bluuebunny/crossref_metadata_2025 huggingface dataset:
Basement membrane protein nidogen‐1 shapes hippocampal synaptic plasticity and excitability
Authors: Vasudevan Anju , Ho Matthew S.P. , Weiergräber Marco , Nischt Roswitha , Schneider Toni , Lie Ailing , Smyth Neil , Köhling Rüdiger
Published: June 2009

The basement membrane (BM) is a specialized form of extracellular matrix (ECM) underlying epithelia and endothelia and surrounding many types of mesenchymal cells. Nidogen, along with collagen IV and laminin, is a major component of BMs. Although certain ECM proteins such as laminin or reelin influence neuronal function via interactions with cell‐surface receptors such as integrins, behavioral neurological impairments due to deficits of BM components have been recognized only recently. Here, alterations in neuronal network function underlying these behavioral changes are revealed. Using nidogen‐1 knockout mice, with or without additional heterozygous nidogen‐2 knockout (NID1−/−/NID2+/+ or NID1−/−/NID2±), we demonstrate that nidogen is essential for normal neuronal network excitability and plasticity. In nidogen‐1 knockouts, seizurelike behavior occurs, and epileptiform spiking was seen in hippocampal in vivo EEG recordings. In vitro, hippocampal field potential recordings revealed that lack of nidogen‐1, while not causing conspicuous morphological changes, led to the appearance of spontaneous and evoked epileptiform activity, significant increase of the input/output ratio of synaptically evoked responses in CA1 and dentate gyrus, as well as of paired pulse accentuation, and loss of perforant‐path long‐term synaptic potentiation. Nidogen‐1 is thus essential for normal network excitability and plasticity. © 2009 Wiley‐Liss, Inc.
Dietary flavonol, flavone and catechin intake and risk of colorectal cancer in the Netherlands Cohort Study
Authors: Simons Colinda C.J.M. , Hughes Laura A.E. , Arts Ilja C.W. , Goldbohm R. Alexandra , van den Brandt Piet A. , Weijenberg Matty P.
Published: June 2009

Dietary flavonoids are hypothesized to be protective against colorectal cancer, yet findings have been inconsistent. We examined the association of dietary flavonol, flavone and catechin intake with colorectal cancer endpoints within the Netherlands Cohort Study (NLCS). In addition, we explored whether body mass index (BMI) may be an effect modifier of this association. The NLCS includes 120,852 men and women who were 55–69 years and completed a self‐administered questionnaire at baseline in 1986. A case‐cohort approach was used for data processing and analysis. After 13.3 years, 1,444 male and 1,041 female colorectal cancer cases were available for estimation of hazard ratios and 95% confidence intervals for quintiles of flavonoid intake. After adjustment for potential confounders, no association of total flavonol and flavone intake and total catechin intake with colorectal cancer endpoints was observed. Analyses stratified for BMI showed significant inverse trends in the association of total catechin intake, (+)‐catechin intake and (–)‐epicatechin intake with rectal cancer in men with a BMI ≥ 25 kg/m2and in the association of total catechin intake and intake of kaempferol, myricetin and all individual catechins with colorectal cancer, in particular colon cancer, in women with a BMI < 25 kg/m2. In conclusion, our findings generally do not support an association of dietary flavonol, flavone and catechin intake with colorectal cancer endpoints. Dietary catechin intake may be associated with a decreased rectal cancer risk in overweight men. Dietary flavonol and catechin intake may be associated with a decreased colorectal cancer risk in normal weight women. © 2009 UICC
Cyr61 downmodulation potentiates the anticancer effects of zoledronic acid in androgen‐independent prostate cancer cells
Authors: Marra Monica , Santini Daniele , Meo Giuseppina , Vincenzi Bruno , Zappavigna Silvia , Baldi Alfonso , Rosolowski Maciej , Tonini Giuseppe , Loeffler Markus , Lupu Ruth , Addeo Santolo Rosario , Abbruzzese Alberto , Budillon Alfredo , Caraglia Michele
Published: June 2009

We have analyzed the gene modulation induced by zoledronic acid (ZOL) in androgen‐resistant prostate cancer PC3 cells with cDNA microarray platform to identify new molecular targets of ZOL in prostate cancer. The gene coding for cysteine‐rich, angiogenic inducer, 61 (CYR61) resulted highly downregulated with a fold change of 5.58. Therefore, we have studied the effects of ZOL on CYR61 protein product, and we have found that CYR61 protein expression was decreased significantly after exposure to ZOL. The effect of ZOL on CYR61 expression was dose and time dependent was due to a reduced transcriptional activity of CYR61 promoter. Moreover, the effects induced by ZOL were paralleled by decreased activation of Ras‐Raf‐1‐ and Akt‐dependent pathways that was dependent from isoprenylation inhibition, since it was antagonized by the addition of geranylgeraniol. Finally, we have investigated the role of CYR61 in the regulation of growth inhibition and invasion/motility of PC3 cells using a shRNA for CYR61 to downregulate the expression of CYR61 protein. The enhanced inhibition of proliferation and motility/invasion induced by ZOL by S‐phase accumulation. In the same experimental conditions, CYR61 protein downregulation potentiated the inactivation of the Ras‐dependent proliferation pathway and cell cycle inhibitors p21 and p27 expression. © 2009 UICC
HER3 is required for the maintenance of neuregulin‐dependent and ‐independent attributes of malignant progression in prostate cancer cells
Authors: Soler Marta , Mancini Francesca , Meca‐Cortés Óscar , Sánchez‐Cid Lourdes , Rubio Nuria , López‐Fernández Sonia , Lozano Juan José , Blanco Jerónimo , Fernández Pedro L. , Thomson Timothy M.
Published: June 2009

HER3 (ERBB3) is a catalytically inactive pseudokinase of the HER receptor tyrosine kinase family, frequently overexpressed in prostate and other cancers. Aberrant expression and mutations of 2 other members of the family, EGFR and HER2, are key carcinogenic events in several types of tumors, and both are well‐ validated therapeutic targets. In this study, we show that HER3 is required to maintain the motile and invasive phenotypes of prostate (DU‐145) and breast (MCF‐7) cancer cells in response to the HER3 ligand neuregulin‐1 (NRG‐1), epidermal growth factor (EGF) and fetal bovine serum. Although MCF‐7 breast cancer cells appeared to require HER3 as part of an autocrine response induced by EGF and FBS, the response of DU‐145 prostate cancer cells to these stimuli, while requiring HER3, did not appear to involve autocrine stimulation of the receptor. DU‐145 cells required the expression of HER3 for efficient clonogenicity in vitro in standard growth medium and for tumorigenicity in immunodeficient mice. These observations suggest that prostate cancer cells derived from tumors that overexpress HER3 are dependent on its expression for the maintenance of major attributes of neoplastic aggressiveness, with or without cognate ligand stimulation. © 2009 UICC
Detection of epidermal growth factor receptor mutations in plasma by mutant‐enriched PCR assay for prediction of the response to gefitinib in patients with non‐small‐cell lung cancer
Authors: He Chen , Liu Ming , Zhou Chengzhi , Zhang Jiexia , Ouyang Ming , Zhong Nanshan , Xu Jun
Published: June 2009

The high frequency of epidermal growth factor receptor (EGFR) mutations in tyrosine kinase inhibitor‐responsive non‐small‐cell lung cancer (NSCLC) cases is now well established, highlighting the predictive value of activating EGFR mutations in guiding the clinical use of EGFR‐targeted therapies. However, specimen source and methods for EGFR mutation analysis are limited by tissue availability and technical feasibility in clinical application. Therefore, the current study is designed to establish a blood‐based approach for the assessment of EGFR mutations in NSCLC patients, in particular the advanced stage, and to test its clinical application. Plasma samples were obtained from the enrolled 134 NSCLC patients. The detection rate of the EGFR exon19 deletions and exon21 L858R was 49.3% (66/134) by the blood‐based, mutant‐enriched polymerase chain reaction. In the paired tumor and plasma samples, the detected mutant types of each pair respectively by direct sequencing and mutant‐enriched polymerase chain reaction were concordant in 17 of 18 (94.4%). In the patients treated with gefitinib as a second‐line therapy, those with plasma EGFR mutation have a prolonged median progression‐free survival compared with those with EGFR wild type (7.609 vs. 2.877 months, p = 0.002). On comparing the efficacy of gefitinib with that of docetaxel, it was found that the median progression‐free survival was significantly longer for patients treated with gefitinib than those with docetaxel in those harboring plasma EGFR mutation (7.609 vs. 3.192 months, p = 0.006). These results suggest that the blood‐based EGFR mutations test has the ability to provide a reliable guidance for clinical decision making for the treatment of the advanced NSCLC patients. © 2009 UICC
Low drug resistance to both platinum and taxane chemotherapy on an in vitro drug resistance assay predicts improved survival in patients with advanced epithelial ovarian, fallopian and peritoneal cancer
Authors: Matsuo Koji , Bond Virginia K. , Eno Michele L. , Im Dwight D. , Rosenshein Neil B.
Published: June 2009

The objective of this study was to evaluate the role of an in vitro drug resistance assay to platinum and taxane in the management of advanced epithelial ovarian, fallopian and primary peritoneal cancer. All patients with FIGO Stage IIIc and IV who received postoperative chemotherapy with platinum and taxane for more than 4 courses after the initial cytoreductive surgery between 1995 and 2008 were evaluated. Patients who received neoadjuvant chemotherapy were not included. An in vitro drug resistance assay (EDR Assay, Oncotech, Tustin, CA) was used to determine drug resistance for each patient's tumor tissue. Level of drug resistance was described as extreme (EDR), intermediate (IDR), or low (LDR). Response to chemotherapy and survival were correlated to the EDR Assay. Of the 335 patients who underwent primary cytoreductive surgery, 173 cases met the criteria for statistical evaluation. The 58 patients (33.5%) whose tumors had LDR to both platinum and taxane had statistically improved progression‐free survival and overall survival (OS) compared with the 115 patients (66.5%) who demonstrated IDR or EDR to platinum and/or taxane (5‐year OS rates, 41.1% vs. 30.9%, p = 0.014). The 5‐year OS rates for the 28 (16.2%) cases that had optimal cytoreduction with LDR to both platinum and taxane was significantly improved over the 62 (35.8%) cases that were suboptimally cytoreduced with IDR or EDR to platinum and/or taxane (54.1% vs. 20.4%, respectively, p < 0.001). In conclusion, LDR to both platinum and taxane chemotherapy, as determined by an in vitro drug resistance assay, independently predicts improved survival in patients with advanced epithelial ovarian, fallopian and peritoneal cancer, especially in those patients who undergo optimal primary cytoreduction. © 2009 UICC
B‐cell differentiation in EBV‐positive Burkitt lymphoma is impaired at posttranscriptional level by miRNA‐altered expression
Authors: Leucci Eleonora , Onnis Anna , Cocco Mario , De Falco Giulia , Imperatore Francesco , Giuseppina Antonicelli , Costanzo Valentina , Cerino Giovanna , Mannucci Susanna , Cantisani Rocco , Nyagol Joshua , Mwanda Walter , Iriso Robert , Owang Martin , Schurfeld Karin , Bellan Cristiana , Lazzi Stefano , Leoncini Lorenzo
Published: June 2009

Endemic, sporadic and HIV‐associated Burkitt lymphoma (BL) all have a B‐cell phenotype and a MYC translocation, but a variable association with the Epstein‐Barr virus (EBV). However, there is still no satisfactory explanation of how EBV participates in the pathogenesis of BL. A recent investigation suggested that EBV‐positive and EBV‐negative BL have different cells of origin. In particular, according to immunoglobulin gene mutation analysis, EBV‐negative BLs may originate from early centroblasts, whereas EBV‐positive BLs seem to arise from postgerminal center B cells or memory B cells. The appearance of a germinal center phenotype in EBV‐positive cells might thus derive from a block in B‐cell differentiation. The exit from the germinal center involves a complex series of events, which require the activation of BLIMP‐1, and the consequent downregulation of several target genes. Here, we investigated the expression of specific miRNAs predicted to be involved in B‐cell differentiation and found that hsa‐miR‐127 is differentially expressed between EBV‐positive and EBV‐negative BLs. In particular, it was strongly upregulated only in EBV‐positive BL samples, whereas EBV‐negative cases showed levels of expression similar to normal controls, including microdissected germinal centers (GC) cells. In addition, we found evidence that hsa‐miR‐127 is involved in B‐cell differentiation process through posttranscriptional regulation of BLIMP1 and XBP1. The overexpression of this miRNA may thus represent a key event in the lymphomagenesis of EBV positive BL, by blocking the B‐cell differentiation process.
Peptide inhibitors of transforming growth factor‐β enhance the efficacy of antitumor immunotherapy
Authors: Llopiz Diana , Dotor Javier , Casares Noelia , Bezunartea Jaione , Díaz‐Valdés Nancy , Ruiz Marta , Aranda Fernando , Berraondo Pedro , Prieto Jesús , Lasarte Juan José , Borrás‐Cuesta Francisco , Sarobe Pablo
Published: June 2009

Transforming growth factor‐β (TGF‐β) is a cytokine with potent immunosuppressive effects and is overexpressed in many tumors. Therefore, development of molecules able to inhibit TGF‐β is of paramount importance to improve the efficacy of antitumor immunotherapy. TGF‐β inhibitor peptides P144 and P17 were combined with the administration of adjuvant molecules poly(I:C) and agonistic anti‐CD40 antibodies, and their effect on the growth of E.G7‐OVA established tumors and on antitumor immune response was evaluated. Tumor rejection efficacy of a single administration of adjuvants was enhanced from 15 to 70 % when combined with repeated injections of TGF‐β inhibitor peptides. Simultaneous administration of adjuvants and TGF‐β inhibitor peptides was required for maximal therapeutic efficacy. Although tumor cells produced TGF‐β, it was found that the beneficial effect of peptide administration was mainly due to the inhibition of TGF‐β produced by regulatory CD4+CD25+ T cells rather than by tumor cells. The enhanced antitumor effect was accompanied by a higher activity of dendritic cells, natural killer cells and tumor antigen‐specific T cells, as well as by a decrease in the number of myeloid‐derived suppressor cells. In conclusion, administration of peptide inhibitors of TGF‐β in therapeutic vaccination enhances the efficacy of immunotherapy by increasing antitumor immune responses. These peptide inhibitors may have important applications for current immunotherapeutic strategies. © 2009 UICC
Measurements of depolarization distribution in the healthy human macula by polarization sensitive OCT
Authors: Baumann Bernhard , Götzinger Erich , Pircher Michael , Hitzenberger Christoph K.
Published: June 2009

Polarization sensitive optical coherence tomography (PS‐OCT) allows for depth resolved imaging of polarization properties of retinal structures. Different layers in the retina can be distinguished not only based on their reflectivity but also due to their birefringent, depolarizing or polarization preserving character. In contrast to other structures in the posterior segment, the retinal pigment epithelium (RPE) is depolarizing, i.e., it scrambles the polarization state of light. A spectral domain (SD) PS‐OCT system was used to record 3D data sets of the retina. The depolarizing effect of the RPE was analyzed by quantitative evaluation of the spatial depolarization distribution in the macula regions of healthy eyes. Depolarization in the RPE is most pronounced close to the center of the fovea and decreases with eccentricity. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Sterilization of medical devices by ethylene oxide, determination of the dissipation of residues, and use of Green Fluorescent Protein as an indicator of process control
Authors: Dias Fábio N. , Ishii Marina , Nogaroto Sergio L. , Piccini Bruno , Penna Thereza C. V.
Published: June 2009

Ethylene oxide (EO) is used to sterilize Oxygenator and Tubing applied to heart surgery. Residual levels of EO and its derivatives, ethylene chlorohydrin (ECH) and ethylene glycol (EG), may be hazardous to the patients. Therefore, it must be removed by the aeration process. This study aimed to estimate the minimum aeration time for these devices to attain safe limits for use (avoiding excessive aeration time) and to evaluate the Green Fluorescent Protein (GFP) as a biosensor capable of best indicating the distribution and penetration of EO gas throughout the sterilization chamber. Sterilization cycles of 2, 4, and 8 h were monitored by Bacillus atrophaeus ATCC 9372 as a biological indicator (BI) and by the GFP. Residual levels of EO, ECH, and EG were determined by gas chromatography (GC), and the residual dissipation was studied. Safe limits were reached right after the sterilization process for Oxygenator and after 204 h of aeration for Tubing. In the 2 h cycle, the GFP concentration decreased from 4.8 (±3.2)% to 7.5 (±2.5)%. For the 4 h cycle, the GFP concentration decreased from 17.4 (±3.0)% to 21.5 (±6.8)%, and in the 8 h cycle, it decreased from 22.5 (±3.2)% to 23.9 (±3.9)%. This finding showed the potentiality for GFP applications as an EO biosensor. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Chem‐bioinformatics: QSTR studies on TIBO derivatives
Authors: Thakur Abhilash , Thakur Mamta
Published: June 2009

In the present study, effort has been made to develop a mathematical model for the set of 19 (tetrahydromidazo [4,5,1‐jk][1,4] benzodizepin‐2(1H)‐one) (TIBO) derivatives. The biological activity modeled in the present investigation is cytotoxic concentration (log 1/C). To investigate the cytotoxic behavior of TIBO derivatives, classical and nonconventional physicochemical properties are tested separately. Out of the two categories, the classical physicochemical properties play a dominating role in the modeling of cytotoxicity. On the basis of the results obtained and with the help of molecular modeling parameters, we discovered that the molecular property is most responsible for the cytotoxicity of TIBO derivatives. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:166–171, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20270
Heptachlor and o‐p′DDT effects on protein kinase activities associated with human placenta particulate fractions
Authors: Magnarelli Gladis , Souza María S. , D'Angelo Ana M. Pechén de
Published: June 2009

Organochlorine pesticides have been detected in placenta. The ability of heptachlor (HC) and 1,1,1‐tricholoro‐2‐(2‐chlorophenyl)‐2‐4‐chlorophenyl)ethane (o‐p′DDT) to interfere with protein phosphorylation was evaluated. In vitro incubations of cell‐free placental villi homogenates with a concentration range 1–100 µM were performed. In particulate fractions, total serine/threonine kinase activity was increased by 10 µM HC and o‐p′ DDT (59% and 82%, respectively). Maximum eightfold increase was observed with 10 µM o‐p′ DDT on protein kinase A activity. By contrast, protein kinase C activity was reduced by 10 µM HC and o‐p′ DDT (40% and 52%, respectively). Endogenous substrate phosphorylation studies demonstrated that slight but significant increase in 24‐kDa band labeling was produced in nuclear samples with 1, 10, and 100 µM HC and 100 µM o‐p′ DDT. Exposition to 100 µM HC increased 85‐kDa band labeling. In mitochondrial fractions, 10 µM HC and o‐p′ DDT increased 24‐ and 65‐kDa bands' labeling. These data indicate that both pesticides affect protein kinase activities in particulate fraction. Nuclear compartmentalization of these compounds, insertion in membranes, and chemical stress production may be associated to the observed effects, thus suggesting deleterious consequences in signaling pathways. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:185–192, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20277
Investigations of the posttranslational mechanism of arsenite‐mediated downregulation of human cytochrome P4501A1 levels: The role of heme oxygenase‐1
Authors: Bessette Erin E. , Fasco Michael J. , Pentecost Brian T. , Reilly Andrew , Kaminsky Laurence S.
Published: June 2009

Arsenite, an environmental cocontaminant of polycyclic aromatic hydrocarbons (PAHs), diminishes the PAH‐mediated upregulation of human CYP1A1, the enzyme that bioactivates PAHs to carcinogenic metabolites. Mechanistically, while transcriptional downregulation contributes to these effects, a role for posttranslational regulation has been implicated but not proven. We hypothesize that arsenite induces heme oxygenase‐1 (HO‐1), which catabolizes CYP1A1 heme or cellular heme pools, thereby downregulating CYP1A1. Arsenite (5 µM), in HepG2 cells, induced HO‐1 mRNA 7.4‐fold over the 48 h observation period, and it upregulated HO‐1 protein expression. Arsenite decreased the induction of CYP1A1 by a PAH, benzo[k]fluoranthene (BKF), by 50%; and transfection of HepG2 cells with siRNA targeting the human HO‐1 gene, reduced the arsenite downregulation of BKF‐induced CYP1A1 from 54% to 27%, relative to untransfected cells. Reconstituted HO‐1 did not significantly catabolize CYP1A1 heme in vitro. Together these findings demonstrate that a posttranslational mechanism involving decreases in the cellular heme pool by arsenite‐induced HO‐1 may contribute to arsenite‐mediated downregulation of CYP1A1. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:222–232, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20283
The Met protooncogene is a transcriptional target of NFkappaB: Implications for cell survival
Authors: Dai James Y. , DeFrances Marie C. , Zou Chunbin , Johnson Carla J. , Zarnegar Reza
Published: June 2009

NFkappaB transcription factor regulates gene expression in response to extracellular stimuli such as TNF alpha. The genes regulated by NFkappaB encode for proteins which control cell growth and survival. Met is the tyrosine kinase receptor for hepatocyte growth factor, and it too promotes cell mitogenesis and survival. Previously, we showed that Met gene expression is regulated by TNF alpha. In this report, we identify and characterize a TNF alpha response element in the Met promoter. This element contains tandem C/EBP sites adjacent to an NFkappaB site. Binding of the NFkappaB p65 subunit and C/EBP beta to this element is induced by TNF alpha. To examine the interplay of NFkappaB and Met in vivo, we determined that Met mRNA and protein levels are reduced in the livers of p65−/− mice as compared to controls. In p65−/− mouse embryonic fibroblasts (MEFs), Met induction by TNF alpha is abrogated while Met's basal gene expression is reduced by half as compared to controls. When overexpressed in p65−/− MEFs, Met confers resistance to TNF‐alpha‐mediated cell death. Conversely, expression of dominant negative Met in wild‐type MEFs renders them sensitive to cell death induced by TNF alpha. A similar response following TNF alpha challenge was observed in hepatocytic cells treated with siRNA to knockdown endogenous Met. Together, these results indicate that the Met gene is a direct target of NFkappaB and that Met participates in NFkappaB‐mediated cell survival. J. Cell. Biochem. 107: 1222–1236, 2009. © 2009 Wiley‐Liss, Inc.
Synchrotron X‐ray imaging reveals a correlation of tumor copper speciation with Clioquinol's anticancer activity
Authors: Barrea Raul A. , Chen Di , Irving Thomas C. , Dou Q. Ping
Published: June 2009

Tumor development and metastasis depend on angiogenesis that requires certain growth factors, proteases, and the trace element copper (Cu). Recent studies suggest that Cu could be used as a novel target for cancer therapies. Clioquinol (CQ), an antibiotic that is able to form stable complexes with Cu or zinc (Zn), has shown proteasome‐inhibitory, androgen receptor‐suppressing, apoptosis‐inducing, and antitumor activities in human cancer cells and xenografts. The mechanisms underlying the interaction of CQ with cellular Cu, the alteration of the Cu/Zn ratio and the antitumor role of CQ in vivo have not been fully elucidated. We report here that Cu accumulates in tumor tissue and that the Cu/Zn balances in tumor, but not normal, tissue change significantly after the treatment with CQ. Cu speciation analysis showed that the Cu(I) species is predominant in both normal and tumor tissues and that Cu(II) content was significantly increased in tumor, but not normal tissue after CQ treatment. Our findings indicate that CQ can interact with cellular Cu in vivo, dysregulates the Cu/Zn balance and is able to convert Cu(I) to Cu(II) in tumor tissue. This conversion of Cu(I) to Cu(II) may be associated with CQ‐induced proteasome inhibition and growth suppression in the human prostate tumor xenografts. J. Cell. Biochem. 108: 96–105, 2009. © 2009 Wiley‐Liss, Inc.
Ginsenoside Rg1 protects rat cardiomyocyte from hypoxia/reoxygenation oxidative injury via antioxidant and intracellular calcium homeostasis
Authors: Zhu Dan , Wu Lei , Li Chun‐Rong , Wang Xiao‐Wei , Ma Yong‐Jie , Zhong Zhi‐yin , Zhao Hai‐Bao , Cui Jian , Xun Si‐Fan , Huang Xiu‐Lan , Zhou Zhe , Wang Sheng‐Qi
Published: June 2009

Ginsenoside Rg1 is a major active ingredient ofPanax notoginseng radixwhich has demonstrated a number of pharmacological actions including a cardioprotective effect in vivo. This study investigated the protective effect and mechanism of ginsenoside Rg1 in cardiomyocytes hypoxia/reoxygenation (H/R) model. Pretreatment with ginsenoside Rg1 (60–120 µM) reduced lactate dehydrogenase release and increased cell viability in a dose‐dependent manner. Fluorescence analysis demonstrated ginsenoside Rg1 reduced intracellular ROS and suppressed the intracellular [Ca2+] level. Cell lysate detected an increase of T‐SOD, CAT, and GSH levels. The myocardial protection of ginsenoside Rg1 during H/R is partially due to its antioxidative effect and intracellular calcium homeostasis. J. Cell. Biochem. 108: 117–124, 2009. © 2009 Wiley‐Liss, Inc.
Rate coefficients for the reaction of OH with CF3CH2CH3 (HFC‐263fb) between 200 and 400 K: Ab initio, DFT, and transition state theory calculations
Authors: Ali Mohamad Akbar , Rajakumar B.
Published: June 2009

Rate coefficients for the reaction of the hydroxyl radical with CF3CH2CH3 (HFC‐263fb) were computed using ab initio methods, viz. MP2, G3MP2, and G3B3 theories between 200 and 400 K. Structures of the reactants in the ground state (GS) and transition state (TS) were optimized at MP2(FULL)/6‐31G*, MP2(FULL)/6‐311+ +G**, and B3LYP/6‐31G* level of theories. Seven TSs were identified for the title reaction in the above theories. However, five out of seven TSs were found to be symmetrically distinct. The kinetic parameters due to these five different TSs are presented in this manuscript. Intrinsic reaction coordinate (IRC) calculations were performed to confirm the existence of transition states. The contributions of all the individual hydrogens in the substrate for the reaction are estimated and compared with the results obtained using Structure Additivity Relationships. The rate coefficients for the title reaction were computed to be k = (7.96 ± 0.93) × 10−13 exp [−(2245 ± 30)/T] cm3 molecule−1 s−1 at MP2, k = (9.50 ± 0.93) × 10−13 exp [−(1162 ± 30)/T] cm3 molecule−1 s−1 at G3MP2, and k = (7.01 ± 0.88) × 10−13 exp [−(753 ± 35)/T] cm3 molecule−1 s−1at G3B3 theories. The theoretically computed rate coefficients are found to be in excellent agreement with the experimentally determined ones. The OH‐driven atmospheric lifetimes of this compound are computed to be 132, 2.2, and 0.7 years at, MP2, G3MP2, and G3B3 level of theories, respectively. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
The use of time‐averaged 3JHH restrained molecular dynamics (tar‐MD) simulations for the conformational analysis of five‐membered ring systems: Methodology and applications
Authors: Hendrickx Pieter M. S. , Corzana Francisco , Depraetere Stefaan , Tourwé Dirk A. , Augustyns Koen , Martins José C.
Published: June 2009

Because of its presence in many molecules of biological relevance, the conformational analysis of five‐membered rings using 3JHH scalar coupling data from NMR is a topic of considerable interest. Typically, conformational analysis involves the use of a well‐established mathematical procedure, originally developed by de Leeuw et al., that fits two rigid conformations to the available experimental data. This so‐called pseudorotation analysis approach is not without problems, however, as chemically unrealistic conformations are sometimes generated from the data. Here, we present our investigations in the use of time‐averaged restrained molecular dynamics simulations as a generic tool to determine the conformations that agree with experimental 3JHH scalar coupling data. For this purpose, a set of six ribose‐based molecules has been used as model compounds. The influence of several modeling parameters is assessed and optimized values are proposed. The results obtained with the tar‐MD approach are compared to those obtained from the two conformer fitting procedure. Interpretation of the latter is facilitated by the introduction of a fitting error analysis that allows mapping the solution space of the fitting procedure. The relative merits of both methods and the advantages that result from the use of a force field and a time‐averaged restraint potential for the experimental data are discussed. When combined, both techniques allow an enhanced understanding of the molecules' conformational behavior and prevent possible overinterpretation. In view of the very reasonable computational burden of a tar‐MD simulation for the systems investigated here, the approach should be generally applicable. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Polarized basis sets for accurate calculations of static and dynamic electric properties of molecules
Authors: Baranowska Angelika , Sadlej Andrzej J.
Published: June 2009

We report on the development and testing of large polarized basis sets (LPolX, where X is the element symbol) for accurate calculations of linear and nonlinear electric properties of molecules. The method used to generate LPolX sets is based on our studies of the analytic dependence of Gaussian functions on external time‐independent and time‐dependent electric fields. At variance with the earlier investigations of small, highly compact (ZPolX) basis sets for moderately accurate calculations of electric properties of large molecules, the present goal is to obtain basis sets that are nearly saturated with respect to the selected class of electric properties and can be used for accurate studies of interaction‐induced properties. This saturation makes the LPolX sets also useful in calculations of optical properties for chiral molecules. In this article, the LPolX sets are generated for X = H, C, N, O, and F, and examined in calculations of linear and nonlinear electric properties of four standard test systems: HF, N2, CO, and HCN. The study of the performance of LPolX basis sets has been carried out at different levels of approximation ranging from the SCF HF method to highly correlated CCSD(T) approach. The results obtained in this study compare favorably with accurate reference data and show a high level of saturation of LPolX basis sets with respect to the polarization effect due to external electric fields. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Novel dimer based descriptors with solvational computation for QSAR study of oxadiazoylbenzoyl‐ureas as novel insect‐growth regulators
Authors: Fan Feng , Cheng Jiagao , Li Zhong , Xu Xiaoyong , Qian Xuhong
Published: June 2009

Molecular aggregation state of bioactive compounds plays a key role in its bio‐interactive procedure. In this article, based on the structure information of dimers, the simplest model of molecular aggregation state, and combined with solvational computation, total four descriptors (ΔV, MR2, ΔE1, and ΔE2) were calculated for QSAR study of a novel insect‐growth regulator, N‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐N′‐benzoyl urea. Two QSAR models were constructed with r2 = 0.671, q2 = 0.516 and r2 = 0.816, q2 = 0.695, respectively. It implicates that the bioactivity may strongly depend on the characters of molecular aggregation state, especially on the dimeric transport ability from oil phase to water phase. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
A new strategy of outlier detection for QSAR/QSPR
Authors: Cao Dong‐Sheng , Liang Yi‐Zeng , Xu Qing‐Song , Li Hong‐Dong , Chen Xian
Published: June 2009

The crucial step of building a high performance QSAR/QSPR model is the detection of outliers in the model. Detecting outliers in a multivariate point cloud is not trivial, especially when several outliers coexist in the model. The classical identification methods do not always identify them, because they are based on the sample mean and covariance matrix influenced by the outliers. Moreover, existing methods only lay stress on some type of outliers but not all the outliers. To avoid these problems and detect all kinds of outliers simultaneously, we provide a new strategy based on Monte‐Carlo cross‐validation, which was termed as the MC method. The MC method inherently provides a feasible way to detect different kinds of outliers by establishment of many cross‐predictive models. With the help of the distribution of predictive residuals such obtained, it seems to be able to reduce the risk caused by the masking effect. In addition, a new display is proposed, in which the absolute values of mean value of predictive residuals are plotted versus standard deviations of predictive residuals. The plot divides the data into normal samples,ydirection outliers andXdirection outliers. Several examples are used to demonstrate the detection ability of MC method through the comparison of different diagnostic methods. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
CANADA: Designing nucleic acid sequences for nanobiotechnology applications
Authors: Feldkamp Udo
Published: June 2009

The design of nucleic acid sequences for a highly specific and efficient hybridization is a crucial step in DNA computing and DNA‐based nanotechnology applications. The CANADA package contains software tools for designing DNA sequences that meet these and other requirements, as well as for analyzing and handling sequences. CANADA is freely available, including a detailed manual and example input files, at http://ls11‐www.cs.uni‐dortmund.de/molcomp/downloads. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Cycle decompositions of complete multigraphs
Authors: Smith Benjamin R.
Published: June 2009

In this paper we establish necessary and sufficient conditions for decomposing the complete multigraph λKn into cycles of length λ, and the λ‐fold complete symmetric digraph λK into directed cycles of length λ. As a corollary to these results we obtain necessary and sufficient conditions for decomposing λKn (respectively, λK) into cycles (respectively, directed cycles) of prime length. © 2009 Wiley Periodicals, Inc. J Combin Designs 18: 85–93, 2010
Partnering with families: multiple family group psychoeducation for schizophrenia
Authors: Jewell Thomas C. , Downing Donna , McFarlane William R.
Published: June 2009

Family psychoeducation (FPE) is one of six evidence‐based practices endorsed by the Center for Mental Health Services for individuals suffering from chronic mental illnesses. Multiple family group psychoeducation (MFG) has been shown to be an effective component of FPE in reducing symptom relapses and rehospitalizations for individuals with schizophrenia. It is especially effective when family members participate on a consistent basis, which allows them to increase their understanding of the biology of the disorder, learn ways to be supportive, reduce stress in the environment and in their own lives, and develop a broader social network. When used in conjunction with medication, MFG can help an individual with schizophrenia progress towards the rehabilitation phase of recovery. A case illustration describes the engagement of a chronically ill, mid‐thirties male in MFG and how his family's participation for 2 years benefits all members, in spite of the longevity of his illness. © 2009 Wiley Periodicals, Inc. J Clin Psychol: In Session 65: 868–878, 2009.
Involvement of ATM‐mediated Chk1/2 and JNK kinase signaling activation in HKH40A‐induced cell growth inhibition
Authors: Wang Ziqiu , Wang Meifang , Kar Sid , Carr Brian I.
Published: June 2009

HKH40A (RTA 502), or 5‐nitro‐2‐(3‐{4‐[3‐(8‐methoxy‐6‐oxo‐6H‐2,10b‐diaza‐aceanthrylen‐5‐ylamino)propyl]piperazin‐1‐yl}‐propyl)‐2‐aza‐phenalene‐1,3‐dione, has been shown to be a potent cell growth inhibitor. To investigate HKH40A actions, we focused on exploring the signal transduction pathways that are involved in its cell growth inhibitory mechanisms. We found that HKH40A activated ataxia telangiectasia mutated (ATM) kinase, which then triggered activation of the Chk1/2 signaling pathway, evidenced by Chk1/2 mediated inhibitory phosphorylation of Cdc25C protein phosphatase. This resulted in Cdk1 tyrosine phosphorylation at Tyr‐15, leading to cell cycle block at G2/M phase. HKH40A also activated the c‐Jun N‐terminal kinase (JNK) pathway, most likely regulated by ATM kinase, since pre‐treatment of Hep3B cells with ATM inhibitor KU‐55933 or ATM siRNA transfection antagonized HKH40A‐induced c‐Jun phosphorylation. HKH40A‐induced apoptosis was probably mediated by JNK–H2A.X interaction, since phospho‐c‐Jun and phospho‐H2A.X were able to co‐localize in the nucleus and to co‐immuno‐precipitate. Furthermore, inhibition of JNK kinase activity by JNK inhibitor SP600125 abolished both HKH40A‐induced H2A.X phosphorylation and apoptosis. Our data support the hypothesis that binding of HKH40A to cellular DNA likely activates ATM kinase, which then induces parallel Chk 1/2 and JNK signaling pathways, leading to G2/M cell cycle block and apoptosis. J. Cell. Physiol. 221: 213–220, 2009. © 2009 Wiley‐Liss, Inc
Profile of exosomes related proteins released by differentiated and undifferentiated human keratinocytes
Authors: Chavez‐Muñoz Claudia , Kilani Ruhangiz T. , Ghahary Aziz
Published: June 2009

Our group has previously demonstrated the capacity of human keratinocytes to release 14‐3‐3σ into conditioned medium through the mechanism of exosome externalization. In this study the release of other proteins through the same mechanism and the differences in the profiles of 14‐3‐3 proteins between differentiated (diff‐K) and undifferentiated keratinocytes (undiff‐K) were investigated. The stimulatory effect of other 14‐3‐3 isoforms on the expression of MMP‐1 in dermal fibroblasts was also evaluated. Exosomes isolated from undiff‐K (low Ca2+) and diff‐K (high Ca2+) were subjected to proteomic and Western blot analysis. The results showed that more than 50 different cytoplasmic proteins including all seven 14‐3‐3 protein isoforms (β, σ, η, ε, τ, ζ, and γ) were released from diff‐K through the mechanism of exosome externalization. However, in exosomes of undiff‐K only four of the 14‐3‐3 protein isoforms (β, η, ζ, and γ) were detected. Ca2+ treatment increased the release of exosomes from undiff‐K by at least two times relative to the control. Consistent with this finding, the stimulatory effect of exosomes containing 14‐3‐3σ from diff‐K had higher MMP‐1 stimulatory effect in fibroblasts relative to those exosomes isolated from undiff‐K. MMP‐1 stimulatory effect of recombinant 14‐3‐3β and η, tested in this study, in dermal fibroblasts, suggests additional anti‐fibrogenic factors other than 14‐3‐3σ. In conclusion, keratinocytes release many proteins through the mechanism of exosome externalization from which some such as 14‐3‐3 isoforms may function as extracellular matrix (ECM) modulating factors for dermal fibroblasts. These findings revealed the presence of a novel mechanism by which keratinocytes can potentially interact with fibroblasts. J. Cell. Physiol. 221: 221–231, 2009. © 2009 Wiley‐Liss, Inc
IGF‐1 released by corneal epithelial cells induces up‐regulation of N‐cadherin in corneal fibroblasts
Authors: Ko Ji‐Ae , Yanai Ryoji , Nishida Teruo
Published: June 2009

Interactions between epithelial cells and fibroblasts play important roles in tissue homeostasis. With the use of a coculture system in which human corneal fibroblasts and epithelial cells are cultured on opposite sides of a collagen (vitrigel) membrane, we have examined the effects of epithelial cells on expression of the adherens‐junction protein N‐cadherin in fibroblasts. Reverse transcription‐polymerase chain reaction and immunoblot analyses showed that the presence of epithelial cells increased the expression of N‐cadherin in fibroblasts at the mRNA and protein levels. This effect of epithelial cells was mimicked by insulin‐like growth factor‐1 (IGF‐1) but not by epidermal growth factor or fibroblast growth factor. Depletion of IGF‐1 in epithelial cells by RNA interference abolished the effect of these cells on N‐cadherin expression in fibroblasts. The presence of epithelial cells activated the IGF‐1 receptor as well as up‐regulated expression of the transcriptional regulator ZEB1 in fibroblasts. RNA interference‐mediated depletion of IGF‐1 in epithelial cells prevented the effect of these cells on ZEB1 expression in fibroblasts. These results suggest that IGF‐1 released from corneal epithelial cells up‐regulates the expression of N‐cadherin in corneal fibroblasts. J. Cell. Physiol. 221: 254–261, 2009. © 2009 Wiley‐Liss, Inc
Effects of di(2‐ethylhexyl) phthalate on gap and tight junction protein expression in the testis of prepubertal rats
Authors: Sobarzo Cristian M. , Lustig Livia , Ponzio Roberto , Suescun María Olga , Denduchis Berta
Published: June 2009

The aim of this study was to analyze whether di(2‐ethylhexyl) phthalate (DEHP), a Sertoli and Leydig cell toxicant, is able to induce alterations in the expression of testicular gap and tight junction proteins. DEHP was administered by gavage (1 g/5 mL corn oil/kg body weight/day) to 25‐day‐old male Sprague–Dawley rats for 2 days (DEHP‐27d) and control rats were treated with corn‐oil vehicle for 2 days (C‐27d); animals were killed 24 h after the last treatment. Testes of DEHP‐27d rats showed different degrees of germ cell sloughing of seminiferous tubules (ST). No alterations of the blood testis barrier (BTB) by lanthanum tracer study were observed. ST of DEHP‐27d rats showed a milder immunofluorescence and more restricted expression of connexin‐43 (Cx43) in the adluminal and basal compartment compared to C‐27d. In DEHP‐27d rats, we found a discontinuous immunofluorescent (IF) pattern for zonula occludens (ZO‐1), contrasting with the continuous IF profile observed in C‐27d, and a delocalization of claudin‐11. A decrease in Cx43 and ZO‐1 and no changes in occludin expression were detected by Western blot in the testes of DEHP‐27d rats. Results from 57‐day‐old rats treated with DEHP for 2 days and held for 30 days without treatment showed that the alterations in protein expression induced by DEHP are reversible. However, a delay of spermatogenesis compared to C‐57d rats, occurred. Data demonstrated that DEHP does not impair BTB permeability but induces germ cell sloughing that might respond to a down regulation of Cx43 and ZO‐1 that alters cell junction proteins. Microsc. Res. Tech. 2009. © 2009 Wiley‐Liss, Inc.
Color‐based tumor tissue segmentation for the automated estimation of oral cancer parameters
Authors: Sun Yung‐nien , Wang Yi‐ying , Chang Shao‐chien , Wu Li‐wha , Tsai Sen‐tien
Published: June 2009

This article presents an automatic color‐based feature extraction system for parameter estimation of oral cancer from optical microscopic images. The system first reduces image‐to‐image variations by means of color normalization. We then construct a database which consists of typical cancer images. The color parameters extracted from this database are then used in automated online sampling from oral cancer images. Principal component analysis is subsequently used to divide the color features into four tissue types. Each pixel in the cancer image is then classified into the corresponding tissue types based on the Mahalanobis distance. The aforementioned procedures are all fully automated; in particular, the automated sampling step greatly reduces the need for intensive labor in manual sampling and training. Experiments reveal high levels of consistency among the results achieved using the manual, semiautomatic, and fully automatic methods. Parameter comparisons between the four cancer stages are conducted, and only the mean parameters between early and late cancer stages are statistically different. In summary, the proposed system provides a useful and convenient tool for automatic segmentation and evaluation for stained biopsy samples of oral cancer. This tool can also be modified and applied to other tissue images with similar staining conditions. Microsc. Res. Tech. 2009. © 2009 Wiley‐Liss, Inc.
Study of intussusceptive angiogenesis in inflammatory regional lymph nodes by scanning electron microscopy
Authors: Rossi‐Schneider Tíssiana Rachel , Verli Flaviana Dornela , Marinho Sandra Aparecida , Yurgel Liliane Soares , De Souza Maria Antonieta Lopes
Published: June 2009

The aim of the present study was to verify the occurrence of intussusceptive angiogenesis in blood vessels from submandibular lymph nodes responsible for lymphatic drainage of the tongue. A surgical wound inflicted on the ventral tongue of male Wistar rats and submandibular regional lymph nodes were evaluated at different postoperative periods. Scanning electron microscopy (SEM) was used to observe 123 lymph nodes at times 2, 3, 7, 10, 14, and 21 postoperative days. During the analysis of the vascular models with SEM, intussusceptive angiogenesis was observed in all groups evaluated. This was more extensive on the second and third postoperative days (83.33% and 80%, respectively), representing in these groups the expansion of the vascular chain of lymph nodes. At 21 postoperative days, intussusceptive angiogenesis (42.85%) was suggestive of vascular remodeling. Microsc. Res. Tech. 2009. © 2009 Wiley‐Liss, Inc.
A possible role of stigma and fears in HIV infection
Authors: Akande Adebowale Will
Published: June 2009

At the onset of AIDS in 1981, it caught everybody (by surprise), with their pants down, openly, scientifically and literally. Fear /Stigma associated with HIV/AIDS continues to avert responses to the epidemic. Data (obtained in Tshwane metropolis) were used to test stigma/fear dimensions of an instrument. Factor analysis identified five foci of fear and stigma. There were significant differences on the factor scale measuring fear of sex, with females and younger respondents having significantly greater fear. Results were interpreted within a cultural context that realises that decreasing AIDS stigma is a vital step in stemming the pandemic. Copyright © 2009 John Wiley & Sons, Ltd.