bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rho GTPase‐mediated cytoskeletal organization in Schlemm's canal cells play a critical role in the regulation of aqueous humor outflow facility
Authors: Kumar Janardan , Epstein David L. 
Published: November 2010

AbstractThe increased intraocular pressure (IOP) has been considered to be an increased resistance of the aqueous humor outflow through the inner wall of Schlemm's canal (SC) and/or the juxtacanalicular tissue (JCT). The Rho GTPase‐regulated actomyosin organization appears to be an important mechanistic determinant of aqueous humor outflow facility. Therefore, in this study, we have evaluated the effects of modulating Rho GTPase activity on actomyosin cytoskeletal organization, monolayer permeability/barrier function of human SC cells, and aqueous humor outflow facility in enucleated porcine eyes ex vivo. Human SC cells, isolated from cadaver eyes, were treated with either Rho GTPase activators such as thrombin and lysophosphatidic acid (LPA), or a specific inhibitor (C3‐exoenzyme) of Rho GTPases. Treatment of SC cells with thrombin and LPA led to increased formation of stress fibers, focal adhesion, and increased myosin light chain phosphorylation, whereas treatment with C3‐exoenzyme showed the opposite effects like H‐7 and ECA, known for increasing the outflow facility in porcine eyes. The findings presented here suggest that LPA and thrombin, presumably through activation of Rho GTPase‐mediated actomyosin cytoskeletal reorganization in SC cells, cause a decrease in monolayer permeability of SC cells as well as a decrease in outflow facility of porcine eyes in ex vivo. Our results suggest that decrease in aqueous humor outflow may be correlated better with the changes in cytoskeletal organizations of SC, which could be the prime locus of the outflow resistance. J. Cell. Biochem. 112: 600–606, 2011. © 2010 Wiley‐Liss, Inc.
Changes in matrix protein gene expression associated with mineralization in the differentiating chick limb‐bud micromass culture system
Authors: Teixeira Cristina C. , Xiang Jenny , Roy Rani , Kudrashov Valery , Binderman Itzhak , Mayer‐Kuckuk Philipp , Boskey Adele L. 
Published: November 2010

AbstractChick limb‐bud mesenchymal stem cells plated in high density culture in the presence of 4 mM inorganic phosphate and vitamin C differentiate and form a mineralizable matrix, resembling that of the chick growth plate. To further elucidate the mechanism that allows these cultures to form physiologic hydroxyapatite deposits, and how the process can be manipulated to gain insight into mineralization mechanisms, we compared gene expression in mineralizing (with 4 mM inorganic phosphate) and non‐mineralizing cultures (containing only 1 mM inorganic phosphate) at the start of mineralization (day 11) and after mineralization reached a plateau (day 17) using a chick specific microarray. Based on replicate microarray experiments and K‐cluster analysis, several genes associated with the mineralization process were identified, and their expression patterns confirmed throughout the culture period by quantitative RT‐PCR. The functions of bone morphogenetic protein 1, BMP1, dentin matrix protein 1, DMP1, the sodium phosphate co‐transporter, NaPi IIb, matrix metalloprotease 13. MMP‐13, and alkaline phosphatase, along with matrix protein genes (type X collagen, bone sialoprotein, and osteopontin) usually associated with initiation of mineralization are discussed. J. Cell. Biochem. 112: 607–613, 2011. © 2010 Wiley‐Liss, Inc.
Stem cell property epithelial‐to‐mesenchymal transition is a core transcriptional network for predicting cetuximab (Erbitux™) efficacy in KRAS wild‐type tumor cells
Authors: Oliveras‐Ferraros Cristina , Vazquez‐Martin Alejandro , Cufí Sílvia , Queralt Bernardo , Báez Luciana , Guardeño Raquel , Hernández‐Yagüe Xavier , Martin‐Castillo Begoña , Brunet Joan , Menendez Javier A. 
Published: November 2010

AbstractBeyond a well‐recognized effect of KRAS mutations in determining de novo inefficacy of cetuximab (CTX) in metastatic colorectal cancer, we urgently need a biomarker signature for predicting CTX efficacy in KRAS wild‐type (WT) tumors. CTX‐adapted EGFR gene‐amplified KRAS WT tumor cell populations were induced by stepwise‐chronic exposure of A431 epidermoid cancer cells to CTX. Genome‐wide analyses of 44K Agilent's whole human arrays were bioinformatically evaluated by Gene Set Enrichment Analysis (GSEA)‐based screening of the KEGG pathway database. Molecular functioning of CTX was found to depend on: (i) The occurrence of a positive feedback loop on Epidermal Growth Factor Receptor (EGFR) activation driven by genes coding for EGFR ligands (e.g., amphiregulin); (ii) the lack of a negative feedback on mitogen‐activated protein kinase (MAPK) activation regulated by dual‐specificity phosphatases (e.g., DUSP6) and; (iii) the transcriptional status of gene pathways controlling the epithelial‐to‐mesenchymal transition (EMT) and its reversal (MET) program (actin cytoskeleton and cell–cell communication—e.g., keratins—focal adhesion signaling—e.g., integrins—and EMT‐inducing cytokines – e.g., transforming growth factor‐β). Quantitative real‐time PCR, high‐content immunostaining, and flow‐cytometry analyses confirmed that CTX efficacy depends on its ability to promote: (i) Stronger cell–cell contacts by up‐regulating the expression of the epithelial markers E‐cadherin and occludin; (ii) down‐regulation of the epithelial transcriptional repressors Zeb, Snail, and Slug accompanied by restoration of cortical F‐actin; and (iii) complete prevention of the CD44pos/CD24neg/low mesenchymal immunophenotype. The impact of EGFR ligands/MAPK phosphatases gene transcripts in predicting CTX efficacy in KRAS WT tumors may be tightly linked with the ability of CTX to concurrently reverse the EMT status, a pivotal property of migrating cancer stem cells. J. Cell. Biochem. 112: 10–29, 2011. © 2010 Wiley‐Liss, Inc.
Role of endogenous TGF‐β family in myogenic differentiation of C2C12 cells
Authors: Furutani Yuuma , Umemoto Takenao , Murakami Masaru , Matsui Tohru , Funaba Masayuki 
Published: November 2010

AbstractThe present study evaluated endogenous activities and the role of BMP and transforming growth factor‐β (TGF‐β), representative members of the TGF‐β family, during myotube differentiation in C2C12 cells. Smad phosphorylation at the C‐terminal serines was monitored, since TGF‐β family members signal via the phosphorylation of Smads in a ligand‐dependent manner. Expression of phosphorylated Smad1/5/8, which is an indicator of BMP activity, was higher before differentiation, and rapidly decreased after differentiation stimulation. Differentiation‐related changes were consistent with those in the expression of Ids, well‐known BMP‐responsive genes. Treatment with inhibitors of BMP type I receptors or noggin in C2C12 myoblasts down‐regulated the expression of myogenic regulatory factors, such as Myf5 and MyoD, leading to impaired myotube formation. Addition of BMP‐2 during the myoblast phase also inhibited myotube differentiation through the down‐regulation of Myf5 and MyoD. In contrast to endogenous BMP activity, the phosphorylation of Smad2, a TGF‐β‐responsive Smad, was higher 8–16 days after differentiation stimulation. A‐83‐01, an inhibitor of TGF‐β type I receptor, increased the expression of Myf5 and MyoD, and enhanced myotube formation. The present results reveal that endogenous activities of the TGF‐β family are changed during myogenesis in a pathway‐specific manner, and that the activities are required for myogenesis. J. Cell. Biochem. 112: 614–624, 2011. © 2010 Wiley‐Liss, Inc.
Hypoxia‐mediated biological control
Authors: Cassavaugh Jessica , Lounsbury Karen M. 
Published: November 2010

AbstractWhen oxygen demand is greater than oxygen supply, cells need to rapidly adjust their metabolism in order for the tissue to survive. Oxygen sensing by an organism influences a host of processes including growth, development, metabolism, pH homeostasis, and angiogenesis. Hypoxia also contributes to a wide number of human diseases including vascular disease, inflammatory conditions and cancer. Recently, major advances have been made in understanding the response of cells and tissues to hypoxia with the goal of providing mechanistic insight and novel therapeutic targets. In this article we review both the normal biological effects of hypoxia as well as the alterations that occur in specific disease conditions with an emphasis on the cell signaling and gene transcription mechanisms that underlie the changes associated with chronic hypoxia. Comparisons of studies in the fields of cardiac ischemia and tumor angiogenesis reveal the complexities within the microenvironment that control responses to hypoxia. It is clear that more interaction between researchers in these fields will improve the development of therapies that either promote or prevent hypoxic responses. J. Cell. Biochem. 112: 735–744, 2011. © 2010 Wiley‐Liss, Inc.
Per‐1 is a specific clock gene regulated by parathyroid hormone (PTH) signaling in osteoblasts and is functional for the transcriptional events induced by PTH
Authors: Hanyu Ryo , Hayata Tadayoshi , Nagao Masashi , Saita Yoshitomo , Hemmi Hiroaki , Notomi Takuya , Nakamoto Tetsuya , Schipani Ernestina , Knonenbery Henry , Kaneko Kazuo , Kurosawa Hisashi , Ezura Yoichi , Noda Masaki 
Published: November 2010

AbstractPer‐1 is one of the clock genes and is known to regulate various biological events including bone mass determination. Parathyroid hormone is anabolic to bone while the mechanism of its action is not fully understood. Here, we examined the role of PTH on Per‐1 gene expression under osteoblast specific PTH signaling. Constitutively active PTH receptor (caPPR) expressed specifically in osteoblasts in transgenic mice activates Per‐1 gene expression in bone. This is specific as expression of other clock gene Bmal‐1 is not affected by caPPR over‐expression. Per‐1 is also expressed in osteoblastic cell line. Interestingly, Per‐1 expression is required for PTH signaling‐induced CRE dependent transcription. This is forming a positive feed back loop in the anabolic action of PTH signaling and Per‐1 in bone. These data indicate that PTH singling in osteoblasts activates Per‐1 gene expression in vivo in association with its anabolic action in bone at least in part through the regulation of transcriptional events. J. Cell. Biochem. 112: 433–438, 2011. © 2010 Wiley‐Liss, Inc.
Neuronal chromatin dynamics of imprinting in development and disease
Authors: Leung Karen N. , Chamberlain Stormy J. , Lalande Marc , LaSalle Janine M. 
Published: November 2010

AbstractEpigenetic mechanisms play essential roles in mammalian neurodevelopment and genetic mutations or chromosomal deletions or duplications of epigenetically regulated loci or pathways result in several important human neurodevelopmental disorders. Postnatal mammalian neurons have among the most structured and dynamic nuclear organization of any cell type. Human chromosome 15q11‐13 is an imprinted locus required for normal neurodevelopment and is regulated by a plethora of epigenetic mechanisms in neurons, including multiple noncoding RNAs, parentally imprinted transcription and histone modifications, large‐scale chromatin decondensation, and homologous pairing in mature neurons of the mammalian brain. Here, we describe the multiple epigenetic layers regulating 15q11‐13 gene expression and chromatin dynamics in neurons and propose a model of how noncoding RNAs may influence the unusual neuronal chromatin structure and dynamics at this locus. We also discuss the need for improved neuronal cell culture systems that model human 15q11‐13 and other neurodevelopmental disorders with epigenetic bases in order to test the mechanisms of chromatin dynamics and nuclear organization in neurons. Induced pluripotent stem cells and other stem cell technologies hold promise for improved understanding of and therapeutic interventions for multiple human neurodevelopmental disorders. J. Cell. Biochem. 112: 365–373, 2011. © 2010 Wiley‐Liss, Inc.
The effects of estrogen receptors α‐ and β‐specific agonists and antagonists on cell proliferation and energy metabolism in human bone cell line
Authors: Somjen D. , Katzburg S. , Sharon O. , Grafi‐Cohen M. , Knoll E. , Stern N. 
Published: November 2010

AbstractIn cultured human osteoblasts estradiol‐17β (E2) modulated DNA synthesis, the specific activity of creatine kinase BB (CK), 12 and 15 lipoxygenase (LO) mRNA expression and formation of 12‐ and 15‐hydroxyeicosatetraenoic acid (HETE). We now investigate the response of human bone cell line (SaOS2) to phytoestrogens and estrogen receptors (ER)‐specific agonists and antagonists. Treatment of SaSO2 with E2, 2,3‐bis (4‐hydroxyphenyl)‐propionitrile (DPN; ERβ‐specific agonist), 4,4′,4″‐[4‐propyl‐(1H)‐pyrazol‐1,3,5‐triyl] tris‐phenol (PPT; ERα‐specific agonist), biochainin A (BA), daidzein (D), genistein (G) and raloxifene (Ral) showed increased DNA synthesis and CK. Ral inhibited completely all stimulations except DPN and to some extent D. The ERα‐specific antagonist methyl‐piperidino‐pyrazole (MPP) and the ERβ‐specific antagonist 4‐[2‐phenyl‐5,7‐bis (tri‐fluoro‐methyl) pyrazolo [1,5‐a]pyrimidin‐3‐yl] phenol (PTHPP) inhibited DNA synthesis, CK and reactive oxygen species (ROS) formation induced by estrogens according to their receptors affinity. The LO inhibitor baicaleine inhibited only E2, DPN and G's effects. E2 and Ral unlike all other compounds had no effect on ERα mRNA expression, while ERβ mRNA expression was stimulated by all compounds. All compounds modulated the expression of 12LO and 15LO mRNA, except E2, PPT and Ral for 12LO, and 12‐ and 15‐HETE productions and stimulated ROS formation which was inhibited by NADPH oxidase inhibitors diphenyleneiodonium chloride (DPI) and N‐acetyl cysteine and the estrogen inhibitor ICI. DPI did not affect hormonal‐induced DNA and CK. In conclusion, we provide evidence for the separation of mediation via ERα and ERβ pathways in the effects of estrogenic compounds on osteoblasts, but the role of LO/HETE/ROS is unclear. J. Cell. Biochem. 112: 625–632, 2011. © 2010 Wiley‐Liss, Inc.
Differential roles of hypoxia inducible factor subunits in multipotential stromal cells under hypoxic condition
Authors: Tamama Kenichi , Kawasaki Haruhisa , Kerpedjieva Svetoslava S. , Guan Jianjun , Ganju Ramesh K. , Sen Chandan K. 
Published: November 2010

AbstractCell therapy with bone marrow multipotential stromal cells (MSCs) represents a promising approach to promote wound healing and tissue regeneration. MSCs expanded in vitro lose early progenitors with differentiation and therapeutic potentials under normoxic condition, whereas hypoxic condition promotes MSC self‐renewal through preserving colony forming early progenitors and maintaining undifferentiated phenotypes. Hypoxia inducible factor (HIF) pathway is a crucial signaling pathway activated in hypoxic condition. We evaluated the roles of HIFs in MSC differentiation, colony formation, and paracrine activity under hypoxic condition. Hypoxic condition reversibly decreased osteogenic and adipogenic differentiation. Decrease of osteogenic differentiation depended on HIF pathway; whereas decrease of adipogenic differentiation depended on the activation of unfolded protein response (UPR), but not HIFs. Hypoxia‐mediated increase of MSC colony formation was not HIF‐dependent also. Hypoxic exposure increased secretion of VEGF, HGF, and basic FGF in a HIF‐dependent manner. These findings suggest that HIF has a limited, but pivotal role in enhancing MSC self‐renewal and growth factor secretions under hypoxic condition. J. Cell. Biochem. 112: 804–817, 2011. © 2010 Wiley‐Liss, Inc.
Combined activin A/LiCl/Noggin treatment improves production of mouse embryonic stem cell‐derived definitive endoderm cells
Authors: Li Fuming , He Zhiying , Li Yangfang , Liu Pingyu , Chen Fei , Wang Minjun , Zhu Haiying , Ding Xiaoyan , Wangensteen Kirk J. , Hu Yiping , Wang Xin 
Published: November 2010

AbstractInduction of definitive endoderm (DE) cells is a prerequisite for the whole process of embryonic stem (ES) cells differentiating into hepatic or pancreatic progenitor cells. We have established an efficient method to induce mouse ES cell‐derived DE cells in suspension embryonic body (EB) culture. Similar to previous studies, mouse ES cell‐derived DE cells, which were defined as Cxcr4+c‐Kit+, Cxcr4+E‐cadherin+ cells or Cxcr4+PDGFRa− cells, could be induced in the serum‐free EBs at Day 4 of induction. The activations of Wnt, Nodal, and FGF signaling pathways in differentiating EBs promoted DE cell differentiation, while activation of BMP4 signaling inhibited the process. In the present study, we found that chemical activation of canonical Wnt signaling pathway by LiCl could synergize with Activin A‐mediated Nodal signaling pathway to promote induction of DE cells, and inhibition of Bmp4 signaling by Noggin along with Activin A/LiCl further improved the efficiency of DE cell differentiation. The derived DE cells were proved for their capacities to become hepatic progenitor cells or pancreatic progenitor cells. In conclusion, we significantly improved the efficiency of generating mouse ES cell‐derived DE cells by combined Activin A/LiCl/Noggin treatment. Our work will be greatly helpful to generate ES cell‐derived hepatic cells and ES cell‐derived pancreatic cells for future regenerative medicine. J. Cell. Biochem. 112: 1022–1034, 2011. © 2010 Wiley‐Liss, Inc.
Bayesian model selection for meta‐analysis of diagnostic test accuracy data: Application to Ddimer for deep vein thrombosis
Authors: Novielli Nicola , Cooper Nicola J. , Sutton Alexander J. , Abrams Keith R. 
Published: November 2010

AbstractA number of statistical models have been developed for meta‐analysis (MA) of diagnostic test (DT) accuracy data. Here we consider these alternative MA models, explore the relationships between them, and consider the use of the deviance information criteria (DIC) to decide which is the most appropriate model for a given dataset. A Bayesian statistical approach is adopted throughout. The alternative MA models are applied to a dataset of 198 assays of Ddimer to diagnose deep vein thrombosis. In this example, based on the DIC, a bivariate random effects model for sensitivity and specificity fitted the data best. When considering the inclusion of study level covariates, allowing sensitivity to vary by study setting further improved the fit of the model. The model fitting approach is then repeated for a subset of the data, which highlights the less decisive results obtained when using the DIC with a more limited dataset. Formal approaches to model selection are often overlooked in an MA context; however, they offer sensible rationale to the analysis, particularly for complex models such as those proposed for DT accuracy. Specifically, the use of the DIC statistic appears to be well suited for deciding between potentially complex mixed‐effect MA models, possibly including covariates. Copyright © 2010 John Wiley & Sons, Ltd.
Family functioning and posttraumatic stress symptoms in youth and their parents after unintentional pediatric injury
Authors: Coakley Rachael M. , Forbes Peter W. , Kelley Susan Douglas , LeBovidge Jennifer , Beasley Pamela , DeMaso David R. , Waber Deborah P. 
Published: November 2010

AbstractThis study examined the association between family functioning and the development of posttraumatic stress symptoms (PTSS) in youth and parents following an unintentional traumatic injury of a child. Fifty‐one parent–child dyads completed questionnaires and a structured interview assessing PTSS and family functioning. Multiple regression analyses were applied to evaluate the contribution of family functioning to the development of PTSS after controlling for demographic characteristics and known predictors. Family functioning had both direct and moderating influences on the development of PTSS in parents. We were unable to demonstrate a systematic impact of family functioning on the development of PTSS in children from the same families.
The dynamics of relational and contractual governance mechanisms in knowledge sharing of collaborative R&D projects
Authors: Olander Heidi , Hurmelinna‐Laukkanen Pia , Blomqvist Kirsimarja , Ritala Paavo 
Published: November 2010

AbstractThe purpose of this paper is to explore the dynamics of relational and contractual governance mechanisms in vertical buyer–supplier R&D projects requiring both knowledge sharing and protection. Prior literature has recognised the mutual impact of relational and contractual governance on knowledge sharing, but treats the linkages in a rather static way. This research introduces a more explicit process perspective, and combines four concepts: trust, relational norms, contracts and intellectual property rights (IPRs). The paper concentrates on the roles and interplay of both types of mechanisms in the different project phases. We collected qualitative interview data from four buyer–supplier R&D collaboration projects, each pair serving as a unit of analysis. Our findings indicate that both contractual and relational governance mechanisms play a role in buyer–supplier R&D collaboration but their relative importance varies according to the collaboration phase. Whereas in the exploration phase trust may even substitute contractual governance, both mechanisms support each other in the development phase. Contractual mechanisms are emphasised in the finalisation phase, although relational mechanisms also play a role. The lesson for management understanding is that both types of mechanisms should be considered simultaneously throughout the collaboration process. Copyright © 2010 John Wiley & Sons, Ltd.
Glycopolymer‐Grafted Polystyrene Nanospheres
Authors: Pfaff André , Shinde Vaishali S. , Lu Yan , Wittemann Alexander , Ballauff Matthias , Müller Axel H. E. 
Published: November 2010

AbstractThe synthesis and characterization of spherical sugar‐containing polymer brushes consisting of PS cores onto which chains of sugar‐containing polymers have been grafted via two different techniques are described. Photopolymerization in aqueous dispersion using the functional monomer MAGlc and crosslinked or non‐crosslinked PS particles covered with a thin layer of photo‐initiator yielded homogeneous glycopolymer brushes attached to spherical PS cores. As an alternative, ATRP was used to graft poly‐(N‐acetylglucosamine) arms from crosslinked PS cores. Deprotection of the grafted brushes led to water‐soluble particles that act as carriers for catalytically active gold nanoparticles. These glycopolymer chains show a high affinity to adsorb WGA whereas no binding to BSA or PNA could be detected.
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Folate‐Decorated Succinylchitosan Nanoparticles Conjugated with Doxorubicin for Targeted Drug Delivery
Authors: Sahu Sumanta Kumar , Maiti Swatilekha , Maiti Tapas Kumar , Ghosh Sudip K. , Pramanik Panchanan 
Published: November 2010

AbstractAmphiphilic biodegradable succinylchitosan nanoparticles modified with folic acid are described that act as an emulsifier to form nanoparticles. Their molecular structures and physicochemical as well as self‐assembly properties are characterized by means of FT‐IR,1H NMR, FESEM, DLS, and TEM. The nanoparticles are 60–80 nm in size and are not toxic in vitro. They are immobilized with the cytostatic drug doxorubicin. Specific transport of doxorubicin by the nanoparticles into the folate‐receptor‐overexpressing cancer cells and its biological activity as well as in vitro release are demonstrated. It is shown that under acidic condition more drug is released. The nanoparticles can thus not only specifically deliver doxorubicin to its target, but also release the drug depending on the pH.magnified image