bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spinal reflexes in normal and sulfite oxidase deficient rats: effect of sulfite exposure
Authors: Küçükatay V , Genç O , Kocamaz E , Emmungil G , Erken HA , Bağcı H 
Published: October 2008

Sulfites, which are commonly used as food preservatives, are continuously formed in the body during metabolism of sulfur-containing amino acids. Sulfite is oxidized to sulfate ion by sulfite oxidase (SOX, EC. 1.8.3.1). Although sulfite treatment has been reported to increase the excitability of some neurons in vitro, the possible effects of sulfite on neuronal excitability in vivo remain unclear. The aim of this study was to investigate the possible effects of sulfite treatment on spinal reflexes in anesthetized SOX competent and deficient rats. For this purpose, male albino rats used in this study were divided into four groups such as control group (C), sulfite group (CS), SOX deficient group (D), and SOX deficient + sulfite group (DS). Rats in SOX deficient groups were made deficient in SOX by the administration of low molybdenum (Mo) diet (AIN 76, Research Dyets Inc., USA) with concurrent addition of 200-ppm tungsten (W) to their drinking water in the form of sodium tungstate (NaWO4). Sulfite in the form of sodium metabisulfite (Na2O5S2, 70 mg/kg) was given orally by adding to drinking water to the S and DS groups. Monosynaptic reflex potentials were recorded from the ipsilateral L5 ventral root. SOX deficient rats had an approximately 15-fold decrease in hepatic SOX activity compared with normal rats. This makes SOX activity of SOXD rats in the range of human SOX activity. The results of this study show that sulfite treatment significantly increases the amplitude of the monosynaptic reflex response in both S and DS groups with respect to their respective control groups (C and D). SOX deficient rats also had enhanced spinal reflexes when compared with control rats. In conclusion, sulfite has increasing effects on the excitability of spinal reflexes and we speculate that this compound may exhibit its effects on nervous system by affecting sodium channels.
Functional proteomic profiling of AML predicts response and survival
Authors: Kornblau Steven M. , Tibes Raoul , Qiu Yi Hua , Chen Wenjing , Kantarjian Hagop M. , Andreeff Michael , Coombes Kevin R. , Mills Gordon B. 
Published: October 2008

AbstractBecause protein function regulates the phenotypic characteristics of cancer, a functional proteomic classification system could provide important information for pathogenesis and prognosis. With the goal of ultimately developing a proteomic-based classification of acute myeloid leukemia (AML), we assayed leukemia-enriched cells from 256 newly diagnosed AML patients, for 51 total and phosphoproteins from apoptosis, cell-cycle, and signal-transduction pathways, using reverse-phase protein arrays. Expression in matched blood and marrow samples were similar for 44 proteins; another 7 had small fold changes (8%-55%), suggesting that functional proteomics of leukemia-enriched cells in the marrow and periphery are similar. Protein expression patterns were independent of clinical characteristics. However, 24 proteins were significantly different between French-American-British subtypes, defining distinct signatures for each. Expression signatures for AML with cytogenetic abnormalities involving −5 or −7 were similar suggesting mechanistic commonalities. Distinct expression patterns for FMS-like tyrosine kinase 3–internal tandem duplication were also identified. Principal component analysis defined 7 protein signature groups, with prognostic information distinct from cytogenetics that correlated with remission attainment, relapse, and overall survival. In conclusion, protein expression profiling patterns in AML correlate with known morphologic features, cytogenetics, and outcome. Confirmation in independent studies may also provide pathophysiologic insights facilitating triage of patients to emerging targeted therapies.
The role of Ephs, Ephrins, and growth factors in Kaposi sarcoma and implications of EphrinB2 blockade
Authors: Scehnet Jeffrey S. , Ley Eric J. , Krasnoperov Valery , Liu Ren , Manchanda Parmeet K. , Sjoberg Eric , Kostecke Anna P. , Gupta Sachin , Kumar S. Ram , Gill Parkash S. 
Published: October 2008

Abstract
Kaposi sarcoma (KS) is associated with human herpesvirus (HHV)-8 and is dependent on the induction of vascular endothelial growth factors (VEGFs). VEGF regulates genes that provide arterial or venous identity to endothelial cells, such as the induction of EphrinB2, which phenotypically defines arterial endothelial cells and pericytes, and represses EphB4, which defines venous endothelial cells. We conducted a comprehensive analysis of the Eph receptor tyrosine kinases to determine which members are expressed and therefore contribute to KS pathogenesis. We demonstrated limited Eph/Ephrin expression; notably, the only ligand highly expressed is EphrinB2. We next studied the biologic effects of blocking EphrinB2 using the extracellular domain of EphB4 fused with human serum albumin (sEphB4-HSA). sEphB4-HSA inhibited migration and invasion of the KS cells in vitro in response to various growth factors. Finally, we determined the biologic effects of combining sEphB4-HSA and an antibody to VEGF. sEphB4-HSA was more active than the VEGF antibody, and combination of the 2 had at least additive activity. sEphB4-HSA reduced blood vessel density, pericyte recruitment, vessel perfusion, and increased hypoxia, with an associated increase in VEGF and DLL4 expression. The combination of sEphB4-HSA and VEGF antibody is a rational treatment combination for further investigation.
Dexamethasone augments CXCR4-mediated signaling in resting human T cells via the activation of the Src kinase Lck
Authors: Ghosh Manik C. , Baatar Dolgor , Collins Gary , Carter Arnell , Indig Fred , Biragyn Arya , Taub Dennis D. 
Published: October 2008

AbstractDexamethasone (DM) is a synthetic member of the glucocorticoid (GC) class of hormones that possesses anti-inflammatory and immunosuppressant activity and is commonly used to treat chronic inflammatory disorders, severe allergies, and other disease states. Although GCs are known to mediate well-defined transcriptional effects via GC receptors (GCR), there is increasing evidence that GCs also initiate rapid nongenomic signaling events in a variety of cell types. Here, we report that DM induces the phosphorylation of Lck and the activation of other downstream mediators, including p59Fyn, Zap70, Rac1, and Vav in resting but not activated human T cells. DM treatment also augments CXCL12-mediated signaling in resting T cells through its cell surface receptor, CXCR4 resulting in the enhanced actin polymerization, Rac activation, and cell migration on ligand exposure. Lck was found to be a critical intermediate in these DM-induced signaling activities. Moreover, DM-mediated Lck phosphorylation in T cells was dependent on the presence of both the GCR and the CD45 molecule. Overall, these results elucidate additional nongenomic effects of DM and the GCR on resting human T cells, inducing Lck and downstream kinase activation and augmenting chemokine signaling and function.
PhySIC_IST: cleaning source trees to infer more informative supertrees
Authors: Scornavacca Celine , Berry Vincent , Lefort Vincent , Douzery Emmanuel JP , Ranwez Vincent 
Published: October 2008

Abstract

Background
Supertree methods combine phylogenies with overlapping sets of taxa into a larger one. Topological conflicts frequently arise among source trees for methodological or biological reasons, such as long branch attraction, lateral gene transfers, gene duplication/loss or deep gene coalescence. When topological conflicts occur among source trees, liberal methods infer supertrees containing the most frequent alternative, while veto methods infer supertrees not contradicting any source tree, i.e. discard all conflicting resolutions. When the source trees host a significant number of topological conflicts or have a small taxon overlap, supertree methods of both kinds can propose poorly resolved, hence uninformative, supertrees.

Results
To overcome this problem, we propose to infer non-plenary supertrees, i.e. supertrees that do not necessarily contain all the taxa present in the source trees, discarding those whose position greatly differs among source trees or for which insufficient information is provided. We detail a variant of the PhySIC veto method called PhySIC_IST that can infer non-plenary supertrees. PhySIC_IST aims at inferring supertrees that satisfy the same appealing theoretical properties as with PhySIC, while being as informative as possible under this constraint. The informativeness of a supertree is estimated using a variation of the CIC (Cladistic Information Content) criterion, that takes into account both the presence of multifurcations and the absence of some taxa. Additionally, we propose a statistical preprocessing step called STC (Source Trees Correction) to correct the source trees prior to the supertree inference. STC is a liberal step that removes the parts of each source tree that significantly conflict with other source trees. Combining STC with a veto method allows an explicit trade-off between veto and liberal approaches, tuned by a single parameter.
Performing large-scale simulations, we observe that STC+PhySIC_IST infers much more informative supertrees than PhySIC, while preserving low type I error compared to the well-known MRP method. Two biological case studies on animals confirm that the STC preprocess successfully detects anomalies in the source trees while STC+PhySIC_IST provides well-resolved supertrees agreeing with current knowledge in systematics.

Conclusion
The paper introduces and tests two new methodologies, PhySIC_IST and STC, that demonstrate the interest in inferring non-plenary supertrees as well as preprocessing the source trees. An implementation of the methods is available at: http://www.atgc-montpellier.fr/physic_ist/.
Pol II promoter prediction using characteristic 4-mer motifs: a machine learning approach
Authors: Anwar Firoz , Baker Syed Murtuza , Jabid Taskeed , Mehedi Hasan Md , Shoyaib Mohammad , Khan Haseena , Walshe Ray 
Published: October 2008

AbstractBackgroundEukaryotic promoter prediction using computational analysis techniques is one of the most difficult jobs in computational genomics that is essential for constructing and understanding genetic regulatory networks. The increased availability of sequence data for various eukaryotic organisms in recent years has necessitated for better tools and techniques for the prediction and analysis of promoters in eukaryotic sequences. Many promoter prediction methods and tools have been developed to date but they have yet to provide acceptable predictive performance. One obvious criteria to improve on current methods is to devise a better system for selecting appropriate features of promoters that distinguish them from non-promoters. Secondly improved performance can be achieved by enhancing the predictive ability of the machine learning algorithms used.ResultsIn this paper, a novel approach is presented in which 128 4-mer motifs in conjunction with a non-linear machine-learning algorithm utilising a Support Vector Machine (SVM) are used to distinguish between promoter and non-promoter DNA sequences. By applying this approach to plant, Drosophila, human, mouse and rat sequences, the classification model has showed 7-fold cross-validation percentage accuracies of 83.81%, 94.82%, 91.25%, 90.77% and 82.35% respectively. The high sensitivity and specificity value of 0.86 and 0.90 for plant; 0.96 and 0.92 for Drosophila; 0.88 and 0.92 for human; 0.78 and 0.84 for mouse and 0.82 and 0.80 for rat demonstrate that this technique is less prone to false positive results and exhibits better performance than many other tools. Moreover, this model successfully identifies location of promoter using TATA weight matrix.ConclusionThe high sensitivity and specificity indicate that 4-mer frequencies in conjunction with supervised machine-learning methods can be beneficial in the identification of RNA pol II promoters comparative to other methods. This approach can be extended to identify promoters in sequences for other eukaryotic genomes.
Prediction of evolutionarily conserved interologs in Mus musculus
Authors: Yellaboina Sailu , Dudekula Dawood B , Ko Minoru SH 
Published: October 2008

Abstract

Background
Identification of protein-protein interactions is an important first step to understand living systems. High-throughput experimental approaches have accumulated large amount of information on protein-protein interactions in human and other model organisms. Such interaction information has been successfully transferred to other species, in which the experimental data are limited. However, the annotation transfer method could yield false positive interologs due to the lack of conservation of interactions when applied to phylogenetically distant organisms.

Results
To address this issue, we used phylogenetic profile method to filter false positives in interologs based on the notion that evolutionary conserved interactions show similar patterns of occurrence along the genomes. The approach was applied to Mus musculus, in which the experimentally identified interactions are limited. We first inferred the protein-protein interactions in Mus musculus by using two approaches: i) identifying mouse orthologs of interacting proteins (interologs) based on the experimental protein-protein interaction data from other organisms; and ii) analyzing frequency of mouse ortholog co-occurrence in predicted operons of bacteria. We then filtered possible false-positives in the predicted interactions using the phylogenetic profiles. We found that this filtering method significantly increased the frequency of interacting protein-pairs coexpressed in the same cells/tissues in gene expression omnibus (GEO) database as well as the frequency of interacting protein-pairs shared the similar Gene Ontology (GO) terms for biological processes and cellular localizations. The data supports the notion that phylogenetic profile helps to reduce the number of false positives in interologs.

Conclusion
We have developed protein-protein interaction database in mouse, which contains 41109 interologs. We have also developed a web interface to facilitate the use of database http://lgsun.grc.nia.nih.gov/mppi/.
RNAi-directed downregulation of OsBADH2 results in aroma (2-acetyl-1-pyrroline) production in rice (Oryza sativa L.)
Authors: Niu Xiangli , Tang Wei , Huang Weizao , Ren Guangjun , Wang Qilin , Luo Di , Xiao Yingyong , Yang Shimei , Wang Feng , Lu Bao-Rong , Gao Fangyuan , Lu Tiegang , Liu Yongsheng 
Published: October 2008

Abstract

Background
Aromatic rice is popular worldwide because of its characteristic fragrance. Genetic studies and physical fine mapping reveal that a candidate gene (fgr/OsBADH2) homologous to betaine aldehyde dehydrogenase is responsible for aroma metabolism in fragrant rice varieties, but the direct evidence demonstrating the functions of OsBADH2 is lacking. To elucidate the physiological roles of OsBADH2, sequencing approach and RNA interference (RNAi) technique were employed to analyze allelic variation and functions of OsBADH2 gene in aroma production. Semi-quantitative, real-time reverse transcription-polymerase chain reaction (RT-PCR), as well as gas chromatography-mass spectrometry (GC-MS) were conducted to determine the expression levels of OsBADH2 and the fragrant compound in wild type and transgenic OsBADH2-RNAi repression lines, respectively.

Results
The results showed that multiple mutations identical to fgr allele occur in the 13 fragrant rice accessions across China; OsBADH2 is expressed constitutively, with less expression abundance in mature roots; the disrupted OsBADH2 by RNA interference leads to significantly increased 2-acetyl-1-pyrroline production.

Conclusion
We have found that the altered expression levels of OsBADH2 gene influence aroma accumulation, and the prevalent aromatic allele probably has a single evolutionary origin.
Upregulated HSP27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability
Authors: Kang Se Hun , Kang Keon Wook , Kim Kyung-Hee , Kwon Bumi , Kim Seok-Ki , Lee Ho-Young , Kong Sun-Young , Lee Eun Sook , Jang Sang-Geun , Yoo Byong Chul 
Published: October 2008

Abstract

Background
Elucidating the molecular mechanisms by which tumors become resistant to Herceptin is critical for the treatment of Her2-overexpressed metastatic breast cancer.

Methods
To further understand Herceptin resistance mechanisms at the molecular level, we used comparative proteome approaches to analyze two human breast cancer cell lines; Her2-positive SK-BR-3 cells and its Herceptin-resistant SK-BR-3 (SK-BR-3 HR) cells.

Results
Heat-shock protein 27 (HSP27) expression was shown to be upregulated in SK-BR-3 HR cells. Suppression of HSP27 by specific siRNA transfection increased the susceptibility of SK-BR-3 HR cells to Herceptin. In the presence of Herceptin, Her2 was downregulated in both cell lines. However, Her2 expression was reduced by a greater amount in SK-BR-3 parent cells than in SK-BR-3 HR cells. Interestingly, co-immunoprecipitation analysis showed that HSP27 can bind to Her2. In the absence of Herceptin, HSP27 expression is suppressed and Her2 expression is reduced, indicating that downregulation of Her2 by Herceptin can be obstructed by the formation of a Her2-HSP27 complex.

Conclusion
Our present study demonstrates that upregulated HSP27 in human breast cancer cells can reduce Herceptin susceptibility by increasing Her2 protein stability.
A construct with fluorescent indicators for conditional expression of miRNA
Authors: Qiu Linghua , Wang Hongyan , Xia Xugang , Zhou Hongxia , Xu Zuoshang 
Published: October 2008

Abstract

Background
Transgenic RNAi holds promise as a simple, low-cost, and fast method for reverse genetics in mammals. It may be particularly useful for producing animal models for hypomorphic gene function. Inducible RNAi that permits spatially and temporally controllable gene silencing in vivo will enhance the power of transgenic RNAi approach. Furthermore, because microRNA (miRNA) targeting specific genes can be expressed simultaneously with protein coding genes, incorporation of fluorescent marker proteins can simplify the screening and analysis of transgenic RNAi animals.

Results
We sought to optimally express a miRNA simultaneously with a fluorescent marker. We compared two construct designs. One expressed a red fluorescent protein (RFP) and a miRNA placed in its 3' untranslated region (UTR). The other expressed the same RFP and miRNA, but the precursor miRNA (pre-miRNA) coding sequence was placed in an intron that was inserted into the 3'-UTR. We found that the two constructs expressed comparable levels of miRNA. However, the intron-containing construct expressed a significantly higher level of RFP than the intron-less construct. Further experiments indicate that the 3'-UTR intron enhances RFP expression by its intrinsic gene-expression-enhancing activity and by eliminating the inhibitory effect of the pre-miRNA on the expression of RFP. Based on these findings, we incorporated the intron-embedded pre-miRNA design into a conditional expression construct that employed the Cre-loxP system. This construct initially expressed EGFP gene, which was flanked by loxP sites. After exposure to Cre recombinase, the transgene stopped EGFP expression and began expression of RFP and a miRNA, which silenced the expression of specific cellular genes.

Conclusion
We have designed and tested a conditional miRNA-expression construct and showed that this construct expresses both the marker genes strongly and can silence the target gene efficiently upon Cre-mediated induction of the miRNA expression. This construct can be used to increase the efficiency of making cell lines or transgenic animals that stably express miRNA targeting specific genes.
Down-regulation of DNMT3b in PC3 cells effects locus-specific DNA methylation, and represses cellular growth and migration
Authors: Yaqinuddin Ahmed , Qureshi Sohail A , Qazi Romena , Abbas Farhat 
Published: October 2008

Abstract

Background
Aberrations in DNA methylation patterns promote changes in gene expression patterns and are invariably associated with neoplasia. DNA methylation is carried out and maintained by several DNA methyltransferases (DNMTs) among which DNMT1 functions as a maintenance methylase while DNMT3a and 3b serve as de novo enzymes. Although DNMT3b has been shown to preferentially target the methylation of DNA sequences residing in pericentric heterochromatin whether it is involved in gene specific methylation remains an open question. To address this issue, we have silenced the expression of DNMT3b in the prostate-derived PC3 cells through RNA interference and subsequently studied the accompanied cellular changes as well as the expression profiles of selected genes.

Results
Our results demonstrate that DNMT3b depletion results in increased apoptosis and reduced migration of PC3 cells compared to the untransfected control cells. Reduced DNMT3b expression resulted in hypomethylation of retinoblastoma (Rb), retinoic-acid receptor β (RAR-β), and adenomatous polyposis coli (APC) gene promoters, and also culminated in increased expression of CDKN3 and cytochrome b5. Although DNMT3b silenced cells were found to have reduced growth and migratory potential, there was no apparent changes in their invasive ability compared to the parental PC3 cell line.

Conclusion
Our findings reveal that DNMT3b preferentially targets certain gene promoters in PC3 cells and that its depletion significantly reduces growth and migration of PC3 cells.
Lentivirus-mediated RNAi silencing targeting ABCC2 increasing the sensitivity of a human nasopharyngeal carcinoma cell line against cisplatin
Authors: Xie Si Ming , Fang Wei Yi , Liu Zhen , Wang Shuang Xi , Li Xin , Liu Teng Fei , Xie Wei Bing , Yao Kai Tai 
Published: October 2008

AbstractBackgroundHigh resistance to drug is taken as a characteristic of human tumors, which is usually mediated by multidrug resistance-associated genes. ABCC2, an ATP-binding cassette multidrug resistance transporter, is found to be expressed in a variety of human cancers. In this study the effect of a RNAi construct targeting ABCC2 on the chemosensitivity of NPC cell line CNE2 against cisplatin was investigated.MethodsLentiviral vectors were constructed to allow an efficient expression of anti-ABCC2 siRNA. The effective target sequence comprised nucleotides 1707–1727 of the human ABCC2 mRNA. The cell clones expressing the construct were picked and expanded, followed by identification using qRT-PCR and western blot method. As control, lentiviral vector containing invalid RNAi sequence was transfected to CNE2 cells.In vitro, cellular accumulation of cisplatin was detected by HPLC. The capacity of cellular growth and sensitivity of cells against cisplatin were detected by MTT assay.In vivo, the sensitivity of the tumor tissues against cisplatin were evaluated by transplanted CNE2 nude mice model.ResultsTwo CNE2 cell clones with reduced expression of targeted ABCC2 mRNA and protein for more than 70% by qRT-PCR and western blot were established, and no differences were shown in proliferation rates compared to control CNE2 cells by growth curves analysis.In vitrothe accumulation of intracellular cisplatin in these CNE2 cell clones with reduced expression of ABCC2 increased markedly, accompanied by increased sensitivity against cisplatin.In vivo, the growth of CNE2 solid tumors with a stably transfected anti-ABCC2 siRNA construct was significantly inhibited by cisplatin in transplanted nude mice model.ConclusionOur investigation demonstrated that lentivirus-mediated RNAi silencing targeting ABCC2 might reverse the ABCC2-related drug resistance of NPC cell line CNE2 against cisplatin.