bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predominance of Interferon-Related Responses in the Brain during Murine Malaria, as Identified by Microarray Analysis
Authors: Miu Jenny , Hunt Nicholas H. , Ball Helen J. 
Published: February 2008

ABSTRACTCerebral malaria (CM) can be a fatal manifestation ofPlasmodium falciparuminfection. We examined global gene expression patterns during fatal murine CM (FMCM) and noncerebral malaria (NCM) by microarray analysis. There was differential expression of a number of genes, including some not yet characterized in the pathogenesis of FMCM. Some gene induction was observed duringPlasmodium bergheiinfection regardless of the development of CM, and there was a predominance of genes linked to interferon responses, even in NCM. However, upon real-time PCR validation and quantitation, these genes were much more highly expressed in FMCM than in NCM. The observed changes included genes belonging to pathways such as interferon signaling, major histocompatibility complex processing and presentation, apoptosis, and immunomodulatory and antimicrobial processes. We further characterized differentially expressed genes by examining the cellular source of their expression as well as their temporal expression patterns during the course of malaria infection. These data identify a number of novel genes that represent interesting candidates for further investigation in FMCM.
THE LEAST COST SUPER REPLICATING PORTFOLIO IN THE BOYLE–VORST MODEL WITH TRANSACTION COSTS
Authors: CHEN GUAN-YU , PALMER KEN , SHEU YUAN-CHUNG 
Published: February 2008

Boyle and Vorst work in the framework of the binomial model and derive self-financing strategies perfectly replicating the final payoffs to long and short positions in call and put options, assuming proportional transactions costs on trades in the stock and no transactions costs on trades in the bond. Even when the market is arbitrage-free and a given contingent claim has a unique replicating portfolio, there may exist super replicating portfolios of lower cost. Bensaid et al. gave conditions under which the cost of the replicating portfolio does not exceed the cost of any super replicating portfolio. These results were generalized by Stettner, Rutkowski and Palmer to the case of asymmetric transaction costs. In this paper, we first determine the number of replicating portfolios and then compute the least cost super replicating portfolio for any contingent claim in a one-period binomial model. By using the fundamental theorem of linear programming, we show that there are only finitely many possibilities for a least cost super replicating portfolio for any contingent claim in a two-period binomial model. As an application of our results, we give an example in which we compute the least cost super replicating portfolio for a butterfly spread in a two-period model.
The Identification of MicroRNAs in a Genomically Unstable Region of Human Chromosome 8q24
Authors: Huppi Konrad , Volfovsky Natalia , Runfola Timothy , Jones Tamara L. , Mackiewicz Mark , Martin Scott E. , Mushinski J. Frederic , Stephens Robert , Caplen Natasha J. 
Published: February 2008

Abstract
The PVT1 locus is identified as a cluster of T(2;8) and T(8;22) “variant” MYC-activating chromosomal translocation breakpoints extending 400 kb downstream of MYC in a subset (≈20%) of Burkitt's lymphoma (vBL). Recent reports that microRNAs (miRNA) may be associated with fragile sites and cancer-associated genomic regions prompted us to investigate whether the PVT1 region on chromosome 8q24 may contain miRNAs. Computational analysis of the genomic sequence covering the PVT1 locus and experimental verification identified seven miRNAs. One miRNA, hsa-miR-1204, resides within a previously described PVT1 exon (1b) that is often fused to the immunoglobulin light chain constant region in vBLs and is present in high copy number in MYC/PVT1–amplified tumors. Like its human counterpart, mouse mmu-miR-1204 represents the closest miRNA to Myc (∼50 kb) and is found only 1 to 2 kb downstream of a cluster of retroviral integration sites. Another miRNA, mmu-miR-1206, is close to a cluster of variant translocation breakpoints associated with mouse plasmacytoma and exon 1 of mouse Pvt1. Virtually all the miRNA precursor transcripts are expressed at higher levels in late-stage B cells (including plasmacytoma and vBL cell lines) compared with immature B cells, suggesting possible roles in lymphoid development and/or lymphoma. In addition, lentiviral vector-mediated overexpression of the miR-1204 precursor (human and mouse) in a mouse pre–B-cell line increased expression of Myc. High levels of expression of the hsa-miR-1204 precursor is also seen in several epithelial cancer cell lines with MYC/PVT1 coamplification, suggesting a potentially broad role for these miRNAs in tumorigenesis. (Mol Cancer Res 2008;6(2):212–21)
Krüppel-Like Factor 4 Is a Novel Mediator of Selenium in Growth Inhibition
Authors: Liu Shuang , Zhang Haitao , Zhu Liyu , Zhao Lijuan , Dong Yan 
Published: February 2008

Abstract
A previous prevention trial showed that selenium supplementation was effective in reducing (by 50%) the incidence of prostate cancer. Selenium has been reported to inhibit the growth of prostate cancer cells in vitro. Multiple mechanisms are likely to be operative in the underlying effect of selenium. Here, we report that Krüppel-like factor 4 (KLF4), a transcription factor of the KLF family, is an important target of selenium. We found that selenium up-regulates KLF4 expression and increases the DNA-binding activity of KLF4 in both the androgen-dependent LNCaP and the androgen-independent PC-3 human prostate cancer cells. The increase of KLF4 mRNA is accounted for primarily by enhanced transcription, although the contribution of a slight abatement in mRNA degradation cannot be ruled out. KLF4 knockdown using short interference RNA significantly weakens the effects of selenium on DNA synthesis inhibition, apoptosis induction, and the expression of three KLF4 target genes, cyclin D1, p21/WAF1, and p27/Kip1. In addition, the overexpression of KLF4 not only leads to an induction of apoptosis in the control cells, but also enhances the DNA synthesis–suppressive and–proapoptotic activities of selenium. Taken together, our results suggest that KLF4 plays a key role in mediating the growth-inhibitory effect of selenium in prostate cancer cells. (Mol Cancer Res 2008;6(2):306–13)
FLICE-Like Inhibitory Protein Blocks Transforming Growth Factor β1–Induced Caspase Activation and Apoptosis in Prostate Epithelial Cells
Authors: Nastiuk Kent L. , Yoo Kiwon , Lo Karen , Su Kevin , Yeung Patricia , Kutaka Julia , Danielpour David , Krolewski John J. 
Published: February 2008

Abstract
Androgen withdrawal induces the regression of human prostate cancers, but such cancers eventually become androgen-independent and metastasize. Thus, deciphering the mechanism of androgen withdrawal–induced apoptosis is critical to designing new therapies for prostate cancer. Previously, we showed that in the rat, castration-induced apoptosis is accompanied by a reduction in the expression of the apical caspase inhibitor FLICE-like inhibitory protein (FLIP). To test the functional role of FLIP in inhibiting prostate epithelial cell apoptosis, we employed the rat prostate epithelial cell line NRP-152, which differentiates to a secretory phenotype in a low-mitogen medium and then undergoes apoptosis following the addition of transforming growth factor β1 (TGFβ1), mimicking androgen withdrawal–induced apoptosis. FLIP levels decline with TGFβ1 treatment, suggesting that apoptosis is mediated by caspase-8 and indeed the caspase inhibitor crmA blocks TGFβ1-induced apoptosis. Small interfering RNA–mediated knockdown of FLIP recapitulates and enhances TGFβ1-induced cell death. NRP-152 cells stably transfected with constitutively expressed FLIP were refractory to TGFβ1-induced apoptosis. TGFβ1-induced caspase-3 activity is proportional to the level of cell death and inversely proportional to the level of FLIP expression in various clones. Moreover, neither caspase-3 nor PARP is cleaved in clones expressing high levels of FLIP. Furthermore, insulin, which inhibits differentiation, increases FLIP and inhibits TGFβ-induced death in a FLIP-dependent manner. Although neither Fas-Fc, sTNFRII-Fc, nor DR5-Fc blocked TGFβ1-induced cell death, there is a significant increase in tumor necrosis factor mRNA following TGFβ stimulation, suggesting both an unexpected role for tumor necrosis factor in this model system and the possibility that FLIP blocks another unknown caspase-dependent mediator of apoptosis. (Mol Cancer Res 2008;6(2):231–12)
A New Verification Method to Ensure Consistent Ensemble Forecasts through Calibrated Precipitation Downscaling Models
Authors: Mascaro Giuseppe , Deidda Roberto , Vivoni Enrique R. 
Published: February 2008

Abstract
A new verification method is proposed to test the consistency of ensemble high-resolution precipitation fields forecasted by calibrated downscaling models. The method is based on a generalization of the verification rank histogram and tests the exceedance probability of a fixed precipitation threshold calculated from the observed or ensemble fields. A graphical tool that accounts for random assignments of the rank is proposed to provide guidance in histogram interpretation and to avoid a possible misunderstanding of model deficiencies. The verification method is applied on three numerical experiments carried out in controlled conditions using the space–time rainfall (STRAIN) downscaling model with the aims of investigating (i) the effect of sampling variability on parameter estimation from the observed fields and (ii) model performance when calibration relations between the parameter and a coarse meteorological observable are used to interpret events arising from one or more physical conditions. Results show that (i) ensemble members generated using the parameters estimated on the observed event are overdispersed; (ii) the adoption of a single calibration relation can lead to the generation of consistent ensemble members; and (iii) when a single calibration relation is not able to explain observed event variability, storm-specific calibration relations should be adopted to return consistent forecasts.
Review Series: Chronic cough: Epidemiology
Authors: Morice AH 
Published: February 2008

Chronic cough is perhaps the commonest symptom of medical importance with some 12% of the general population having the symptom on a daily or weekly basis. Chronic cough causes a large degree of morbidity, with both the physical e.g. incontinence, and the psychological e.g. social isolation, domains. The causes of chronic cough are numerous, but fall into two broad categories; that causing an asthma-like syndrome characterized by eosinophilic infiltration of the airways, and oesophageal disease, particularly weakly acid reflux. Failure to make, particularly this latter, diagnosis leads to enormous consequences in terms of loss of employment, healthcare utilisation and a psychosocial morbidity. Chronic Respiratory Disease 2008; 5: 43—47
Quality of life measurements and bronchodilator responsiveness in prescribing nebulizer therapy in COPD
Authors: Brophy C. , Kastelik JA , Gardiner E. , Greenstone MA 
Published: February 2008

Nebulized bronchodilators are widely regarded as the optimal treatment for maintenance therapy in patients with severe chronic obstructive pulmonary disease (COPD). The aim of the study was to assess whether detailed physiological, functional and quality of life-related measurements can assist in determining the requirement for nebulized bronchodilator therapy in patients with moderate to severe COPD. This was an unblinded, randomized, crossover study that compared intermediate (120mcg ipratropium bromide and 600mcg of salbutamol using metered dose inhaler (MDI) and spacer) and high dose (nebulized 500 mcg ipratropium bromide and 2.5 mg salbutamol) bronchodilator therapy, on physiological, functional and quality of life-related measurements in patients with COPD. A total of 25 patients (12 female), mean (SD) age 68 (7) years, FEV1 45 (10) % predicted completed the study. There was no statistically significant difference between the treatments in the pre- and post-bronchodilator lung function values, six-minute walk distance, breathlessness score or quality of life questionnaires. Fifteen patients preferred bronchodilator therapy with nebulizer and 10 with MDI and spacer. In 20 patients at least one positive response in quality of life score, lung function or six-minute walk, was observed on the preferred treatment. Only a proportion of patients with moderate or severe COPD prefer nebulized bronchodilator therapy. This study found that none of the parameters singly or in combination were consistently predictive of patients' preference for nebulized bronchodilator therapy. Therefore, we suggest that clinicians institute a trial of stepping up to an intermediate dose of bronchodilators prior to introducing nebulized therapy. Chronic Respiratory Disease 2008; 5: 13—18
A functional 14-3-3ζ–independent association of PI3-kinase with glycoprotein Ibα, the major ligand-binding subunit of the platelet glycoprotein Ib-IX-V complex
Authors: Mu Fi-Tjen , Andrews Robert K. , Arthur Jane F. , Munday Adam D. , Cranmer Susan L. , Jackson Shaun P. , Stomski Frank C. , Lopez Angel F. , Berndt Michael C. 
Published: February 2008

AbstractEngagement of the adhesion receptor glycoprotein (GP) Ib-IX-V by von Willebrand factor (VWF) mediates platelet adhesion to damaged vessels and triggers platelet activation and thrombus formation in heart attack and stroke. GPIb-IX-V contains distinct 14-3-3ζ–binding sites at the GPIbα C-terminus involving phosphorylation of Ser609, an upstream site involving phosphorylated Ser587/Ser590, and a protein kinase A (PKA)–dependent site on GPIbβ involving Ser166. 14-3-3ζ regulates the VWF-binding affinity of GPIb-IX-V and inhibiting 14-3-3ζ association blocks receptor signaling, suggesting a key functional role for 14-3-3ζ. We used deletion mutants of GPIbα expressed in Chinese hamster ovary (CHO) cells to define the relationship of 14-3-3ζ binding to another GPIb-IX-V–associated signaling protein, phosphoinositide 3-kinase (PI3-kinase). Pull-down experiments involving glutathione S-transferase (GST)–PI3-kinase/p85-subunit and GST–14-3-3ζ indicated that both proteins interacted with contiguous GPIbα sequences 580 to 590/591 to 610. Deleting these, but not upstream sequences of GPIbα expressed in CHO cells, inhibited VWF/ristocetin-dependent Akt phosphorylation, relative to wild-type receptor, confirming this region encompassed a functional PI3-kinase–binding site. Pull-down experiments with GST-p85 truncates indicated the GPIbα-binding region involved the p85 breakpoint cluster region (BCR) domain, containing RSXSXP. However, pull-down of GPIb-IX was unaltered by mutation/deletion/phosphorylation of this potential 14-3-3ζ–binding sequence in mutant constructs of GST-p85, suggesting PI3-kinase bound GPIbα independently of 14-3-3ζ; 14-3-3ζ inhibitor peptide R18 also blocked pull-down of receptor by GST-14-3-3ζ but not GST-p85, and GST-p85 pull-downs were unaffected by excess 14-3-3ζ. Together, these data suggest the GPIbα C-terminus regulates signaling through independent association of 14-3-3ζ and PI3-kinase.
Strategies for measuring evolutionary conservation of RNA secondary structures
Authors: Gruber Andreas R , Bernhart Stephan H , Hofacker Ivo L , Washietl Stefan 
Published: February 2008

AbstractBackgroundEvolutionary conservation of RNA secondary structure is a typical feature of many functional non-coding RNAs. Since almost all of the available methods used for prediction and annotation of non-coding RNA genes rely on this evolutionary signature, accurate measures for structural conservation are essential.ResultsWe systematically assessed the ability of various measures to detect conserved RNA structures in multiple sequence alignments. We tested three existing and eight novel strategies that are based on metrics of folding energies, metrics of single optimal structure predictions, and metrics of structure ensembles. We find that the folding energy based SCI score used in the RNAz program and a simple base-pair distance metric are by far the most accurate. The use of more complex metrics like for example tree editing does not improve performance. A variant of the SCI performed particularly well on highly conserved alignments and is thus a viable alternative when only little evolutionary information is available. Surprisingly, ensemble based methods that, in principle, could benefit from the additional information contained in sub-optimal structures, perform particularly poorly. As a general trend, we observed that methods that include a consensus structure prediction outperformed equivalent methods that only consider pairwise comparisons.ConclusionStructural conservation can be measured accurately with relatively simple and intuitive metrics. They have the potential to form the basis of future RNA gene finders, that face new challenges like finding lineage specific structures or detecting mis-aligned sequences.
Links between core promoter and basic gene features influence gene expression
Authors: Moshonov Sandra , Elfakess Rofa , Golan-Mashiach Michal , Sinvani Hadar , Dikstein Rivka 
Published: February 2008

Abstract

Background
Diversity in rates of gene expression is essential for basic cell functions and is controlled by a variety of intricate mechanisms. Revealing general mechanisms that control gene expression is important for understanding normal and pathological cell functions and for improving the design of expression systems. Here we analyzed the relationship between general features of genes and their contribution to expression levels.

Results
Genes were divided into four groups according to their core promoter type and their characteristics analyzed statistically. Surprisingly we found that small variations in the TATA box are linked to large differences in gene length. Genes containing canonical TATA are generally short whereas long genes are associated with either non-canonical TATA or TATA-less promoters. These differences in gene length are primarily determined by the size and number of introns. Generally, gene expression was found to be tightly correlated with the strength of the TATA-box. However significant reduction in gene expression levels were linked with long TATA-containing genes (canonical and non-canonical) whereas intron length hardly affected the expression of TATA-less genes. Interestingly, features associated with high translation are prevalent in TATA-containing genes suggesting that their protein production is also more efficient.

Conclusion
Our results suggest that interplay between core promoter type and gene size can generate significant diversity in gene expression.
Gene conversion in the rice genome
Authors: Xu Shuqing , Clark Terry , Zheng Hongkun , Vang Søren , Li Ruiqiang , Wong Gane Ka-Shu , Wang Jun , Zheng Xiaoguang 
Published: February 2008

AbstractBackgroundGene conversion causes a non-reciprocal transfer of genetic information between similar sequences. Gene conversion can both homogenize genes and recruit point mutations thereby shaping the evolution of multigene families. In the rice genome, the large number of duplicated genes increases opportunities for gene conversion.ResultsTo characterize gene conversion in rice, we have defined 626 multigene families in which 377 gene conversions were detected using the GENECONV program. Over 60% of the conversions we detected were between chromosomes. We found that the inter-chromosomal conversions distributed between chromosome 1 and 5, 2 and 6, and 3 and 5 are more frequent than genome average (Z-test, P < 0.05). The frequencies of gene conversion on the same chromosome decreased with the physical distance between gene conversion partners. Ka/Ks analysis indicates that gene conversion is not tightly linked to natural selection in the rice genome. To assess the contribution of segmental duplication on gene conversion statistics, we determined locations of conversion partners with respect to inter-chromosomal segment duplication. The number of conversions associated with segmentation is less than ten percent. Pseudogenes in the rice genome with low similarity toArabidopsisgenes showed greater likelihood for gene conversion than those with high similarity toArabidopsisgenes. Functional annotations suggest that at least 14 multigene families related to disease or bacteria resistance were involved in conversion events.ConclusionThe evolution of gene families in the rice genome may have been accelerated by conversion with pseudogenes. Our analysis suggests a possible role for gene conversion in the evolution of pathogen-response genes.
Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids
Authors: L'Espérance Sylvain , Bachvarova Magdalena , Tetu Bernard , Mes-Masson Anne-Marie , Bachvarov Dimcho 
Published: February 2008

AbstractBackgroundChemotherapy (CT) resistance in ovarian cancer (OC) is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155), following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours.ResultsExposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism), signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes), cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses.ConclusionMost alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular growth conditions that are known to alter gene expression (including cell adhesion and cytoskeleton organization), could substantially contribute in reducing the initial effectiveness of CT drugs in OC spheroids. Results described in this study underscore the potential of the microarray technology for unraveling the complex mechanisms of CT drugs actions in OC spheroids and early cellular response to treatment.