bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells
Authors: Meyers Valerie E. , Zayzafoon Majd , Gonda Steve R. , Gathings William E. , McDonald Jay M. 
Published: August 2004

AbstractSpaceflight leads to reduced bone mineral density in weight bearing bones that is primarily attributed to a reduction in bone formation. We have previously demonstrated severely reduced osteoblastogenesis of human mesenchymal stem cells (hMSC) following 7 days culture in modeled microgravity (MMG). One potential mechanism for reduced osteoblastic differentiation is disruption of type I collagen (Col I)–integrin interactions and reduced integrin signaling. Integrins are heterodimeric transmembrane receptors that bind extracellular matrix (ECM) proteins and produce signals essential for proper cellular function, survival, and differentiation. Therefore, we investigated the effects of MMG on integrin expression and function in hMSC. We demonstrate that 7 days of culture in MMG leads to reduced expression of the ECM protein, Col I. Conversely, MMG consistently increases Col I‐specific α2 and β1 integrin protein expression. Despite this increase in integrin subunit expression, autophosphorylation of adhesion‐dependent kinases, focal adhesion kinase (FAK) and proline‐rich tyrosine kinase 2 (PYK2), is significantly reduced. Activation of Akt protein kinase (Akt) is unaffected by the reduction in FAK activation. However, reduced downstream signaling via the Ras‐mitogen activated protein kinase (MAPK) pathway is evidenced by a reduction in Ras and extracellular signal‐related protein kinase (ERK) activation. Taken together, our findings indicate that MMG decreases integrin/MAPK signaling, which likely contributes to the observed reduction in osteoblastogenesis. © 2004 Wiley‐Liss, Inc.
Abnormal cell cycle regulation in primary human uveal melanoma cultures
Authors: Pardo María , Piñeiro Antonio , de la Fuente María , García Angel , Prabhakar Sripadi , Zitzmann Nicole , Dwek Raymond A. , Sánchez‐Salorio Manuel , Domínguez Fernando , Capeans Carmen 
Published: August 2004

AbstractUveal malignant melanoma is the most frequent primary intraocular tumor in adult humans. The cellular events leading to neoplasic transformation of normal uveal melanocytes are not well known when compared to other cancers. In this study, we investigated the role of G1 and G1/S regulatory proteins of the cell cycle in human uveal melanoma (UM) primary cell cultures, since these proteins are common targets in tumor development. Further, freshly established and characterized tumor cells are a better model for in vitro studies when compared to cell lines established long ago. Human primary cell cultures from eight different UM were established, as well as one primary culture from rhesus uveal normal melanocytes (UNM). Primary human UM cultures were characterized by a low establishment and growing rate. From four successful cultures, three showed a high expression of cyclin D1, cyclin E, p16INK4A, and p27KIP1 with no variations in cyclin A, cyclin‐dependent kinase 2 (CDK2), and CDK4. Interestingly, in one of the cultured tumors, tumor suppressor protein retinoblastoma (Rb) did not bind E2F despite the fact that Rb was found in its hypophosphorylated form. No mutations in either RB1 or the Rb‐binding pocket of E2F‐1 were detected. Furthermore, we identified seven proteins co‐immunoprecipitating with Rb in this tumor, including Lamin A/C and six proteins not previously reported to bind Rb: Hsc70, high mobility group protein 1 (HMG‐1), hnRPN, glyceraldehyde 3 phosphate dehydrogenase (G3PDH), EF‐1, and EF‐2. Our results indicate that the overexpression of cyclins D1/E and CDKIs p16 and p27, together with a deregulation of the Rb/E2F pathway, may be implicated in the development of human UM. © 2004 Wiley‐Liss, Inc.
Dominant‐negative CREB inhibits heparanase functionality and melanoma cell invasion
Authors: Aucoin Rebecca , Reiland Jane , Roy Madhuchhanda , Marchetti Dario 
Published: August 2004

AbstractHeparanase (HPSE‐1) is an endo‐β‐d‐glucuronidase involved in the degradation of cell‐surface/extracellular matrix heparan sulfate (HS) in normal and neoplastic tissues. HPSE‐1 represents the first example of purification and cloning of a mammalian HS‐degradative enzyme. Elevated HPSE‐1 levels are known to be associated with metastatic cancers, directly implicating HPSE‐1 in metastatic events. The purpose of this study was to determine the role of cAMP response element‐binding protein (CREB) in modulating HPSE‐1‐mediated effects on human melanoma cell invasion. Highly invasive, brain‐metastatic melanoma cells (70W) were transfected with the dominant‐negative CREB (KCREB) and subsequently analyzed for changes in their HPSE‐1 content, functionality, and cell invasive properties. KCREB‐transfected cells showed a decrease in HPSE‐1 mRNA expression and activity. This correlated with a significantly decreased invasion of these cells through Matrigel™‐coated filters. Furthermore, adenoviral vectors containing the full‐length human HPSE‐1 cDNA in sense orientation (Ad‐S/hep) were constructed to investigate CREB effects on HPSE‐1. Restoration of HPSE‐1 expression and functionality following Ad‐S/hep infection of KCREB‐transfected 70W cells recovered melanoma cell invasiveness. These results demonstrate that KCREB inhibits HPSE‐1 and suggest that one of the roles CREB plays in the acquisition of melanoma cells metastatic phenotype is affecting HPSE‐1 activity. © 2004 Wiley‐Liss, Inc.
Cytoskeletal organization of human mesenchymal stem cells (MSC) changes during their osteogenic differentiation
Authors: Pablo Rodríguez J. , González Mauricio , Ríos Susana , Cambiazo Verónica 
Published: August 2004

AbstractHuman MSCs have been studied to define the mechanisms involved in normal bone remodeling and the regulation of osteogenesis. During osteogenic differentiation, MSCs change from their characteristic fibroblast‐like phenotype to near spherical shape. In this study, we analyzed the correlation between the organization of cytoskeleton of MSCs, changes in cell morphology, and the expression of specific markers (alkaline phosphatase activity and calcium deposition) of osteogenic differentiation. For osteoblastic differentiation, cells were cultured in a culture medium supplemented with 100 nM dexamethasone, 10 mM β‐ glycerophosphate, and 50 μg/ml ascorbic acid. The organization of microfilaments and microtubules was examined by inmunofluorescence using Alexa fluor 594 phalloidin and anti α‐tubulin monoclonal antibody. Cytochalasin D and nocodazole were used to alter reversibly the cytoskeleton dynamic. A remarkable change in cytoskeleton organization was observed in human MSCs during osteogenic differentiation. Actin cytoskeleton changed from a large number of thin, parallel microfilament bundles extending across the entire cytoplasm in undifferentiated MSCs to a few thick actin filament bundles located at the outermost periphery in differentiated cells. Under osteogenic culture conditions, a reversible reorganization of microfilaments induced by an initial treatment with cytochalasin D but not with nocodazole reduced the expression of differentiation markers, without affecting the final morphology of the cells. The results indicate that changes in the assembly and disassembly kinetics of microfilaments dynamic of actin network formation may be critical in supporting the osteogenic differentiation of human MSCs; also indicated that the organization of microtubules appears to have a regulatory role on the kinetic of this process. © 2004 Wiley‐Liss, Inc.
PM3‐compatible zinc parameters optimized for metalloenzyme active sites
Authors: Brothers Edward N. , Suarez Dimas , Deerfield David W. , Merz Kenneth M. 
Published: August 2004

AbstractRecent studies have shown that semiempirical methods (e.g., PM3 and AM1) for zinc‐containing compounds are unreliable for modeling structures containing zinc ions with ligand environments similar to those observed in zinc metalloenzymes. To correct these deficiencies a reparameterization of zinc at the PM3 level was undertaken. In this effort we included frequency corrected B3LYP/6‐311G* zinc metalloenzyme ligand environments along with previously utilized experimental data. Average errors for the heats of formation have been reduced from 46.9 kcal/mol (PM3) to 14.2 kcal/mol for this new parameter set, termed ZnB for “Zinc, Biological.” In addition, the new parameter sets predict geometries for the Bacillus fragilis active site model and other zinc metalloenzyme mimics that are qualitatively in agreement with high‐level ab initio results, something existing parameter sets failed to do. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1677–1692, 2004
Solvation effects on alanine dipeptide: A MP2/cc‐pVTZ//MP2/6‐31G** study of (Φ, Ψ) energy maps and conformers in the gas phase, ether, and water
Authors: Wang Zhi‐Xiang , Duan Yong 
Published: August 2004

AbstractThe effects of solvation on the conformations and energies of alanine dipeptide (AD) have been studied by ab initio calculations up to MP2/cc‐pVTZ//MP2/6‐31G**, utilizing the polarizable continuum model (PCM) to mimic solvation effects. The energy surfaces in the gas phase, ether, and water bear similar topological features carved by the steric hindrance, but the details differ significantly due to the solvent effects. The gas‐phase energy map is qualitatively consistent with the Ramachandran plot showing seven energy minima. With respect to the gas‐phase map, the significant changes of the aqueous map include (1) the expanded low‐energy regions, (2) the emergence of an energy barrier between C5‐β and αR‐β2 regions, (3) a clearly pronounced αR minimum, a new β‐conformer, and the disappearance of the gas‐phase global minimum, and (4) the shift of the dominant region in LEII from the gas‐phase C7ax region to the αL region. These changes bring the map in water to be much closer to the Ramachandran plot than the gas‐phase map. The solvent effects on the geometries include the elongation of the exposed NH and CO bonds, the shortening of the buried HNCO peptide bonds, and the enhanced planarity of the peptide bonds. The energy surface in ether has features similar to those both in the gas phase and in water. The free energy order computed in the gas phase and in ether is in good agreement with experimental studies that concluded that C5 and C7eq are the dominant species in both the gas phase and nonpolar solvents. The free energy order in water is consistent with the experimental observation that the dominant C7eq in the nonpolar solvent was largely replaced by PII‐like (i.e., β) and αR in the strong polar solvents. Based on calculations on AD + 4H2O and other AD–water clusters, we suggest that explicit water–AD interactions may distort C5 and β (or αR and β) to an intermediate conformation. Our analysis also shows that the PCM calculations at the MP2/cc‐pVTZ//MP2/6‐31G** level give good descriptions to the bulk solvent polarization effect. The results presented in this article should be of sufficient quality to characterize the peptide bonds in the gas phase and solvents. The energy surfaces may serve as the basis for developing of strategies enabling the inclusion of solvent polarization in the force field. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1699–1716, 2004
Hybridized particle swarm algorithm for adaptive structure training of multilayer feed‐forward neural network: QSAR studies of bioactivity of organic compounds
Authors: Shen Qi , Jiang Jian‐Hui , Jiao Chen‐Xu , Lin Wei‐Qi , Shen Guo‐Li , Yu Ru‐Qin 
Published: August 2004

AbstractThe multilayer feed‐forward ANN is an important modeling technique used in QSAR studying. The training of ANN is usually carried out only to optimize the weights of the neural network and without paying attention to the network topology. Some other strategies used to train ANN are, first, to discover an optimum structure of the network, and then to find weights for an already defined structure. These methods tend to converge to local optima, and may also lead to overfitting. In this article, a hybridized particle swarm optimization (PSO) approach was applied to the neural network structure training (HPSONN). The continuous version of PSO was used for the weight training of ANN, and the modified discrete PSO was applied to find appropriate the network architecture. The network structure and connectivity are trained simultaneously. The two versions of PSO can jointly search the global optimal ANN architecture and weights. A new objective function is formulated to determine the appropriate network architecture and optimum value of the weights. The proposed HPSONN algorithm was used to predict carcinogenic potency of aromatic amines and biological activity of a series of distamycin and distamycin‐like derivatives. The results were compared to those obtained by PSO and GA training in which the network architecture was kept fixed. The comparison demonstrated that the HPSONN is a useful tool for training ANN, which converges quickly towards the optimal position, and can avoid overfitting in some extent. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1726–1735, 2004
A dynamic lattice searching method for fast optimization of Lennard–Jones clusters
Authors: Shao Xueguang , Cheng Longjiu , Cai Wensheng 
Published: August 2004

AbstractA highly efficient unbiased global optimization method called dynamic lattice searching (DLS) was proposed. The method starts with a randomly generated local minimum, and finds better solution by a circulation of construction and searching of the dynamic lattice (DL) until the better solution approaches the best solution. The DL is constructed adaptively based on the starting local minimum by searching the possible location sites for an added atom, and the DL searching is implemented by iteratively moving the atom located at the occupied lattice site with the highest energy to the vacant lattice site with the lowest energy. Because the DL can greatly reduce the searching space and the number of the time‐consuming local minimization procedures, the proposed DLS method runs at a very high efficiency, especially for the clusters of larger size. The performance of the DLS is investigated in the optimization of Lennard–Jones (LJ) clusters up to 309 atoms, and the structure of the LJ500 is also predicted. Furthermore, the idea of dynamic lattice can be easily adopted in the optimization of other molecular or atomic clusters. It may be a promising approach to be universally used for structural optimizations in the chemistry field. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1693–1698, 2004
Dexamethasone regulation of cFos mRNA in osteoprogenitors
Authors: Shur Irena , Socher Rina , Benayahu Dafna 
Published: August 2004

AbstractThe glucocorticoid, dexamethasone (Dex), has a beneficial effect on osteogenesis by increasing the activation and differentiation of osteoblastic cells. We investigated the effect of Dex on osteoblasts and detected changes in pattern of expression of cFos mRNA. cFos is an early response gene that is expressed as unspliced and spliced mRNAs. We analyzed the regulation of cFos mRNA in correlation with the cell proliferation status and following the induction by Dex. Treatment of osteoblastic cells with Dex for 30 min resulted in elevated levels of spliced form of cFos mRNA, which was maintained with extended treatment of cultured cells for 24 h. In addition, we demonstrated interaction between glucocorticoid receptor (GR) and cFos mRNA. This study provides evidence for the action of Dex on osteoblasts through dynamic cell responses involving with cFos. © 2005 Wiley‐Liss, Inc.
14‐3‐3 regulation of cell spreading and migration requires a functional amphipathic groove
Authors: Rodriguez Luis G. , Guan Jun‐Lin 
Published: August 2004

AbstractThe 14‐3‐3 proteins associate with many cellular proteins that participate in the regulation of various cellular events including apoptosis, the cell cycle, spreading, and migration. We have previously described that 14‐3‐3β binds the β1‐integrin and overexpression of 14‐3‐3β promoted increased cell spreading and migration (Han et al. [2001] Oncogene 20: 346–357). In this study, we find that mutation of Ser 60 of 14‐3‐3β, outside of the amphipathic groove which is involved in 14‐3‐3 protein interactions with other ligands, abolished its interaction with integrin. Surprisingly, this mutant retained its ability to promote cell spreading, suggesting that 14‐3‐3β interaction with the β1‐integrin is not required for its regulation of cell adhesion. We next showed that mutations of several critical residues in the amphipathic groove did not affect 14‐3‐3β interaction with the β1‐integrin. As expected, these mutants disrupted their association with the phosphoserine dependent ligands Raf and Cas. Analysis of the groove mutant LF (mutation of Arg129Tyr130 to Leu and Phe) indicated that, unlike wild type 14‐3‐3β, it could not stimulate cell spreading or migration, suggesting that a functional amphipathic groove is required for 14‐3‐3 regulation of cell adhesion and migration. Consistent with this, cells expressing the LF mutant exhibited a delay in F‐actin organization compared to cells expressing wild type or the S60A mutant (Ser 60 to Ala mutation) upon cell adhesion to fibronectin (FN). Taken together, these studies identified a novel binding site on 14‐3‐3 for integrin β1 and showed that a functional amphipathic groove, rather than its interaction with integrin β1, is required for 14‐3‐3 regulation of cell spreading and migration. © 2005 Wiley‐Liss, Inc.
Ortho‐selective vapour phase methylation of phenol over nanocrystalline ferrospinels of varying Zn2+/Mn2+ ionic composition
Authors: Reddy Vanga S , Shyam A Radhe , Dwivedi R , Gupta RK , Chumbale VR , Prasad R 
Published: August 2004

AbstractOrtho‐selective vapour phase methylation of phenol with methanol has been carried out over Zn(1−x)MnxFe2O4 (x = 0, 0.25, 0.5, 0.75, 1.0) in the temperature range 423–698K in a fixed‐bed, down‐flow reactor. o‐Cresol and 2,6‐xylenol were found to be the major products. Reaction parameters were optimized over MnFe2O4 (MF). Maximum yields of 68.3% and 14% with selectivities of 81% and 17% were obtained for 2,6‐xylenol and o‐cresol respectively, giving a total selectivity of 98% over MnFe2O4 at 598K, methanol to phenol molar ratio 6, and 0.4 h−1 weight hour space velocity. It was found that the product selectivity is greatly influenced by the acido‐basic properties of the catalysts. o‐Cresol formation is favoured over catalysts with weak acid sites whereas formation of 2,6‐xylenol occurs in the presence of stronger acid sites. Catalyst characterization has been carried out by X‐ray diffraction, infrared spectroscopy and ammonia desorption methods. X‐ray diffractograms were used to determine the unit cell length and correlated with the acidity and catalytic activity of the spinel systems. IR absorption bands observed around 700 cm−1 and 500 cm−1 are respectively attributed to the tetrahedral and octahedral metal‐oxygen stretching mode of the spinel. Shifting of bands towards lower wave numbers is correlated with composition and acidity of the spinel systems. The results are discussed on the basis of the Zn2+ and Mn2+ composition and acidity of the spinel systems. Copyright © 2004 Society of Chemical Industry
Positioning the non‐least‐developed developing countries based on vulnerability‐related indicators
Authors: Liou Fen‐May , Ding Cherng G. 
Published: August 2004

AbstractA structure presenting relevant constructs of vulnerability for developing but not least‐developed countries in the global trade regime shift was first proposed. Based on the structure, the vulnerability constructs were empirically summarized as three independent factors: economic scale, volatility degree, and development level. A map, showing the overall vulnerability positioning of the countries, with dimensions of ‘economic scale’ and ‘volatility with resilience of development’, was further created. The map reveals that most small‐population states are more vulnerable. Nevertheless, some large economies may not be less vulnerable and should not be excluded if special treatments are offered to non‐least‐developed small states. Copyright © 2004 John Wiley & Sons, Ltd.
Tax performance: a comparative study
Authors: Teera Joweria M. , Hudson John 
Published: August 2004

AbstractThis paper seeks to analyse tax performance across countries, utilizing what Musgrave (1969) referred to as the stochastic approach, where tax performance is analysed by comparisons with the average performance. The regression approach to tax performance assessment is used and a tax effort index is constructed. Among the variables that are identified to be important determinants of tax shares is a measure of tax evasion. The tax effort indices obtained show that generally the upper middle‐income and high‐income OECD groups are making better use of their tax bases to increase revenue. There are also economies of scale with respect to population density. Copyright © 2004 John Wiley & Sons, Ltd.
What is the enabling state? The views of textiles and garments entrepreneurs in Zimbabwe
Authors: Jackson Paul 
Published: August 2004

AbstractThis paper summarizes the approach and findings of a piece of research sponsored by the Department for International Development (DFID) in the UK and carried out in 1998 and 1999 mainly in Harare and Bulawayo. The primary aim of the work was to contribute to an improvement in facilitating an enabling environment for the private sector in Zimbabwe. It aimed to achieve this objective by developing and testing a participative methodology based on the use of historical profiles, checklists, Venn diagrams, master charts, workshops and other participative methodologies. These processes were introduced and developed with a group of 40 entrepreneurs and managers and several representatives from trade unions, government, and agencies. The design aimed to allow participants to express their own agendas, ideas and approaches instead of reacting to a more rigid approach reflecting the agendas of the research team.The research team adopted a broad structure based around three main areas affecting firms: the policy, agency and firm environments. The use of semi‐structured interviews and workshops allowed a detailed exploration of these issues and produced a comprehensive list of problems identified and proposed solutions. The importance of the research is in its ability to construct a firm level, rather than government or donor level view of the enabling environment. Copyright © 2004 John Wiley & Sons, Ltd.
Explaining corruption: are open countries less corrupt?
Authors: Gatti Roberta 
Published: August 2004

AbstractThis paper analyses whether the presence of barriers to international trade and capital flows is associated with higher corruption. The evidence suggests that the main impact of trade barriers on corruption comes through the incentive to collusive behaviors between individuals and customs officials, rather than from the decreased foreign competition pressure on the domestic sector induced by restrictive trade policy. Interestingly, no clear association emerges between corruption and variables proxying for presence and intensity of controls on capital flows. Copyright © 2004 John Wiley & Sons, Ltd.