bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphodiesterase 6 subunits are expressed and altered in idiopathic pulmonary fibrosis
Authors: Nikolova Sevdalina , Guenther Andreas , Savai Rajkumar , Weissmann Norbert , Ghofrani Hossein A , Konigshoff Melanie , Eickelberg Oliver , Klepetko Walter , Voswinckel Robert , Seeger Werner , Grimminger Friedrich , Schermuly Ralph T , Pullamsetti Soni S 
Published: October 2010

Abstract
Background
Idiopathic Pulmonary Fibrosis (IPF) is an unresolved clinical issue. Phosphodiesterases (PDEs) are known therapeutic targets for various proliferative lung diseases. Lung PDE6 expression and function has received little or no attention. The present study aimed to characterize (i) PDE6 subunits expression in human lung, (ii) PDE6 subunits expression and alteration in IPF and (iii) functionality of the specific PDE6D subunit in alveolar epithelial cells (AECs).

Methodology/Principal Findings
PDE6 subunits expression in transplant donor (n = 6) and IPF (n = 6) lungs was demonstrated by real-time quantitative (q)RT-PCR and immunoblotting analysis. PDE6D mRNA and protein levels and PDE6G/H protein levels were significantly down-regulated in the IPF lungs. Immunohistochemical analysis showed alveolar epithelial localization of the PDE6 subunits. This was confirmed by qRT-PCR from human primary alveolar type (AT)II cells, demonstrating the down-regulation pattern of PDE6D in IPF-derived ATII cells. In vitro, PDE6D protein depletion was provoked by transforming growth factor (TGF)-β1 in A549 AECs. PDE6D siRNA-mediated knockdown and an ectopic expression of PDE6D modified the proliferation rate of A549 AECs. These effects were mediated by increased intracellular cGMP levels and decreased ERK phosphorylation.

Conclusions/Significance
Collectively, we report previously unrecognized PDE6 expression in human lungs, significant alterations of the PDE6D and PDE6G/H subunits in IPF lungs and characterize the functional role of PDE6D in AEC proliferation.
Assessment of genetic variation for the LINE-1 retrotransposon from next generation sequence data
Authors: Rouchka Eric , Montoya-Durango Diego E , Stribinskis Vilius , Ramos Kenneth , Kalbfleisch Ted 
Published: October 2010

Abstract

Background
In humans, copies of the Long Interspersed Nuclear Element 1 (LINE-1) retrotransposon comprise 21% of the reference genome, and have been shown to modulate expression and produce novel splice isoforms of transcripts from genes that span or neighbor the LINE-1 insertion site.

Results
In this work, newly released pilot data from the 1000 Genomes Project is analyzed to detect previously unreported full length insertions of the retrotransposon LINE-1. By direct analysis of the sequence data, we have identified 22 previously unreported LINE-1 insertion sites within the sequence data reported for a mother/father/daughter trio.

Conclusions
It is demonstrated here that next generation sequencing data, as well as emerging high quality datasets from individual genome projects allow us to assess the amount of heterogeneity with respect to the LINE-1 retrotransposon amongst humans, and provide us with a wealth of testable hypotheses as to the impact that this diversity may have on the health of individuals and populations.
Consistent levels of A-to-I RNA editing across individuals in coding sequences and non-conserved Alu repeats
Authors: Greenberger Shoshana , Levanon Erez Y , Paz-Yaacov Nurit , Barzilai Aviv , Safran Michal , Osenberg Sivan , Amariglio Ninette , Rechavi Gideon , Eisenberg Eli 
Published: October 2010

Abstract

Background
Adenosine to inosine (A-to-I) RNA-editing is an essential post-transcriptional mechanism that occurs in numerous sites in the human transcriptome, mainly within Alu repeats. It has been shown to have consistent levels of editing across individuals in a few targets in the human brain and altered in several human pathologies. However, the variability across human individuals of editing levels in other tissues has not been studied so far.

Results
Here, we analyzed 32 skin samples, looking at A-to-I editing level in three genes within coding sequences and in the Alu repeats of six different genes. We observed highly consistent editing levels across different individuals as well as across tissues, not only in coding targets but, surprisingly, also in the non evolutionary conserved Alu repeats.

Conclusions
Our findings suggest that A-to-I RNA-editing of Alu elements is a tightly regulated process and, as such, might have been recruited in the course of primate evolution for post-transcriptional regulatory mechanisms.
A bacteria-specific 2[4Fe-4S] ferredoxin is essential in Pseudomonas aeruginosa
Authors: Elsen Sylvie , Efthymiou Georgios , Peteinatos Panagiotis , Diallinas George , Kyritsis Panayotis , Moulis Jean-Marc 
Published: October 2010

Abstract

Background
Ferredoxins are small iron-sulfur proteins belonging to all domains of life. A sub-group binds two [4Fe-4S] clusters with unequal and extremely low values of the reduction potentials. These unusual properties are associated with two specific fragments of sequence. The functional importance of the very low potential ferredoxins is unknown.

Results
A bioinformatic screening of the sequence features defining very low potential 2[4Fe-4S] ferredoxins has revealed the almost exclusive presence of the corresponding fdx gene in the Proteobacteria phylum, without occurrence in Archaea and Eukaryota. The transcript was found to be monocistronic in Pseudomonas aeruginosa, and not part of an operon in most bacteria. Only fdx genes of bacteria which anaerobically degrade aromatic compounds belong to operons. As this pathway is not present in all bacteria having very low potential 2[4Fe-4S] ferredoxins, these proteins cannot exclusively be reductants of benzoyl CoA reductases. Expression of the ferredoxin gene did not change in response to varying growth conditions, including upon macrophage infection or aerobic growth with 4-hydroxy benzoate as carbon source. However, it increased along the growth curve in Pseudomonas aeruginosa and in Escherichia coli. The sequence immediately 5' upstream of the coding sequence contributed to the promotor activity. Deleting the fdx gene in Pseudomonas aeruginosa abolished growth, unless a plasmid copy of the gene was provided to the deleted strain.

Conclusions
The gene of the very low potential 2[4Fe-4S] ferredoxin displays characteristics of a housekeeping gene, and it belongs to the minority of genes that are essential in Pseudomonas aeruginosa. These data identify a new potential antimicrobial target in this and other pathogenic Proteobacteria.
Whole genome wide expression profiles of Vitis amurensisgrape responding to downy mildew by using Solexa sequencing technology
Authors: Wu Jiao , Zhang Yali , Zhang Huiqin , Huang Hong , Folta Kevin M , Lu Jiang 
Published: October 2010

AbstractBackgroundDowny mildew (DM), caused by pathogenPlasmopara viticola(PV) is the single most damaging disease of grapes (VitisL.) worldwide. However, the mechanisms of the disease development in grapes are poorly understood. A method for estimating gene expression levels using Solexa sequencing of Type I restriction-endonuclease-generated cDNA fragments was used for deep sequencing the transcriptomes resulting from PV infected leaves ofVitis amurensisRupr. cv. Zuoshan-1. Our goal is to identify genes that are involved in resistance to grape DM disease.ResultsApproximately 8.5 million (M) 21-nt cDNA tags were sequenced in the cDNA library derived from PV pathogen-infected leaves, and about 7.5 M were sequenced from the cDNA library constructed from the control leaves. When annotated, a total of 15,249 putative genes were identified from the Solexa sequencing tags for the infection (INF) library and 14,549 for the control (CON) library. Comparative analysis between these two cDNA libraries showed about 0.9% of the unique tags increased by at least five-fold, and about 0.6% of the unique tags decreased more than five-fold in infected leaves, while 98.5% of the unique tags showed less than five-fold difference between the two samples. The expression levels of 12 differentially expressed genes were confirmed by Real-time RT-PCR and the trends observed agreed well with the Solexa expression profiles, although the degree of change was lower in amplitude. After pathway enrichment analysis, a set of significantly enriched pathways were identified for the differentially expressed genes (DEGs), which associated with ribosome structure, photosynthesis, amino acid and sugar metabolism.ConclusionsThis study presented a series of candidate genes and pathways that may contribute to DM resistance in grapes, and illustrated that the Solexa-based tag-sequencing approach was a powerful tool for gene expression comparison between control and treated samples.
Can near real-time monitoring of emergency department diagnoses facilitate early response to sporadic meningococcal infection? - prospective and retrospective evaluations
Authors: O'Toole Libby , Muscatello David J , Zheng Wei , Churches Tim 
Published: October 2010

AbstractBackgroundMeningococcal infection causes severe, rapidly progressing illness and reporting of cases is mandatory in New South Wales (NSW), Australia. The NSW Department of Health operates near real-time Emergency Department (ED) surveillance that includes capture and statistical analysis of clinical preliminary diagnoses. The system can provide alerts in response to specific diagnoses entered in the ED computer system. This study assessed whether once daily reporting of clinical diagnoses of meningococcal infection using the ED surveillance system provides an opportunity for timelier public health response for this disease.MethodsThe study involved a prospective and retrospective component. First, reporting of ED diagnoses of meningococcal infection from the ED surveillance system prospectively operated in parallel with conventional surveillance which requires direct telephone reporting of this scheduled medical condition to local public health authorities by hospitals and laboratories when a meningococcal infection diagnosis is made. Follow-up of the ED diagnoses determined whether meningococcal infection was confirmed, and the time difference between ED surveillance report and notification by conventional means. Second, cases of meningococcal infection reported by conventional surveillance during 2004 were retrospectively matched to ED visits to determine the sensitivity and positive predictive value (PPV) of ED surveillance.ResultsDuring the prospective evaluation, 31 patients were diagnosed with meningococcal infection in participating EDs. Of these, 12 had confirmed meningococcal disease, resulting in a PPV of 38.7%. All confirmed cases were notified earlier to public health authorities by conventional reporting.Of 149 cases of notified meningococcal disease identified retrospectively, 130 were linked to an ED visit. The sensitivity and PPV of the ED diagnosis for meningococcal infection was 36.2% and 36.7%, respectively.ConclusionsBased on prospective evaluation, it is reassuring that existing mechanisms for reporting meningococcal infection perform well and are timely. The retrospective evaluation found low sensitivity and PPV of ED diagnoses for meningococcal disease. Even if more rapid forwarding of ED meningococcal diagnoses to public health authorities were possible, the low sensitivity and PPV do not justify this. In this study, use of an ED surveillance system to augment conventional surveillance of this scheduled medical condition did not demonstrate a benefit.
Resveratrol represses YKL-40 expression in human glioma U87 cells
Authors: Zhang Wei , Murao Koji , Zhang Xiang , Matsumoto Kensuke , Diah Suwarni , Okada Masaki , Miyake Keisuke , Kawai Nobuyuki , Fei Zhou , Tamiya Takashi 
Published: October 2010

Abstract

Background
Glioblastoma multiforme (GBM) is the most malignant intracranial tumour that develops in both adults and children. Microarray gene analyses have confirmed that the human YKL-40 gene is one of the most over-expressed genes in these tumours but not in normal brain tissue. Clinical studies have shown that serum YKL-40 levels are positively correlated with tumour burden in addition to being an independent prognostic factor of a short relapse-free interval as well as short overall survival in patients with various cancers. Our previous study revealed that YKL-40 was closely correlated with the pathological grades of human primary astrocytomas and played a crucial role in glioma cell proliferation. Hence, YKL-40 could be an attractive target in the design of anti-cancer therapies.

Methods
Cell viability and invasion assays were performed to detect the cell proliferation and invasive ability of U87 cells induced by resveratrol (3, 5, 4'-trihydroxystilbene; Res) or YKL-40 small-interfering RNAs (siRNAs). In addition, the luciferase assay, real-time RT-PCR, western blotting, and ELISA were used to measure YKL-40 promoter activity, mRNA, and protein expression, respectively. The expressions of phosphor-ERK1/2 and ERK1/2 were determined by western blotting.

Results
Res inhibited U87 cell proliferation and invasion in vitro and repressed YKL-40 in U87 cells by decreasing the activity of its promoter and reducing mRNA transcription and protein expression in vitro. YKL-40 siRNA treatment also impaired the invasiveness of U87 cells. When U87 cells were cultured with 20 μM PD98059 (an ERK1/2 inhibitor) alone, with 20 μM PD98059 and 100 μM Res, or with 100 μM Res alone for 48 h, YKL-40 protein expression decreased most significantly in the Res-treated group. PD98059 partially reversed the decrease of YKL-40 protein expression induced by Res. Furthermore, phosphor-ERK1/2 expression was reduced by Res treatment in a time-dependent manner.

Conclusions
We demonstrated for the first time that Res represses YKL-40 expression in vitro; in addition, the ERK1/2 pathway is involved in this repression. This finding could extend the prospective use of Res in glioma research and enlarge the armamentarium for treating gliomas.
Stages of chronicity in fibromyalgia and pain catastrophising: a cross-sectional study
Authors: Rodero Baltasar , Casanueva Benigno , García-Campayo Javier , Roca Miquel , Magallón Rosa , López del Hoyo Yolanda 
Published: October 2010

Abstract

Background
Fibromyalgia (FM) is a prevalent and disabling disorder characterised by widespread pain and other symptoms such as insomnia, fatigue and depression. Catastrophisation is considered to be a key clinical symptom in FM; however, few studies have investigated how contextual factors, such as catastrophisation, might contribute to the duration of the pain. The present research examined the relationship among pain, catastrophic thinking and FM impact, as a function of stage of chronicity.

Methods
In this cross-sectional study, the sample of 328 patients diagnosed with FM was divided into 3 groups based on level of chronicity: Group A (6 months to 2 years, N = 46); Group B (2-4 years, N = 59); and Group C (more than 4 years, N = 223). The three subscales of the Pain Catastrophising Scale (PCS), rumination, magnification, and helplessness, were used as predictors of dysfunction. The Fibromyalgia Impact Questionnaire and the McGill Pain Questionnaire were also administered. A hierarchical regression analysis was performed on the entire sample and, subsequently, for each group to determine the effect of the continuous process variables (castastrophising and pain) on the stages of chronicity.

Results
Total score and PCS subscales were strongly associated with pain and impact in all the stages of chronicity in FM patients (r = 0.27-0.73, p < 0.05). For Group A, a regression analysis revealed that rumination predicted FM impact beyond the variance accounted for by age and pain. Both magnification and helplessness predicted impact in Group B, and helplessness was a significant predictor of impact in Group C.

Conclusion
These findings provide preliminary evidence that stage of chronicity is an important moderator of psychological vulnerability for FM impact and should be taken into account by tailoring psychological interventions.
A miniaturized sandwich immunoassay platform for the detection of protein-protein interactions
Authors: Liu Qiongming , Chen Qing , Wang Jian , Zhang Ying , Zhou Ying , Lin Cong , He Wei , He Fuchu , Xu Danke 
Published: October 2010

Abstract

Background
Analysis of protein-protein interactions (PPIs) is a valuable approach for the characterization of huge networks of protein complexes or proteins of unknown function. Co-immunoprecipitation (coIP) using affinity resins coupled to protein A/G is the most widely used method for PPI detection. However, this traditional large scale resin-based coIP is too laborious and time consuming. To overcome this problem, we developed a miniaturized sandwich immunoassay platform (MSIP) by combining antibody array technology and coIP methods.

Results
Based on anti-FLAG antibody spotted aldehyde slides, MSIP enables simple, rapid and large scale detection of PPIs by fluorescent labeling anti-myc antibody. By analyzing well-known interacting and non-interacting protein pairs, MSIP was demonstrated to be highly accurate and reproducible. Compared to traditional resin-based coIP, MSIP results in higher sensitivity and enhanced throughput, with the additional benefit of digital read-outs. In addition, MSIP was shown to be a highly useful validation platform to confirm PPI candidates that have been identified from yeast two hybrid systems.

Conclusions
In conclusion, MSIP is proved to be a simple, cost-saving and highly efficient technique for the comprehensive study of PPIs.
Determination of the differentiation capacities of murines' primary mononucleated cells and MC3T3-E1 cells
Authors: Yazid Muhammad Dain , Ariffin Shahrul Hisham Zainal , Senafi Sahidan , Razak Mohamad Abdul , Wahab Rohaya Megat Abdul 
Published: October 2010

Abstract

Background
The main morphological features of primitive cells, such as stem and progenitor cells, are that these cells consists only one nucleus. The main purpose of this study was to determine the differentiation capacities of stem and progenitor cells. This study was performed using mononucleated cells originated from murine peripheral blood and MC3T3-E1 cells. Three approaches were used to determine their differentiation capacities: 1) Biochemical assays, 2) Gene expression analysis, and 3) Morphological observations.

Results
We found that both cells were able to differentiate into mature osteoblasts, as assayed by ALP activity. RT-PCR analysis showed the activation of the Opn gene after osteoblast differentiation. Morphological observations of both cells revealed the formation of black or dark-brown nodules after von Kossa staining. Nevertheless, only mononucleated cells showed the significant increase in TRAP activity characteristic of mature osteoclasts. The osteoclast-specific CatK gene was only upregulated in mononucleated cells. Morphological observations indicated the existence of multinucleated osteoclasts. Sca-1 was activated only in undifferentiated mononucleated cells, indicating that the cells were hematopoietic stem cells. In both cell lines, the housekeeping Gapdh gene was activated before and after differentiation.

Conclusion
The isolated mononucleated cells were able to differentiate into both osteoblasts and osteoclasts; indicating that they are stem cells. On the other hand, MC3T3-E1 cells can only differentiate into osteoblasts; a characteristic of progenitor cells.
Fine specificity of anti-MSP119 antibodies and multiplicity of Plasmodium falciparum Merozoite Surface Protein 1 types in individuals in Nigeria with sub-microscopic infection
Authors: Ngoundou-Landji Josiane , Nwuba Roseangela I , Anumudu Chiaka I , Odaibo Alexander B , Matondo Maya Wenceslas D , Awobode Henrietta O , Okafor Christian M , Morenikeji Olajumoke A , Asinobi Adanze , Nwagwu Mark , Holder Anthony A , Ntoumi Francine 
Published: October 2010

Abstract

Background
The absence of antibodies specific for the 19 kDa C-terminal domain of merozoite surface protein 1 (MSP119) has been associated with high-density malaria parasitaemia in African populations. The hypothesis that a high prevalence and/or level of anti-MSP119 antibodies that may inhibit erythrocyte invasion would be present in apparently healthy individuals who harbour a sub-microscopic malaria infection was tested in this study.

Methods
Plasma samples were collected from residents in a region in Nigeria hyperendemic for malaria, who had no detectable parasitaemia by microscopy. Using a competition-based enzyme-linked-immunosorbent assay with two invasion-inhibitory monoclonal antibodies (mAbs) 12.10 and 12.8, the levels and prevalence of specific antibodies were measured. The minimum multiplicity of infection was determined using PCR. The prevalence of anaemia was also measured.

Results
Plasma samples from 85% of individuals contained antibodies that bound to MSP119. The inhibition of mAb 12.10 binding was strongly correlated with the prevalence (Spearman correlation test, p < 0.0001) and mean titre of anti-MSP119 antibodies (Spearman correlation test, p < 0.001) in the samples. Comparing samples from individuals with multiple infection (group M) and single infection (Group S), group M contained a higher (p = 0.04) prevalence of anti-MSP119 antibodies that competed with mAb 12.10. Using a logistic regression model, it was found that the presence of antibodies competitive with mAb 12.10 was affected negatively by anaemia (p = 0.0016) and positively by the carriage of multiple parasite genotypes (p = 0.04).

Conclusions
In the search for correlates of protection against malaria, which will be essential to evaluate clinical trials of malaria vaccines based on MSP1, this study examines some potential assays and the factors that need to taken into account during their evaluation, using samples from individuals naturally exposed to malaria infection.
Decoding hand movement velocity from electroencephalogram signals during a drawing task
Authors: Lv Jun , Li Yuanqing , Gu Zhenghui 
Published: October 2010

Abstract

Background
Decoding neural activities associated with limb movements is the key of motor prosthesis control. So far, most of these studies have been based on invasive approaches. Nevertheless, a few researchers have decoded kinematic parameters of single hand in non-invasive ways such as magnetoencephalogram (MEG) and electroencephalogram (EEG). Regarding these EEG studies, center-out reaching tasks have been employed. Yet whether hand velocity can be decoded using EEG recorded during a self-routed drawing task is unclear.

Methods
Here we collected whole-scalp EEG data of five subjects during a sequential 4-directional drawing task, and employed spatial filtering algorithms to extract the amplitude and power features of EEG in multiple frequency bands. From these features, we reconstructed hand movement velocity by Kalman filtering and a smoothing algorithm.

Results
The average Pearson correlation coefficients between the measured and the decoded velocities are 0.37 for the horizontal dimension and 0.24 for the vertical dimension. The channels on motor, posterior parietal and occipital areas are most involved for the decoding of hand velocity. By comparing the decoding performance of the features from different frequency bands, we found that not only slow potentials in 0.1-4 Hz band but also oscillatory rhythms in 24-28 Hz band may carry the information of hand velocity.

Conclusions
These results provide another support to neural control of motor prosthesis based on EEG signals and proper decoding methods.