bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting direction shifts on Canadian–US exchange rates with artificial neural networks
Authors: Davis Jefferson T. , Episcopos Athanasios , Wettimuny Sannaka 
Published: August 2002

AbstractThe paper presents a variety of neural network models applied to Canadian–US exchange rate data. Networks such as backpropagation, modular, radial basis functions, linear vector quantization, fuzzy ARTMAP, and genetic reinforcement learning are examined. The purpose is to compare the performance of these networks for predicting direction (sign change) shifts in daily returns. For this classification problem, the neural nets proved superior to the naïve model, and most of the neural nets were slightly superior to the logistic model. Using multiple previous days' returns as inputs to train and test the backpropagation and logistic models resulted in no increased classification accuracy. The models were not able to detect a systematic affect of previous days' returns up to fifteen days prior to the prediction day that would increase model performance. Copyright © 2001 John Wiley & Sons, Ltd.
Decreased serum testosterone levels in rats exposed intraperitoneally to bismuth subnitrate
Authors: Stoltenberg Meredin , Flyvbjerg Allan , Søndergaard Liselotte G , Rungby Jørgen 
Published: August 2002

AbstractThe consumption of bismuth is increasing and knowledge of the potential teratogenic and reproductive damage of bismuth exposure is fragmentary. In the present study we used autometallography (AMG)—the histochemical silver amplification technique—to trace bismuth in the testis and pituitary glands of Wistar rats injected intraperitoneally with bismuth subnitrate. Large amounts of bismuth AMG grains were concentrated in the lysosomes of Leydig cells, and serum testosterone levels were reduced when compared with controls. No histochemical traces of bismuth were found in the anterior lobe of the pituitary gland. Compared with their corresponding controls, neither follicle‐stimulating hormone nor luteinizing hormone were affected. The selective uptake of bismuth in Leydig cells, followed by decreased testosterone levels, emphasizes a potential hazard of bismuth‐provoked male reproductive impairment. Copyright © 2002 John Wiley & Sons, Ltd.
Viability, adhesion, and bone phenotype of osteoblast‐like cells on polyelectrolyte multilayer films
Authors: Tryoen‐Tóth Petra , Vautier Dominique , Haikel Youssef , Voegel Jean‐Claude , Schaaf Pierre , Chluba Johanna , Ogier Joëlle 
Published: August 2002

AbstractThe aim of this study was to develop new biocompatible coatings for bone implants by the alternating deposition of oppositely charged polyelectrolytes. Polyelectrolyte films were built up with different terminating layers on which SaOS‐2 osteoblast‐like cells and human periodontal ligament (PDL) cells were grown. The terminating layer was made of one of the following polyelectrolytes: poly(ethylene imine) (PEI), poly(sodium 4‐styrenesulfonate) (PSS), poly(allylamine hydrochloride) (PAH), poly(L‐glutamic acid) (PGA), or poly(L‐lysine) (PLL). Cell adherence, viability, stability of osteoblast phenotype, and inflammatory response were studied. Adherence and viability were good on all terminating layers except the PEI‐terminating layer, which was cytotoxic. Maintenance of osteoblast phenotype marker expression was observed on PSS‐ and PGA‐terminating films for both cell types, whereas downregulation, associated with the induction of Interleukin‐8 (IL‐8) secretion, was detected on PEI and PAH for both cell types and on PLL for PDL cells. These results suggested a good biocompatibility of PSS‐ and PGA‐ending films for PDL cells and of PSS‐, PGA‐, and PLL‐terminating films for SaOS‐2 cells. As a result, polyelectrolyte multilayer films could emerge as new alternatives for implant coatings. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 657–667, 2002
Interactions of 3T3 fibroblasts and endothelial cells with defined pore features
Authors: Salem A. K. , Stevens R. , Pearson R. G. , Davies M. C. , Tendler S. J. B. , Roberts C. J. , Williams P. M. , Shakesheff K. M. 
Published: August 2002

AbstractThe colonization of biodegradable polymer scaffolds with cell populations has been established as the foundation for the engineering of a number of tissues, including cartilage, liver, and bone. Within these scaffolds, the cells encounter a porous environment in which they must migrate across the convoluted polymer surface to generate a homogenous cell distribution. Predicting the interactions between cells and pores is important if scaffold characteristics are to be optimized. Therefore, we investigated the behavior of two model cell types over a range of defined pore features. These pore features range from 5 to 90 μm in diameter and have been fabricated by photolithographic techniques. Quantitatively, the behavior of the cells is dependent on three factors: 1) percentage cell coverage of the surface; 2) pore size; and 3) cell type. Fibroblast cells displayed a co‐operative pattern of cell spreading in which pores with diameters greater than the cell dimensions were bridged by groups of cells using their neighbors as supports. Endothelial cells were unable to use neighbors as support structures and failed to bridge pores greater than the cell diameter. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 212–217, 2002
Modulation of insulin transport in rat brain microvessel endothelial cells by an ecto‐phosphatase activity
Authors: Calhau C. , Martel F. , Pinheiro‐Silva S. , Pinheiro H. , Soares‐da‐Silva P. , Hipólito‐Reis C. , Azevedo I. 
Published: August 2002

AbstractThe physiological function of alkaline phosphatase (ALP) remains controversial. It was recently suggested that this membrane‐bound enzyme has a role in the modulation of transmembranar transport systems into hepatocytes and Caco‐2 cells. ALP activity expressed on the apical surface of blood‐brain barrier cells, and its relationship with 125I‐insulin internalization were investigated under physiological conditions using p‐nitrophenylphosphate (p‐NPP) as substrate. For this, an immortalized cell line of rat capillary cerebral endothelial cells (RBE4 cells) was used. ALP activity and 125I‐insulin internalization were evaluated in these cells. The results showed that RBE4 cells expressed ALP, characterized by an ecto‐oriented active site which was functional at physiological pH. Orthovanadate (100 μM), an inhibitor of phosphatase activities, decreased both RBE4‐ALP activity and 125I‐insulin internalization. In the presence of l‐arginine (1 mM) or adenosine (100 μM) RBE4‐ALP activity and 125I‐insulin, internalization were significantly reduced. However, d‐arginine (1 mM) had no significant effect. Additionally, RBE4‐ALP activity and 125I‐insulin internalization significantly increased in the presence of the bioflavonoid kaempferol (100 μM), of the phorbol ester PMA (80 nM), IBMX (1 mM), progesterone (200 μM and 100 μM), β‐estradiol (100 μM), iron (100 μM) or in the presence of all‐trans retinoic acid (RA) (10 μM). The ALP inhibitor levamisole (500 μM) was able to reduce 125I‐insulin internalization to 69.1 ± 7.1% of control. Our data showed a positive correlation between ecto‐ALP activity and 125I‐insulin incorporation (r = 0.82; P < 0.0001) in cultured rat brain endothelial cells, suggesting that insulin entry into the blood‐brain barrier may be modulated through ALP. J. Cell. Biochem. 84: 389–400, 2002. © 2001 Wiley‐Liss, Inc.
IGF‐1 induces Pin1 expression in promoting cell cycle S‐phase entry
Authors: You Han , Zheng Hongwu , Murray Steven A. , Yu Qiang , Uchida Takafumi , Fan Daiming , Xiao Zhi‐Xiong Jim 
Published: August 2002

AbstractInsulin‐like growth factor I (IGF‐1) is a well‐established mitogen to many different cell types and is implicated in progression of a number of human cancers, notably breast cancer. The prolyl isomerase Pin1 plays an important role in cell cycle regulation through its specific interaction with proteins that are phosphorylated at Ser/Thr‐Pro motifs. Pin1 knockout mice appear to have relatively normal development yet the Pin1−/−mouse embryo fibroblast (MEF) cells are defective in re‐entering cell cycle in response to serum stimulation after G0 arrest. Here, we report that Pin1−/− MEF cells display a delayed cell cycle S‐phase entry in response to IGF stimulation and that IGF‐1 induces Pin1 protein expression which correlates with the induction of cyclin D1 and RB phosphorylation in human breast cancer cells. The induction of Pin1 by IGF‐1 is mediated via the phosphatidylinositol 3‐kinase as well as the MAP kinase pathways. Treatment of PI3K inhibitor LY294002 and the MAP kinase inhibitor PD098059, but not p38 inhibitor SB203580, effectively blocks IGF‐1‐induced upregulation of Pin1, cyclin D1 and RB phosphorylation. Furthermore, we found that Cyclin D1 expression and RB phosphorylation are dramatically decreased in Pin1−/− MEF cells. Reintroducing a recombinant adenovirus encoding Pin1 into Pin1−/− MEF cells restores the expression of cyclin D1 and RB phosphorylation. Thus, these data suggest that the mitogenic function of IGF‐1 is at least partially linked to the induction of Pin1, which in turn stimulates cyclin D1 expression and RB phosphorylation, therefore contributing to G0/G1‐S transition. J. Cell. Biochem. 84: 211–216, 2002. © 2001 Wiley‐Liss, Inc.
Modulation of HeLa cells spreading by the non‐receptor tyrosine kinase ACK‐2
Authors: Coon Melissa , Herrera Roman 
Published: August 2002

AbstractThe CDC42 regulated non‐receptor tyrosine kinase ACK‐2 has been associated with integrin signaling. In this report, the effect of ACK‐2 on the modulation of cell spreading and motility was examined. HeLa cells expressing epitope‐tagged wild type ACK‐2 showed a slower rate of spreading on fibronectin when compared with untransfected cells. An ACK‐2 protein lacking its SH3 domain was still capable of modulating HeLa cell spreading suggesting that its tyrosine kinase activity is sufficient to induce the observed phenotype. The ACK‐2 effect on the rate of cell spreading did not involve inhibition of integrin‐mediated activation of PI‐3K signaling, since it did not alter membrane translocation of a GFP‐PH‐AKT domain (AKT pleckstrin homology domain) used as a reporter for PI‐3K products induced by cell adhesion. The ACK‐2 effect appears to be upstream from the adapter protein CrkII, since co‐expression of CrkII and ACK‐2 results in a neutralization of ACK‐2 mediated effects on HeLa cell spreading. Similarly, co‐expression of p130Cas, which interacts with the adapter protein CrkII, with ACK‐2, also results in a partial reversion of the ACK‐2 effects on cell spreading. CrkII mediated reversal of the ACK‐2 induced phenotype requires the activity of the small GTPase, Rap1. Co‐expression of ACK‐2 and CrkII with a dominant negative form of Rap1 reverses the neutralization by CrkII suggesting that CrkII mediated activation of Rap1 is required. However, an active form of Rap1 is not sufficient to reverse the ACK‐2 phenotype by itself. A role for Rac1 in ACK‐2 effects was also established. An activated Rac1 protein neutralized the ACK‐2 mediated inhibition of cell spreading. A direct measurement of cell motility by either a modified Boyden chamber or wounding assay demonstrates that ACK‐2 overexpression increases the motility of the cells. These results suggest that ACK‐2 modulates HeLa cells spreading upstream of pathways regulated by CrkII and that ACK‐2 may regulate cell motility by controlling the activation of small GTPases such as Rap1 and Rac1. J. Cell. Biochem. 84: 655–665, 2002. © 2001 Wiley‐Liss, Inc.
Phytoestrogen genistein stimulates the production of osteoprotegerin by human trabecular osteoblasts
Authors: Viereck Volker , Gründker Carsten , Blaschke Sabine , Siggelkow Heide , Emons Günter , Hofbauer Lorenz C. 
Published: August 2002

AbstractThe anti‐resorptive effects of estrogen on bone metabolism are thought to be mediated through modulation of paracrine factors produced by osteoblastic lineage cells that act on osteoclastic lineage cells. Receptor activator of nuclear factor‐κB ligand (RANKL) is the essential factor for osteoclast formation and activation and enhances bone resorption. By contrast, osteoprotegerin (OPG), which is produced by osteoblastic lineage cells acts as a decoy receptor that neutralizes RANKL and prevents bone loss. Recently, 17β‐estradiol was found to stimulate OPG mRNA levels and protein secretion in a human osteoblastic cell line through activation of the estrogen receptor (ER)‐α. In this study, we assessed the effects of the phytoestrogen genistein on OPG mRNA steady state levels (by semiquantitative RT‐PCR and Northern analysis) and protein production (by ELISA) in primary human trabecular osteoblasts (hOB) obtained from healthy donors. Genistein increased OPG mRNA levels and protein secretion by hOB cells by up to two‐ to six‐fold in a dose‐ (P < 0.0001) and time‐dependent (P < 0.0001) fashion with a maximum effect at 10−7 M. Co‐treatment with the pure ER antagonist ICI 182,780 completely abrogated the stimulatory effects of genistein on OPG protein secretion, indicating that these effects were specific and directly mediated through the ER. Pre‐treatment with genistein partially prevented the inhibitory effects of the glucocorticoid dexamethasone on OPG mRNA and protein production. The stimulation of OPG mRNA levels by genistein was not affected by the protein synthesis inhibitor, cycloheximide and was shown to be due to enhancement of OPG gene transcription. In conclusion, our data suggest that the phytoestrogen genistein is capable of upregulating the production of OPG by human osteoblasts. Thus, dietary sources of phytoestrogens may help to prevent bone resorption and bone loss by enhanced osteoblastic production of OPG. J. Cell. Biochem. 84: 725–735, 2002. © 2002 Wiley‐Liss, Inc.
Suppression of tissue factor expression, cofactor activity, and metastatic potential of murine melanoma cells by the N‐terminal domain of adenovirus E1A 12S protein
Authors: Voigtländer Constanze , Rand Arlymae , Liu Su‐Ling , Wilson Timothy J. , Pittelkow Mark R. , Getz Michael J. , Kelm Robert J. 
Published: August 2002

AbstractTissue factor, the cellular initiator of blood coagulation, has been implicated as a determinant of metastatic potential in human melanoma cells. Here, we report that differential expression of tissue factor in murine melanoma cell lines of known metastatic behavior is mediated by AP‐1‐dependent and 12S E1A oncoprotein‐repressible gene transcription. When compared to weakly metastatic C10 cells, highly metastatic M4 cells possessed elevated levels of tissue factor cofactor activity, transfected promoter activity, and heterodimeric AP‐1 DNA‐binding complexes containing Fra‐1. Transient co‐expression of the adenovirus E1A 12S oncoprotein strongly repressed transcription of an AP‐1‐driven tissue factor reporter gene indicating the additional requirement of N‐terminal E1A‐interacting coactivators. Stable expression of E1A mutants defective in CBP/p300‐binding failed to suppress tissue factor expression and experimental metastasis by M4 cells while clones expressing wild type E1A exhibited greatly reduced tissue factor cofactor activity and metastatic potential in vivo. Overexpression of functional tissue factor in cells containing wild type E1A failed to restore the highly metastatic M4 phenotype suggesting that additional E1A‐responsive and CBP/p300‐dependent genes are required to facilitate metastasis of murine melanoma cells demonstrating high tissue factor expression and cofactor activity. J. Cell. Biochem. 85: 54–71, 2002. © 2002 Wiley‐Liss, Inc.
NERF2, a member of the Ets family of transcription factors, is increased in response to hypoxia and angiopoietin‐1: A potential mechanism for Tie2 regulation during hypoxia
Authors: Christensen Rial A. , Fujikawa Koshi , Madore Rebecca , Oettgen Peter , Varticovski Lyuba 
Published: August 2002

AbstractVascular endothelial growth factor (VEGF) and angiopoietins regulate endothelial cell survival and migration and are essential for angiogenesis. Considerable progress has been made towards understanding hypoxia‐mediated regulation of VEGF and its receptors. In contrast, little is known about the regulation of angiopoietins and their receptors in hypoxic cells. Using RT–PCR, RNAase protection assay, and Western blotting, we found that Tie1 and Tie2 mRNA and protein levels increased in response to hypoxia in human umbilical vein endothelial cells. Previously, we have shown that NERF2, a member of Ets family of transcription factors that is specifically expressed in endothelial cells, binds to the promoter region of Tie2 and transactivates Tie2 expression. In this study, we show that expression of NERF2 was increased under hypoxia and that this increase temporally correlated with the increase in Tie2 expression. Hypoxia‐induced expression of NERF2 and Tie2 was blocked by angiopoietin‐2, a competitive inhibitor of angiopoietin‐1, and by recombinant soluble extracellular domain of Tie2 but not by VEGF‐neutralizing antibodies. In addition, angiopoietin‐1 directly induced expression of NERF2 in quiescent cells. These novel findings suggest that angiopoietin‐1 regulates expression of NERF2 and its own receptor in hypoxic cells. J. Cell. Biochem. 85: 505–515, 2002. © 2002 Wiley‐Liss, Inc.
Characterization of tissue‐specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of a human LIM‐only protein (FHL1)
Authors: Ng Enders Kai On , Lee Simon M. Y. , Li Hoi‐Yeung , Ngai Sai‐Ming , Tsui Stephen K. W. , Waye Mary M. Y. , Lee Cheuk‐Yu , Fung Kwok‐Pui 
Published: August 2002

AbstractWe have cloned and characterized another alternatively spliced isoform of the human four‐and‐a‐half LIM domain protein 1 (FHL1), designated FHL1C. FHL1C contains a single zinc finger and two tandem repeats of LIM domains at the N‐terminus followed by a putative RBP‐J binding region at the C‐terminus. FHL1C shares the same N‐terminal two‐and‐a‐half LIM domains with FHL1 but different C‐terminal protein sequences. Due to the absence of the exon 4 in FHL1C, there is a frame‐shift in the 3′ coding region. Sequence analysis indicated that FHL1C is the human homolog of murine KyoT2. The Northern blot and RT‐PCR results revealed that FHL1 is widely expressed in human tissues, including skeletal muscle and heart at a high level, albeit as a relatively low abundance transcript in brain, placenta, lung, liver, kidney, pancreas, and testis. In contrast, FHL1C is specifically expressed in testis, skeletal muscle, and heart at a relatively low level compared with FHL1. The expression of FHL1C transcripts was also seen in aorta, left atrium, left, and right ventricles of human heart at low level. Immunoblot analysis using affinity‐purified anti‐FHL1C antipeptide antibodies confirmed a 20 kDa protein of FHL1C in human skeletal muscle and heart. Unlike FHL1B, which is another FHL1 isoform recently reported by our group and localized predominantly in the nucleus [Lee et al., 1999], FHL1C is localized both in the nucleus and cytoplasm of mammalian cell. J. Cell. Biochem. 82: 1–10, 2001. © 2001 Wiley‐Liss, Inc.
Human T cell responses to endogenously presented HLA‐A*0201 restricted peptides of simian virus 40 large T antigen
Authors: Velders Markwin P. , Macedo M. Fatima , Provenzano Maurizio , Elmishad Amira G. , Holzhütter Hermann‐Georg , Carbone Michele , Kast W. Martin 
Published: August 2002

AbstractPresence of the simian virus 40 (SV40) has recently been demonstrated in a relatively high percentage of human mesotheliomas and it is associated with the development of these malignancies in pleural cavities. Therefore, we have initiated a study to identify candidate peptides presented by the human HLA‐A*0201 molecule for vaccination approaches against SV40 and monitoring of SV40 directed human immune responses. Initial screening of SV40 large T (Tag) domains required for transformation of cells for HLA‐A*0201 binding motifs revealed ten possible binding peptides. Screening of these candidate peptides showed that seven of the ten peptides could bind and stabilize HLA‐A*0201 molecules. In an in vitro immunization assay the two peptides with the highest binding affinity for HLA‐A*0201, Tag aa 396–405 and aa 577–585, were tested for their ability to induce peptide specific cytotoxic T cells in two healthy donors. One donor developed cytotoxic T cells against Tag aa 396–405 and in T cell cultures of both donors Tag aa 577–585 specific T cells were initiated. The T cells against Tag aa 577–585 not only recognized and killed peptide pulsed cells, but, most importantly, SV40 transformed human mesothelial cells. This is the first demonstration of the induction of SV40 specific human cytotoxic T lymphocytes that recognize endogenously processed peptides from SV40. This peptide identification study opens the possibility to investigate immune responses against SV40 in mesothelioma patients and in individuals exposed to SV40. J. Cell. Biochem. 82: 155–162, 2001. © 2001 Wiley‐Liss, Inc.
Nerve growth factor stimulates the interaction of ZIP/p62 with atypical protein kinase C and targets endosomal localization: Evidence for regulation of nerve growth factor‐induced differentiation
Authors: Samuels Ivy S. , Seibenhener M. Lamar , Neidigh Kimberly B.W. , Wooten Marie W. 
Published: August 2002

AbstractAtypical protein kinase Cs zeta and lambda/iota play a functional role in the regulation of NGF‐induced differentiation and survival of pheochromocytoma, PC12 cells [Coleman and Wooten, 1994; Wooten et al., 1999]. Here we demonstrate an NGF‐dependent interaction of aPKC with its binding protein, ZIP/p62. Although, ZIP/p62 was not a PKC‐ι substrate, the formation of a ZIP/p62‐aPKC complex in PC12 cells by NGF occurred post activation of PKC‐ι and was regulated by the tyrosine phosphorylation state of aPKC. Furthermore, NGF‐dependent localization of ZIP/p62 was observed within vesicular structures, identified as late endosomes by colocalization with a Rab7 antibody. Both ZIP/p62 as well as PKC‐ι colocalized with Rab7 upon NGF stimulation. Inhibition of the tyrosine phosphorylation state of PKC‐ι did not prevent movement of ZIP/p62 to the endosomal compartment. These observations indicate that the subcellular localization of ZIP/p62 does not depend entirely upon activation of aPKC itself. Of functional importance, transfection of an antisense p62 construct into PC12 cells significantly diminished NGF‐induced neurite outgrowth. Collectively, these findings demonstrate that ZIP/p62 acts as a shuttling protein involved in routing activated aPKC to an endosomal compartment and is required for mediating NGF's biological properties. J. Cell. Biochem. 82:452–466, 2001. © 2001 Wiley‐Liss, Inc.