bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide-p38 MAPK signaling stabilizes mRNA through AU-rich element-dependent and -independent mechanisms
Authors: Wang Shuibang , Zhang Jianhua , Zhang Yi , Kern Steven , Danner Robert L 
Published: January 2008

AbstractRegulation of mRNA stability by p38 MAPK has been linked to adenosine-uridine-rich elements (AURE) within the 3′-untranslated region (3′UTR) of mRNA. Using microarrays, we previously found that AURE-containing mRNA is over-represented among transcripts up-regulated by NO•, an activator of p38 MAPK. Here, we investigated NO•-induced mRNA stabilization of specific AURE-containing genes to determine the sequence specificity and protein-binding interactions associated with this effect. IL-8, TNF-α, and p21/Waf1 3′UTRs were inserted into a luciferase (LUC) reporter gene system and found to decrease LUC activity and mRNA half-life in transfected THP-1 cells. The inhibitory effect of these 3′UTRs on LUC expression inversely correlated with the number of AUUUA motifs. Sequence truncation of the IL-8 3′UTR revealed that two segments, one with AURE sites and another without, contributed to mRNA destabilization. NO• activation of p38 MAPK increased LUC activity and mRNA half-life for reporter constructs that contained either of these IL-8 3′UTR segments. AURE-dependent and -independent NO• effects were blocked by p38 MAPK inhibition, and AURE-dependent effects were also blocked by site-directed mutagenesis of AUUUA sites. Two proteins, HuR and heterogeneous nuclear ribonucleoprotein A0, were identified, which bound to the AURE-containing region of exogenous and endogenous IL-8 mRNA in a NO•-p38 MAPK-dependent manner. These results demonstrate that NO•-p38 MAPK signaling can stabilize mRNA via AURE-dependent and -independent mechanisms.
C-Jun NH2 terminal kinase (JNK) is an essential mediator of Toll-like receptor 2-induced corneal inflammation
Authors: Adhikary Gautam , Sun Yan , Pearlman Eric 
Published: January 2008

AbstractTLRs play an important role in the host inflammatory response to bacteria and bacterial products by activating a cascade of intracellular events leading to production of proinflammatory and chemotactic cytokines. To determine the role of MAPKs in TLR- induced corneal inflammation, we stimulated human corneal epithelial (HCE) cells with TLR2 ligands, tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3Cys) or inactivated Staphylococcus aureus, and examined the time course of expression of MAPKs and the effect of MAPK inhibition on IkBα degradation and CXC chemokine production. We found that S. aureus and Pam3Cys stimulate phosphorylation of JNK, p38 MAPK, and ERK within 4 h and that blockade of JNK, but not p38 or ERK phosphorylation, had an inhibitory effect on IkBα degradation and CXC chemokine production. To determine if JNK is also important in TLR2-induced corneal inflammation in vivo, we examined JNK1−/− mice and pharmacological inhibitors in a murine model of TLR2-induced corneal inflammation which is characterized by neutrophil recruitment to the corneal stroma and development of corneal haze. We found that corneal inflammation was significantly impaired in JNK1−/− mice compared with control mice, and in mice treated with the JNK inhibitor compared with vehicle control. Taken together with results from HCE cells, these findings demonstrate that JNK has an essential role in TLR2-induced corneal inflammation.
Measurement of Allelic-Expression Ratios in Trisomy 21 Placentas by Quencher Extension of Heterozygous Samples Identified by Partially Denaturing HPLC
Authors: Go Attie T J I , Visser Allerdien , Betsalel Ofir T , van Vugt John M G , Blankenstein Marinus A , Oudejans Cees B M 
Published: January 2008

Abstract
Background: Measuring the allelic ratios of placental transcripts in maternal plasma permits noninvasive prenatal detection of chromosomal aneuploidy. Current methods, however, require highly specialized equipment (MALDI-TOF), limiting the widespread implementation of this powerful RNA single-nucleotide polymorphism (SNP) strategy in routine diagnostic settings. We adapted and applied the Transgenomic WAVE System and quencher extension (QEXT) for this purpose.
Methods: The expressed SNP (rs2187247) in exon 2 of the placentally expressed C21orf105 gene (chromosome 21 open reading frame 105) on chromosome 21 was tested in a trisomy 21 model system in which we obtained RNA selectively released from syncytiotrophoblasts of normal and trisomy 21 placentas during first trimester.
Results: In identifying heterozygous samples, we observed an exact correspondence between sequencing results and results obtained with the WAVE System. With respect to the analysis time required, the WAVE System was superior. In addition, the real-time QEXT assay (as optimized and validated with calibration standards consisting of 262-bp C21orf105 cDNA amplicons) accurately measured allele ratios after we optimized fragment purification, concentrations of input DNA and quencher label, and calculations of reporter signals. Finally, the optimized and validated QEXT assay correctly distinguished normal placentas from trisomy 21 placentas in tests of the following clinically relevant combinations: diploid homozygous (CC), diploid heterozygous (AC), triploid homozygous (AAA), and triploid heterozygous (AAC or ACC).
Conclusion: The QEXT method, which is directly adaptable to current real-time PCR equipment, along with rapid identification of informative samples with the WAVE System, may facilitate routine implementation of the RNA-SNP assay for noninvasive aneuploidy diagnostics.
Variation in Leukocyte Subset Concentrations Affects Calcineurin Activity Measurement: Implications for Pharmacodynamic Monitoring Strategies
Authors: van Rossum Huub H , Romijn Fred P H T M , Sellar Kathryn J , Smit Nico P M , van der Boog Paul J M , de Fijter Johan W , van Pelt Johannes 
Published: January 2008

AbstractBackground: In renal transplantation patients, therapeutic drug monitoring of the calcineurin (CN) inhibitor cyclosporin A (CsA) is mandatory because of the drug’s narrow therapeutic index. Pharmacodynamic monitoring of CN inhibition therapy could provide a tool to define and maintain the therapeutic efficacy of CsA therapy. We investigated the effect of variation in cell counts of leukocyte subsets on leukocyte CN activity measurement in renal transplant recipients.Methods: We measured leukocyte CN activity, whole blood CsA concentrations, and leukocyte subset cell counts in 25 renal transplant recipients. Blood was collected before graft implantation and CsA therapy, 1 day before transplantation when CsA therapy was already started, and 5 days after transplantation. Monocyte, granulocyte, CD4+ T-cell, CD8+ T-cell, B-cell, and natural killer–cell CN activities and CsA inhibition sensitivities were determined in vitro by a spectrophotometric CN assay.Results: Leukocyte CN activity was inhibited after drug intake. Inter- and intrapatient variation in leukocyte subset cell counts resulted in variation of sample composition. The mean (SD) CN activity varied among leukocyte cell subsets, ranging from 650 (230) to 166 (26) pmol/min/106 cells for monocytes and CD4+ T cells, respectively. CsA half maximal inhibitory concentration (IC50) values ranged from 15 to 78 μg/L for monocytes and B cells, respectively.Conclusion: Inter- and intraindividual leukocyte subset cell count variation can affect measured CN activity independent of CsA concentration. Cell-specific activity and drug sensitivity should be considered for sample validation to optimize method specificity when pharmacodynamic monitoring strategies are applied in a clinical setting.
Anti–α-enolase Antibodies in Patients with Inflammatory Bowel Disease
Authors: Vermeulen Nathalie , Arijs Ingrid , Joossens Sofie , Vermeire Severine , Clerens Stefan , Van den Bergh Karolien , Michiels Georges , Arckens Lutgarde , Schuit Frans , Van Lommel Leentje , Rutgeerts Paul , Bossuyt Xavier 
Published: January 2008

AbstractBackground: Patients with inflammatory bowel disease (IBD) carry autoantibodies such as perinuclear antineutrophil cytoplasmic antibodies (pANCA). α-Enolase has been proposed as a target antigen in IBD. We evaluated the prevalence and diagnostic value of anti–α-enolase antibodies in IBD and related disorders.Methods: We used a classic proteomic approach with extracts from granulocytes and pANCA-positive ulcerative colitis (UC) sera to confirm α-enolase as a target antigen. By means of Western blot analysis, we screened a cohort of 525 subjects for the presence of anti–α-enolase antibodies. We performed GeneArray experiments on RNA extracted from colonic mucosal biopsies from 35 IBD and 6 control patients.Results: We detected anti–α-enolase antibodies 49.0% of patients with UC, 50.0% of patients with Crohn’s disease, 30.5% of patients with primary sclerosing cholangitis, 37.8% of patients with autoimmune hepatitis, 34.0% of patients with ANCA-positive vasculitis, 31.0% of non-IBD gastrointestinal controls, and 8.5% of healthy controls. Gene array experiments showed a significant upregulation of α-enolase mRNA in colonic mucosal biopsies from patients with IBD, but not from controls. There was no association between the presence of pANCA and anti–α-enolase antibodies. Preabsorption with α-enolase did not eliminate the pANCA pattern on indirect immunofluorescence.Conclusions: Anti–α-enolase antibodies are present in a substantial proportion of patients with IBD, patients with various inflammatory/autoimmune disorders, and non-IBD gastrointestinal controls. Therefore, anti–α-enolase antibodies are of limited diagnostic value for the diagnosis of IBD.
Enumeration of Neural Stem and Progenitor Cells in the Neural Colony-Forming Cell Assay
Authors: Louis Sharon A. , Rietze Rodney L. , Deleyrolle Loic , Wagey Ravenska E. , Thomas Terry E. , Eaves Allen C. , Reynolds Brent A. 
Published: January 2008

Abstract
Advancement in our understanding of the biology of adult stem cells and their therapeutic potential relies heavily on meaningful functional assays that can identify and measure stem cell activity in vivo and in vitro. In the mammalian nervous system, neural stem cells (NSCs) are often studied using a culture system referred to as the neurosphere assay. We previously challenged a central tenet of this assay, that all neurospheres are derived from a NSC, and provided evidence that it overestimates NSC frequency, rendering it inappropriate for quantitation of NSC frequency in relation to NSC regulation. Here we report the development and validation of the neural colony-forming cell assay (NCFCA), which discriminates stem from progenitor cells on the basis of their proliferative potential. We anticipate that the NCFCA will provide additional clarity in discerning the regulation of NSCs, thereby facilitating further advances in the promising application of NSCs for therapeutic use.
Disclosure of potential conflicts of interest is found at the end of this article.
Investigation of Clinical Effects of High- and Low-Resistance Training for Patients With Knee Osteoarthritis: A Randomized Controlled Trial
Authors: Jan Mei-Hwa , Lin Jiu-Jeng , Liau Jiann-Jong , Lin Yeong-Fwu , Lin Da-Hon 
Published: January 2008

Background and PurposeMuscle strength training is important for people with knee osteoarthritis (OA). High-resistance exercise has been demonstrated to be more beneficial than low-resistance exercise for young subjects. The purpose of this study was to compare the effects of high- and low-resistance strength training in elderly subjects with knee OA.Subjects and MethodsOne hundred two subjects were randomly assigned to groups that received 8 weeks of high-resistance exercise (HR group), 8 weeks of low-resistance exercise (LR group), or no exercise (control group). Pain, function, walking time, and muscle torque were examined before and after intervention.ResultsSignificant improvement for all measures was observed in both exercise groups. There was no significant difference in any measures between HR and LR groups. However, based on effect size between exercise and control groups, the HR group improved more than the LR group.Discussion and ConclusionBoth high- and low-resistance strength training significantly improved clinical effects in this study. The effects of high-resistance strength training appear to be larger than those of low-resistance strength training for people with mild to moderate knee OA, although the differences between the HR and LR groups were not statistically significant.
Can functional classification of tropical trees predict population dynamics after disturbance?
Authors: Delcamp M. , Gourlet‐Fleury S. , Flores O. , Gamier E. 
Published: January 2008

AbstractQuestion: How far can we simplify the fioristic complexity of a tropical rainforest into functional groups in order to predict tree population dynamics after logging‐induced disturbance?Location: Paracou experimental site, French Guiana.Methods: We used data from over 15 years in control and disturbed plots from a silvicultural trial started in 1984. We selected 53 common tree species assigned to five functional groups based on potential size and light requirement. For each species, we quantified: the fate, i.e. variation in population size, and dynamic processes, i.e. mortality, recruitment and growth, driving this fate. We investigated the links between dynamic processes, fate and functional groups.Results: Disturbance stimulated growth and recruitment for most species, but had a heterogeneous impact on mortality. Species fate in disturbed plots depended on recruitment and was more favourable than in control plots. The functional classification was more predictive for most separate dynamic processes than for species fate: after disturbance, significant differences were found between all functional groups for growth. Pioneer+heliophilous species showed significantly higher recruitment rates. Mortality of shade‐tolerant species slightly increased and of mid‐tolerant and heliophilous species decreased.Conclusions: A combination of three species classifications separately built from the growth, recruitment and mortality processes is more informative than a global classification combining the processes. Identifying the pioneer+heliophilous species on the basis of their growth rate is crucial to predict species fate after disturbance. We showed that potential growth rate could be used as a reliable indicator to identify this group.
Polymer nanocomposites containing carbon nanotubes and miscible polymer blends based on poly[ethylene‐co‐(acrylic acid)]
Authors: Antolín‐Cerón V. H. , Gómez‐Salazar S. , Soto V. , Ávalos‐Borja M. , Nuño‐Donlucas S. M. 
Published: January 2008

AbstractFour binary polymer blends containing poly [ethylene‐co‐(acrylic acid)] (PEAA) as one component, and poly(4‐vinyl phenol‐co‐2‐hydroxy ethyl methacrylate) (P4VPh‐co‐2HEMA) or poly(2‐ethyl‐2‐oxazoline) (PEOx) or poly(vinyl acetate‐co‐vinyl alcohol) (PVAc‐co‐VA) or poly (vinylpyrrolidone‐co‐vinyl acetate) (PVP‐co‐VAc) as the other component were prepared and used as a matrix of a series of composite materials. These binary mixtures were either partially or completely miscible within the composition range studied and were characterized by differential scanning calorimetry (DSC) and Fourier transformed infrared spectroscopy (FTIR). Carbon nanotubes (CNTs) were prepared by a thermal treatment of polyester synthesized through the chemical reaction between ethylene glycol and citric acid over an alumina boat. High resolution transmission electron microscopy (HRTEM) was used to characterize the synthesized CNTs. Films of composite materials containing CNTs were obtained after evaporation of the solvent used to prepare solutions of the four types of binary polymer blends. Young's moduli of the composites were obtained by thermomechanical analysis at room temperature. Only one glass transition temperature was detected for several compositions on both binary blends and the composite material matrices. Evidence of hydrogen bond formation was recorded for both miscible blends and composite materials. The degree of crystallinity and Young's moduli of the CNT‐polymer composites increased compared to the single polymer blends. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci 2008
Linear viscoelastic properties and crystallization behavior of multi‐walled carbon nanotube/polypropylene composites
Authors: Wu Defeng , Sun Yurong , Wu Liang , Zhang Ming 
Published: January 2008

AbstractMulti‐walled carbon nanotube/polypropylene composites (PPCNs) were prepared by melt compounding. The linear viscoelastic properties, nonisothermal crystallization behavior, and kinetics of PPCNs were, respectively, investigated by the parallel plate rheometer, differential scanning calorimeter (DSC), X‐ray diffractometer (XRD), and polarized optical microscope (POM). PPCNs show the typical nonterminal viscoelastic response because of the percolation of nanotubes. The rheological percolation threshold of about 2 wt % is determined using Cole‐Cole method. Small addition of nanotube can highly promote crystallization of PP matrix because of the heterogeneous nucleating effect. With increasing nanotube loadings, however, the crystallization rate decreases gradually because the mobility of PP chain is restrained by the presence of nanotube, especially at high loading levels. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci 2008
A Frailty Mixture Cure Model with Application to Hospital Readmission Cata
Authors: Yu Binbing 
Published: January 2008

AbstractMixture cure models have been utilized to analyze survival data with possible cure. This paper considers the inclusion of frailty into the mixture cure model to model recurrent event data with a cure fraction. An attractive feature of the proposed model is the allowance for heterogeneity in risk among those individuals experiencing the event of interest in addition to the incorporation of a cured component. Maximum likelihood estimates can be obtained using the Expectation Maximization algorithm and standard errors are calculated from the Bootstrap method. The model is applied to hospital readmission data among colorectal cancer patients. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Comparative Analyses of N‐Acylated Homoserine Lactones Reveal Unique Structural Features that Dictate Their Ability to Activate or Inhibit Quorum Sensing
Authors: Geske Grant D. , O'Neill Jennifer C. , Miller David M. , Wezeman Rachel J. , Mattmann Margrith E. , Lin Qi , Blackwell Helen E. 
Published: January 2008

AbstractBacterial quorum sensing is mediated by low molecular‐weight signals and plays a critical role in both the pathogenesis of infectious disease and beneficial symbioses. There is significant interest in the development of synthetic ligands that can intercept bacterial quorum sensing signals and modulate these outcomes. Here, we report the design and comparative analysis of the effects of ∼90 synthetic N‐acylated homoserine lactones (AHLs) on quorum sensing in three Gram negative bacterial species and a critical examination of the structural features of these ligands that dictate agonistic and antagonistic activity, and selectivity for different R protein targets. These studies have revealed the most comprehensive set of structure–activity relationships to date that direct AHL‐mediated quorum sensing and a new set of chemical probes with which to study this complex signaling process. Furthermore, this work provides a foundation on which to design next‐generation quorum sensing modulators with improved activities and selectivities.
Diagnostic value of integrin α3, β4, and β5 gene expression levels for the clinical outcome of tongue squamous cell carcinoma
Authors: Kurokawa Akira , Nagata Masaki , Kitamura Nobutaka , Noman Arhab A. , Ohnishi Makoto , Ohyama Tokio , Kobayashi Takanori , Shingaki Susumu , Takagi Ritsuo 
Published: January 2008

AbstractBACKGROUND.The objective of the current study was to identify biomarkers that reflect the clinical course of squamous cell carcinoma of the tongue (TSCC).METHODS.TSCC tissue samples from 66 patients were subjected to gene expression analysis by real‐time polymerase chain reaction. Eleven integrin family genes and 14 genes used for normalization, including housekeeping genes and genes that encode desmosomal, cytoskeletal, and extracellular matrix molecules, were considered. Multivariate statistical analysis was performed on 154 expression ratios of integrin genes with clinical parameters.RESULTS.In principal‐component analysis, the first principal component was related to the outcome of death, and the second principal component mainly reflected the tendency for cervical lymph node (LN) metastasis. The former axis consisted of the variance of the integrin β4 gene (ITGB4) and ITGB5 expression levels, and the latter axis agreed with the expression level of the integrin α3 gene (ITGA3). Multivariate logistic regression analysis with cervical LN metastasis as the response variable concordantly identified ITGA3/junction plakoglobin gene (JUP) expression (P = .02) and ITGB5/paxillin gene (PXN) expression (P = .04) as significant factors. Only ITGB4/JUP expression was identified as a significant factor in terms of the outcome of death (P < .00049) by a Cox proportional hazards model. The group with high ITGB4/JUP levels exhibited a significantly high death rate on a Kaplan‐Meier curve (P < .0001; Wilcoxon and log‐rank tests).CONCLUSIONS.The expression levels of ITGA3, ITGB4, and ITGB5 with functional normalization by desmosomal or cytoskeletal molecule genes were selected as candidate biomarkers for cervical LN metastasis or for the outcome of death in TSCC. Cancer 2008. © 2008 American Cancer Society.
Dose‐intensive chemotherapy with growth factor or autologous bone marrow/stem cell transplant support in first‐line treatment of advanced or metastatic adult soft tissue sarcoma
Authors: Verma Shailendra , Younus Jawaid , Stys‐Norman Denise , Haynes Adam E. , Blackstein Martin 
Published: January 2008

AbstractA systematic review was performed to determine whether first‐line dose‐intensive chemotherapy supported by growth factor or autologous bone marrow/stem cell transplantation improves response rate, time‐to‐disease progression, or survival compared with standard‐dose chemotherapy in patients with inoperable, locally advanced, or metastatic soft tissue sarcoma. The MEDLINE, EMBASE, and Cochrane Library databases were searched. Three randomized trials (2 phase 3, 1 phase 2), 12 phase 2, and 5 phase 1 dose‐escalation trials were located. One randomized trial (N = 314) did not detect significant differences in response rate (P = .65) or survival (log‐rank P = .98) between high‐dose doxorubicin plus ifosfamide with granulocyte macrophage colony‐stimulating factor and doxorubicin plus ifosfamide at standard doses. Progression‐free survival, however, was significantly longer in the high‐dose arm (log‐rank P = .03). Higher rates of thrombocytopenia, infection, grade 3 of 4 asthenia, and stomatitis were observed with high‐dose compared with standard‐dose chemotherapy. Preliminary results from a second randomized trial (N = 162) indicated no benefit with respect to tumor response for an intensified mesna, doxorubicin (Adriamycin), ifosfamide, and dacarbazine regimen with granulocyte colony‐stimulating factor support compared with standard doxorubicin, ifosfamide, and dacarbazine. Grade 4 thrombocytopenia was significantly higher with the high‐dose regimen. Four phase 2 trials of high‐dose regimens observed tumor response rates greater than 50%. Phase 1 trials reported dose‐limiting toxicity for dose‐intensive chemotherapy regimens. On the basis of the available evidence, high‐dose chemotherapy with growth factor or autologous bone marrow/stem cell transplantation should not be used in the routine treatment of patients with inoperable, locally advanced, or metastatic soft tissue sarcoma. Cancer 2008. © 2008 American Cancer Society.