bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting prostate cancer angiogenesis through metastasis‐associated protein 1 (MTA1)
Authors: Kai Li , Wang Jun , Ivanovic Marina , Chung Yeon‐Tae , Laskin William B. , Schulze‐Hoepfner Frank , Mirochnik Yelena , Satcher Robert L. , Levenson Anait S. 
Published: August 2010

AbstractBACKGROUNDMetastasis‐associated protein 1 (MTA1) is overexpressed in many forms of cancer types but its role in prostate cancer (PCa) progression and metastasis has not been explored. In this study, we addressed the functional and biological role of MTA1 in PCa.METHODSGene expression profiling was used to determine MTA1 overexpression during PCa cell–bone interaction. Immunohistochemistry was used to detect MTA1 on tissue microarrays (TMA) and vascular endothelial growth factor (VEGF), CD31, and Ki67 in xenografts. We used retroviral or lentiviral RNAi transduction of PCa cells to establish MTA1 knockdowns. RT‐PCR, Western blot, invasion, and endothelial cell migration assays were used to characterize the cells in vitro. The role of MTA1 in PCa tumorigenesis was evaluated in mouse xenografts.RESULTSWe identified MTA1 as a component of bone metastasis signature in PCa, which suggested a possible role for MTA1 in PCa progression and metastasis. MTA1 was expressed at higher levels in PCa cell lines than in normal prostate epithelial cells. Silencing MTA1 significantly suppressed the invasion and angiogenic activity of the cells in vitro and delayed tumor formation and development in mouse xenografts. Tumors that express MTA1 had higher proliferative indices, secreted higher levels of VEGF and were more vascularized. Analysis of the human TMA showed positive correlation between MTA1 nuclear localization/staining intensity and PCa aggressiveness.CONCLUSIONSMTA1 pro‐angiogenic and pro‐invasive functions create permissive environment for PCa tumor growth and likely support metastasis. Taken together with its predictive values, MTA1 can be utilized both as a prognostic marker and a therapy target in PCa. Prostate 71:268–280, 2011. © 2010 Wiley‐Liss, Inc.
Long‐Term corticosterone treatment induced lobe‐specific pathology in mouse prostate
Authors: Simanainen Ulla , Lampinen Anita , Henneicke Holger , Brennan Tara C. , Heinevetter Uta , Harwood D. Tim , McNamara Keely , Herrmann Markus , Seibel Markus J. , Handelsman David J. , Zhou Hong 
Published: August 2010

AbstractBACKGROUNDGlucocorticoids influence prostate development and pathology, yet the underlying mechanisms including possible direct glucocorticoid effect on the prostate are not well characterized.METHODSWe evaluated the expression of the glucocorticoid receptor (GR) together with the effects of supraphysiological glucocorticoid (corticosterone) on mouse prostate morphology and epithelial proliferation. Mature male mice were treated by weekly subdermal implantation of depot pellets containing either 1.5 mg corticosterone or placebo providing steady‐state release for 4 weeks.RESULTSCorticosterone treatment significantly increased dorsolateral and anterior prostate weights as well as prostate epithelial cell proliferation while epithelial apoptosis remained low upon corticosterone treatment. Histological analysis of the anterior lobe demonstrated abnormal, highly disorganized luminal epithelium with frequent formation of bridge‐like structures lined by continuous layer of basal cells not observed following placebo treatment. Molecular analysis revealed corticosterone‐induced increase in expression of stromal growth factor Fgf10 which, together with prominent stromal GR expression, suggest that glucocorticoid modify stromal‐to‐epithelial signaling in the mouse prostate. The mitogenic effects were prostate specific and not mediated by systemic effects on testosterone production suggesting that corticosterone effects were primarily mediated via prostate GR expression.CONCLUSIONThese data demonstrate that murine prostate is significantly and directly influenced by corticosterone treatment via aberrant stromal‐to‐epithelial growth factor signaling. Prostate 71:289–297, 2011. © 2010 Wiley‐Liss, Inc.
Epigenetic silencing of SOCS3 identifies a subset of prostate cancer with an aggressive behavior
Authors: Pierconti Francesco , Martini Maurizio , Pinto Francesco , Cenci Tonia , Capodimonti Sara , Calarco Alessandro , Bassi Pier Francesco , Larocca Luigi Maria 
Published: August 2010

AbstractBACKGROUNDChronic inflammation and subsequent tissutal alterations may play a key role in prostate carcinogenesis. In this way, molecular alterations of the suppressor of cytokine signaling 3 (SOCS3), one of the most important inhibitory molecule of inflammatory signal transduction circuitries, could contribute to explain the pleiotropic role of interleukin‐6 (IL‐6) in this type of cancer.METHODSWe analyzed the methylation status and mRNA expression of SOCS3 in 20 benign prostate hyperplasias (BPH) and in 51 prostate cancer specimens. We analyzed the SOCS3 methylation status using methylation‐specific PCR. Hypermethylation was confirmed by sequencing after subcloning. Epigenetic silencing of this gene was also demonstrated by real‐time PCR and by immunohistochemestry. Results and correlation with clinical data were statistically analyzed.RESULTSWe found that the promoter of SOCS3 was methylated in 39.2% of prostate cancer. On the contrary, all BPH and normal controls had an unmethylated pattern. Real‐time analysis showed that in methylated cases SOCS3 mRNA expression was reduced by three and four folds as compared to BPH and unmethylated cases, respectively. Interestingly, SOCS3 mRNA level was higher in unmethylated prostate cancer than in BPH. The immunohistochemical staining analysis for SOCS 3 confirmed mRNA results. Moreover, methylation of SOCS3 promoter significantly associated with intermediate–high grade Gleason score (P = 0.0007) and with an unfavorable clinical outcome (P = 0.0019).CONCLUSIONSOur data suggest that SOCS3 hypermethylation may be involved in the pathogenesis of prostate cancer and could identify a tumor subset with an aggressive behavior. Prostate 71:318–325, 2011. © 2010 Wiley‐Liss, Inc.
How different from random are docking predictions when ranked by scoring functions?
Authors: Feliu Elisenda , Oliva Baldomero 
Published: August 2010

AbstractDocking algorithms predict the structure of protein–protein interactions. They sample the orientation of two unbound proteins to produce various predictions about their interactions, followed by a scoring step to rank the predictions. We present a statistical assessment of scoring functions used to rank near‐native orientations, applying our statistical analysis to a benchmark dataset of decoys of protein–protein complexes and assessing the statistical significance of the outcome in the Critical Assessment of PRedicted Interactions (CAPRI) scoring experiment. A P value was assigned that depended on the number of near‐native structures in the sampling. We studied the effect of filtering out redundant structures and tested the use of pair‐potentials derived using ZDock and ZRank. Our results show that for many targets, it is not possible to determine when a successful reranking performed by scoring functions results merely from random choice. This analysis reveals that changes should be made in the design of the CAPRI scoring experiment. We propose including the statistical assessment in this experiment either at the preprocessing or the evaluation step. Proteins 2010. © 2010 Wiley‐Liss, Inc.
The repeat domain of the type III effector protein PthA shows a TPR‐like structure and undergoes conformational changes upon DNA interaction
Authors: Murakami Mário Tyago , Sforça Mauricio Luis , Neves Jorge Luiz , Paiva Joice Helena , Domingues Mariane Noronha , Pereira André Luiz Araujo , de Mattos Zeri Ana Carolina , Benedetti Celso Eduardo 
Published: August 2010

AbstractMany plant pathogenic bacteria rely on effector proteins to suppress defense and manipulate host cell mechanisms to cause disease. The effector protein PthA modulates the host transcriptome to promote citrus canker. PthA possesses unusual protein architecture with an internal region encompassing variable numbers of near‐identical tandem repeats of 34 amino acids termed the repeat domain. This domain mediates protein–protein and protein–DNA interactions, and two polymorphic residues in each repeat unit determine DNA specificity. To gain insights into how the repeat domain promotes protein–protein and protein–DNA contacts, we have solved the structure of a peptide corresponding to 1.5 units of the PthA repeat domain by nuclear magnetic resonance (NMR) and carried out small‐angle X‐ray scattering (SAXS) and spectroscopic studies on the entire 15.5‐repeat domain of PthA2 (RD2). Consistent with secondary structure predictions and circular dichroism data, the NMR structure of the 1.5‐repeat peptide reveals three α‐helices connected by two turns that fold into a tetratricopeptide repeat (TPR)‐like domain. The NMR structure corroborates the theoretical TPR superhelix predicted for RD2, which is also in agreement with the elongated shape of RD2 determined by SAXS. Furthermore, RD2 undergoes conformational changes in a pH‐dependent manner and upon DNA interaction, and shows sequence similarities to pentatricopeptide repeat (PPR), a nucleic acid‐binding motif structurally related to TPR. The results point to a model in which the RD2 structure changes its compactness as it embraces the DNA with the polymorphic diresidues facing the interior of the superhelix oriented toward the nucleotide bases. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Computational studies of the interaction between the HIV‐1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the Informational spectrum method
Authors: Tintori Cristina , Veljkovic Nevena , Veljkovic Veljko , Botta Maurizio 
Published: August 2010

AbstractA crystal structure of the integrase binding domain (IBD) of the lens epithelium‐derived growth factor (LEDGF/p75) in complex with the dimer of the HIV‐1 integrase (IN) catalytic core domain (CCD) provides useful information that might help in the understanding of essential protein‐protein contacts in HIV‐1. However, mutagenic studies indicated that interactions between the full‐length proteins were more extensive than the contacts observed in the co‐crystal structure of the isolated domains. On the other hand, the biochemical characterization of the interaction between full‐length IN and LEDGF/p75 has recently proved that LEDGF/p75 promotes IN tetramerization with two LEDGF/p75 IBD molecules bound to the IN tetramer. This experimental evidence suggests that to obtain a complete structural description of the interactions between the two proteins, the full‐length tetrameric structure of IN should be considered. Our aim was to obtain a detailed picture of HIV‐1 IN interactions with cellular co‐factors that was of general interest, particularly for the development of small molecule IN inhibitors, which mimic the IBD of LEDGF/p75. To this end, we performed bioinformatics analyses to identify protein sequence domains involved in long‐range recognition. Subsequently, we applied molecular dynamics techniques to investigate the detailed interactions between the complete tetrameric form of IN and two molecules of the IBD of LEDGF/p75. Our dynamic picture is in agreement with experimental data and, thereby, provides new details of the IN‐LEDGF/p75 interaction. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Protein loop modeling by using fragment assembly and analytical loop closure
Authors: Lee Julian , Lee Dongseon , Park Hahnbeom , Coutsias Evangelos A. , Seok Chaok 
Published: August 2010

AbstractProtein loops are often involved in important biological functions such as molecular recognition, signal transduction, or enzymatic action. The three dimensional structures of loops can provide essential information for understanding molecular mechanisms behind protein functions. In this article, we develop a novel method for protein loop modeling, where the loop conformations are generated by fragment assembly and analytical loop closure. The fragment assembly method reduces the conformational space drastically, and the analytical loop closure method finds the geometrically consistent loop conformations efficiently. We also derive an analytic formula for the gradient of any analytical function of dihedral angles in the space of closed loops. The gradient can be used to optimize various restraints derived from experiments or databases, for example restraints for preferential interactions between specific residues or for preferred backbone angles. We demonstrate that the current loop modeling method outperforms previous methods that employ residue‐based torsion angle maps or different loop closure strategies when tested on two sets of loop targets of lengths ranging from 4 to 12. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Simulations of carrier confinement in boron δ‐doped diamond devices
Authors: Fiori Alexandre , Pernot Julien , Gheeraert Etienne , Bustarret Etienne 
Published: August 2010

AbstractDiamond delta‐doped field effect transistors are expected to combine high speed and high power commutation. Critical parameters for the design of a diamond 2D hole gas were determined. The investigated diamond structures were made of an infinite or semi‐infinite diamond crystal with a low boron concentration and of a thin highly boron‐doped 2D diamond layer called the delta‐layer. The carrier density, wave‐function extension, energy spectrum, and band‐edges along the device depth were calculated depending on the delta‐layer thickness, boron concentration, and device geometry. The simulations showed that the thickness of the delta‐layer and the boron doping concentration were the most important parameters, the fraction of holes delocalized out of the delta‐layer decreasing from 90% for an ideal single atomic plane boron doped at 1021 cm−3 down to 30% for a 3 nm thick layer.
Lamé spheroconal harmonics in atoms and molecules
Authors: Méndez‐Fragoso R. , Ley‐Koo E. 
Published: August 2010

AbstractSpheroconal harmonics are the natural basis for the description of asymmetric‐molecule rotations (Kramers and Ittmann, Zeitschrift für Physik, 1929, 53, 553; Piña, J Mol Str 1999, 493, 159) and also an alternative to the familiar spherical harmonics as the angular part of the Schrödringer equation eigenfunctions for central potentials (Kalnins et al. SIAM J Appl Math 1976, 30, 360). We have dealt with their properties and matrix evaluation in connection with the rotations of asymmetric molecules (Ley‐Koo and Méndez‐Fragoso, Rev Mex Fís 2008, 54, 162) and the construction of a generating function for the complete wave functions of the Hydrogen atom (Ley‐Koo and Góngora, Int J Quantum Chem 2009, 109, 790). For these cases, the spheroconal harmonics are products of Lamé polynomials Λ(χ1)Λ(χ2) in the respective angular coordinates χ1, χ2, with n1 + n2 = ℓ, the angular momentum label. More recently during the investigations of the Hydrogen atom (Méndez‐Fragoso and Ley‐Koo, Int J Quantum Chem. In press) and the rotations of asymmetric molecules (Méndez‐Fragoso and Ley‐Koo, to be submitted), confined in elliptical cones associated with the spheroconal coordinates in which the respective Schrödinger equations are separable, we have recognized the need to use and to construct quasi‐periodic Lamé functions. In fact, the new boundary conditions require that the angular momentum label becomes noninteger ℓ → λ, and the respective Lamé functions become infinite series. This contribution contains details about the evaluation of the polynomial and quasi‐periodic Lamé functions, and their applications in the free particle confined by an elliptical cone with a spherical cap and the harmonic oscillator confined by an elliptical cone. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Mechanical properties of thin polymer films on stiff substrates
Authors: Silbernagl Dorothee , Cappella Brunero 
Published: August 2010

AbstractForce–displacement curves have been acquired with a commercial atomic force microscope on thin films of poly(n‐butyl methacrylate) on glass substrates in order to examine the so‐called “mechanical double layer” topic, i.e. the influence of the substrate on the mechanical properties of the film in dependence of the film thickness. The hyperbolic fit, a novel semi‐empirical equation introduced in previous articles, has been further corroborated. The interpretation of this equation has been deepened, yielding a quantitative and demonstrative characterization of the mechanical properties of double layers. Provided that the Young's moduli of bulk polymer and substrate are measured from the deformation curves, this mathematical model permits to fit the deformation–force curves on the double layers and to determine the thickness of the polymer films in wide range (0–200 nm). SCANNING 32: 282–293, 2010. © 2010 Wiley Periodicals, Inc.
B-Myb is Critical for Proper DNA Duplication During an Unperturbed S Phase in Mouse Embryonic Stem Cells
Authors: Lorvellec Maëlle , Dumon Stéphanie , Maya-Mendoza Apolinar , Jackson Dean , Frampton Jon , García Paloma 
Published: August 2010

Abstract
A common feature of early embryo cells from the inner cell mass (ICM) and of ESCs is an absolute dependence on an atypical cell cycle in which the G1 phase is shortened to preserve their self-renewing and pluripotent nature. The transcription factor B-Myb has been attributed a role in proliferation, in particular during the G2/M phases of the cell cycle. Intriguingly, B-Myb levels in ICM/ESCs are greater than 100 times compared with those in normal proliferating cells, suggesting a particularly important function for this transcription factor in pluripotent stem cells. B-Myb is essential for embryo development beyond the preimplantation stage, but its role in ICM/ESCs remains unclear. Using a combination of mouse genetics, single DNA fiber analyses and high-resolution three-dimensional (3D) imaging, we demonstrate that B-Myb has no influence on the expression of pluripotency factors, but instead B-Myb ablation leads to stalling of replication forks and superactivation of replication factories that result in disorganization of the replication program and an increase in double-strand breaks. These effects are partly due to aberrant transcriptional regulation of cell cycle proliferation factors, namely c-Myc and FoxM1, which dictate normal S phase progression. We conclude that B-Myb acts crucially during the S phase in ESCs by facilitating proper progression of replication, thereby protecting the cells from genomic damage. Our findings have particular relevance in the light of the potential therapeutic application of ESCs and the need to maintain their genomic integrity.
Efficient Generation of Functional Dopaminergic Neurons from Human Induced Pluripotent Stem Cells Under Defined Conditions
Authors: Swistowski Andrzej , Peng Jun , Liu Qiuyue , Mali Prashant , Rao Mahendra S. , Cheng Linzhao , Zeng Xianmin 
Published: August 2010

Abstract
Human induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells represent a promising unlimited cell source for generating patient-specific cells for biomedical research and personalized medicine. As a first step, critical to clinical applications, we attempted to develop defined culture conditions to expand and differentiate human iPSCs into functional progeny such as dopaminergic neurons for treating or modeling Parkinson's disease (PD). We used a completely defined (xeno-free) system that we previously developed for efficient generation of authentic dopaminergic neurons from human embryonic stem cells (hESCs), and applied it to iPSCs. First, we adapted two human iPSC lines derived from different somatic cell types for the defined expansion medium and showed that the iPSCs grew similarly as hESCs in the same medium regarding pluripotency and genomic stability. Second, by using these two independent adapted iPSC lines, we showed that the process of differentiation into committed neural stem cells (NSCs) and subsequently into dopaminergic neurons was also similar to hESCs. Importantly, iPSC-derived dopaminergic neurons were functional as they survived and improved behavioral deficits in 6-hydroxydopamine-leasioned rats after transplantation. In addition, iPSC-derived NSCs and neurons could be efficiently transduced by a baculoviral vector delivering episomal DNA for future gene function study and disease modeling using iPSCs. We also performed genome-wide microarray comparisons between iPSCs and hESCs, and we derived NSC and dopaminergic neurons. Our data revealed overall similarity and visible differences at a molecular level. Efficient generation of functional dopaminergic neurons under defined conditions will facilitate research and applications using PD patient-specific iPSCs.
Monodisperse α-Fe2O3 Mesoporous Microspheres: One-Step NaCl-Assisted Microwave-Solvothermal Preparation, Size Control and Photocatalytic Property
Authors: Cao Shao-Wen , Zhu Ying-Jie 
Published: August 2010

AbstractA simple one-step NaCl-assisted microwave-solvothermal method has been developed for the preparation of monodisperse α-Fe2O3 mesoporous microspheres. In this approach, Fe(NO3)3 · 9H2O is used as the iron source, and polyvinylpyrrolidone (PVP) acts as a surfactant in the presence of NaCl in mixed solvents of H2O and ethanol. Under the present experimental conditions, monodisperse α-Fe2O3 mesoporous microspheres can form via oriented attachment of α-Fe2O3 nanocrystals. One of the advantages of this method is that the size of α-Fe2O3 mesoporous microspheres can be adjusted in the range from ca. 170 to ca. 260 nm by changing the experimental parameters. High photocatalytic activities in the degradation of salicylic acid are observed for α-Fe2O3 mesoporous microspheres with different specific surface areas.
Proteomics of AML1/ETO Target Proteins: AML1–ETO Targets a C/EBP–NM23 Pathway
Authors: Singh Sheo Mohan , Trivedi Arun Kumar , Lochab Savita , Christopeit Maximilian , Hiddemann Wolfgang , Behre Gerhard 
Published: August 2010

Abstract

Introduction
The rational design of targeted therapies for acute myeloid leukemia (AML) requires the discovery of novel protein pathways in the systems biology of a specific AML subtype. We have shown that in the AML subtype with translocation t(8;21), the leukemic fusion protein AML1–ETO inhibits the function of transcription factors PU.1 and C/EBPα via direct protein–protein interaction. In addition, recently using proteomics, we have also shown that the AML subtypes differ in their proteome, interactome, and post-translational modifications.

Methods
We, therefore, hypothesized that the systematic identification of target proteins of AML1–ETO on a global proteome-wide level will lead to novel insights into the systems biology of t(8;21) AML on a post-genomic functional level. Thus, 6 h after inducible expression of AML1–ETO, protein expression changes were identified by two-dimensional gel electrophoresis and subsequent mass spectrometry analysis.

Results
Twenty-eight target proteins of AML1–ETO including prohibitin, NM23, HSP27, and Annexin1 were identified by MALDI-TOF mass spectrometry. AML1–ETO upregulated the differentiation inhibitory factor NM23 protein expression after 6 h, and the NM23 mRNA expression was also elevated in t(8;21) AML patient samples in comparison with normal bone marrow. AML1–ETO inhibited the ability of C/EBP transcription factors to downregulate the NM23 promoter. These data suggest a model in which AML1–ETO inhibits the C/EBP-induced downregulation of the NM23 promoter and thereby increases the protein level of differentiation inhibitory factor NM23.

Conclusions
Proteomic pathway discovery can identify novel functional pathways in AML, such as the AML1–ETO–C/EBP–NM23 pathway, as the main step towards a systems biology and therapy of AML.