bluuebunny/crossref_metadata_2025 huggingface dataset:
Data aided symbol timing estimation in space–time coding systems with continuous phase modulation
Authors: Shen Wenli , Zhao Minjian , Qiu Peiliang
Published: January 2009

Space–time coding has been proposed recently in the MIMO wireless communication systems for improving the capacity and data rate without bandwidth expansion. Symbol timing synchronisation is an important issue in such systems. In this paper, a novel data aided symbol timing estimation algorithm was proposed for burst‐mode transmission systems of space–time trellis coding combined with continuous phase modulation (CPM) for Rayleigh fading channels. A training sequence is embedded before transmission of each packet. The receiver calculates the Digital Fourier Transformation (DFT) of the phase of the differential signals. The symbol timing offset can be estimated from the phase of the tone component of the DFT outputs. MATLAB simulation results show that the variance of the timing estimation error is very small. This algorithm can estimate the initial timing offset rapidly and accurately. Space–time coding has been proposed recently in the MIMO wireless communication systems for improving the capacity and data rate without bandwidth expansion. Symbol timing synchronisation is an important issue in such systems. In this paper, a novel data aided symbol timing estimation algorithm was proposed for burst‐mode transmission systems of space–time trellis coding combined with continuous phase modulation (CPM) for Rayleigh fading channels. A training sequence is embedded before transmission of each packet. The receiver calculates the Digital Fourier Transformation (DFT) of the phase of the differential signals. The symbol timing offset can be estimated from the phase of the tone component of the DFT outputs. MATLAB simulation results show that the variance of the timing estimation error is very small. This algorithm can estimate the initial timing offset rapidly and accurately. Copyright © 2009 John Wiley & Sons, Ltd.
Is reversal of large stock‐price declines caused by overreaction or information asymmetry: Evidence from stock and option markets
Authors: Choi Hyung‐Suk , Jayaraman Narayanan
Published: January 2009

The role of option markets is reexamined in the reversal process of stock prices following stock price declines of 10% or more. A matched pair of optionable and nonoptionable firms is randomly selected when their price declines by 10% or more on the same date. The authors examine the 1,443 and 1,018 matched pairs of New York Stock Exchange/American Stock Exchange (AMEX) and National Association of Securities Dealers Automated Quotations firms over the period from 1996 to 2004. It was found that the positive rebounds for nonoptionable firms are caused by an abnormal increase in bid–ask spread on and before the large price decline date. On the other hand, the bid–ask spreads for optionable firms decrease on and before the large price decline date. An abnormal increase in the open interest and volume in the option market on and before the large price decline date was also found. Overall, the results suggest that the stock‐price reversal neither is a result of overreaction nor can it be simply explained by the bid–ask bounce. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 29:348–376, 2009
Genotype‐based matching to correct for population stratification in large‐scale case‐control genetic association studies
Authors: Guan Weihua , Liang Liming , Boehnke Michael , Abecasis Gonçalo R.
Published: January 2009

Genome‐wide association studies are helping to dissect the etiology of complex diseases. Although case‐control association tests are generally more powerful than family‐based association tests, population stratification can lead to spurious disease‐marker association or mask a true association. Several methods have been proposed to match cases and controls prior to genotyping, using family information or epidemiological data, or using genotype data for a modest number of genetic markers. Here, we describe a genetic similarity score matching (GSM) method for efficient matched analysis of cases and controls in a genome‐wide or large‐scale candidate gene association study. GSM comprises three steps: (1) calculating similarity scores for pairs of individuals using the genotype data; (2) matching sets of cases and controls based on the similarity scores so that matched cases and controls have similar genetic background; and (3) using conditional logistic regression to perform association tests. Through computer simulation we show that GSM correctly controls false‐positive rates and improves power to detect true disease predisposing variants. We compare GSM to genomic control using computer simulations, and find improved power using GSM. We suggest that initial matching of cases and controls prior to genotyping combined with careful re‐matching after genotyping is a method of choice for genome‐wide association studies.Genet. Epidemiol. 33:508–517, 2009. © 2009 Wiley‐Liss, Inc.
Peripheral myelin protein 22 is regulated post‐transcriptionally by miRNA‐29a
Authors: Verrier Jonathan D. , Lau Pierre , Hudson Lynn , Murashov Alexander K. , Renne Rolf , Notterpek Lucia
Published: January 2009

Peripheral myelin protein 22 (PMP22) is a dose‐sensitive, disease‐associated protein primarily expressed in myelinating Schwann cells. Either reduction or overproduction of PMP22 can result in hereditary neuropathy, suggesting a requirement for correct protein expression for peripheral nerve biology. PMP22 is post‐transcriptionally regulated and the 3′untranslated region (3′UTR) of the gene exerts a negative effect on translation. MicroRNAs (miRNAs) are small regulatory molecules that function at a post‐transcriptional level by targeting the 3′UTR in a reverse complementary manner. We used cultured Schwann cells to demonstrate that alterations in the miRNA biogenesis pathway affect PMP22 levels, and endogenous PMP22 is subjected to miRNA regulation. GW‐body formation, the proposed cytoplasmic site for miRNA‐mediated repression, and Dicer expression, an RNase III family ribonuclease involved in miRNA biogenesis, are co‐regulated with the differentiation state of Schwann cells. Furthermore, the levels of Dicer inversely correlate with PMP22, while the inhibition of Dicer leads to elevated PMP22. Microarray analysis of actively proliferating and differentiated Schwann cells, in conjunction with bioinformatics programs, identified several candidate PMP22‐targeting miRNAs. Here we demonstrate that miR‐29a binds and inhibits PMP22 reporter expression through a specific miRNA seed binding region. Over‐expression of miR‐29a enhances the association of PMP22 RNA with Argonaute 2, a protein involved in miRNA function, and reduces the steady‐state levels of PMP22. In contrast, inhibition of endogenous miR‐29a relieves the miRNA‐mediated repression of PMP22. Correlation analyses of miR‐29 and PMP22 in sciatic nerves reveal an inverse relationship, both developmentally and in post‐crush injury. These results identify PMP22 as a target of miRNAs and suggest that myelin gene expression by Schwann cells is regulated by miRNAs. © 2009 Wiley‐Liss, Inc.
Ca2+‐ and thromboxane‐dependent distribution of MaxiK channels in cultured astrocytes: From microtubules to the plasma membrane
Authors: Ou J. W. , Kumar Y. , Alioua A. , Sailer C. , Stefani E. , Toro L.
Published: January 2009

Large‐conductance, voltage‐ and Ca2+‐activated K+ channels (MaxiK) are broadly expressed ion channels minimally assembled by four pore‐forming α‐subunits (MaxiKα) and typically observed as plasma membrane proteins in various cell types. In murine astrocyte primary cultures, we show that MaxiKα is predominantly confined to the microtubule network. Distinct microtubule distribution of MaxiKα was visualized by three independent labeling approaches: (1) MaxiKα‐specific antibodies, (2) expressed EGFP‐labeled MaxiKα, and (3) fluorophore‐conjugated iberiotoxin, a specific MaxiK pore‐blocker. This MaxiKα association with microtubules was further confirmed by in vitro His‐tag pulldown, co‐immunoprecipitation from brain lysates, and microtubule depolymerization experiments. Changes in intracellular Ca2+ elicited by general pharmacological agents, caffeine or thapsigargin, resulted in increased MaxiKα labeling at the plasma membrane. More notably, U46619, an analog of thromboxane A2 (TXA2), which triggers Ca2+‐release pathways and whose levels increase during cerebral hemorrhage/trauma, also elicits a similar increase in MaxiKα surface labeling. Whole‐cell patch clamp recordings of U46619‐stimulated cells develop a ∼3‐fold increase in current amplitude indicating that TXA2 stimulation results in the recruitment of additional, functional MaxiK channels to the surface membrane. While microtubules are largely absent in mature astrocytes, immunohistochemistry results in brain slices show that cortical astrocytes in the newborn mouse (P1) exhibit a robust expression of microtubules that significantly colocalize with MaxiKα. The results of this study provide the novel insight that suggests that Ca2+ released from intracellular stores may play a key role in regulating the traffic of intracellular, microtubule‐associated MaxiKα stores to the plasma membrane of developing murine astrocytes. © 2009 Wiley‐Liss, Inc.
Impact of pretransplant hyponatremia on outcome following liver transplantation #
Authors: Yun Byung Cheol , Kim Ray W. , Benson Joanne T. , Biggins Scott W. , Therneau Terry M. , Kremers Walter K. , Rosen Charles B. , Klintmalm Goran B.
Published: January 2009

Hyponatremia is associated with reduced survival in patients with cirrhosis awaiting orthotopic liver transplantation (OLT). However, data are sparse regarding the impact of hyponatremia on outcome following OLT. We investigated the effect of hyponatremia at the time of OLT on mortality and morbidity following the procedure. The study included 2,175 primary OLT recipients between 1990 and 2000. Serum sodium concentrations obtained immediately prior to OLT were correlated with subsequent survival using proportional hazards analysis. Morbidity associated with hyponatremia was assessed, including length of hospitalization, length of intensive care unit (ICU) admission, and occurrence of central pontine myelinolysis (CPM). Out of 2,175 subjects, 1,495 (68.7%) had normal serum sodium (>135 mEq/L) at OLT, whereas mild hyponatremia (125-134 mEq/L) was present in 615 (28.3%) and severe hyponatremia (<125 mEq/L) in 65 (3.0%). Serum sodium had no impact on survival up to 90 days after OLT (multivariate hazard ratio = 1.00, P = 0.99). Patients with severe hyponatremia tended to have a longer stay in the ICU (median = 4.5 days) and hospital (17.0 days) compared to normonatremic recipients (median ICU stay = 3.0 days, hospital stay = 14.0 days; P = 0.02 and 0.08, respectively). There were 10 subjects that developed CPM, with an overall incidence of 0.5%. Although infrequent, the incidence of CPM did correlate with serum sodium levels (P < 0.01). Conclusion: Pre-OLT serum sodium does not have a statistically significant impact on survival following OLT. The incidence of CPM correlates with hyponatremia, although its overall incidence is low. Incorporation of serum sodium in organ allocation may not adversely affect the overall post-OLT outcome. (Hepatology 2009;49:1610–1615.)
Fibrin accumulation plays a critical role in the sensitization to lipopolysaccharide-induced liver injury caused by ethanol in mice #
Authors: Beier Juliane I. , Luyendyk James P. , Guo Luping , von Montfort Claudia , Staunton Donald E. , Arteel Gavin E.
Published: January 2009

The early stages of alcohol-induced liver injury involve chronic inflammation. Whereas mechanisms by which this effect is mediated are not completely understood, it is hypothesized that enhanced sensitivity to circulating lipopolysaccharide (LPS) contributes to this process. It has recently been shown that ethanol induces activation of plasminogen activator inhibitor-1 (PAI-1). PAI-1 causes fibrin accumulation in liver by inhibiting degradation of fibrin (fibrinolysis). LPS also enhances fibrin accumulation by activating the coagulation cascade. It was therefore hypothesized that ethanol will synergistically increase fibrin accumulation caused by LPS, enhancing liver damage. Accordingly, the effect of ethanol pretreatment on LPS-induced liver injury and fibrin deposition was determined in mice. Ethanol enhanced liver damage caused by LPS, as determined by plasma parameters and histological indices of inflammation and damage. This effect was concomitant with a significant increase in PAI-1 expression. Extracellular fibrin accumulation caused by LPS was also robustly increased by ethanol preexposure. Coadministration of the thrombin inhibitor hirudin or the MEK (mitogen-activated protein kinase) inhibitor U0126 significantly attenuated the enhanced liver damage caused by ethanol preexposure; this protection correlated with a significant blunting of the induction of PAI-1 caused by ethanol/LPS. Furthermore, thrombin/MEK inhibition prevented the synergistic effect of ethanol on the extracellular accumulation of fibrin caused by LPS. Similar protective effects on fibrin accumulation were observed in tumor necrosis factor receptor 1 (TNFR-1)−/−mice or in wild-type injected with PAI-1-inactivating antibody.Conclusion:These results suggest that enhanced LPS-induced liver injury caused by ethanol is mediated, at least in part, by fibrin accumulation in livers, mediated by an inhibition of fibrinolysis by PAI-1. These results also support the hypothesis that fibrin accumulation may play a critical role in the development of early alcohol-induced liver injury. (Hepatology 2009.)
Hepatitis C virus core protein triggers hepatic angiogenesis by a mechanism including multiple pathways #
Authors: Hassan Mohamed , Selimovic Denis , Ghozlan Hanan , Abdel-kader Ola
Published: January 2009

Chronic hepatitis C virus (HCV) infection is associated with the production of serum cytokines, including transforming growth factor (TGF)-β2. Despite the occurrence of hepatic angiogenesis in liver conditions, the role of HCV proteins in this context is currently unknown. We demonstrated that the development of hepatic neoangiogenesis in patients infected with HCV is associated with the expression of TGF-β2 and vascular endothelial growth factor (VEGF) and with activation of endothelial cells, as evidenced by CD34 expression. The analysis of liver biopsies of HCV-positive and HCV-negative patients using immunostaining showed significant elevation of TGF-β2, VEGF, and CD34 expression in patients who were HCV-positive. Using an HCV established culture system, we confirmed further the production of both TGF-β2 and VEGF proteins, in the hepatoma cell lines HepG2 and Huh7 by transfection with full-length HCV RNA (JFH1) or by the regulated expression of core. In addition, regulated expression of core protein in HepG2 or Huh7 cells was found to induce expression and activation of the transcription factor E2F1 and apoptosis signal-regulating kinase 1 (ASK1), activation of c-jun-N-terminal kinase (JNK) and p38, and extracellular-regulated kinase (ERK), and transcription factors activator protein 1 (AP-1), activating transcription factor 2 (ATF-2), cyclic adenosine monophosphate response element binding (CREB), E2F1, hypoxia inducing factor 1 alpha (HIF-1α), and specificity protein 1. Furthermore, data obtained from inhibitor experiments revealed the importance of E2F1 and ASK1 in the modulation of core-induced activation of JNK and p38 pathways and suggested an essential role for JNK, p38, and ERK pathways in the regulation of core-induced production of TGF-β2 and VEGF proteins. Thus, our data provide insight into the molecular mechanisms whereby core protein mediates the development of hepatic angiogenesis in patients with chronic HCV infection. (Hepatology 2009.)
Motor acquisition rate in Brazilian infants
Authors: Lopes Virlaine Bardella , de Lima Carolina Daniel , Tudella Eloisa
Published: January 2009

This study used the Alberta Infant Motor Scale (AIMS) with the aim of characterizing motor acquisition rate in 70 healthy 0–6‐month‐old Brazilian infants, as well as comparing both emergence (initial age) and establishment (final age) of each skill between the study sample and the AIMS normative data. New motor skills were continuously acquired from 0 to 6 months of age by the Brazilian infants, but their acquisition rate was non‐linear. When compared to the AIMS sample, Brazilian infants achieved lower percentiles, and their initial age to acquire skills requiring greater antigravity demand was higher. In contrast, Brazilian infants stopped exhibiting primitive patterns earlier, and their final age to acquire antigravity skills was lower. These differences in motor development are suggested to be a consequence of different parental practices and not necessarily indicate motor delay. Thus, the AIMS normative values should be adapted to cultural particularities so as to avoid that infants are misclassified as at risk for motor delay. Furthermore, an adequate assessment of motor development should consider not only the age at which a skill is emerged, but also the age at which such a skill is established in the infant's motor repertoire. Copyright © 2009 John Wiley & Sons, Ltd.
What do infants see in faces? ERP evidence of different roles of eyes and mouth for face perception in 9‐month‐old infants
Authors: Key Alexandra P. F. , Stone Wendy , Williams Susan M.
Published: January 2009

The study examined whether face‐specific perceptual brain mechanisms in 9‐month‐old infants are differentially sensitive to changes in individual facial features (eyes versus mouth) and whether sensitivity to such changes is related to infants' social and communicative skills. Infants viewed photographs of a smiling unfamiliar female face. On 30% of the trials, either the eyes or the mouth of that face were replaced by corresponding parts from a different female. Visual event‐related potentials were recorded to examine face‐sensitive brain responses. Results revealed that increased competence in expressive communication and interpersonal relationships was associated with a more mature response to faces, as reflected in a larger occipito‐temporal N290 with shorter latency. Both eye‐ and mouth changes were detected, though infants derived different information from these features. Eye changes had a greater impact on the face perception mechanisms and were not correlated with social or communication development, whereas mouth changes had a minimal impact on face processing but were associated with levels of language and communication understanding. Copyright © 2009 John Wiley & Sons, Ltd.
Evaluation of the osteogenic potential and vascularization of 3D poly(3)hydroxybutyrate scaffolds subcutaneously implanted in nude rats
Authors: Rentsch Claudia , Rentsch Barbe , Breier Annette , Hofmann Andre , Manthey Suzanne , Scharnweber Dieter , Biewener Achim , Zwipp Hans
Published: January 2009

The aim of this study was to evaluate the osteogenic potential and the vascularization of embroidered, tissue engineered, and cell‐seeded 3D poly(3)hydroxybutyrate (PHB) scaffolds in nude rats. Collagen I (coll I)‐ and collagen I/chondroitin sulfate (coll I/CS)‐coated PHB scaffolds were seeded with human mesenchymal stem cells (hMSCs). Proliferation and differentiation were characterized by different biochemical assays in vitro. For animal experiments, the cells were cultivated on coll I‐ or coll I/CS‐coated scaffolds and either expanded or osteogenically differentiated. Scaffolds were piled up to create a 3D scaffold pad and implanted subcutaneously into nude rats. In vitro hMSC showed proliferation and differentiation on PHB scaffolds. Alkaline phosphatase (ALP) and calcium increased in the differentiation medium and in the presence of coll I/CS. In vivo blood vessels were found in the scaffold‐stack. Histological/immunohistological analyses of explanted scaffolds showed osteogenic markers such as osteopontin, osteonectin, and coll I around the PHB fibers. Coll I/CS‐coated scaffolds with expanded hMSC showed higher values of ALP and calcium than the other combinations. Embroidered PHB scaffolds, coated with extracellular matrix components, provided an adequate environment and, therefore, a template for hMSC which could be differentiated in osteogenic direction. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Nerve growth factor promotes differentiation of odontoblast‐like cells
Authors: Arany Szilvia , Koyota Souichi , Sugiyama Toshihiro
Published: January 2009

Contemporary strategies in tooth repair markedly rely on the newest findings on the cellular and biological components of dental development. Among several identified bioactive molecules, neurotrophins were recently proposed to affect tooth germ cell proliferation, differentiation, and cell–extracellular matrix interactions. The present study attempted to explore the effect of nerve growth factor (NGF) on a spontaneously immortalized dental papilla mesenchymal cell line. NGF induced differentiation of odontoblast‐lineage cells with subsequent biomineralization in vitro. Here we showed that normalized transcript levels of tissue‐specific markers such as DSPP and DMP1 were elevated significantly, indicating cell differentiation and maturation processes. We performed innovative gene expression analysis of TM14, a matricellular protein and novel member of the fibulin family. TM14 expression followed a pattern similar to that of DMP1, which suggests its important role in cell–matrix and intercellular interactions during dentin calcification. Alkaline phosphatase enzyme assay confirmed the extracellular matrix calcifications in NGF‐supplemented groups. Thus, NGF was characterized as a potent promoter of mineralization during dentin formation. For the first time, we included TM14 in odontoblast genotype analysis and proved that NGF also promotes in vitro odontoblast differentiation. Collectively, these results highlight the importance of NGF during tooth morphogenesis, as well as urge the elaboration of complex epithelial–mesenchymal tissue cultures, where further elucidation of the signaling factor network could be completed. J. Cell. Biochem. 106: 539–545, 2009. © 2009 Wiley‐Liss, Inc.
Gastrointestinal pathology in a mouse model of mucopolysaccharidosis type IIIA
Authors: Roberts Ainslie L.K. Derrick , Howarth Gordon S. , Liaw Wan Chin , Moretta Simon , Kritas Stamatiki , Lymn Kerry A. , Yazbeck Roger , Tran Cuong , Fletcher Janice M. , Butler Ross N. , Byers Sharon
Published: January 2009

Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused by a deficiency in sulphamidase (NS), a lysosomal enzyme required for the degradation of heparan sulphate glycosaminoglycans (gags). The MPS IIIA mouse is a naturally occurring model that accurately reflects the human pathology and disease course. It displays primarily central nervous system pathology accompanied by widespread accumulation of gag in somatic tissues. MPS IIIA mice exhibit greater bodyweight gain than normal littermates and attain a higher mature bodyweight. In this study, gastrointestinal morphology and function was characterised in the IIIA mouse. Stomach and duodenum weight increased in MPS IIIA mice and duodenum length also increased. An increased submucosal thickness was observed in MPS IIIA intestine compared to normal mice and lysosomal storage of gag was observed in this region. Storage was also observed in the lamina propria of the villus tip. All other morphometric measurements including villus height and crypt depth fell within the normal range. The gastric emptying half‐life of solid and liquid meals decreased with age in normal mice whereas the T½ of solid meals did not alter with age in MPS IIA mice such that they were elevated above normal by 38 weeks of age. Sucrase activity was higher than normal in MPS IIIA at all ages tested. These abnormalities in GI structure and function observed in MPS IIIA may contribute to weight gain in this disorder. J. Cell. Physiol. 219: 259–264, 2009. © 2009 Wiley‐Liss, Inc.
CDK inhibitors selectively diminish cell cycle controlled activation of the histone H4 gene promoter by p220NPAT and HiNF‐P
Authors: Mitra Partha , Ghule Prachi N. , van der Deen Margaretha , Medina Ricardo , Xie Rong‐lin , Holmes William F. , Ye Xin , Nakayama Keiichi I. , Harper J. Wade , Stein Janet L. , Stein Gary S. , van Wijnen Andre J.
Published: January 2009

Cell cycle progression into S phase requires the induction of histone gene expression to package newly synthesized DNA as chromatin. Cyclin E stimulation of CDK2 at the Restriction point late in G1 controls both histone gene expression by the p220NPAT/HiNF‐P pathway and initiation of DNA replication through the pRB/E2F pathway. The three CDK inhibitors (CKIs) p21CIP1/WAF1, p27KIP1, and p57KIP2 attenuate CDK2 activity. Here we find that γ‐irradiation induces p21CIP1/WAF1 but not the other two CKIs, while reducing histone H4 mRNA levels but not histone H4 gene promoter activation by the p220NPAT/HiNF‐P complex. We also show that p21CIP1/WAF1 is less effective than p27KIP1 and p57KIP2 in inhibiting the CDK2 dependent phosphorylation of p220NPAT at subnuclear foci and transcriptional activation of histone H4 genes. The greater effectiveness of p57KIP2 in blocking the p220NPAT/HiNF‐P pathway is attributable in part to its ability to form a specific complex with p220NPAT that may suppress CDK2/cyclin E phosphorylation through direct substrate inhibition. We conclude that CKIs selectively control stimulation of the histone H4 gene promoter by the p220NPAT/HiNF‐P complex. J. Cell. Physiol. 219: 438–448, 2009. © 2009 Wiley‐Liss, Inc.
Cytotoxicity induced by inhibition of thioredoxin reductases via multiple signaling pathways: Role of cytosolic phospholipase A2α‐dependent and ‐independent release of arachidonic acid
Authors: Kurosawa Takeshi , Nakamura Hiroyuki , Yamaura Erika , Fujino Hiromichi , Matsuzawa Yasuo , Kawashima Tatsuo , Murayama Toshihiko
Published: January 2009

The thioredoxin (Trx) system, comprising Trx, the selenoprotein thioredoxin reductase (TrxR), and NADPH, functions as an antioxidant system. Trx has various biological activities including growth control and anti‐apoptotic properties, and the Trx system offers a target for the development of drugs to treat and/or prevent cancer. We evaluated the role of TrxR inhibition in the release of arachidonic acid (AA), cell toxicity, and intracellular signaling pathways in L929 mouse fibrosarcoma cells. Treatment with 1‐chloro‐2,4‐dinitrobenzene (DNCB, an inhibitor of TrxR) under conditions involving limited inhibition of TrxR activity in cells, released AA before causing cytotoxicity. Treatment with an inhibitor of p38 kinase, a downstream enzyme of the apoptosis signal‐regulating kinase 1 pathway, and pyrrophenone (an inhibitor of α‐type cytosolic phospholipase A2, cPLA2α) partially but significantly decreased the DNCB‐induced release of AA and cell death. The responses were much weaker in cPLA2α knockdown L929 cells. Exogenously added AA showed cytotoxicity. DNCB increased intracellular reactive oxygen species (ROS) levels, and butylated hydroxyanisole (an antioxidant) reduced DNCB‐induced ROS formation and cell toxicity but not the phosphorylation of p38 kinase and release of AA. Auranofin, another inhibitor of TrxR having a different formula, released AA resulting in toxicity in L929 cells. DNCB caused the release of AA and cytotoxicity in A549 human lung carcinoma cells, and caused p38 kinase‐dependent toxicity in PC12 rat pheochromocytoma cells. Our data suggest that a dysfunctional Trx system triggers multiple signaling pathways, and that the AA released by cPLA2α‐dependent and ‐independent pathways is important to cytotoxicity. J. Cell. Physiol. 219: 606–616, 2009. © 2009 Wiley‐Liss, Inc.
Thyroid hormone treatment of cultured chondrocytes mimics in vivo stimulation of collagen X mRNA by increasing BMP 4 expression
Authors: Lassová Luisa , Niu Zeling , Golden Eleanor B. , Cohen Arthur J. , Adams Sherrill L.
Published: January 2009

During endochondral bone formation, chondrocytes undergo terminal differentiation, during which the rate of proliferation decreases, cells become hypertrophic, and the extracellular matrix is altered by production of collagen X, as well as proteins required for matrix mineralization. This maturation process is responsible for most longitudinal bone growth, both during embryonic development and in postnatal long bone growth plates. Among the major signaling molecules implicated in regulation of this process are the positive regulators thyroid hormone (T3) and bone morphogenetic proteins (BMPs). Both T3 and BMPs are essential for endochondral bone formation and cannot compensate for each other, suggesting interaction of the two signaling pathways. We have analyzed the temporal and spatial expression patterns of numerous genes believed to play a role in chondrocyte maturation. Our results show that T3 stimulates collagen X gene expression in cultured chondrocytres with kinetics and magnitude similar to those observed in vivo. Stimulation of collagen X gene expression by T3 occurs only after a significant delay, implying that this hormone may act indirectly. We show further that T3 rapidly stimulates production of BMP 4, concomitant with a decrease in the BMP inhibitor Noggin, potentially resulting in a net increase in BMP signaling. Finally, inhibition of BMP signaling with exogenous Noggin prevents T3 stimulation of collagen X expression, indicating that BMP signaling is essential for this process. These data position thyroid hormone at the top of a T3/BMP cascade, potentially explaining why both pathways are essential for chondrocyte maturation. J. Cell. Physiol. 219: 595–605, 2009. © 2009 Wiley‐Liss, Inc.
p53‐mediated regulation of cell cycle progression: Pronounced impact of cellular microenvironment
Authors: Schmid Gerald , Kramer Matthias P. , Węsierska‐Gądek Józefa
Published: January 2009

Data on the biological effects of some overexpressed oncogenes and their cooperation with cellular factors are, at least partially, contradictory. There are reports on the strong pro‐apoptotic action of temperature‐sensitive (ts) p53135val in transformed cells at permissive temperature. However, in our experience very high levels of p53135val induce in transformed rat cells at permissive temperature cell cycle arrest but not apoptosis. Comparison of the experimental protocols reveals that cells used for transfection strongly differ. Therefore, we decided to explore the impact of primary cells used for generation of cell clones on the biological effects evoked by p53 and c‐Ha‐Ras. In the present study, we used primary rat cells (RECs) isolated from rat embryos of different age: at 13.5 gd (y) and 15.5 gd (o). We immortalized rat cells using ts p53135val mutant and additionally generated transformed cells after co‐transfection with oncogenic Ras. The RECs were transfected with a constitutively activated Ha‐Ras protein, a mutation that is found in a wide variety of human tumors. The ts p53135Val mutant, switching between wild‐type (wt) and mutant conformation, offers the possibility to study the escape from p53‐mediated cell cycle control in a model of malignant transformation in cells with the same genetic background. Surprisingly, the kinetics of cell proliferation at non‐permissive temperature and that of cell cycle arrest at 32°C strongly differed between cell clones established from yRECs and oRECs, thereby indicating that overexpression of genes such as ts p53135Val mutant and oncogenic‐Ha‐Ras does not fully override the intrinsic cellular program. J. Cell. Physiol. 219: 459–469, 2009. © 2009 Wiley‐Liss, Inc.
Prolactin's role in the early stages of liver regeneration in rats
Authors: Olazabal Isabel M. , Muñoz Jaime A. , Rodríguez‐Navas Carmen , Alvarez Luis , Delgado‐Baeza Emilio , García‐Ruiz Josefa P.
Published: January 2009

Liver regeneration after partial hepatectomy (PHx) is a complex process that is regulated by hemodynamic changes, the modulation of cytokines and growth factors, and the activation of immediate early transcription factors that lead to a round of hepatocyte mitosis. Among the factors involved, the pituitary hormone prolactin (PRL) has been shown to induce a hepatotrophic response after partial hepatectomy similar to that caused by phorbol esters; and in isolated hepatocytes PRL triggers a mitogenic response. However, it is becoming clear that PRL exerts a dual role acting in proliferation and differentiation processes. In this work, we have assessed the role of PRL in the early stages of liver regeneration in rats. To this end, three groups of rats were compared: Sham operated, regenerant and regenerant with PRL i.p. administration. Results show that PRL administration prior to partial hepatectomy caused an increase in the binding activity of several transcription factors involved in cell proliferation: AP‐1, c‐Jun and STAT‐3, and in liver‐specific differentiation and maintenance of energetic metabolism: CEBPα, HNF‐1, HNF‐4 at early time points and at later time points HNF‐3. Hepatic sections show that PRL administration increases the number of proliferating cells within 5 h post‐partial hepatectomy. The mRNA of the angiogenic and survival factors VEGF and HIF‐1α, was also induced by PRL treatment. Data indicate that PRL triggers, either directly or indirectly, an acceleration of liver regeneration, preserving liver function and fulfilling a hepatoprotective role. J. Cell. Physiol. 219: 626–633, 2009. © 2009 Wiley‐Liss, Inc.
Mitochondrial localization, ELK‐1 transcriptional regulation and growth inhibitory functions of BRCA1, BRCA1a, and BRCA1b proteins
Authors: Maniccia Anna W. , Lewis Catherine , Begum Nurjahan , Xu Jingyao , Cui Jianqi , Chipitsyna Galina , Aysola Kartik , Reddy Vaishali , Bhat Ganapathy , Fujimura Yasuo , Henderson Beric , Reddy E. Shyam P. , Rao Veena N.
Published: January 2009

BRCA1 is a tumor suppressor gene that is mutated in families with breast and ovarian cancer. Several BRCA1 splice variants are found in different tissues, but their subcellular localization and functions are poorly understood at the moment. We previously described BRCA1 splice variant BRCA1a to induce apoptosis and function as a tumor suppressor of triple negative breast, ovarian and prostate cancers. In this study we have analyzed the function of BRCA1 isoforms (BRCA1a and BRCA1b) and compared them to the wild‐type BRCA1 protein using several criteria like studying expression in normal and tumor cells by RNase protection assays, subcellular localization/fractionation by immunofluorescence microscopy and Western blot analysis, transcription regulation of biological relevant proteins and growth suppression in breast cancer cells. We are demonstrating for the first time that ectopically expressed GFP‐tagged BRCA1, BRCA1a, and BRCA1b proteins are localized to the mitochondria, repress ELK‐1 transcriptional activity and possess antiproliferative activity on breast cancer cells. These results suggest that the exon 9, 10, and 11 sequences (aa 263–1365) which contain two nuclear localization signals, p53, Rb, c‐Myc, γ‐tubulin, Stat, Rad51, Rad50 binding domains, angiopoietin‐1 repression domain are not absolutely required for mitochondrial localization and growth suppressor function of these proteins. Since mitochondrial dysfunction is a hallmark of cancer, we can speculate that the mitochondrial localization of BRCA1 proteins may be functionally significant in regulating both the mitochondrial DNA damage as well as apoptotic activity of BRCA1 proteins and mislocalization causes cancer. J. Cell. Physiol. 219: 634–641, 2009. © 2009 Wiley‐Liss, Inc.
Critical role of the N‐terminal cyclic AMP‐binding domain of Epac2 in its subcellular localization and function
Authors: Niimura Manabu , Miki Takashi , Shibasaki Tadao , Fujimoto Wakako , Iwanaga Toshihiko , Seino Susumu
Published: January 2009

cAMP is a well‐known regulator of exocytosis, and cAMP‐GEFII (Epac2) is involved in the potentiation of cAMP‐dependent, PKA‐independent regulated exocytosis in secretory cells. However, the mechanisms of its action are not fully understood. In the course of our study of Epac2 knockout mice, we identified a novel splicing variant of Epac2, which we designate Epac2B, while renaming the previously identified Epac2 Epac2A. Epac2B, which lacks the first cAMP‐binding domain A in the N‐terminus but has the second cAMP‐binding domain B of Epac2A, possesses GEF activity towards Rap1, as was found for Epac2A. Immunocytochemical analysis revealed that exogenously introduced Epac2A into insulin‐secreting MIN6 cells was localized near the plasma membrane, while Epac2B was found primarily in the cytoplasm. Interestingly, cAMP‐binding domain A alone introduced into MIN6 cells was also localized near the plasma membrane. In MIN6 cells, Epac2A was involved in triggering hormone secretion by stimulation with 5.6 mM glucose plus 1 mM 8‐Bromo‐cAMP, but Epac2B was not. The addition of a membrane‐targeting signal to the N‐terminus of Epac2B was able to mimic the effect of Epac2A on hormone secretion. Thus, the present study indicates that the N‐terminal cAMP‐binding domain A of Epac2A plays a critical role in determining its subcellular localization and potentiating insulin secretion by cAMP. J. Cell. Physiol. 219: 652–658, 2009. © 2009 Wiley‐Liss, Inc.
Hemin promotes proliferation and differentiation of endothelial progenitor cells via activation of AKT and ERK
Authors: Wang Jir‐You , Lee Yi‐Tsun , Chang Pi‐Fei , Chau Lee‐Young
Published: January 2009

Increased neovascularization is commonly observed in hemorrhagic plaques and associated with rupture of atherosclerotic lesions. This study aims to investigate whether hemin accumulated at the site of hematoma promotes neovascularization through affecting the growth and function of endothelial progenitor cells (EPCs) and the possible mechanism involved. Here we demonstrated that hemin promoted a significant increase in neovessel formation in matrigel plugs embedded in vivo and enhanced the proliferation and endothelial gene expression in EPCs in vitro. VEGF‐induced migration response and the capability to incorporate into the vascular networks were markedly enhanced in hemin‐treated EPCs. Hemin induced the phosphorylation of ERK and AKT but not p38 or JNK. The inhibition of AKT or ERK activation significantly attenuated the effect of hemin on cell proliferation. However, the enhanced migration response induced by hemin was significantly suppressed by the inhibition of AKT but not ERK. Hemin induced significant increase in reactive oxygen species (ROS) production and hemin‐induced angiogenic response of EPCs was substantially reduced by treatment with N‐acetylcysteine. Collectively, these data support that hemin‐induced ROS mediates the activation of AKT and ERK signaling pathways, which in turn promotes the cell proliferation and function of EPCs. J. Cell. Physiol. 219: 617–625, 2009. © 2009 Wiley‐Liss, Inc.
Chemoenzymatic synthesis: a strategy to obtain xylitol monoesters
Authors: Rufino Alessandra R. , Biaggio Francisco C. , Santos Júlio C. , de Castro Heizir F.
Published: January 2009

BACKGROUND: Fatty acid sugar esters are used as non‐ionic surfactants in cosmetics, foodstuffs and pharmaceuticals. In particular, monoesters of xylitol have attracted industrial interest due to their outstanding biological activities. In this work, xylitol monoesters were obtained by chemoenzymatic synthesis, in which, first, xylitol was made soluble in organic solvent by chemo‐protecting reaction, followed by enzymatic esterification reaction using different acyl donors. A commercial immobilized Candida antartica lipase was used as catalyst, and reactions with pure xylitol were carried out to generate data for comparison.

RESULTS: t‐BuOH was found to be the most suitable solvent to carry out esterification reactions with both pure and protected xylitol. The highest yields were obtained for reactions carried out with pure xylitol, but in this case by‐products, such as di‐ and tri‐esters isomers were formed, which required a multi‐step purification process. For the systems with protected xylitol, conversions of 86%, 58% and 24% were achieved using oleic, lauric and butyric acids, respectively. The structures of the monoesters were confirmed by 13C‐ and 1H‐NMR and microanalysis.

CONCLUSION: The chemoenzymatic synthesis of xylitol monoesters avoided laborious downstream processing when compared with reactions performed with pure xylitol. Monoesters production from protected xylitol was shown to be a practical, economical, and clean route for this process, allowing a simple separation, because there are no other products formed besides xylitol monoesters and residual xylitol. Copyright © 2009 Society of Chemical Industry
Ozonation of complex industrial park wastewater: effects on the change of wastewater characteristics
Authors: Fanchiang Jen‐Mao , Tseng Dyi‐Hwa , Guo Gia‐Luen , Chen Hsi‐Jien
Published: January 2009

BACKGROUND: Ozonation of complex industrial park wastewater was carried out in a semi‐batch reactor. The variation of wastewater characteristics was evaluated based on the analysis of 5‐day biochemical oxygen demand (BOD5) concentration, BOD5/chemical oxygen demand (COD) ratio, COD fractionation, and dissolved organic carbon (DOC) molecular size distribution before and after ozonation.

RESULTS: The experimental results indicated that low efficiency of COD removal with increasing tendency of BOD5 concentration generally appeared after ozonation. Also, the BOD5/COD ratio increased from an initial of 0.27 to a maximum of 0.38. The COD fractionation tests revealed that most of the inert soluble COD was transformed to biodegradable soluble COD at 30 min of reaction time. Additionally, the DOC molecular size distribution tests showed that the fraction larger than 500 kDa was significantly decreased and the fraction smaller than 2 kDa was increased when the reaction time was prolonged to 240 min.

CONCLUSION: This study verified that partial oxidation of the complex industrial park wastewater by ozonation could enhance wastewater biodegradability. The biodegradability enhancement was primarily because the inert soluble COD fraction was converted to the biodegradable soluble COD and the high molecular weight fraction of DOC was shifted toward the low molecular weight fraction. Copyright © 2009 Society of Chemical Industry
Glutathione peroxidase overexpression does not rescue impaired neurogenesis in the injured immature brain
Authors: Potts Matthew B. , Rola Radoslaw , Claus Catherine P. , Ferriero Donna M. , Fike John R. , Noble‐Haeusslein Linda J.
Published: January 2009

Traumatic brain injury (TBI) is a leading cause of disability among young children and is associated with long‐term cognitive deficits. These clinical findings have prompted an investigation of the hippocampus in an experimental model of trauma to the developing brain at postnatal day (p21). Previous studies using this model have revealed a progressive loss of neurons in the hippocampus as brain‐injured animals mature to young adulthood. Here we determined whether this hippocampal vulnerability is likewise reflected in altered neurogenesis and whether the antioxidant glutathione peroxidase (GPx) modulates neurogenesis during maturation of the injured immature brain. Male transgenic mice that overexpress GPx and wild‐type littermates were subjected to controlled cortical impact or sham surgery on p21. At 2 weeks postinjury, the numbers of proliferating cells and immature neurons within the subgranular zone were measured by using Ki‐67 and doublecortin, respectively. Bromodeoxyuridine (BrdU) was used to label dividing cells beginning 2 weeks postinjury. Survival (BrdU+) and neuronal differentiation (BrdU+/NeuN+) were then measured 4 weeks later via confocal microscopy. Two‐way ANOVA revealed no significant interaction between genotype and injury. Subsequent analysis of the individual effects of injury and genotype, however, showed a significant reduction in subgranular zone proliferation (Ki‐67) at 2 weeks postinjury (P = 0.0003) and precursor cell survival (BrdU+) at 6 weeks postinjury (P = 0.016) and a trend toward reduced neuronal differentiation (BrdU+/NeuN+) at 6 weeks postinjury (P = 0.087). Overall, these data demonstrate that traumatic injury to the injured immature brain impairs neurogenesis during maturation and suggest that GPx cannot rescue this reduced neurogenesis. © 2009 Wiley‐Liss, Inc.
NMDA receptor–dependent signaling pathways that underlie amyloid β‐protein disruption of LTP in the hippocampus
Authors: Yamin Ghiam
Published: January 2009

Alzheimer's disease (AD), the most common neurodegenerative disease in the elderly population, is characterized by the hippocampal deposition of fibrils formed by amyloid β‐protein (Aβ), a 40‐ to 42‐amino‐acid peptide. The folding of Aβ into neurotoxic oligomeric, protofibrillar, and fibrillar assemblies is believed to mediate the key pathologic event in AD. The hippocampus is especially susceptible in AD and early degenerative symptoms include significant deficits in the performance of hippocampal‐dependent cognitive abilities such as spatial learning and memory. Transgenic mouse models of AD that express C‐terminal segments or mutant variants of amyloid precursor protein, the protein from which Aβ is derived, exhibit age‐dependent spatial memory impairment and attenuated long‐term potentiation (LTP) in the hippocampal CA1 and dentate gyrus (DG) regions. Recent experimental evidence suggests that Aβ disturbs N‐methyl‐D‐aspartic acid (NMDA) receptor–dependent LTP induction in the CA1 and DG both in vivo and in vitro. Furthermore, these studies suggest that Aβ specifically interferes with several major signaling pathways downstream of the NMDA receptor, including the Ca2+‐dependent protein phosphatase calcineurin, Ca2+/calmodulin‐dependent protein kinase II (CaMKII), protein phosphatase 1, and cAMP response element–binding protein (CREB). The influence of Aβ on each of these downstream effectors of the NMDA receptor is reviewed in this article. Additionally, other mechanisms of LTP modulation, such as Aβ attenuation of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor currents, are briefly discussed. © 2009 Wiley‐Liss, Inc.
Disposition of axonal caspr with respect to glial cell membranes: Implications for the process of myelination
Authors: Pedraza Liliana , Huang Jeffrey K. , Colman David
Published: January 2009

Neurofascin‐155 (NF155) and caspr are transmembrane proteins found at discrete locations early during development of the nervous system. NF155 is present in the oligodendrocyte cell body and processes, whereas caspr is on the axonal surface. In mature nerves, these proteins are clustered at paranodes, flanking the node of Ranvier. To understand how NF155 and caspr become localized to the paranodal regions of myelinated nerves, we have studied their distribution over time in myelinating cultures. Our observations indicate that these two proteins are recruited to the cell surface at the contact zone between axons and oligodendrocytes, where they trans‐interact. This association explains the early pattern of caspr distribution, a helical coil that winds around the axon, resembling the turns of the myelin sheath. Caspr, an axonal membrane protein, therefore seems to move in register with the overlying myelinating cell via its interactions with myelin proteins. We suggest that NF155 is the glial cell membrane protein responsible for caspr distribution. The pair act as interacting partners on either side of the axoglial contact area. Most likely, there are other proteins on the axonal surface whose distribution is equally influenced by interaction with the nascent myelin sheath. The fact that caspr follows the movement of the spiraling membrane has a direct affect on the interpretation of the way in which myelin is formed. © 2009 Wiley‐Liss, Inc.