bluuebunny/crossref_metadata_2025_split huggingface dataset:
NGSQC: cross-platform quality analysis pipeline for deep sequencing data
Authors: Dai Manhong , Thompson Robert C , Maher Christopher , Contreras-Galindo Rafael , Kaplan Mark H , Markovitz David M , Omenn Gil , Meng Fan 
Published: December 2010

Abstract

Background
While the accuracy and precision of deep sequencing data is significantly better than those obtained by the earlier generation of hybridization-based high throughput technologies, the digital nature of deep sequencing output often leads to unwarranted confidence in their reliability.

Results
The NGSQC (N ext G eneration S equencing Q uality C ontrol) pipeline provides a set of novel quality control measures for quickly detecting a wide variety of quality issues in deep sequencing data derived from two dimensional surfaces, regardless of the assay technology used. It also enables researchers to determine whether sequencing data related to their most interesting biological discoveries are caused by sequencing quality issues.

Conclusions
Next generation sequencing platforms have their own share of quality issues and there can be significant lab-to-lab, batch-to-batch and even within chip/slide variations. NGSQC can help to ensure that biological conclusions, in particular those based on relatively rare sequence alterations, are not caused by low quality sequencing.
Discovery and characterization of medaka miRNA genes by next generation sequencing platform
Authors: Li Sung-Chou , Chan Wen-Ching , Ho Meng-Ru , Tsai Kuo-Wang , Hu Ling-Yueh , Lai Chun-Hung , Hsu Chun-Nan , Hwang Pung-Pung , Lin Wen-chang 
Published: December 2010

Abstract

Background
MicroRNAs (miRNAs) are endogenous non-protein-coding RNA genes which exist in a wide variety of organisms, including animals, plants, virus and even unicellular organisms. Medaka (Oryzias latipes) is a useful model organism among vertebrate animals. However, no medaka miRNAs have been investigated systematically. It is beneficial to conduct a genome-wide miRNA discovery study using the next generation sequencing (NGS) technology, which has emerged as a powerful sequencing tool for high-throughput analysis.

Results
In this study, we adopted ABI SOLiD platform to generate small RNA sequence reads from medaka tissues, followed by mapping these sequence reads back to medaka genome. The mapped genomic loci were considered as candidate miRNAs and further processed by a support vector machine (SVM) classifier. As result, we identified 599 novel medaka pre-miRNAs, many of which were found to encode more than one isomiRs. Besides, additional minor miRNAs (also called miRNA star) can be also detected with the improvement of sequencing depth. These quantifiable isomiRs and minor miRNAs enable us to further characterize medaka miRNA genes in many aspects. First of all, many medaka candidate pre-miRNAs position close to each other, forming many miRNA clusters, some of which are also conserved across other vertebrate animals. Secondly, during miRNA maturation, there is an arm selection preference of mature miRNAs within precursors. We observed the differences on arm selection preference between our candidate pre-miRNAs and their orthologous ones. We classified these differences into three categories based on the distribution of NGS reads. Finally, we also investigated the relationship between conservation status and expression level of miRNA genes. We concluded that the evolutionally conserved miRNAs were usually the most abundant ones.

Conclusions
Medaka is a widely used model animal and usually involved in many biomedical studies, including the ones on development biology. Identifying and characterizing medaka miRNA genes would benefit the studies using medaka as a model organism.
Merging transcriptomics and metabolomics - advances in breast cancer profiling
Authors: Borgan Eldrid , Sitter Beathe , Lingjærde Ole Christian , Johnsen Hilde , Lundgren Steinar , Bathen Tone F , Sørlie Therese , Børresen-Dale Anne-Lise , Gribbestad Ingrid S 
Published: December 2010

Abstract

Background
Combining gene expression microarrays and high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) of the same tissue samples enables comparison of the transcriptional and metabolic profiles of breast cancer. The aim of this study was to explore the potential of combining these two different types of information.

Methods
Breast cancer tissue from 46 patients was analyzed by HR MAS MRS followed by gene expression microarrays. Two strategies were used to combine the gene expression and metabolic data; first using multivariate analyses to identify different groups based on gene expression and metabolic data; second correlating levels of specific metabolites to transcripts to suggest new hypotheses of connections between metabolite levels and the underlying biological processes. A parallel study was designed to address experimental issues of combining microarrays and HR MAS MRS.

Results
In the first strategy, using the microarray data and previously reported molecular classification methods, the majority of samples were classified as luminal A. Three subgroups of luminal A tumors were identified based on hierarchical clustering of the HR MAS MR spectra. The samples in one of the subgroups, designated A2, showed significantly lower glucose and higher alanine levels than the other luminal A samples, suggesting a higher glycolytic activity in these tumors. This group was also enriched for genes annotated with Gene Ontology (GO) terms related to cell cycle and DNA repair. In the second strategy, the correlations between concentrations of myo-inositol, glycine, taurine, glycerophosphocholine, phosphocholine, choline and creatine and all transcripts in the filtered microarray data were investigated. GO-terms related to the extracellular matrix were enriched among the genes that correlated the most to myo-inositol and taurine, while cell cycle related GO-terms were enriched for the genes that correlated the most to choline. Additionally, a subset of transcripts was identified to have slightly altered expression after HR MAS MRS and was therefore removed from all other analyses.

Conclusions
Combining transcriptional and metabolic data from the same breast carcinoma sample is feasible and may contribute to a more refined subclassification of breast cancers as well as reveal relations between metabolic and transcriptional levels.
See Commentary: http://www.biomedcentral.com/1741-7015/8/73
Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax
Authors: Wang Peng , Zhen Haining , Jiang Xinbiao , Zhang Wei , Cheng Xin , Guo Geng , Mao Xinggang , Zhang Xiang 
Published: December 2010

Abstract

Background
Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation.

Methods
The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [60Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [60Co] γ-rays; Group C included cells treated with 8 Gy of [60Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis.

Results
Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [60Co] γ-rays (P < 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E treated with BPA-BNCT were significantly higher than those in Group B and Group C irradiated by [60Co] γ-rays (P < 0.01). The clonogenicity of glioma cells was reduced by BPA-BNCT compared with cells treated in the reactor (Group F, G, H, I), and with the control cells (P < 0.01). Upon BPA-BNCT treatment, the Bax level increased in glioma cells, whereas Bcl-2 expression decreased.

Conclusions
Compared with γ-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by BNCT may be related to activation of Bax and downregulation of Bcl-2.
Specific genomic aberrations in primary colorectal cancer are associated with liver metastases
Authors: Bruin Sjoerd C , Klijn Christiaan , Liefers Gerrit-Jan , Braaf Linde M , Joosse Simon A , van Beers Eric H , Verwaal Victor J , Morreau Hans , Wessels Lodewyk F , van Velthuysen Marie-Louise F , Tollenaar Rob AEM , van't Veer Laura J 
Published: December 2010

Abstract

Background
Accurate staging of colorectal cancer (CRC) with clinicopathological parameters is important for predicting prognosis and guiding treatment but provides no information about organ site of metastases. Patterns of genomic aberrations in primary colorectal tumors may reveal a chromosomal signature for organ specific metastases.

Methods
Array Comparative Genomic Hybridization (aCGH) was employed to asses DNA copy number changes in primary colorectal tumors of three distinctive patient groups. This included formalin-fixed, paraffin-embedded tissue of patients who developed liver metastases (LM; n = 36), metastases (PM; n = 37) and a group that remained metastases-free (M0; n = 25).
A novel statistical method for identifying recurrent copy number changes, KC-SMART, was used to find specific locations of genomic aberrations specific for various groups. We created a classifier for organ specific metastases based on the aCGH data using Prediction Analysis for Microarrays (PAM).

Results
Specifically in the tumors of primary CRC patients who subsequently developed liver metastasis, KC-SMART analysis identified genomic aberrations on chromosome 20q. LM-PAM, a shrunken centroids classifier for liver metastases occurrence, was able to distinguish the LM group from the other groups (M0&PM) with 80% accuracy (78% sensitivity and 86% specificity). The classification is predominantly based on chromosome 20q aberrations.

Conclusion
Liver specific CRC metastases may be predicted with a high accuracy based on specific genomic aberrations in the primary CRC tumor. The ability to predict the site of metastases is important for improvement of personalized patient management.
The first three years of screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD) by newborn screening ontario
Authors: Kennedy Shelley , Potter Beth K , Wilson Kumanan , Fisher Lawrence , Geraghty Michael , Milburn Jennifer , Chakraborty Pranesh 
Published: December 2010

Abstract

Background
Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of mitochondrial fatty acid oxidation and is one of the most common inborn errors of metabolism. Identification of MCADD via newborn screening permits the introduction of interventions that can significantly reduce associated morbidity and mortality. This study reports on the first three years of newborn screening for MCADD in Ontario, Canada.

Methods
Newborn Screening Ontario began screening for MCADD in April 2006, by quantification of acylcarnitines (primarily octanoylcarnitine, C8) in dried blood spots using tandem mass spectrometry. Babies with positive screening results were referred to physicians at one of five regional Newborn Screening Treatment Centres, who were responsible for diagnostic evaluation and follow-up care.

Results
From April 2006 through March 2009, approximately 439 000 infants were screened for MCADD in Ontario. Seventy-four infants screened positive, with a median C8 level of 0.68 uM (range 0.33-30.41 uM). Thirty-one of the screen positive infants have been confirmed to have MCADD, while 36 have been confirmed to be unaffected. Screening C8 levels were higher among infants with MCADD (median 8.93 uM) compared to those with false positive results (median 0.47 uM). Molecular testing was available for 29 confirmed cases of MCADD, 15 of whom were homozygous for the common c.985A > G mutation. Infants homozygous for the common mutation tended to have higher C8 levels (median 12.13 uM) relative to compound heterozygotes for c.985A > G and a second detectable mutation (median 2.01 uM). Eight confirmed mutation carriers were identified among infants in the false positive group. The positive predictive value of a screen positive for MCADD was 46%. The estimated birth prevalence of MCADD in Ontario is approximately 1 in 14 000.

Conclusions
The birth prevalence of MCADD and positive predictive value of the screening test were similar to those identified by other newborn screening programs internationally. We observed some evidence of correlation between genotype and biochemical phenotype (C8 levels), and between C8 screening levels and eventual diagnosis. Current research priorities include further examining the relationships among genotype, biochemical phenotype, and clinical phenotype, with the ultimate goal of improving clinical risk prediction in order to provide tailored disease management advice and genetic counselling to families.
Signal transducer and activator of transcription 3 activation up-regulates interleukin-6 autocrine production: a biochemical and genetic study of established cancer cell lines and clinical isolated human cancer cells
Authors: Huang Wei-Lun , Yeh Hsuan-Heng , Lin Chien-Chung , Lai Wu-Wei , Chang Jang-Yang , Chang Wen-Tsan , Su Wu-Chou 
Published: December 2010

AbstractBackgroundSpontaneous interleukin-6 (IL-6) production has been observed in various tumors and implicated in the pathogenesis, progression and drug resistance in cancer. However, the regulation of IL-6 autocrine production in cancer cells is not fully understood. IL-6 is auto-regulated in many types of cell. Two of the three major downstream pathways of IL-6, MEK/extracellular signal-related kinase (Erk) pathway and phosphatidylinositol 3-kinase (PI3-K)/Akt pathway, have been shown to regulate IL-6 expression through the activation of AP-1 and NF-κB. However, it is not clear what the role of Janus kinase (Jak) 2/signal transducer and activator of transcription (Stat) 3 pathway. This study was designed to determine the role of Jak2/Stat3 pathway in the regulation of IL-6 autocrine production in cancer cells.ResultsInhibitors of Jak2/Stat3, MEK/Erk and PI3-K/Akt pathways down-regulated IL-6 secretion in the lung adenocarcinoma PC14PE6/AS2 (AS2) cells, which spontaneously secreted IL-6 and possessed constitutively activated Stat3. Transfection with dominant-negative Stat3, Stat3 siRNA, or Stat3 shRNA decreased IL-6 expression in AS2 cells. Conversely, transfection with constitutively-activated Stat3 increased the production of IL-6. In AS2 derived cells, resistance to paclitaxel was positively correlated with Stat3 activation status and the expression of IL-6, which is commonly secreted in drug resistant cancer cells. The pharmacological inhibition of NF-κB, PI3-K/Akt and MEK/Erk and the pharmacological inhibition and genetic inhibition (Stat3 siRNA) of Jak2/Stat3 pathway decreased IL-6 autocrine production in various drug resistant cancer cell lines and similarly decreased IL-6 autocrine production in clinically isolated lung cancer cells.ConclusionsThis study is the first to directly address the role Stat3 plays on the autocrine production of IL-6, which occurs through a positive-feedback loop. Our biochemical and genetic studies clearly demonstrated that Jak2/Stat3, in combination with other IL-6 downstream pathways, contributed frequently and substantially to IL-6 autocrine production in a broad spectrum of cancer cell lines as well as in clinical cancer samples. Our findings suggest that Stat3 could potentially be regulated to suppress IL-6 autocrine production in cancer cells to inhibit the progression of cancer and reduce drug resistance.
Expression of hepatocytic- and biliary-specific transcription factors in regenerating bile ducts during hepatocyte-to-biliary epithelial cell transdifferentiation
Authors: Limaye Pallavi B , Bowen William C , Orr Anne , Apte Udayan M , Michalopoulos George K 
Published: December 2010

AbstractBackgroundUnder compromised biliary regeneration, transdifferentiation of hepatocytes into biliary epithelial cells (BEC) has been previously observed in rats, upon exposure to BEC-specific toxicant methylene dianiline (DAPM) followed by bile duct ligation (BDL), and in patients with chronic biliary liver disease. However, mechanisms promoting such transdifferentiation are not fully understood. In the present study, acquisition of biliary specific transcription factors by hepatocytes leading to reprogramming of BEC-specific cellular profile was investigated as a potential mechanism of transdifferentiation in two different models of compromised biliary regeneration in rats.ResultsIn addition to previously examined DAPM + BDL model, an experimental model resembling chronic biliary damage was established by repeated administration of DAPM. Hepatocyte to BEC transdifferentiation was tracked using dipetidyl dipeptidase IV (DDPIV) chimeric rats that normally carry DPPIV only in hepatocytes. Following DAPM treatment, ~20% BEC population turned DPPIV-positive, indicating that they are derived from DPPIV-positive hepatocytes. New ductules emerging after DAPM + BDL and repeated DAPM exposure expressed hepatocyte-associated transcription factor hepatocyte nuclear factor (HNF) 4α and biliary specific transcription factor HNF1β. In addition, periportal hepatocytes expressed biliary marker CK19 suggesting periportal hepatocytes as a potential source of transdifferentiating cells. Although TGFβ1 was induced, there was no considerable reduction in periportal HNF6 expression, as observed during embryonic biliary development.ConclusionsTaken together, these findings indicate that gradual loss of HNF4α and acquisition of HNF1β by hepatocytes, as well as increase in TGFβ1 expression in periportal region, appear to be the underlying mechanisms of hepatocyte-to-BEC transdifferentiation.
The G Protein regulators EGL-10 and EAT-16, the Giα GOA-1 and the Gqα EGL-30 modulate the response of the C. elegansASH polymodal nociceptive sensory neurons to repellents
Authors: Esposito Giovanni , Amoroso Maria R , Bergamasco Carmela , Di Schiavi Elia , Bazzicalupo Paolo 
Published: December 2010

Abstract

Background
Polymodal, nociceptive sensory neurons are key cellular elements of the way animals sense aversive and painful stimuli. In Caenorhabditis elegans, the polymodal nociceptive ASH sensory neurons detect aversive stimuli and release glutamate to generate avoidance responses. They are thus useful models for the nociceptive neurons of mammals. While several molecules affecting signal generation and transduction in ASH have been identified, less is known about transmission of the signal from ASH to downstream neurons and about the molecules involved in its modulation.

Results
We discovered that the regulator of G protein signalling (RGS) protein, EGL-10, is required for appropriate avoidance responses to noxious stimuli sensed by ASH. As it does for other behaviours in which it is also involved, egl-10 interacts genetically with the Go/iα protein GOA-1, the Gqα protein EGL-30 and the RGS EAT-16. Genetic, behavioural and Ca2+ imaging analyses of ASH neurons in live animals demonstrate that, within ASH, EGL-10 and GOA-1 act downstream of stimulus-evoked signal transduction and of the main transduction channel OSM-9. EGL-30 instead appears to act upstream by regulating Ca2+ transients in response to aversive stimuli. Analysis of the delay in the avoidance response, of the frequency of spontaneous inversions and of the genetic interaction with the diacylglycerol kinase gene, dgk-1, indicate that EGL-10 and GOA-1 do not affect signal transduction and neuronal depolarization in response to aversive stimuli but act in ASH to modulate downstream transmission of the signal.

Conclusions
The ASH polymodal nociceptive sensory neurons can be modulated not only in their capacity to detect stimuli but also in the efficiency with which they respond to them. The Gα and RGS molecules studied in this work are conserved in evolution and, for each of them, mammalian orthologs can be identified. The discovery of their role in the modulation of signal transduction and signal transmission of nociceptors may help us to understand how pain is generated and how its control can go astray (such as chronic pain) and may suggest new pain control therapies.
Detection of porcine parvovirus using a taqman-based real-time pcr with primers and probe designed for the NS1 gene
Authors: Song Cuiping , Zhu Chao , Zhang Chaofan , Cui Shangjin 
Published: December 2010

Abstract
A TaqMan-based real-time polymerase chain reaction (PCR) assay was devised for the detection of porcine parvovirus (PPV). Two primers and a TaqMan probe for the non-structural protein NS1 gene were designed. The detection limit was 1 × 102 DNA copies/μL, and the assay was linear in the range of 1 × 102 to 1 × 109 copies/μL. There was no cross-reaction with porcine circovirus 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), pseudorabies virus (PRV), classical swine fever virus (CSFV), or Japanese encephalitis virus (JEV). The assay was specific and reproducible. In 41 clinical samples, PPV was detected in 32 samples with the real-time PCR assay and in only 11 samples with a conventional PCR assay. The real-time assay using the TaqMan-system can therefore be practically used for studying the epidemiology and management of PPV.