bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superior temporal lobe dysfunction and frontotemporal dysconnectivity in subjects at risk of psychosis and in first‐episode psychosis
Authors: Crossley Nicolas A. , Mechelli Andrea , Fusar‐Poli Paolo , Broome Matthew R. , Matthiasson Pall , Johns Louise C. , Bramon Elvira , Valmaggia Lucia , Williams Steven C.R. , McGuire Philip K. 
Published: June 2009

AbstractBackground: Superior temporal lobe dysfunction is a robust finding in functional neuroimaging studies of schizophrenia and is thought to be related to a disruption of fronto‐temporal functional connectivity. However, the stage of the disorder at which these functional alterations occur is unclear. We addressed this issue by using functional MRI (fMRI) to study subjects in the prodromal and first episode phases of schizophrenia. Methods: Subjects with an at risk mental state (ARMS) for psychosis, a first psychotic episode (FEP), and controls were studied using fMRI while performing a working memory task. Activation in the superior temporal gyrus (STG) was assessed using statistical parametric mapping, and its relationship to frontal activation was examined using dynamic causal modeling. Results: The STG was differentially engaged across the three groups. There was deactivation of this region during the task in controls, whereas subjects with FEP showed activation and the response in subjects with ARMS was intermediately relative to the two other groups. There were corresponding differences in the effective connectivity between the STG and the middle frontal gyrus across the three groups, with a negative coupling between these areas in controls, a positive coupling in the FEP group, and an intermediate value in the ARMS group. Conclusions: A failure to deactivate the superior temporal lobe during tasks that engage prefrontal cortex is evident at the onset of schizophrenia and may reflect a disruption of fronto‐temporal connectivity. Qualitatively similar alterations are evident in people with prodromal symptoms of the disorder. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Changes in spatial memory and BDNF expression to concurrent dietary restriction and voluntary exercise
Authors: Khabour Omar F. , Alzoubi Karem H. , Alomari Mahmoud A. , Alzubi Mohammad A. 
Published: June 2009

AbstractSubstantial data suggest that cognitive function can be influenced by many lifestyle activities associated with changes in energy metabolism such as exercise and diet. In the current study, we investigated the combined effects of voluntary exercise (access to running wheels) and dietary restriction (every other day fasting, EODF) on spatial memory formation and on the levels of brain‐derived neurotrophic factor (BDNF) in the hippocampus of Wistar male rats. Spatial learning and memory formation was assessed using the radial arm water maze (RAWM) paradigm, while BDNF protein was measured using ELISA test. Voluntary exercise and/or EODF were instituted for 6 weeks. Voluntary exercise alone significantly enhanced short‐term, intermediate‐term, and long‐term memory formation, and increased BDNF protein levels in the hippocampus. EODF enhanced mean running wheel activity by approximately twofold. However, EODF did not modulate the effects of exercise on memory formation and expression of BDNF. In addition, EODF alone had no effect on memory and BDNF protein in the hippocampus. In conclusion, results of this study indicate that exercise enhanced while EODF had neutral effect on both spatial memory formation and hippocampus BDNF levels. © 2009 Wiley‐Liss, Inc.
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

AbstractThe 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

AbstractDietary 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

AbstractWe 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

AbstractHER3 (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

AbstractThe 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

AbstractThe 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

AbstractEndemic, 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

AbstractTransforming 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

AbstractPolarization 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

AbstractEthylene 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

AbstractIn 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

AbstractOrganochlorine 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