins had not been previously characterized at the protein level in monocytes. Among the 231 protein spots, 19 proteins revealed distinct modification by protein phosphorylation.Conclusion:The results of this study offer the most detailed monocyte proteomic database to date and provide new perspectives into the study of monocyte biology.
Pseudomyxoma peritonei – a revisit: report of 2 cases and literature review
Authors: Li Chunyanca , Kanthan Rani , Kanthan SC 
Published: September 2006

Abstract

Background
Pseudomyxoma peritonei (PMP) is a rare, chronic, relapsing, diagnostically challenging and poorly understood disease characterized by disseminated mucinous ascites and peritoneal implants.

Case presentation
We report two cases of PMP that represent the two biological variants of d isseminated p eritoneal a denom ucinosis (DPAM) – the benign variant and the p eritoneal m ucinous c arcinoma tosis (PMCA) – the malignant variant, both of which were characterized by multiple relapses and progression of the disease despite aggressive management.

Conclusion
Even with a better understanding and recent advances in the management of these cases, PMP remains an enigmatic disease with a protracted clinical course characterized by multiple recurrences despite surgery and/or chemotherapy. Recognition of PMP as a delayed consequence years later should alert all surgeons to be extremely vigilant when treating mucinous neoplasms of the appendix, with special care being directed towards adequate excision and thorough debridement at the initial diagnosis.
Molecular signatures induced by interleukin-2 on peripheral blood mononuclear cells and T cell subsets
Authors: Jin Ping , Wang Ena , Provenzano Maurizio , Deola Sara , Selleri Silvia , Ren Jiaqiang , Voiculescu Sonia , Stroncek David , Panelli Monica C , Marincola Francesco M 
Published: August 2006

AbstractExperimentally, interleukin-2 (IL-2) exerts complex immunological functions promoting the proliferation, survival and activation of T cells on one hand and inducing immune regulatory mechanisms on the other. This complexity results from a cross talk among immune cells which sways the effects of IL-2 according to the experimental or clinical condition tested. Recombinant IL-2 (rIL-2) stimulation of peripheral blood mononuclear cells (PBMC) from 47 donors of different genetic background induced generalized T cell activation and anti-apoptotic effects. Most effects were dependent upon interactions among immune cells. Specialized functions of CD4 and CD8 T cells were less dependent upon and often dampened by the presence of other PBMC populations. In particular, cytotoxic T cell effector function was variably affected with a component strictly dependent upon the direct stimulation of CD8 T cells in the absence of other PBMC. This observation may provide a roadmap for the interpretation of the discrepant biological activities of rIL-2 observed in distinct pathological conditions or treatment modalities.