bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unusually marked hypoxic sensitization to indoloquinone E09 and mitomycin C in a human colon‐tumour cell line that lacks DT‐diaphorase activity
Authors: Plumb Jane A. , Workman Paul 
Published: July 2010

AbstractStudies with purified DT‐diaphorase have shown that the enzyme is capable of catalyzing a two‐electron reduction of the novel indoloquinone E09 to a DNA‐damaging alkylating species. The aim of this study was to determine to what extent DT‐diaphorase may be involved in the metabolic activation of E09 and mitomycin C in both aerobic and hypoxic conditions. Two human colon‐carcinoma cell lines were used; HT29 has high levels of DT‐diaphorase whilst BE lacks this activity because of a point mutation in the NQOI gene. In aerobic conditions the 2 cell lines show similar sensitivities to a number of cytotoxic drugs including cisplatin, doxorubicin and etopo‐side. They are equally sensitive to the benzotriazine di‐N‐oxide SR 4233 but HT29 is more sensitive than BE to mitomycin C and E09. Sensitivity to SR 4233 is increased by about 100‐fold for both cell lines in hypoxic conditions. DT‐diaphorase‐deficient BE cells show markedly increased sensitivity to mitomycin C and particularly E09 in hypoxic conditions, whereas DT‐diaphorase‐rich HT29 cells show little hypoxic sensitization to these agents unless exposed in the presence of dicoumarol. These results suggest that DT‐diaphorase can reduce E09 and mitomycin C to potent cytotoxic species in aerobic conditions, and this activity predominates over the one‐electron‐reducing enzymes even in hypoxic conditions. In the absence of DT‐diaphorase activity, E09 and mitomycin C are reduced in hypoxic conditions, presumably by one‐electron‐reducing enzymes, to a similar or greater extent than is achieved with DT‐diaphorase.
Aryl hydrocarbon hydroxylase activity in chemically induced and toremifene‐treated mammary tumors in rats
Authors: Pyykkö Kaija , Ala‐Uotila Sari , Jaakkola Ulla‐Marjut , Lähde Matti 
Published: July 2010

AbstractAryl hydrocarbon hydroxylase (AHH) and NADPH‐cyto‐chrome P450 reductase (NCR) activity of microsomes from liver, lungs, uterus and mammary tumors in dimethylbenz‐antrachene‐induced and torem'rfene‐treated female Sprague‐Dawley rats were studied. AHH and NCR activity in tumors and uteri was low compared with that in livers and lungs. The distribution of AHH in tumors was wide and skewed. It varied in different tumors of the same animal as widely as between different animals. The enzyme activity in tumors did not correlate with that in the liver, lungs or uterus of the same animal. Toremifene had no effect on AHH or NCR in tumor or liver, but it decreased them in lungs. Tumor AHH activity correlated with its overall growth rate and development stage. The results suggest that malignant transformation leading to the defect in growth regulation also confuses the complex regulatory system of AHH activity.
Carcinogenicity of 4‐methoxyphenol and 4‐methylcatechol in F344 rats
Authors: Asakawa Emiko , Hirose Masao , Hagiwara Akihiro , Takahashi Satoru , Ito Nobuyuki 
Published: July 2010

AbstractThe carcinogenic potentials of 4‐methoxyphenol (4‐MP) and 4‐methylcatechol (4‐MC), phenolic compounds which are structurally similar to the known forestomach carcinogen BHA and the glandular stomach carcinogen catechol respectively, and cause considerably enhanced cell proliferation and cytotoxicities in rat forestomach and/or glandular stomach epithelium, were examined in male and female F344 rats. Groups of 30 male and female animals were administered diets containing 2% 4‐MP or 2% 4‐MC for 104 weeks. Histopathological findings in the 4‐MP case included atypical hyperplasias (male, 67%, female, 37%), papillomas (50%, 23%) and squamous‐cell carcinomas (77%, 20%) in the forestomach. 4‐MC induced forestomach papillomas (70%, 93%) and squamous‐cell carcinomas (53%, 37%), also glandular stomach submucosal hyperplasias (90%, 93%), adenomas (100%, 100%) and adenocarcinomas (57%, 47%), with ulceration or erosion. The degree of differentiation of the squamous‐cell carcinomas induced by 4‐MP was less than with 4‐MC. The present study demonstrated unequivocal forestomach carcinogenicity for 4‐MP and forestomach and glandular stomach carcinogenicity for 4‐MC, with cytotoxicity and cell proliferation both appearing as important factors for these non‐genotoxic carcinogens.
A novel composite construct increases the vascularization potential of PEG hydrogels through the incorporation of large fibrin ribbons
Authors: Mason Mariah N. , Mahoney Melissa J. 
Published: July 2010

AbstractDeveloping a mechanism to vascularize tissue‐engineered constructs is imperative for transplant function and integration, particularly when delivering hypoxia‐sensitive tissues, such as pancreatic islets. Previous efforts have focused on bulk modifications of scaffold materials rendering the entire construct permissive to vessel penetration or the formation of a porous structure where vessels can infiltrate the empty spaces. Here, we describe a novel construct composed of large fibrin ribbons encapsulated within a poly(ethylene glycol) (PEG) hydrogel. The PEG/fibrin ribbon composite scaffold facilitates coculture of adhesive and nonadhesive cell types, thus providing closely neighboring environments with distinct material properties specific to the needs of two clinically relevant cell populations. This advantage is demonstrated here by the successful coculture of pancreatic islets in the PEG component and vessel‐forming endothelial cells in entrapped fibrin ribbons. Transplanted endothelial cells can form anastomosies with host vasculature, suggesting that our cocultures may lead to more rapid scaffold vascularization. Additionally, we show that surface‐seeded endothelial cells form multicellular projections that migrate into nonadhesive PEG hydrogels along permissive fibrin ribbons, further demonstrating composite construct vascularization potential. Distribution of large fibrin ribbons throughout PEG hydrogels provide a potential mechanism for vascularization of a well‐established biomaterial without inherently changing its desirable properties. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Controlled induction of distributed microdeformation in wounded tissue via a microchamber array dressing
Authors: Kane Bartholomew J. , Younan George , Helm Douglas , Dastouri Pouya , Prentice‐Mott Harrison , Irimia Daniel , Chan Rodney K. , Toner Mehmet , Orgill Dennis P. 
Published: July 2010

AbstractMechanical stimuli are known to play an important role in determining the structure and function of living cells and tissues. Recent studies have highlighted the role of mechanical signals in mammalian dermal wound healing. However, the biological link between mechanical stimulation of wounded tissue and the subsequent cellular response has not been fully determined. The capacity for researchers to study this link is partially limited by the lack of instrumentation capable of applying controlled mechanical stimuli to wounded tissue. The studies outlined here tested the hypothesis that it was possible to control the magnitude of induced wound tissue deformation using a microfabricated dressing composed of an array of open‐faced, hexagonally shaped microchambers rendered in a patch of silicone rubber. By connecting the dressing to a single vacuum source, the underlying wounded tissue was drawn up into each of the microchambers, thereby inducing tissue deformation. For these studies, the dressings were applied to full‐thickness murine dermal wounds with 200 mmHg vacuum for 12 h. These studies demonstrated that the dressing was capable of inducing wound tissue deformation with values ranging from 11 to 29%. Through statistical analysis, the magnitude of the induced deformation was shown to be a function of both microchamber height and width. These results demonstrated that the dressing was capable of controlling the amount of deformation imparted in the underlying tissue. By allowing the application of mechanical stimulation with varying intensities, such a dressing will enable the performance of sophisticated mechanobiology studies in dermal wound healing. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Calcium supplementation and the risks of atherosclerotic vascular disease in older women: Results of a 5-year RCT and a 4.5-year follow-up
Authors: Lewis Joshua R , Calver Janine , Zhu Kun , Flicker Leon , Prince Richard L 
Published: July 2010

Abstract
Concern has been expressed that calcium supplementation, a key intervention for preventing osteoporotic fracture in older women, may increase the risk of atherosclerotic vascular disease. To evaluate the risk further, an examination of complete verified atherosclerotic vascular hospitalization and mortality data from a 5-year randomized, controlled trial (RCT) of calcium carbonate and 4.5 years of posttrial follow-up was undertaken. This study used data from a published 5-year randomized, double-blinded, placebo-controlled trial [Calcium Intake Fracture Outcome Study (CAIFOS)]. The participants were 1460 women aged 75.1 ± 2.7 years at baseline (1998) recruited from the general population and randomized to receive 1200 mg of calcium carbonate daily or an identical placebo. All hospital admission and deaths during the 5-year study and the 4.5-year follow-up were derived from the Western Australian Data Linkage Service (WADLS). Hazard ratios (HRs) for the combined endpoint of atherosclerotic vascular mortality or first hospitalization were calculated using prespecified intention-to-treat and per-protocol models. The intervention group that received calcium supplementation did not have a higher risk of death or first-time hospitalization from atherosclerotic vascular disease in either the 5-year RCT [multivariate-adjusted HR = 0.938, 95% confidence interval (CI) 0.690–1.275] or during the 9.5 years of observational study (multivariate-adjusted HR = 0.919, 95% CI 0.737–1.146). Further analysis suggested that calcium supplementation may reduce the risk of hospitalization and mortality in patients with preexisting atherosclerotic cardiovascular disease. This trial provides compelling evidence that calcium supplementation of 1200 mg daily does not significantly increase the risk of atherosclerotic vascular disease in elderly women. © 2011 American Society for Bone and Mineral Research.
Impact of race on hyperparathyroidism, mineral disarrays, administered vitamin D mimetic, and survival in hemodialysis patients
Authors: Kalantar-Zadeh Kamyar , Miller Jessica E , Kovesdy Csaba P , Mehrotra Rajnish , Lukowsky Lilia R , Streja Elani , Ricks Joni , Jing Jennie , Nissenson Allen R , Greenland Sander , Norris Keith C 
Published: July 2010

Abstract
Blacks have high rates of chronic kidney disease, are overrepresented among the US dialysis patients, have higher parathyroid hormone levels, but greater survival compared to nonblacks. We hypothesized that mineral and bone disorders (MBDs) have a bearing on survival advantages of black hemodialysis patients. In 139,328 thrice-weekly treated hemodialysis patients, including 32% blacks, in a large dialysis organization, where most laboratory values were measured monthly for up to 60 months (July 2001 to June 2006), we examined differences across races in measures of MBDs and survival predictabilities of these markers and administered the active vitamin D medication paricalcitol. Across each age increment, blacks had higher serum calcium and parathyroid hormone (PTH) levels and almost the same serum phosphorus and alkaline phosphatase levels and were more likely to receive injectable active vitamin D in the dialysis clinic, mostly paricalcitol, at higher doses than nonblacks. Racial differences existed in mortality predictabilities of different ranges of serum calcium, phosphorus, and PTH but not alkaline phosphatase. Blacks who received the highest dose of paricalcitol (&gt;10 µg/week) had a demonstrable survival advantage over nonblacks (case-mix-adjusted death hazard ratio = 0.87, 95% confidence level 0.83–0.91) compared with those who received lower doses (&lt;10 µg/week) or no active vitamin D. Hence, in black hemodialysis patients, hyperparathyroidism and hypercalcemia are more prevalent than in nonblacks, whereas hyperphosphatemia or hyperphosphatasemia are not. Survival advantages of blacks appear restricted to those receiving higher doses of active vitamin D. Examining the effect of MBD modulation on racial survival disparities of hemodialysis patients is warranted. © 2010 American Society for Bone and Mineral Research.
Co‐chaperone BAG3 and adenovirus penton base protein partnership
Authors: Gout E. , Gutkowska M. , Takayama S. , Reed J.C. , Chroboczek J. 
Published: July 2010

AbstractThe BAG family of Hsp70/Hsc70 co‐chaperones is characterised by the presence of a conserved BAG domain at the carboxyl‐terminus. BAG3 protein is the only member of this family containing also the N‐terminally located WW domain. We describe here the identification of adenovirus (Ad) penton base protein as the first BAG3 partner recognising BAG3 WW domain. Ad penton base is the viral capsid constituent responsible for virus internalisation. It contains in the N‐terminal part two conserved PPxY motifs, known ligands of WW domains. In cells producing Ad penton base protein, cytoplasmic endogenous BAG3 interacts with it and co‐migrates to the nucleus. Preincubation of BAG3 with Ad base protein results in only slight modulation of BAG3 co‐chaperone activity, suggesting that this interaction is not related to the classical BAG3 co‐chaperone function. However, depletion of BAG3 impairs the cell entry of the virus and viral progeny production in Ad‐infected cells, suggesting that the interaction between virus penton base protein and cellular co‐chaperone BAG3 positively influences virus life cycle. These results thus demonstrate a novel host–pathogen interaction, which contributes to the successful infectious life cycle of adenoviruses. In addition, these data enrich our knowledge about the multifunctionality of the BAG3 co‐chaperone. J. Cell. Biochem. 111: 699–708, 2010. © 2010 Wiley‐Liss, Inc.
AKT1 leader gene and downstream targets are involved in a rat model of kidney allograft tolerance
Authors: Jovanovic Vojislav , Giacomelli Luca , Sivozhelezov Victor , Degauque Nicolas , Lair David , Soulillou Jean‐Paul , Pechkova Eugenia , Nicolini Claudio , Brouard Sophie 
Published: July 2010

AbstractTolerance is the so‐called “Holy Grail” of transplantation but achieving this state is proving a major challenge, particularly in the clinical settings. This tolerance state can be induced in rodent models using a variety of maneuvers. This phenomenon is classically characterized by donor specificity (recipients accept a secondary donor‐specific allograft but reject third‐party allograft) as well as by the absence of chronic rejection lesion. We previously showed that administration and anti‐donor anti‐class II serum on the day of transplantation induce tolerance to a kidney allograft in the LEW‐1W to LEW‐1A strain combination. In this study, we used DNA microarrays to compare gene patterns involved in anti‐donor anti‐class II tolerated or untreated syngeneic kidney transplants in this strain combination. Statistical and non‐statistical analyses were combined with ab initio analysis, using the recently developed leader gene approach, to shed new light on this phenomenon. Theoretical and experimental results suggest that tolerance and rejection outcome may be in large part determined by low expression variations of some genes, which can form a core gene network around specific genes such as Rac1, NFKB1, RelA, AKT1, IKBKB, BCL2, BCLX, and CHUK. Through this model, we showed that AKT1 gene, WNT pathway and NO synthesis are strictly connected to each other and may play an important role in kidney tolerance and rejection processes, with AKT1 gene being the center of this complex network of interactions. J. Cell. Biochem. 111: 709–719, 2010. © 2010 Wiley‐Liss, Inc.
Homology modeling and molecular dynamics simulation studies of human type 1 3β‐hydroxysteroid dehydrogenase: Toward the understanding of cofactor specificity
Authors: Zhao Yongbing , Xiao Jingfa 
Published: July 2010

AbstractThe human type 1 isoform of 3β‐hydroxysteroid dehydrogenase is a member of short‐chain oxidoreductase family that catalyzes the conversion of dehydroepiandrosterone to androstenedione. To compare the molecular events underlying cofactor specificity in the wild‐type and D35A/K36R mutant enzymes, molecular dynamics (MD) simulations of fully solvated cofactor‐3β‐HSD1 (wild‐type and mutant) complex are performed. Molecular modeling methods are applied to construct three‐dimensional models of cofactor‐3β‐HSD1 complexes based on Uridine diphosphate (UDP)‐galactose 4‐epimerase crystal structure from Escherichia coli. The binding mode and binding energy analysis between four different complexes indicate that Asp35 and Lys36 are key residues for the cofactor specificity of 3β‐HSD1, which is in agreement with mutagenesis studies results obtained by Thomas et al.8 The MD results also display that the residue Glu41 may be another important residue except Asp35 and Lys36 for the cofactor specificity and that this result needs further mutational experiment for validation. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Parallel implementation of γ‐point pseudopotential plane‐wave DFT with exact exchange
Authors: Bylaska Eric J. , Tsemekhman Kiril , Baden Scott B. , Weare John H. , Jonsson Hannes 
Published: July 2010

AbstractSemi‐local functionals commonly used in density functional theory (DFT) studies of solids usually fail to reproduce localized states such as trapped holes, polarons, excitons, and solitons. This failure is ascribed to self‐interaction which creates a Coulomb barrier to localization. Pragmatic approaches in which the exchange correlation functionals are augmented with small amount of exact exchange (hybrid‐DFT, e.g., B3LYP and PBE0) have shown to promise in rectifying this type of failure, as well as producing more accurate band gaps and reaction barriers. The evaluation of exact exchange is challenging for large, solid state systems with periodic boundary conditions, especially when plane‐wave basis sets are used. We have developed parallel algorithms for implementing exact exchange into pseudopotential plane‐wave DFT program and we have implemented them in the NWChem program package. The technique developed can readily be employed in Γ‐point plane‐wave DFT programs. Furthermore, atomic forces and stresses are straightforward to implement, making it applicable to both confined and extended systems, as well as to Car‐Parrinello ab initio molecular dynamic simulations. This method has been applied to several systems for which conventional DFT methods do not work well, including calculations for band gaps in oxides and the electronic structure of a charge trapped state in the Fe(II) containing mica, annite. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Gabedit—A graphical user interface for computational chemistry softwares
Authors: Allouche Abdul‐Rahman 
Published: July 2010

AbstractGabedit is a freeware graphical user interface, offering preprocessing and postprocessing adapted (to date) to nine computational chemistry software packages. It includes tools for editing, displaying, analyzing, converting, and animating molecular systems. A conformational search tool is implemented using a molecular mechanics or a semiempirical potential. Input files can be generated for the computational chemistry software supported by Gabedit. Some molecular properties of interest are processed directly from the output of the computational chemistry programs; others are calculated by Gabedit before display. Molecular orbitals, electron density, electrostatic potential, nuclear magnetic resonance shielding density, and any other volumetric data properties can be displayed. It can display electronic circular dichroism, UV–visible, infrared, and Raman‐computed spectra after a convolution. Gabedit can generate a Povray file for geometry, surfaces, contours, and color‐coded planes. Output can be exported to a selection of popular image and vector graphics file formats; the program can also generate a series of pictures for animation. Quantum mechanical electrostatic potentials can be calculated using the partial charges on atoms, or by solving the Poisson equation using the multigrid method. The atoms in molecule charges can also be calculated. Gabedit is platform independent. The code is distributed under free open source X11 style license and is available at http://gabedit.sourceforge.net/. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Lysophosphatidylcholine‐mediated functional inactivation of syndecan‐4 results in decreased adhesion and motility of dendritic cells
Authors: Bühligen Johannes , Himmel Mirko , Gebhardt Carl , Simon Jan C. , Ziegler Wolfgang , Averbeck Marco 
Published: July 2010

AbstractFollowing antigen contact, maturation and migration of DCs into lymphatic tissues are crucial to the developing immune response or maintenance of tolerance. Lysophosphatidylcholine (LysoPC) is generated during apoptosis of cells and acts as a “find‐and‐eat‐me” signal thought to prevent autoimmunity. Moreover, LysoPC can activate PKCδ and initiates a signaling cascade that leads to phosphorylation and inactivation of syndecan‐4 (SDC4), a heparansulfate proteoglycan integrin co‐receptor. In human monocyte‐derived DCs, we recently demonstrated that SDC4 is upregulated during maturation thereby stimulating DC motility. Here, we investigate the effects of LysoPC on DC motility as well as on the involvement of PKCδ phosphorylation‐dependent regulation of DC motility by SDC4 and PKCα. Employing a static adhesion assay and videomicroscopy, we show that LysoPC inhibits adhesion of DCs to fibronectin and motility of DCs by decreasing podosome formation. Moreover, DC podosome formation and motility, which both are regulated by SDC4 and subject to control by PKCδ‐dependent phosphorylation of SDC4, were inhibited in LysoPC‐matured DCs. Thus, these DC are defective in adhesion and migration. Based on our results, we hypothesize that LysoPC released during apoptosis might delay DC migration to lymphoid organs and thus prevent autoimmunity. J. Cell. Physiol. 225: 905–914, 2010. © 2010 Wiley‐Liss, Inc.
To chew or not to chew: fecal particle size in herbivorous reptiles and mammals
Authors: Fritz Julia , Hummel Jürgen , Kienzle Ellen , Streich W. Jürgen , Clauss Marcus 
Published: July 2010

AbstractA major difference between reptile and mammalian herbivores is that the former do not masticate their food. Actually, food particle size reduction by chewing is usually considered one of the adaptations facilitating the higher metabolic rates of mammals. However, quantitative comparisons of ingesta particle size between the clades have, to our knowledge, not been performed so far. We measured mean fecal particle size (MPS) in 79 captive individuals of 14 reptile herbivore species (tortoises, lizards, and Corucia zebrata) by wet sieving and compared the results with a mammalian dataset. MPS increased with body mass in both clades, but at a significantly higher level in reptiles. Limited evidence in free‐ranging and captive individuals of Testudo hermanni indicates that in reptiles, the ability to crop food and food particle size significantly influence fecal particle size. The opportunistic observation of a drastic particle size difference between stomach and intestinal contents corroborates findings that in reptiles, in contrast to terrestrial mammals, significant ingesta particle size reduction does occur in the gastrointestinal tract, most likely owing to microbial action during very long ingesta retention. Whether behavioral adaptations to controlling ingesta particle size, such as deliberate small bite sizes, are adaptive strategies in reptiles remains to be investigated. J. Exp. Zool. 313A:579–586, 2010. © 2010 Wiley‐Liss, Inc.