bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation and characterization of DNA microarray gene expression data distribution and associated moments
Authors: Thomas Reuben , de la Torre Luis , Chang Xiaoqing , Mehrotra Sanjay 
Published: November 2010

Abstract

Background
The data from DNA microarrays are increasingly being used in order to understand effects of different conditions, exposures or diseases on the modulation of the expression of various genes in a biological system. This knowledge is then further used in order to generate molecular mechanistic hypotheses for an organism when it is exposed to different conditions. Several different methods have been proposed to analyze these data under different distributional assumptions on gene expression. However, the empirical validation of these assumptions is lacking.

Results
Best fit hypotheses tests, moment-ratio diagrams and relationships between the different moments of the distribution of the gene expression was used to characterize the observed distributions. The data are obtained from the publicly available gene expression database, Gene Expression Omnibus (GEO) to characterize the empirical distributions of gene expressions obtained under varying experimental situations each of which providing relatively large number of samples for hypothesis testing. All data were obtained from either of two microarray platforms - the commercial Affymetrix mouse 430.2 platform and a non-commercial Rosetta/Merck one. The data from each platform were preprocessed in the same manner.

Conclusions
The null hypotheses for goodness of fit for all considered univariate theoretical probability distributions (including the Normal distribution) are rejected for more than 50% of probe sets on the Affymetrix microarray platform at a 95% confidence level, suggesting that under the tested conditions a priori assumption of any of these distributions across all probe sets is not valid. The pattern of null hypotheses rejection was different for the data from Rosetta/Merck platform with only around 20% of the probe sets failing the logistic distribution goodness-of-fit test. We find that there are statistically significant (at 95% confidence level based on the F-test for the fitted linear model) relationships between the mean and the logarithm of the coefficient of variation of the distributions of the logarithm of gene expressions. An additional novel statistically significant quadratic relationship between the skewness and kurtosis is identified. Data from both microarray platforms fail to identify with any one of the chosen theoretical probability distributions from an analysis of the l-moment ratio diagram.
Principal-component-based multivariate regression for genetic association studies of metabolic syndrome components
Authors: Mei Hao , Chen Wei , Dellinger Andrew , He Jiang , Wang Meng , Yau Canddy , Srinivasan Sathanur R , Berenson Gerald S 
Published: November 2010

Abstract

Background
Quantitative traits often underlie risk for complex diseases. For example, weight and body mass index (BMI) underlie the human abdominal obesity-metabolic syndrome. Many attempts have been made to identify quantitative trait loci (QTL) over the past decade, including association studies. However, a single QTL is often capable of affecting multiple traits, a quality known as gene pleiotropy. Gene pleiotropy may therefore cause a loss of power in association studies focused only on a single trait, whether based on single or multiple markers.

Results
We propose using principal-component-based multivariate regression (PCBMR) to test for gene pleiotropy with comprehensive evaluation. This method generates one or more independent canonical variables based on the principal components of original traits and conducts a multivariate regression to test for association with these new variables. Systematic simulation studies have shown that PCBMR has great power. PCBMR-based pleiotropic association studies of abdominal obesity-metabolic syndrome and its possible linkage to chromosomal band 3q27 identified 11 susceptibility genes with significant associations. Whereas some of these genes had been previously reported to be associated with metabolic traits, others had never been identified as metabolism-associated genes.

Conclusions
PCBMR is a computationally efficient and powerful test for gene pleiotropy. Application of PCBMR to abdominal obesity-metabolic syndrome indicated the existence of gene pleiotropy affecting this syndrome.
Rnnotator: an automated de novo transcriptome assembly pipeline from stranded RNA-Seq reads
Authors: Martin Jeffrey , Bruno Vincent M , Fang Zhide , Meng Xiandong , Blow Matthew , Zhang Tao , Sherlock Gavin , Snyder Michael , Wang Zhong 
Published: November 2010

Abstract

Background
Comprehensive annotation and quantification of transcriptomes are outstanding problems in functional genomics. While high throughput mRNA sequencing (RNA-Seq) has emerged as a powerful tool for addressing these problems, its success is dependent upon the availability and quality of reference genome sequences, thus limiting the organisms to which it can be applied.

Results
Here, we describe Rnnotator, an automated software pipeline that generates transcript models by de novo assembly of RNA-Seq data without the need for a reference genome. We have applied the Rnnotator assembly pipeline to two yeast transcriptomes and compared the results to the reference gene catalogs of these organisms. The contigs produced by Rnnotator are highly accurate (95%) and reconstruct full-length genes for the majority of the existing gene models (54.3%). Furthermore, our analyses revealed many novel transcribed regions that are absent from well annotated genomes, suggesting Rnnotator serves as a complementary approach to analysis based on a reference genome for comprehensive transcriptomics.

Conclusions
These results demonstrate that the Rnnotator pipeline is able to reconstruct full-length transcripts in the absence of a complete reference genome.
Long descending cervical propriospinal neurons differ from thoracic propriospinal neurons in response to low thoracic spinal injury
Authors: Siebert Justin R , Middleton Frank A , Stelzner Dennis J 
Published: November 2010

Abstract

Background
Propriospinal neurons, with axonal projections intrinsic to the spinal cord, have shown a greater regenerative response than supraspinal neurons after axotomy due to spinal cord injury (SCI). Our previous work focused on the response of axotomized short thoracic propriospinal (TPS) neurons following a low thoracic SCI (T9 spinal transection or moderate spinal contusion injury) in the rat. The present investigation analyzes the intrinsic response of cervical propriospinal neurons having long descending axons which project into the lumbosacral enlargement, long descending propriospinal tract (LDPT) axons. These neurons also were axotomized by T9 spinal injury in the same animals used in our previous study.

Results
Utilizing laser microdissection (LMD), qRT-PCR, and immunohistochemistry, we studied LDPT neurons (located in the C5-C6 spinal segments) between 3-days, and 1-month following a low thoracic (T9) spinal cord injury. We examined the response of 89 genes related to growth factors, cell surface receptors, apoptosis, axonal regeneration, and neuroprotection/cell survival. We found a strong and significant down-regulation of ~25% of the genes analyzed early after injury (3-days post-injury) with a sustained down-regulation in most instances. In the few genes that were up-regulated (Actb, Atf3, Frs2, Hspb1, Nrap, Stat1) post-axotomy, the expression for all but one was down-regulated by 2-weeks post-injury. We also compared the uninjured TPS control neurons to the uninjured LDPT neurons used in this experiment for phenotypic differences between these two subpopulations of propriospinal neurons. We found significant differences in expression in 37 of the 84 genes examined between these two subpopulations of propriospinal neurons with LDPT neurons exhibiting a significantly higher base line expression for all but 3 of these genes compared to TPS neurons.

Conclusions
Taken collectively these data indicate a broad overall down-regulation in the genes examined, including genes for neurotrophic/growth factor receptors as well as for several growth factors. There was a lack of a significant regenerative response, with the exception of an up-regulation of Atf3 and early up-regulation of Hspb1 (Hsp27), both involved in cell stress/neuroprotection as well as axonal regeneration. There was no indication of a cell death response over the first month post-injury. In addition, there appear to be significant phenotypic differences between uninjured TPS and LDPT neurons, which may partly account for the differences observed in their post-axotomy responses. The findings in this current study stand in stark contrast to the findings from our previous work on TPS neurons. This suggests that different approaches will be needed to enhance the capacity for each population of propriospinal neuron to survive and undergo successful axonal regeneration after SCI.
Identification and expression analysis of microRNAs and targets in the biofuel crop sugarcane
Authors: Zanca Almir S , Vicentini Renato , Ortiz-Morea Fausto A , Del Bem Luiz EV , da Silva Marcio J , Vincentz Michel , Nogueira Fabio TS 
Published: November 2010

Abstract

Background
MicroRNAs (miRNAs) are small regulatory RNAs, some of which are conserved in diverse plant genomes. Therefore, computational identification and further experimental validation of miRNAs from non-model organisms is both feasible and instrumental for addressing miRNA-based gene regulation and evolution. Sugarcane (Saccharum spp.) is an important biofuel crop with publicly available expressed sequence tag and genomic survey sequence databases, but little is known about miRNAs and their targets in this highly polyploid species.

Results
In this study, we have computationally identified 19 distinct sugarcane miRNA precursors, of which several are highly similar with their sorghum homologs at both nucleotide and secondary structure levels. The accumulation pattern of mature miRNAs varies in organs/tissues from the commercial sugarcane hybrid as well as in its corresponding founder species S. officinarum and S. spontaneum. Using sugarcane MIR827 as a query, we found a novel MIR827 precursor in the sorghum genome. Based on our computational tool, a total of 46 potential targets were identified for the 19 sugarcane miRNAs. Several targets for highly conserved miRNAs are transcription factors that play important roles in plant development. Conversely, target genes of lineage-specific miRNAs seem to play roles in diverse physiological processes, such as SsCBP1. SsCBP1 was experimentally confirmed to be a target for the monocot-specific miR528. Our findings support the notion that the regulation of SsCBP1 by miR528 is shared at least within graminaceous monocots, and this miRNA-based post-transcriptional regulation evolved exclusively within the monocots lineage after the divergence from eudicots.

Conclusions
Using publicly available nucleotide databases, 19 sugarcane miRNA precursors and one new sorghum miRNA precursor were identified and classified into 14 families. Comparative analyses between sugarcane and sorghum suggest that these two species retain homologous miRNAs and targets in their genomes. Such conservation may help to clarify specific aspects of miRNA regulation and evolution in the polyploid sugarcane. Finally, our dataset provides a framework for future studies on sugarcane RNAi-dependent regulatory mechanisms.
Effect of the rs2259816 polymorphism in the HNF1A gene on circulating levels of c-reactive protein and coronary artery disease (the ludwigshafen risk and cardiovascular health study)
Authors: Kleber Marcus E , Grammer Tanja B , Renner Wilfried , März Winfried 
Published: November 2010

AbstractBackgroundC-reactive protein is a well established marker of inflammation and has been used to predict future cardiovascular disease. It is still controversial if it plays an active role in the development of cardiovascular disease. Recently, polymorphisms in the gene for HNF1α have been linked to the levels of C-reactive protein and coronary artery disease.MethodsWe investigated the association of the rs2259816 polymorphism in the HNF1A gene with the circulating level of C-reactive protein and the hazard of coronary artery disease in the LURIC Study cohort.ResultsCompared to CC homozygotes, the level of C-reactive protein was decreased in carriers of at least one A-allele. Each A-allele decreased CRP by approximately 15%. The odds ratio for coronary artery disease was only very slightly increased in carriers of the A-allele and this association did not reach statistical significance.ConclusionsIn the LURIC Study cohort the A-allele of rs2259816 is associated with decreased CRP but not with coronary artery disease.
Process evaluation of a school based physical activity related injury prevention programme using the RE-AIM framework
Authors: Collard Dorine CM , Chinapaw Mai JM , Verhagen Evert ALM , van Mechelen Willem 
Published: November 2010

Abstract

Background
In general, only information regarding the effectiveness of an intervention programme is ever published. However, in recent years evaluating the translatability and feasibility of an intervention programme has become more important. Therefore, this paper presents the results of the evaluation of the iPlay programme aimed at preventing physical activity related injuries in primary school children.

Methods
The iPlay programme targeted injuries gained through physical activity, and consisted of a teacher's manual, informative newsletters and posters, a website, and set exercises to be carried out during physical education (PE) classes. In order to evaluate the iPlay programme for translatability and feasibility, teachers, children and parents who participated in the iPlay programme filled out a questionnaire
The objective of this study is to describe the results of the process-evaluation of the iPlay programme based on the five dimensions of the RE-AIM framework.

Results
The results showed that the participation rate of the children was 100% (reach). Nine percent of the schools who were invited to take part were willing to participate in the study (adoption rate). Teachers stated that they implemented the different elements of the programme partly as intended (implementation). The percentage of children and parents who followed the programme was less than expected. In addition, 52% of the teachers indicated that the current iPlay programme could become standard practice in their teaching routine (maintenance).

Conclusion
The iPlay programme is a first start in the prevention of physical activity related injuries in children, but further improvements need to be made to the programme on the basis of this process evaluation.

Trial registration
ISRCTN78846684; http://www.controlled-trials.com
Loss of glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma
Authors: Falck Eva , Karlsson Sandra , Carlsson, Jessica , Helenius Gisela , Karlsson Mats , Klinga-Levan Karin 
Published: November 2010

Abstract
Glutathione peroxidase 3 (GPX3) is one of the key enzymes in the cellular defense against oxidative stress and the hepatocyte growth factor receptor, (MET) has been suggested to be influenced by the GPX3 gene expression. In a previous microarray study performed by our group, Gpx3 was identified as a potential biomarker for rat endometrial adenocarcinoma (EAC), since the expression was highly downregulated in rat EAC tumors. Herein, we have investigated the mRNA expression and Gpx3 and Met in rat EAC by real time quantitative PCR (qPCR), and the methylation status of Gpx3. In addition we have examined the expression of GPX3 and MET in 30 human EACs of different FIGO grades and 20 benign endometrial tissues. We found that the expression of GPX3 was uniformly down regulated in both rat and human EAC, regardless of tumor grade or histopathological subtype, implying that the down-regulation is an early event in EAC. The rate of Gpx3 promoter methylation reaches 91%, where biallelic methylation was present in 90% of the methylated tumors. The expression of the Met oncogene was slightly upregulated in EACs that showed loss of expression of Gpx3, but no tumor suppressor activity of Gpx3/GPX3 was detected. Preliminary results also suggest that the production of H2O2 is higher in rat endometrial tumors with down-regulated Gpx3 expression. A likely consequence of loss of GPX3 protein function would be a higher amount of ROS in the cancer cell environment. Thus, the results suggest important clinical implications of the GPX3 expression in EAC, both as a molecular biomarker for EAC and as a potential target for therapeutic interventions.
Increased prevalence of the pfdhfr/phdhps quintuple mutant and rapid emergence of pfdhps resistance mutations at codons 581 and 613 in Kisumu, Kenya
Authors: Spalding Maroya D , Eyase Fredrick L , Akala Hoseah M , Bedno Sheryl A , Prigge Sean T , Coldren Rodney L , Moss William J , Waters Norman C 
Published: November 2010

Abstract

Background
Anti-malarial drug resistance in Kenya prompted two drug policy changes within a decade: sulphadoxine-pyrimethamine (SP) replaced chloroquine (CQ) as the first-line anti-malarial in 1998 and artemether-lumefantrine (AL) replaced SP in 2004. Two cross-sectional studies were conducted to monitor changes in the prevalence of molecular markers of drug resistance over the period in which SP was used as the first-line anti-malarial. The baseline study was carried out from 1999-2000, shortly after implementation of SP, and the follow-up study occurred from 2003-2005, during the transition to AL.

Materials and methods
Blood was collected from malaria smear-positive, symptomatic patients presenting to outpatient centers in Kisumu, Kenya, during the baseline and follow-up studies. Isolates were genotyped at codons associated with SP and CQ resistance. In vitro IC50 values for antifolates and quinolones were determined for isolates from the follow-up study.

Results
The prevalence of isolates containing the pfdhfr N51I/C59R/S108N/pfdhps A437G/K540E quintuple mutant associated with SP-resistance rose from 21% in the baseline study to 53% in the follow-up study (p < 0.001). Isolates containing the pfdhfr I164L mutation were absent from both studies. The pfdhps mutations A581G and A613S/T were absent from the baseline study but were present in 85% and 61%, respectively, of isolates from the follow-up study. At follow-up, parasites with mutations at five pfdhps codons, 436, 437, 540, 581, and 613, accounted for 39% of isolates. The CQ resistance-associated mutations pfcrt K76T and pfmdr1 N86Y rose from 82% to 97% (p = 0.001) and 44% to 76% (p < 0.001), respectively, from baseline to follow-up.

Conclusions
During the period in which SP was the first-line anti-malarial in Kenya, highly SP-resistant parasites emerged, including isolates harboring pfdhps mutations not previously observed there. SP continues to be widely used in Kenya; however, given the highly resistant genotypes observed in this study, its use as a first-line anti-malarial should be discouraged, particularly for populations without acquired immunity to malaria. The increase in the pfcrt K76T prevalence, despite efforts to reduce CQ use, suggests that either these efforts are not adequate to alleviate CQ pressure in Kisumu, or that drug pressure is derived from another source, such as the second-line anti-malarial amodiaquine.
Quantitative pinch stimulator for exploring evoked nociceptive responses: A pilot study
Authors: Chen Chih-Ping , Liao Wen-Li , Tseng Yi-Li , Lu Pen-Li , Lo Yu-Chun , Chen You-Yin , Jaw Fu-Shan 
Published: November 2010

Abstract

Background
A mechanical noxious stimulator is useful for studies of pain, both for clinic and basic research. We propose to use a pinch stimulator that can not only generate a quantitative, reproducible noxious pinch but also simultaneously provide a synchronous external trigger signal, which is essential for acquisition of evoked potentials.

Methods
For ethical considerations, audible and visual aids were incorporated so that pinch force could be regulated within a predetermined level. Reproducibility of the nociceptive responses evoked by this device was validated. The device was constructed with a simple circuit, and the element build-in was delicately selected for the minimum required to produce evoked potentials.

Results
The magnitude of the force output is linearly proportional to the volts produced by the device (i.e., during the pinch). Increases in force correspond to increases in the number of action potentials induced.

Conclusions
This device may be useful for studying the mechanisms of nociceptive signal processing in the brain through application of reproducible, noxious pinch stimuli.
Suppression of nitric oxide production from nasal fibroblasts by metabolized clarithromycin in vitro
Authors: Furuya Ayako , Asano Kazuhito , Shoji Naruo , Hirano Kojiro , Hamasaki Taisuke , Suzaki Harumi 
Published: November 2010

AbstractBackgroundLow-dose and long-term administration of 14-membered macrolide antibiotics, so called macrolide therapy, has been reported to favorably modify the clinical conditions of chronic airway diseases. Since there is growing evidence that macrolide antibiotic-resistant bacteria's spreaders in the populations received macrolide therapy, it is strongly desired to develop macrolide antibiotics, which showed only anti-inflammatory action. The present study was designed to examine the influence of clarithromycin (CAM) and its metabolized materials, M-1, M-4 and M-5, on free radical generation from nasal polyp fibroblasts (NPFs) through the choice of nitric oxide (NO), which is one of important effector molecule in the development of airway inflammatory diseasein vitro.MethodsNPFs (5 × 105cells/ml) were stimulated with 1.0 μg/ml lipopolysaccharide (LPS) in the presence of agents for 24 hours. NO levels in culture supernatants were examined by the Griess method. We also examined the influence of agents on the phosphorylation of MAPKs, NF-κB activation, iNOS mRNA expression and iNOS production in NPFs cultured for 2, 4, 8, and 12 hours, respectively.ResultsThe addition of CAM (> 0.4 μg/ml) and M-4 (> 0.04 μg/ml) could suppress NO production from NPFs after LPS stimulation through the suppression of iNOS mRNA expression and NF-κB activation. CAM and M-4 also suppressed phosphorylation of MAPKs, ERK and p38 MAPK, but not JNK, which are increased LPS stimulation. On the other hand, M-1 and M-5 could not inhibit the NO generation, even when 0.1 μg/ml of the agent was added to cell cultures.ConclusionThe present results may suggest that M-4 will be a good candidate for the agent in the treatment of chronic airway inflammatory diseases, since M-4 did not have antimicribiological effects on gram positive and negative bacteria.