bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonistic modulation of gliomagenesis by Pax6 and Olig2 in PDGF‐induced oligodendroglioma
Authors: Appolloni Irene , Calzolari Filippo , Barilari Manuela , Terrile Marta , Daga Antonio , Malatesta Paolo 
Published: April 2012

AbstractGliomas are aggressive tumors of the central nervous system originating from proliferating neural cells. Regulators of neural stem or progenitor cells biology may thus influence aspects of brain tumorigenesis, such as the maintenance of tumor‐propagating potential. We investigated the role of Pax6, a neurogenic transcription factor already suggested as a positive prognostic marker for human gliomas, in a well‐characterized in vivo model of PDGF‐B‐driven oligodendroglioma. In this system, the expression of Pax6 severely impairs tumor propagation by inducing a reduction of cell proliferation and the acquisition of differentiation traits in tumor‐initiating cells. The overexpression of Pax6 correlates with a downregulation of Olig2, a bHLH transcription factor that normally antagonizes Pax6 in adult neurogenic niches and that plays a key role in the maintenance of neural stem and progenitor cells. Furthermore, we found that Olig2 is strictly required to maintain the malignancy of oligodendroglioma cells, since its silencing by interfering RNA abrogates tumor propagation. We finally show evidence that this function depends, at least in part, on the silencing of ID4, a dominant negative bHLH protein, whose upregulation follows Olig2 loss. In our model, the upregulation of ID4 mimics the loss of Olig2 in impairing the tumor‐propagating potential of glioma cells. Our data, therefore, establish the relevance of physiological regulators of neural stem cell biology in regulating glial tumor malignancy and provide support for their functional interactions in this context.
Long‐term mechanical durability of dental nanocomposites containing amorphous calcium phosphate nanoparticles
Authors: Moreau Jennifer L. , Weir Michael D. , Giuseppetti Anthony A. , Chow Laurence C. , Antonucci Joseph M. , Xu Hockin H. K. 
Published: April 2012

AbstractHalf of all dental restorations fail within 10 years, with secondary caries and restoration fracture being the main reasons. Calcium phosphate (CaP) composites can release Ca and PO4 ions and remineralize tooth lesions. However, there has been no report on their long‐term mechanical durability. The objective of this study was to investigate the wear, thermal‐cycling, and water‐aging of composites containing amorphous calcium phosphate nanoparticles (NACP). NACP of 112‐nm and glass particles were used to fabricate four composites: (1) 0% NACP+75% glass; (2) 10% NACP+65% glass; (3) 15% NACP+60% glass; and (4) 20% NACP+50% glass. Flexural strength and elastic modulus of NACP nanocomposites were not degraded by thermal‐cycling. Wear depth increased with increasing NACP filler level. Wear depths of NACP nanocomposites after 4 × 105 cycles were within the range for commercial controls. Mechanical properties of all the tested materials decreased with water‐aging time. After 2 years, the strengths of NACP nanocomposites were moderately higher than the control composite, and much higher than the resin‐modified glass ionomers. The mechanism of strength loss for resin‐modified glass ionomer was identified as microcracking and air‐bubbles. NACP nanocomposites and control composite were generally free of microcracks and air‐bubbles. In conclusion, combining NACP nanoparticles with reinforcement glass particles resulted in novel nanocomposites with long‐term mechanical properties higher than those of commercial controls, and wear within the range of commercial controls. These strong long‐term properties, plus the Ca‐PO4 ion release and acid‐neutralization capability reported earlier, suggest that the new NACP nanocomposites may be promising for stress‐bearing and caries‐inhibiting restorations. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2012.
GPU accelerated numerical simulations of viscoelastic phase separation model
Authors: Yang Keda , Su Jiaye , Guo Hongxia 
Published: April 2012

AbstractWe introduce a complete implementation of viscoelastic model for numerical simulations of the phase separation kinetics in dynamic asymmetry systems such as polymer blends and polymer solutions on a graphics processing unit (GPU) by CUDA language and discuss algorithms and optimizations in details. From studies of a polymer solution, we show that the GPU‐based implementation can predict correctly the accepted results and provide about 190 times speedup over a single central processing unit (CPU). Further accuracy analysis demonstrates that both the single and the double precision calculations on the GPU are sufficient to produce high‐quality results in numerical simulations of viscoelastic model. Therefore, the GPU‐based viscoelastic model is very promising for studying many phase separation processes of experimental and theoretical interests that often take place on the large length and time scales and are not easily addressed by a conventional implementation running on a single CPU. © 2012 Wiley Periodicals, Inc.
Novel methods for the quantification of changes in actin organization in chondrocytes using fluorescent imaging and linear profiling
Authors: Qusous Ala , Parker Eleanor , Geewan Corinne , Kapasi Arva , Getting Stephen J. , Hucklebridge Frank , Keshavarz Tajalli , Kerrigan Mark J.P. 
Published: April 2012

AbstractWe present three novel reproducible methodologies for the quantification of changes in actin organization from microscope images. Striation and integrative analysis were devised for the investigation of trans‐cellular filaments and F‐actin localization, respectively, in response to physiological or mechanical actin‐modulatory conditions. Additionally, the Parker‐Qusous (PQ) formula was developed as a measure of total quantity of F‐actin, independent of cell volume changes, whereby fluorescence intensity was divided by the cube root of cell volume, squared. Values obtained were quantified in Mauricean Units (Mu; pixel/μm3). Upon isolation, there was a 49% decrease in total F‐actin fluorescence from 1.91 ± 0.16 pixel/μm3 (Mu) to 0.95 ± 0.55 Mu, whereas upon culture, an apparent increase in total fluorescence was deemed insignificant due to an increase in average cell volume, with a rise, however, in striation units (StU) from 1 ± 1 to 5 ± 1 StU/cell, and a decrease in percentage cortical fluorescence to 30.45% ± 1.52% (P = 7.8 × 10−5). Freshly isolated chondrocytes exhibited a decrease in total F‐actin fluorescence to 0.61 ± 0.05 Mu and 0.32 ± 0.02 Mu, 10 min posthypertonic and hypotonic challenges, respectively. Regulatory volume decrease was inhibited in the presence of REV5901 with maintenance of actin levels at 1.15 Mu. Following mechanical impact in situ, there was a reduction in total F‐actin fluorescence to 0.95 ± 0.08 Mu and 0.74 ± 0.06 Mu under isotonic and hypotonic conditions, respectively, but not under hypertonic conditions. We report simple methodologies for quantification of changes in actin organization, which will further our understanding of the role of actin in various cellular stress responses. These techniques can be applied to better quantify changes in localization of various proteins using fluorescent labeling. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
Automated quantification of white matter disease extent at 3 T: Comparison with volumetric readings
Authors: Hulsey Keith M. , Gupta Mohit , King Kevin S. , Peshock Ronald M. , Whittemore Anthony R. , McColl Roderick W. 
Published: April 2012

AbstractPurpose:To develop and validate an algorithm to automatically quantify white matter hyperintensity (WMH) volume.Materials and Methods:Images acquired as part of the Dallas Heart Study, a multiethnic, population‐based study of cardiovascular health, were used to develop and validate the algorithm. 3D magnetization prepared rapid acquisition gradient echo (MP‐RAGE) and 2D fluid‐attenuated inversion recovery (FLAIR) images were acquired from 2082 participants. Images from 161 participants (7.7% of the cohort) were used to set an intensity threshold to maximize the agreement between the algorithm and a qualitative rating made by a radiologist. The resulting algorithm was run on the entire cohort and outlier analyses were used to refine the WMH volume measurement. The refined, automatic WMH burden estimate was then compared to manual quantitative measurements of WMH volume in 28 participants distributed across the range of volumes seen in the entire cohort.Results:The algorithm showed good agreement with the volumetric readings of a trained analyst: the Spearman's Rank Order Correlation coefficient was r = 0.87. Linear regression analysis showed a good correlation WMHml[automated] = 1.02 × WMHml[manual] − 0.48. Bland–Altman analysis showed a bias of 0.34 mL and a standard deviation of 2.8 mL over a range of 0.13 to 41 mL.Conclusion:We have developed an algorithm that automatically estimates the volume of WMH burden using an MP‐RAGE and a FLAIR image. This provides a tool for evaluating the WMH burden of large populations to investigate the relationship between WMH burden and other health factors. J. Magn. Reson. Imaging 2012;36:305–311. ©2012 Wiley Periodicals, Inc.
Reproducibility of total choline/water ratios in mouse U87MG xenograft tumors by 1H‐MRS
Authors: Zhu Mingming , Fischl Anthony S. , Trowbridge Melissa A. , Shannon Harlan E. 
Published: April 2012

AbstractPurpose:To evaluate the reproducibility of the measurement of the total choline‐to‐water ratio, and the effect of repositioning the subject between scans, using 1H‐magnetic resonance spectroscopy in a mouse U87MG xenograft model.Materials and Methods:In vivo single‐voxel MR spectra at 7T from xenograft tumors were obtained using both a water‐suppressed and a nonwater‐suppressed point‐resolved spectroscopy (PRESS) sequence. Reproducibility of the total choline/water ratio was evaluated under the conditions of immediate rescan with no change in position of the animal or voxel, immediate reposition, and reposition after 1 or 7 days.Results:Total choline‐to‐water ratios in U87MG tumor xenografts averaged ≈0.018 across all of the groups. The average percent difference between the two scans in each condition was always less than ≈3.0%, and the coefficient of variation was always less than ≈12%. Bias was unrelated to the testing condition and relatively negligible in magnitude (<3%). Due to heteroscedasticity in the ratios, the limits of agreement were calculated after log transformation of the data and ranged from ≈12% when animals were maintained in the same position and immediately rescanned to ≈52% when the two scans were 7 days apart.Conclusion:The total choline‐to‐water ratio provides a reproducible measure of choline‐containing metabolites in subcutaneous U87MG xenograft tumors in mice. J. Magn. Reson. Imaging 2012;36:459–467. ©2012 Wiley Periodicals, Inc.
Re‐establishment of cytoskeletal tensional homeostasis in lax tendons occurs through an actin‐mediated cellular contraction of the extracellular matrix
Authors: Gardner Keri , Lavagnino Michael , Egerbacher Monika , Arnoczky Steven P. 
Published: April 2012

AbstractCytoskeletal tensional homeostasis is known to be an important factor in controlling catabolic gene expression in tendon cells. Loss of cell tension in lax rat tail tendon fascicles (RTTfs) has been associated with an upregulation of MMP‐13 gene expression and protein synthesis. To determine the role of the actin cytoskeleton in re‐establishing tensional homeostasis in lax tendons, RTTfs were allowed to freely contract in vitro for 8 days. The cultured RTTfs contracted rapidly, reaching 50% of their initial length by 3 days. This contraction was associated with the presence of α‐smooth muscle actin positive cells within the tendon. Disruption of the actin network by cytochalasian D caused an immediate and significant elongation of the contracted RTTfs. Subsequent removal of the cytochalasian D re‐initiated the contraction process. When lax RTTfs were allowed to contract between fixed clamps in culture and become taut, they demonstrated a marked decrease in MMP‐13 staining intensity when compared to freely contracting RTTfs. The ability of native tendon cells to contract lax tendons and re‐establish their homeostatic “set point” with respect to collagenase production may be an important mechanism in the recovery of tendons elongated by injury, surgical positioning, or cyclic, viscoelastic creep secondary to repetitive exercise. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1695–1701, 2012
Hydrodynamic and Molecular Study of Poly{4‐[4‐(hexyloxy)phenyl]ethynylphenyl methacrylate} in Dilute Solutions and Conformational Peculiarities of Brush‐Like Macromolecules
Authors: Pavlov Georges M. , Breul Alexander M. , Hager Martin D. , Schubert Ulrich S. 
Published: April 2012

AbstractBrush‐like poly{4‐[4‐(hexyloxy)phenyl]ethynylphenyl methacrylate}s are synthesized using RAFT polymerization, fractionated and studied by molecular hydrodynamic methods. The values of the velocity sedimentation coefficient, the frictional ratio, and the intrinsic viscosity are obtained in toluene. The conformational and structural parameters of the studied polymer chains are estimated by the use of theories that describe the hydrodynamic behavior of the wormlike cylinders without intra‐chain excluded volume effects and the hydrodynamic behavior of bending rods. The intrinsic viscosity data obtained for poly{4‐[4‐(hexyloxy)phenyl]ethynylphenyl methacrylate}s and for other brush‐like macromolecules are discussed in terms of a doubly‐normalized scaling plot.
Reduction of inflammatory bowel disease‐induced tumor development in IL‐10 knockout mice with soluble epoxide hydrolase gene deficiency
Authors: Zhang Wanying , Liao Jie , Li Haonan , Dong Hua , Bai Han , Yang Allison , Hammock Bruce D. , Yang Guang‐Yu 
Published: April 2012

AbstractSoluble epoxide hydrolase (sEH) quickly inactivates anti‐inflammatory epoxyeicosatrienoic acids (EETs) by converting them to dihydroxyeicosatrienoic acids (DHETs). Inhibition of sEH has shown effects against inflammation, but little is studied about the role of sEH in inflammatory bowel disease (IBD) and its induced carcinogenesis. In the present study, the effect of sEH gene deficiency on the development of IBD‐induced tumor development was determined in IL‐10 knockout mice combined with sEH gene deficiency. Tumor development in the bowel was examined at the age of 25 wk for male mice and 35 wk for female mice. Compared to IL‐10(−/−) mice, sEH (−/−)/IL‐10(−/−) mice exhibited a significant decrease of tumor multiplicity (2 ± 0.9 tumors/mouse vs. 1 ± 0.3 tumors/mouse) and tumor size (344.55 ± 71.73 mm3 vs. 126.94 ± 23.18 mm3), as well as a marked decrease of precancerous dysplasia. The significantly lower inflammatory scores were further observed in the bowel in sEH(−/−)/IL‐10(−/−) mice as compared to IL‐10(−/−) mice, including parameters of inflammation‐involved area (0.70 ± 0.16 vs. 1.4 ± 0.18), inflammation cell infiltration (1.55 ± 0.35 vs. 2.15 ± 0.18), and epithelial hyperplasia (0.95 ± 0.21 vs. 1.45 ± 0.18), as well as larger ulcer formation. qPCR and Western blotting assays demonstrated a significant downregulation of cytokines/chemokines (TNF‐α, MCP‐1, and IL‐12, 17, and 23) and NF‐κB signals. Eicosanoid acid metabolic profiling revealed a significant increase of ratios of EETs to DHETs and EpOMEs to DiOMEs. These results indicate that sEH plays an important role in IBD and its‐induced carcinogenesis and could serve as a highly potential target of chemoprevention and treatment for IBD. © 2012 Wiley Periodicals, Inc.
Limit cycles in a Gause‐type predator–prey model with sigmoid functional response and weak Allee effect on prey
Authors: González‐Olivares Eduardo , Rojas‐Palma Alejandro 
Published: April 2012

The goal of this work is to examine the global behavior of a Gause‐type predator–prey model in which two aspects have been taken into account: (i) the functional response is Holling type III; and (ii) the prey growth is affected by a weak Allee effect.Here, it is proved that the origin of the system is a saddle point and the existence of two limit cycles surround a stable positive equilibrium point: the innermost unstable and the outermost stable, just like with the strong Allee effect.Then, for determined parameter constraints, the trajectories can have different  ω − limit sets. The coexistence of a stable limit cycle and a stable positive equilibrium point is an important fact for ecologists to be aware of the kind of bistability shown here.So, these models are undoubtedly rather sensitive to disturbances and require careful management in applied contexts of conservation and fisheries. Copyright © 2012 John Wiley & Sons, Ltd.
Development of a Large‐Scale Stopped‐Flow System for Heterogeneous Olefin Polymerization Kinetics
Authors: Taniike Toshiaki , Sano Shinya , Ikeya Mitsuhiro , Thang Vu Quoc , Terano Minoru 
Published: April 2012

AbstractStopped‐flow (SF) polymerization is a powerful tool to investigate the nature of the active site of heterogeneous Ziegler‐Natta catalysts, but poor polymer yields due to short polymerization times limit detailed structural analyses of the obtained polymer. A new large‐scale SF polymerization system is described in which an arbitrary volume of slurry can be transferred to obtain a polymer yield sufficient for a variety of analytic purposes. The developed LSF system is proven to be highly scalable and stable, leading to reproducible polymerization in an expanded time range from 0.03 s to a few seconds. The accurate polymerization below 0.1 s is promising for future studies to evaluate accurate kinetics as well as dormant processes in Ziegler‐Natta olefin polymerization. magnified image
Future directions of sickle cell disease research: The NIH perspective
Authors: Hoots W. Keith , Shurin Susan B. 
Published: April 2012

AbstractEfforts to enhance therapy for children and adults with sickle cell disease (SCD) have proven more challenging than might have been predicted from the fact that an understanding of the underlying pathogenesis antedated that of many other diseases for which good treatments presently exist. The multi‐organ injury that occurs with SCD certainly contributes to this clinical reality. Research over decades indicates that the primary defect in hemoglobin that results in polymerization of the protein under low oxygen conditions and resultant cellular deformity of the red blood cell initiates a complex downstream pathogenesis associated with vascular injury and organ ischemia. Deciphering this in a manner that informs successful therapies that improve all target organs continues to challenge hematologists. The National Heart, Lung and Blood Institute (NHLBI) is dedicated to support research across the basic science, translational and clinical spectrum to achieve these clinical outcomes. The following provides a brief summary of the research strategies which NHLBI is presently supporting and will support in the future to enhance care and ultimately, to effect cure of this hemoglobin disease that causes such suffering to those who inherit this monogenic disease. Pediatr Blood Cancer 2012;59:353–357. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
High‐resolution crystal structure of FKBP12 from Aedes aegypti
Authors: Rajan Sreekanth , Saw Kai Qian , Nguyen Quoc Toan , Baek Kwanghee , Yoon Ho Sup 
Published: April 2012

AbstractDengue is one of the most infectious viral diseases prevalent mainly in tropical countries. The virus is transmitted by Aedes species of mosquito, primarily Aedes aegypti. Dengue remains a challenging drug target for years as the virus eludes the immune responses. Currently, no vaccines or antiviral drugs are available for dengue prevention. Previous studies suggested that the immunosuppressive drug FK506 shows antimalarial activity, and its molecular target, FK506‐binding protein (FKBP), was identified in the Plasmodium parasite. Likewise, a FKBP family protein has been identified in A. aegypti (AaFKBP12) in which AaFKBP12 is assumed to play a similar role in its life cycle. FKBPs belong to a highly conserved class of proteins and are considered as an attractive pharmacological target. Herein, we present a high‐resolution crystal structure of AaFKBP12 at 1.3 Å resolution and discuss its structural features throwing light in facilitating the design of potential antagonists against the dengue‐transmitting mosquito.
Choice of synonymous codons associated with protein folding
Authors: Huang Jitao T. , Xing Dajie J. , Huang Wei 
Published: April 2012

AbstractBioinformatical studies suggest that additional information provided by nucleic acids is necessary to construct protein three‐dimensional structures. We find underlying correlations between the contents of bases. All correlations occur at the third codon position of a gene sequence. Four inverse relationships are observed between u3 and c3, between a3 and g3, between u3 and g3, and between c3 and a3; and two positive relationships are apparent between u3 and a3, and between c3 and g3. Their correlation coefficients reach −0.92, −0.89, −0.83, −0.85, 0.83, and 0.66, respectively, for large proteins with multistate folding kinetics. The interconnection of bases can be ascribed to choice of synonymous codons associated with protein folding in vivo. In this study, the refolding rate constants of large proteins correlate with the contents of the third base, suggesting that there is underlying biochemical rationale of guiding protein folding in choosing synonymous codons. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Computational analysis predicts the Kaposi's sarcoma‐associated herpesvirus tegument protein ORF63 to be alpha helical
Authors: Boyle Joseph P. , Monie Tom P. 
Published: April 2012

AbstractThe innate immune response provides our first line of defence against infection. Over the course of evolution, pathogens have evolved numerous strategies to either avoid activating or to limit the effectiveness of the innate immune system. The Kaposi's sarcoma‐associated herpesvirus (KSHV) contains tegument proteins in the virion that contribute to immune evasion and aid the establishment of viral infection. For example, the KSHV tegument protein ORF63 modulates inflammasome activation to inhibit the innate immune response against the virus. Understanding the likely structure of proteins involved in immune evasion enables potential mechanisms of action to be proposed. To understand more fully how ORF63 modulates the innate immune system we have utilized widely available bioinformatics tools to analyze the primary protein sequence of ORF63 and to predict its secondary and tertiary structure. We found that ORF63 is predicted to be almost entirely alpha‐helical and may possess similarity to HEAT repeat containing proteins. Consequently, ORF63 is unlikely to be a viral homolog of the NLR protein family. ORF63 may inhibit the innate immune response by flexibly interacting with its target protein and inhibiting the recruitment of protein co‐factors and/or conformational changes required for immune signaling. Proteins 2012; © 2012 Wiley Periodicals, Inc.