bluuebunny/crossref_metadata_2025_split huggingface dataset:
Static magnetic fields‐induced bone sialoprotein (BSP) expression is mediated through FGF2 response element and pituitary‐specific transcription factor‐1 motif
Authors: Shimizu Emi , Matsuda‐Honjyo Yuko , Samoto Hiroshi , Saito Ryoichiro , Nakajima Yu , Nakayama Youhei , Kato Naoko , Yamazaki Muneyoshi , Ogata Yorimasa 
Published: March 2004

AbstractBone sialoprotein (BSP) is a sulfated and phosphorylated glycoprotein found almost exclusively in mineralized connective tissues. Recent studies on the developmental expression of BSP mRNA and temporo‐spatial appearance of the protein during bone formation in vivo and in vitro have demonstrated that BSP is expressed by differentiated osteoblasts, and that it may function in the initial nucleation of hydroxyapatite crystals in de novo bone formation. Physical forces may play a fundamental role in the regulation of cell function in bone, but little is known about how cells are able to sense mechanical loads and signal transduction. Magnetic fields of sufficient magnitude have been shown to affect various biologic systems at organ, tissue, cellular, and subcellular levels. In the present study, rat osteosarcoma‐derived osteoblast‐like cells, UMR 106, were used to assess the effect of static magnetic fields (SMF) on gene transcription of BSP. In our culture system, application of 300 and 800 Gauss SMF increased BSP mRNA levels after 24 h stimulation. To determine the molecular basis of the transcriptional regulation of BSP gene transcription by SMF, we conducted transient transfection analyses with chimeric constructs of the rat BSP gene promoter linked to a luciferase (LUC) reporter gene. SMF (300 and 800 Gauss) increased expression of the construct (pLUC3; −116 to +60) after 24 h treatment. Further deletion analysis of the BSP promoter showed that a region within nt −116 to −84 was targeted by SMF, the effect of which was inhibited by the tyrosine kinase inhibitor herbimycin A (HA). Mutations (2 bp) were made in an inverted CCAAT box between nt −50 and −46, a cyclicAMP response element (CRE; between nt −75 and −68), a fibroblast growth factor‐2 response element (FRE; −92 to −85), and a pituitary‐specific transcription factor‐1 motif (Pit‐1; nt −111 to −105) within the pLUC3 construct. Transcriptional stimulation by SMF was almost completely abrogated in constructs that included 2‐bp mutations in the FRE and Pit‐1. Binding of nuclear proteins to a radiolabeled FRE was increased and that to a Pit‐1 was decreased in nuclear extracts prepared from SMF‐stimulated UMR 106 cells. Further, the stimulatory and inhibitory effects of SMF on FRE and Pit‐1 DNA‐protein complexes were completely abolished by HA treatment. These studies, therefore, show that SMF increases BSP transcription through a tyrosine kinase‐dependent pathway and that the SMF effects are mediated through juxtaposed FRE and Pit‐1elements in the proximal promoter of the BSP gene. © 2004 Wiley‐Liss, Inc.
ATP‐dependent nucleosome remodeling complexes: Enzymes tailored to deal with chromatin
Authors: Sif Saïd 
Published: March 2004

AbstractChromatin remodeling complexes play a central role in the control of nuclear processes that utilize genomic DNA as a template including transcription, replication, recombination, and repair. Modulation of chromatin structure is mediated by a wide variety of enzymes which can affect nucleosome stability by either disrupting histone‐DNA contacts or by covalently modifying histones and/or DNA. Although the biochemical properties of most chromatin‐modifying enzymes have been well characterized and links between histone and DNA‐modifying enzymes and ATP‐dependent chromatin remodeling complexes have been established, the importance of their concerted action has just begun to emerge. As more and more genes are examined, new rules are being established about their transcriptional regulation, and it is becoming clear that diverse mechanisms are used to modify chromatin and either promote or hinder accessibility to DNA and histones. Moreover, the involvement of ATP‐dependent chromatin remodelers in transcriptional regulation of cyclin genes and the association of misregulated expression of chromatin remodeling subunits with many cancers highlight the importance of chromatin remodeling complexes in the control of cell growth and proliferation. © 2004 Wiley‐Liss, Inc.
Tranferrins receptor association and endosomal localization of soluble HFE are not sufficient for regulation of cellular iron homeostasis
Authors: Laham Nihay , Rotem‐Yehudar Rinat , Shechter Chana , Coligan John E. , Ehrlich Rachel 
Published: March 2004

AbstractIron uptake and storage are tightly regulated to guarantee sufficient iron for essential cellular processes and to prevent the production of damaging free radicals. A non‐classical class I MHC molecule, the hemochromatosis factor HFE, has been shown to regulate iron metabolism, potentially via its direct interaction with the transferrin receptor (TfR). In this study, we demonstrate that a soluble β2microglobulin‐HFE monochain (sHFE) folds with β2microglobulin (β2m) and associates with the TfR, indicating that the transmembrane and cytoplasmic domains are not necessary for assembly and trafficking through the ER‐Golgi network. We also demonstrate human TfR‐specific uptake and accumulation of extracellular sHFE by treated cells. The sHFE localized to the endosomal compartment albeit we observed variation in the time taken for endosomal trafficking between different cell types. The sHFE monochain was effective in reducing Tf uptake into cells, however this did not correlate to any changes in TfR or ferritin synthesis, in contrast to the HFE‐induced increase and decrease of TfR and ferritin, respectively. These findings of incongruent sHFE activity suggest that either variation in affinity binding of sHFE to TfR prevents efficient modulation of iron‐regulated proteins or that HFE has multiple functions some of which may be independent of TfR but dependent on interactions within the endosomal compartment for effective modulation of iron metabolism. © 2004 Wiley‐Liss, Inc.
Proliferation marker pKi‐67 occurs in different isoforms with various cellular effects
Authors: Schmidt Mirko H.H. , Broll Rainer , Bruch Hans‐Peter , Finniss Susan , Bögler Oliver , Duchrow Michael 
Published: March 2004

AbstractThe Ki‐67 antigen, pKi‐67, is a commonly used proliferation marker in research and pathology. It has been recognized that the protein exists in two different splice variants that differ in one exon. In the current work, we present three new splice variants of human pKi‐67 consisting of two naturally occurring isoforms and one atypical version. Additionally, data is presented indicating that alternative splicing of the pKi‐67 N‐terminus is common in tumor cell lines. Analyzing 93 tissues mainly consisting of brain tumor specimens, we found evidence that long and short isoform can be expressed independently of each other. Induction of mitosis in human peripheral blood mononuclear cells revealed that short pKi‐67 appears earlier in the cell cycle than the long isoform and reaches its expression maximum when transcription of the latter sets in. Finally, transfection of mammalian culture cells with exon 7 (specific for the long pKi‐67 isoform and not present in the short isoform) in a tetracycline regulated expression system decreased the rate of cell proliferation without affecting the cell cycle. In summary, we present evidence that the pKi‐67 N‐terminus is differentially spliced resulting in at least five different isoforms with different functions. © 2004 Wiley‐Liss, Inc.
Promoter activity and regulation of the corneal CYP4B1 gene by hypoxia
Authors: Mastyugin Vladimir , Mezentsev Alexandre , Zhang Wen‐Xiang , Ashkar Silvia , Dunn Michael W. , Laniado‐Schwartzman Michal 
Published: March 2004

AbstractHypoxic injury to the ocular surface provokes an inflammatory response that is mediated, in part, by corneal epithelial‐derived 12‐hydroxyeicosanoids. Recent studies indicate that a cytochrome P450 (CYP) monooxygenase, identified as CYP4B1, is involved in the production of these eicosanoids which exhibit potent inflammatory and angiogenic properties. We have isolated and cloned a corneal epithelial CYP4B1 full‐length cDNA and demonstrated that the CYP4B1 mRNA is induced by hypoxia in vitro and in vivo. To further understand the molecular regulation that underlies the synthesis of these potent inflammatory eicosanoids in response to hypoxic injury, we isolated and cloned the CYP4B1 promoter region. GenomeWalker libraries constructed from rabbit corneal epithelial genomic DNA were used as templates for primary and nested PCR amplifications with gene‐ and adaptor‐specific primers. A 3.41‐kb DNA fragment of the 5′‐flanking region of the CYP4B1 promoter was isolated, cloned, sequenced, and analyzed by computer software for the presence of knowncis‐acting elements. Analysis of the promoter sequence revealed the presence of consensus DNA binding sequences for factors known to activate gene transcription in response to hypoxia including HIF‐1, NFκB, and AP‐1. Transient transfection of luciferase reporter (pGL3‐Basic) vectors containing different lengths of the CYP4B1 promoter fragment demonstrated hypoxia‐induced transcription in rabbit corneal epithelial (RCE) cells. Electrophoretic mobility shift assay (EMSA) revealed a marked induction of nuclear binding activity for the labeled HIF‐1 probe from the CYP4B1 promoter in nuclear extracts of cells exposed to hypoxia. This binding activity was due to sequence‐specific binding to the HIF‐1 oligonucleotide probe as shown by competition with excess unlabeled probe for the HIF‐1 but not with unlabeled NFκB probe. The nuclear binding activity of AP‐1 and NFκB probes from the CYP4B1 promoter was also enhanced in response to hypoxia suggesting that these transcription factors contribute to the hypoxic induction of CYP4B1 expression. The results of this study provide the first molecular mechanistic explanation for the induction of CYP4B1 and, thereby, the production of inflammatory eicosanoids in response to hypoxic injury. Further studies are needed to fully evaluate the molecular regulation of this gene during inflammation. © 2004 Wiley‐Liss, Inc.
Distinct functions of BMP4 and GDF5 in the regulation of chondrogenesis
Authors: Hatakeyama Yuji , Tuan Rocky S. , Shum Lillian 
Published: March 2004

AbstractBone morphogenetic protein 4 (BMP4) and growth/differentiation factor 5 (GDF5) are closely related protein family members and regulate early cartilage patterning and differentiation. In this study, we compared the functional outcome of their actions systematically at various stages of chondrogenesis in mouse embryonic limb bud mesenchyme grown in micromass cultures. Overall, both growth factors enhanced cartilage growth and differentiation in these cultures. Uniquely, BMP4 not only accelerated the formation and maturation of cartilaginous nodules, but also induced internodular mesenchymal cells to express cartilage differentiation markers. On the other hand, GDF5 increased the number of prechondrogenic mesenchymal cell condensation and cartilaginous nodules, without altering the overall pattern of differentiation. In addition, GDF5 caused a more sustained elevated expression level of Sox9 relative to that associated with BMP4. BMP4 accelerated chondrocyte maturation throughout the cultures and sustained an elevated level of Col10 expression, whereas GDF5 caused a transient increase in Col10 expression. Taken together, we conclude that BMP4 is instructive to chondrogenesis and induces mesenchymal cells toward the chondrogenic lineage. Furthermore, BMP4 accelerates the progression of cartilage differentiation to maturation. GDF5 enhances cartilage formation by promoting chondroprogenitor cell aggregation, and amplifying the responses of cartilage differentiation markers. These differences may serve to fine‐tune the normal cartilage differentiation program, and can be exploited for the molecular manipulation in biomimetics. Published 2004 Wiley‐Liss, Inc.
Sp1‐dependent regulation of the tissue inhibitor of metalloproteinases‐1 promoter
Authors: Lee Minhyung , Song Sun U. , Ryu Ji Kan , Suh Jun Kyu 
Published: March 2004

AbstractExtracellular matrix (ECM) remodeling is involved in many cellular properties such as division, migration, differentiation, and death. The turnover of ECM is regulated by matrix metalloproteinases (MMPs) and the MMPs are inhibited by the tissue inhibitors of metalloproteinases (TIMPs). In this study, the transcriptional regulation of the TIMP‐1 promoter was investigated. The 5′‐deletion assay showed that the region between −1,200 and −1,101 was responsible for the TIMP‐1 promoter activity. The mutations of the two Sp1 sites in this region reduced the transcription activity. In addition, the co‐transfection with antisense Sp1 oligonucleotide decreased the promoter activity, suggesting that the transcription of the TIMP‐1 promoter is mediated by Sp1. Previously, it was reported that the TIMP‐1 expression was enhanced under hypoxia. Therefore, the TIMP‐1 promoter activity was investigated with or without cobalt ion, which elicits the same physiological effect as hypoxia. The results showed that the TIMP‐1 promoter was induced in the presence of cobalt ion and that the promoter activity was regulated by Sp1 as well as HIF‐1. Therefore, this study suggests that Sp1 is involved in the regulation of the TIMP‐1 promoter in the presence of cobalt ion as well as in the basal level transcription. © 2004 Wiley‐Liss, Inc.
Nuclear matrix protein expressions in hepatocytes of normal and cirrhotic rat livers under normal and regenerating conditions
Authors: Yun Jing‐Ping , Liew Choong‐Tsek , Chew Eng Ching , Yin Xiao‐Yu , Lai Paul Bo San , Fai Yam Hin , Li H.K. Richard , Jin Mei‐Lin , Ding Ming‐Xiao , Li Ming‐Tao , Lin Han‐Liang , Lau Wan Yee 
Published: March 2004

AbstractWe explored the feasibility of studying nuclear matrix protein (NMP) expressions of the hepatocytes in normal and cirrhotic rat livers with liver regeneration after partial hepatectomy. Sixteen Wistar healthy rats were studied with experimental liver regeneration and/or liver cirrhosis. Two‐dimensional (2‐D) gel electrophoresis was used to generate these NMP compositions from these rat liver samples. Several antibodies against cytokeratin, vimentin, actin, B23, HNF4alpha, and heat shock protein 70 were used for identification by Western blot. Totally, 41 strongly stained protein spots were characterized on the 2‐D gels. Thirty‐four protein spots were detected in all of these rat livers, of which, cytokeratin, vimentin, actin, HNF4alpha, and heat shock protein 70 were identified. B23 was detected in the regenerated livers. Three protein spots (s33, s34, and s35) were detectable only in NMP preparation extracted from the regenerating rat livers after hepatectomy. Another three protein spots (s36, s37, and s38) were detectable only in NMP preparation extracted from thioacetamide‐induced cirrhotic rat livers. Under these conditions including experimental liver regeneration and/or liver cirrhosis, Over thirty higher abundance NMPs of hepatocytes were consistently expressed and considered as common and basic NMPs. Some of the NMPs are specific for liver regeneration and may play a critical role in cell proliferation and cell cycle, and some are specific for liver cirrhosis. © 2004 Wiley‐Liss, Inc.
TOR kinase and ran are downstream from PI3K/Akt in H2O2‐induced mitosis
Authors: Radisavljevic Ziv Manasija , González‐Flecha Beatriz 
Published: March 2004

AbstractHydrogen peroxide (H2O2) activates signaling cascades essential for cell proliferation via phosphatidylinositol‐3‐kinase (PI3K) and Akt. Here we show that induction of mitogenic signaling by H2O2 activates sequentially PI3K, Akt, mammalian target of rapamycin (mTOR), and Ran protein. Akt activation is followed by signaling through the mTOR kinase and upregulation of Ran in primary type II pneumocytes, a cell type implicated in the development of lung adenocarcinoma. Pretreatment of the cells with wortmannin, a specific inhibitor of PI3K, or rapamycin, a specific inhibitor of mTOR kinase, prevented H2O2‐increased mitosis. H2O2‐induced Akt ser‐473 phosphorylation and upregulation of Ran protein were prevented by wortmannin but not by rapamycin, indicating that PI3K is upstream of Akt and mTOR is downstream from Akt. Overexpression of myr‐Akt or Ran‐wt in type II pneumocytes increased Akt ser‐473 phosphorylation and mitosis in a catalase‐dependent manner, indicating that H2O2 is essential for Akt and Ran signaling. These results indicate that H2O2‐induced mitogenic signaling in primary type II pneumocytes is mediated by PI3K, Akt, mTOR‐kinase, and Ran protein. © 2004 Wiley‐Liss, Inc.
Establishment and characterization of a stable cell line to evaluate cellular Runx2 activity
Authors: Kim Hyun‐Jung , Park Hee‐Dae , Kim Jung‐Hwan , Cho Je‐Yoel , Choi Je‐Yong , Kim Jung‐Keun , Kim Hyun‐Jung , Shin Hong‐In , Ryoo Hyun‐Mo 
Published: March 2004

AbstractRunx2 is an essential transcription factor for osteoblast differentiation from early commitment step to final differentiation. Based on its crucial role in osteoblast differentiation, the transcriptional activity of Runx2 protein implies more valuable information for osteoblast differentiation than any other parameters, such as Runx2 mRNA or protein level. Thus, a sensitive, specific, and consistent method to determine the Runx2 transcriptional activity has long been expected. Here we suggest a stable cell line that carries 6xOSE2‐Luciferase reporter vector would be a good evaluation system to determine biological Runx2 transcriptional activity. The proliferation rate, cell shape, and the myogenic differentiation potential of the cloned cell line were similar to those of parental premyoblastic C2C12 cells. The cells specifically responded to Runx2 modulating agent such as FGF2. The stable cell line responded 5–6 folds more sensitively than the transiently transfected cells with Runx2. Though overexpression of any Runx gene stimulated the luciferase activity, Runx2 enhanced the reporter activity the highest. Collectively, the 6xOSE2‐luc stable cells would be a good biological evaluation system to assess the activity of extracellular Runx2 modulating stimulations as well as the signal transduction pathways involved in the stimulations. © 2004 Wiley‐Liss, Inc.
The phenomenon of quantum change
Authors: Miller William R. 
Published: March 2004

AbstractQuantum change—the subject of this issue of In Session—refers to sudden, dramatic, and enduring transformations that affect a broad range of personal emotion, cognition, and behavior. This phenomenon has been described since the beginnings of psychology, most notably by William James in Varieties of Religious Experience. Quantum changes occur both within and (mostly) outside the context of psychotherapy and show certain common features in both process and content. This introduction provides an overview of the phenomenon of quantum change, describing its essential features, two qualitative subtypes, antecedents, course, and the nature of the enduring changes that ensue. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Epiphany in autobiography: The quantum changes of Dostoevsky and Tolstoy
Authors: Bidney Martin 
Published: March 2004

AbstractThe quantum changes of Dostoevsky and Tolstoy are clarified by the partly overlapping concept of a literary epiphany. The qualities of an epiphany—intensity, resonance, and mystery—are much like the vividness and surprise of a quantum change (which also is felt to be beneficent and permanent). Epiphanic intensity and mystery reinforce the quantum attributes of love and lasting transformation in Dostoevsky's sudden memory of the motherlike tenderness of the peasant Marey. Tolstoy underlines the quantum effects of the embracing light seen inA Confession, but this epiphany is more abstract and attenuated than Dostoevsky'sDiaryepisode. Tolstoy's earlier memoir shows how the shock of identity questioning introduces a complicating factor: the trauma of remorse. Clinical implications of the two authors' quantum‐change accounts are discussed. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Quantum change and psychotherapy
Authors: Bien Thomas H. 
Published: March 2004

AbstractDeep change in psychotherapy more typically comes slowly rather than suddenly, but this difference between therapeutic change and quantum change may be one of perspective rather than substance. Psychotherapy may be understood as a kind of mindfulness practice similar to working with koans in that the client presents a life dilemma incapable of rational solution. While quantum change cannot be engineered, the psychotherapist can create an environment conducive to such transformation by producing true presence and modeling calm, concerned, sustained attention to the dilemma that precipitated treatment. Psychotherapists who also maintain a sense of their work as a high art and a way of being, and who in consequence cultivate their own emotional and spiritual development, may be more likely to create such an environment. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
De profundis: Spiritual transformations in Alcoholics Anonymous
Authors: Forcehimes Alyssa A. 
Published: March 2004

AbstractThe mechanism of change in Alcoholics Anonymous is described as “spiritual transformation.” A.A. acknowledges that such transformation can occur gradually; however, nearly all of the examples presented in the Big Book of A.A. involve discrete and sudden experiences that resemble the phenomenon of quantum change. The sequence offered describes how spiritual transformations transpire. The sequence begins with hitting bottom, recognition of inability to control the problem. A feeling of contrition follows, describing not only sorrow for the present state, but also desire for a new way. The final step is the act of surrendering one's will to a higher power. The de profundis sequence sets the process of spiritual transformation in motion, offering stabilization to sobriety. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Evil by default: The origins of dark visions
Authors: Nowinski Joseph 
Published: March 2004

AbstractThe growing body of literature on transformational change reflects an increasing interest among professionals in understanding epiphany and visionary change. However, we typically assume that such quantum changes are positive and pro‐social ones. It is equally possible for an individual to lead a life that is organized around a motivating vision that is destructive to self, others, or both. The author examines the phenomenon of “dark visions,” offering some hypotheses as to their origins. The article also offers strategies to minimize the number of individuals who choose dark visions, with all their unfortunate consequences. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Sacred changes: Spiritual conversion and transformation
Authors: Mahoney Annette , Pargament Kenneth I. 
Published: March 2004

AbstractWe use Pargament's (1997) definition of religion—“the search for significance in ways related to the sacred”—as a framework to understand spiritual conversion. Like other life‐changing transformations, spiritual conversion alters the destinations that clients perceive to be of greatest importance in life (significance) and the pathways by which clients discover what is most significant in life (search). Unlike other transformative experiences, however, spiritual conversion incorporates the third element of religion, “the sacred,” into the content of change. To illustrate these points, we discuss two theological models of spiritual conversion rooted in Christianity: a traditional model based on classic western theology and an alternative model based on feminist theology. We then compare processes of spiritual conversion to nonreligious models of transformation. We also highlight the importance for clinical work of the fit between the context of a client's life and the type of spiritual conversion experienced. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.