bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic K‐ras promotes early carcinogenesis in the mouse proximal colon
Authors: Calcagno Shelly R. , Li Shuhua , Colon Migdalisel , Kreinest Pamela A. , Thompson E. Aubrey , Fields Alan P. , Murray Nicole R. 
Published: February 2008

AbstractOncogenic K‐ras mutations are frequently observed in colon cancers and contribute to transformed growth. Oncogenic K‐ras is detected in aberrant crypt foci (ACF), precancerous colonic lesions, demonstrating that acquisition of a K‐ras mutation is an early event in colon carcinogenesis. Here, we investigate the role of oncogenic K‐ras in neoplastic initiation and progression. Transgenic mice in which an oncogenic K‐rasG12D allele is activated in the colonic epithelium by sporadic recombination (K‐rasLA2 mice) develop spontaneous ACF that are morphologically indistinguishable from those induced by the colon carcinogen azoxymethane (AOM). Similar neoplastic changes involving the entire colon are induced in transgenic mice constitutively expressing K‐rasG12D throughout the colon (LSL‐K‐rasG12D/Villin‐Cre mice). However, the biochemistry and fate of K‐ras‐induced lesions differ depending upon their location within the colon in these mice. In the proximal colon, K‐rasG12D induces increased expression of procarcinogenic protein kinase CβII (PKCβII), activation of the MEK/ERK signaling axis and increased epithelial cell proliferation. In contrast, in the distal colon, K‐rasG12D inhibits expression of procarcinogenic PKCβII and induces apoptosis. Treatment of K‐rasLA2 mice with AOM leads to neoplastic progression of small ACF to large, dysplastic microadenomas in the proximal, but not the distal colon. Thus, oncogenic K‐ras functions differently in the proximal and distal colon of mice, inducing ACF capable of neoplastic progression in the proximal colon, and ACF with little or no potential for progression in the distal colon. Our data indicate that acquisition of a K‐ras mutation is an initiating neoplastic event in proximal colon cancer development in mice. © 2008 Wiley‐Liss, Inc.
Efficient model chemistries for peptides. I. General framework and a study of the heterolevel approximation in RHF and MP2 with Pople split‐valence basis sets
Authors: Echenique Pablo , Alonso José Luis 
Published: February 2008

AbstractWe present an exhaustive study of more than 250 ab initio potential energy surfaces (PESs) of the model dipeptide HCO‐L‐Ala‐NH2. The model chemistries (MCs) investigated are constructed as homo‐ and heterolevels involving possibly different RHF and MP2 calculations for the geometry and the energy. The basis sets used belong to a sample of 39 representants from Pople's split‐valence families, ranging from the small 3‐21G to the large 6‐311++G(2df,2pd). The reference PES to which the rest are compared is the MP2/6‐311++G(2df,2pd) homolevel, which, as far as we are aware, is the most accurate PES in the literature. All data sets have been analyzed according to a general framework, which can be extended to other complex problems and which captures the nearness concept in the space of MCs. The great number of MCs evaluated has allowed us to significantly explore this space and show that the correlation between accuracy and computational cost of the methods is imperfect, thus justifying a systematic search for the combination of features in a MC that is optimal to deal with peptides. Regarding the particular MCs studied, the most important conclusion is that the potentially very cost‐saving heterolevel approximation is a very efficient one to describe the whole PES of HCO‐L‐Ala‐NH2. Finally, we show that, although RHF may be used to calculate the geometry if a MP2 single‐point energy calculation follows, pure RHF//RHF homolevels are not recommendable for this problem. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
The effect of electron correlation on the conformational space of melatonin
Authors: Csontos József , Kálmán Péter , Tasi Gyula , Kálmán Miklós , Murphy Richard F. , Lovas Sándor 
Published: February 2008

AbstractThe pineal gland hormone melatonin regulates several physiological processes including circadian rhythm and also alleviates oxidative stress‐induced degenerative diseases. In spite of its important biological roles, no high level ab initio conformational study has been conducted to reveal its structural features. In this work, the conformational flexibility of melatonin was investigated using correlated ab initio calculations. Conformers, obtained previously at the Hartree‐Fock level (HF/6‐31G*), were fully optimized using second order Møller‐Plesset perturbation theory applying the frozen core approximation (MP2(FC)/6‐31G*). Furthermore, single‐point MP4(SDQ,FC)/6‐31G*//MP2(FC)/6‐31G* computations were performed to investigate the effect of higher order perturbation terms. The HF and MP2 conformational spaces are considerably different: the initial 128 structures converged into 102 different local minima as confirmed by frequency calculations; 28 new minima appeared and 26 previous HF local minima disappeared; no “all‐trans” C3 side chain conformations are seen at the MP2(FC) level. The MP2 global minimum conformation is stabilized by an aromatic‐side chain interaction. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Blue shifts of the CH stretching vibrations in hydrogen‐bonded and protonated trimethylamine. Effect of hyperconjugation on bond properties
Authors: Chandra Asit K. , Parveen Salma , Das Subojit , Zeegers‐Huyskens Thérèse 
Published: February 2008

AbstractThe optimized geometry of isolated trimethylamine (TMA), its hydrogen bond complexes with phenol derivatives and protonated TMA is calculated at the B3LYP/6‐31++G(d,p) level. A natural bond orbital (NBO) analysis on these systems is carried out at the same level of theory. In isolated TMA, one of the CH bond in each of the three CH3groups is more elongated than the two other ones. As revealed by the NBO data, this results from a hyperconjugative interaction from the N lone pair to the σ*(CH) orbitals of the CH bonds being in a transoid position with respect to the N lone pair. The formation of an intermolecular OH···N hydrogen bond with phenols results in a decrease of the lone pair effect. A linear correlation is found between the decrease in occupation of the σ*(CH) orbitals and the decrease in the hyperconjugative interaction energy in the complexes and isolated TMA. Complex formation with phenols results in a blue shift of 55–74 cm−1of the CH stretching vibrations involved in the lone pair effect. Smaller blue shifts between 14 and 23 cm−1are predicted for the other CH bonds. In these complexes, a linear correlation is found between the frequency shifts and the elongation of the CH bonds. Protonation of TMA results in a nearly equalization of all the CH distances and a blue shift of 180 cm−1of the CH bonds involved in hyperconjugation with the N lone pair. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
On the performance of some aromaticity indices: A critical assessment using a test set
Authors: Feixas Ferran , Matito Eduard , Poater Jordi , Solà Miquel 
Published: February 2008

AbstractAromaticity is a central chemical concept widely used in modern chemistry for the interpretation of molecular structure, stability, reactivity, and magnetic properties of many compounds. As such, its reliable prediction is an important task of computational chemistry. In recent years, many methods to quantify aromaticity based on different physicochemical properties of molecules have been proposed. However, the nonobservable nature of aromaticity makes difficult to assess the performance of the numerous existing indices. In the present work, we introduce a series of fifteen aromaticity tests that can be used to analyze the advantages and drawbacks of a group of aromaticity descriptors. On the basis of the results obtained for a set of ten indicators of aromaticity, we conclude that indices based on the study of electron delocalization in aromatic species are the most accurate among those examined in this work. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
The influence of television on willingness to seek therapy
Authors: Vogel David L. , Gentile Douglas A. , Kaplan Scott A. 
Published: February 2008

AbstractTelevision portrayals of psychologists may be contributing to an unfavorable perception of mental health services. The present study (N=369) used structural equation modeling to examine the relationship between exposure to television programs, perceptions of therapy (i.e., perceived stigma, anticipated risks and benefits, and attitudes towards therapy), and intentions to seek therapy. The results demonstrated that (a) the relationship between television exposure and attitudes was fully mediated by stigma and anticipated benefits, and (b) the relationship between television exposure and intentions to seek therapy was fully mediated by attitudes, stigma, and anticipated benefits. Furthermore, 54% of the variance in attitudes and 47% of the variance in intentions was accounted for by the variables in the model. © 2008 Wiley Periodicals, Inc. J Clin Psychol. 64: 1–20, 2008.
A content analysis of advertisements for psychotherapy workshops: implications for disseminating empirically supported treatments
Authors: Cook Joan M. , Weingardt Kenneth R. , Jaszka Jacqueline , Wiesner Michael 
Published: February 2008

AbstractThis study involved a content analysis of 261 unique advertisements for psychotherapy workshops that appeared in two bimonthly clinical magazines, Psychotherapy Networker and Counselor, during a 2‐year period. Two independent judges coded each advertisement and documented the type and prevalence of advertising appeals used. From the seminal diffusion of innovations model, Rogers' (2003) five perceived characteristics of innovations found to influence adoption in diverse fields were not well represented in these workshops appeals, appearing less than 10% each. Few advertisements cited specific empirically supported treatments or presented any evidence of treatment effectiveness beyond expert testimonials. The most frequently noted appeals were to benefit the clinician (e.g., earning education credit or developing skills), characteristics that enhance credibility of the workshop (e.g., reference to storied history or mention of faculty), and features of the advertisements itself (e.g., use of superlatives and exclamation points). Promotional strategies to advertise psychotherapy workshops can be used to inform the dissemination of empirically supported treatments. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64: 1–12, 2008.
A model for diabetic nephropathy: Advantages of the inducible cAMP early repressor transgenic mouse over the streptozotocin‐induced diabetic mouse
Authors: Inada Akari , Kanamori Hiroshi , Arai Hidenori , Akashi Tomoyuki , Araki Makoto , Weir Gordon C. , Fukatsu Atsushi 
Published: February 2008

AbstractWe have previously found progressive diabetic nephropathy in inducible cAMP early repressor (ICER Iγ) transgenic (Tg) mice. The ICER Iγ Tg mouse is an interesting model of sustained hyperglycemia due to its low production of insulin and insulin‐producing β cells. Here in a longitudinal study we further analyzed diabetic nephropathy and structural and functional alterations in other organs, comparing our model with streptozotocin (STZ)‐diabetic model mice. The high‐dose STZ‐diabetic model showed marked variation in blood glucose levels and severe toxicity of STZ in the liver and kidney. The low‐dose STZ‐diabetic model showed less toxicity, but the survival rate was very low. STZ‐diabetic mice had much more variation of glomerular hypertrophy and sclerosis. Furthermore, non‐specific toxicity of STZ or insulin injections to maintain optimal blood glucose levels might have another effect upon the diabetic renal changes. In contrast, ICER Iγ Tg mice exhibited a stable and progressive phenotype of diabetic kidney disease solely due to chronic hyperglycemia without other modulating factors. Thus, ICER Iγ Tg mouse has advantages for examining diabetic renal disease, and offers unique and very different perspectives compared to STZ model. J. Cell. Physiol. 215: 383–391, 2008. © 2008 Wiley‐Liss, Inc.
Redox‐regulation of Erk1/2‐directed phosphatase by reactive oxygen species: Role in signaling TPA‐induced growth arrest in ML‐1 cells
Authors: Traore Kassim , Sharma Rajni , Thimmulappa Rajesh K. , Watson Walter H. , Biswal Shyam , Trush Michael A. 
Published: February 2008

AbstractExtracellular signal‐regulated kinase (Erk)1/2 activity signals myeloid cell differentiation induced by 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Previously, we reported that Erk1/2 activation (phosphorylation) induced by TPA required reactive oxygen species (ROS) as a second messenger. Here, we hypothesized that ROS generated in response to TPA inhibit Erk1/2‐directed phosphatase activity, which leads to an increase phosphorylation of Erk1/2 to signal p21WAF1/Cip1‐mediated growth arrest in ML‐1 cells. Incubation of ML‐1 cells with TPA resulted in a marked accumulation of phosphorylated Erk1/2, and is subsequent to H2O2 generation. Interestingly, post‐TPA‐treatment with N‐acetylcysteine (NAC) stimulated a marked and a rapid dephosphorylation of Erk1/2, suggesting a regeneration of Erk1/2‐directed phospahatase activity by NAC. ROS generation in ML‐1 cells induced by TPA was suggested to occur in the mitochondrial electron transport chain (METC) based on the following observations: (i) undifferentiated ML‐1 cells not only lack p67‐phox and but also express a low level of p47‐phox key components required for NADPH oxidase enzymatic activity, (ii) pretreatment with DPI, an inhibitor of NADH‐ and NADPH‐dependent enzymes, or rhein, an inhibitor of complex I, blocked the ROS generation, and (iii) examination of the microarray analysis data and Western blot analysis data revealed an induction of MnSOD expression at both mRNA and protein levels in response to TPA. MnSOD is a key member of the mitochondrial defense system against mitochondrial‐derived superoxide. Together, this study suggested that TPA stimulated ROS generation as a second messenger to activate Erk1/2 via a redox‐mediated inhibition of Erk1/2‐directed phosphatase in ML‐1 cells. J. Cell. Physiol. 216: 276–285, 2008. © 2008 Wiley‐Liss, Inc.
Response surface methodology as a tool to study the lipase‐catalyzed synthesis of betulinic acid ester
Authors: Yasin Yamin , Basri Mahiran , Ahmad Faujan , Salleh Abu Bakar 
Published: February 2008

AbstractBACKGROUND: The synthesis of betulinic acid ester using betulinic acid and oleyl alcohol catalyzed by Novozym 435 (immobilized Candida antarctica lipase) was carried out. Response surface methodology (RSM) based on a five‐level, three‐variable, central composite rotatable design (CCRD) was employed to evaluate the interactive effects of various parameters. The parameters were reaction time (8–16 h), temperature (20–60 °C) and enzyme amount (120–160 mg).RESULTS: Simultaneously increasing reaction time, temperature and amount of enzyme increased the yields of betulinic acid ester produced.CONCLUSION: The optimum conditions derived via RSM for the reaction were reaction time of 10.2 h, temperature of 53.1 °C and enzyme amount of 138 mg. The actual experimental yield was 48.5% under optimum conditions, which compared well with the maximum predicted value of 47.6%. Copyright © 2008 Society of Chemical Industry
Impact of the addition of an enzyme pool on an activated sludge system treating dairy wastewater under fat shock loads
Authors: Damasceno Fernanda R C , Freire Denise M G , Cammarota Magali C 
Published: February 2008

AbstractBACKGROUND: The application of lipase‐rich enzyme pools (such as the crude solid enzymatic preparation (SEP) obtained from Penicillium restrictum solid‐state fermentation of agro‐industrial wastes) to activated sludge systems may be an effective strategy for preventing various operational problems. The continuous addition of SEP to the treatment system can become cost‐prohibitive when in situ production and/or storage are factored in. The application of SEP to high‐fat wastewater treatment would only be justified as an emergency measure, such as a sudden increase in the fat content of the bioreactor influent. Therefore, the primary objective of this work was to investigate the efficiency of a crude SEP during fat shock loads, simulated through the periodic addition of dairy industry waste containing high fat concentrations to the feed stock of an activated sludge system, operated in continuous mode.RESULTS: The test bioreactor exhibited a higher average chemical oxygen demand (COD) removal efficiency than the control bioreactor (83% for control and 90% for test) and the fat accumulation in the biological flocs of the test bioreactor was 3.2 times lower than that in the control bioreactor. Turbidity was also lower in the effluent of the test bioreactor (123 and 66 FTU in control and test, respectively) and it had a shorter recovery time between shock loads, especially when the interval between loads was shorter than one month (biweekly and weekly shock loads).CONCLUSION: The addition of SEP during fat overloads in the reactor feed maintained efficient COD removal in the test bioreactor for 270 days without any operational problems. Copyright © 2008 Society of Chemical Industry
Artificial neural networks to infer biomass and product concentration during the production of penicillin G acylase from Bacillus megaterium
Authors: Silva Rosineide G , Pinotti Laura M , Cruz Antonio J G , Giordano Raquel L C , Giordano Roberto C 
Published: February 2008

AbstractBACKGROUND: Production of microbial enzymes in bioreactors is a complex process including such phenomena as metabolic networks and mass transport resistances. The use of neural networks (NNs) to infer the state of bioreactors may be an interesting option that may handle the nonlinear dynamics of biomass growth and protein production.RESULTS: Feedforward multilayer perceptron (MLP) NNs were used for identification of the cultivation phase of Bacillus megaterium to produce the enzyme penicillin G acylase (EC. 3.5.1.11). The following variables were used as input to the net: run time and carbon dioxide concentration in the exhausted gas. The NN output associates a numerical value to the metabolic state of the cultivation, close to 0 during the lag phase, close to 1 during the exponential phase and approximately 2 for the stationary phase. This is a non‐conventional approach for pattern recognition. During the exponential phase, another MLP was used to infer cellular concentration. Time, carbon dioxide concentration and stirrer speed form an integrated net input vector. Cellular concentrations provided by the NN were used in a hybrid approach to estimate product concentrations of the enzyme. The model employed a first‐order approximation.CONCLUSION: Results showed that the algorithm was able to infer accurate values of cellular and product concentrations up to the end of the exponential growth phase, where an industrial run should stop. Copyright © 2008 Society of Chemical Industry
Synthesis of biodiesel from sunflower oil with silica‐supported NaOH catalysts
Authors: Arzamendi Gurutze , Campo Idoia , Arguiñarena Eider , Sánchez Maialen , Montes Mario , Gandía Luis M. 
Published: February 2008

AbstractBACKGROUND: A series of NaOH catalysts supported on commercial silica have been prepared by conventional incipient wetness impregnation and their activity tested in the reaction of transesterification of refined sunflower oil with methanol at 323 K and atmospheric pressure. The effects of the molar methanol/oil ratio, catalyst concentration, NaOH loading and calcination of the supported catalysts have been investigated.RESULTS: It has been found that the transesterification rate largely depends on the catalyst/methanol ratio and that calcination of the NaOH catalysts supported on silica, even at moderate temperatures, had a very negative effect on their activity. Selectivity, on the other hand, is more affected by the methanol/oil ratio. Selectivity for methyl esters (biodiesel) improved with the methanol/oil ratio due to an increased transesterification rate of diglycerides, whereas the selectivity for monoglycerides was not affected.CONCLUSION: The NaOH/silica catalysts suffered from a significant lack of chemical stability under reaction conditions as evidenced by measurements of sodium extracted during the reaction progress; therefore, their performance was affected by the presence of Na dissolved in the methanol phase. Copyright © 2008 Society of Chemical Industry
In vivo bioluminescence imaging study to monitor ectopic bone formation by luciferase gene marked mesenchymal stem cells
Authors: Olivo Cristina , Alblas Jacqueline , Verweij Vivienne , Van Zonneveld Anton‐Jan , Dhert Wouter J. A. , Martens Anton C. M. 
Published: February 2008

AbstractMesenchymal stem cells (MSCs) represent a powerful tool for applications in regenerative medicine. In this study, we used in vivo bioluminescence imaging to noninvasively investigate the fate and the contribution to bone formation of adult MSCs in tissue engineered constructs. Goat MSCs expressing GFP‐luciferase were seeded on ceramic scaffolds and implanted subcutaneously in immune‐deficient mice. The constructs were monitored weekly with bioluminescence imaging and were retrieved after 7 weeks to quantify bone formation by histomorphometry. With increasing amounts of seeded MSCs (from 0 to 1 × 106 MSC/scaffold), a cell‐dose related increase in bioluminescence was observed at all time points, correlating with increased bone formation at 7 weeks. To investigate the relevance of MSC proliferation to bone deposition, cell‐seeded scaffolds were irradiated. The irradiated cells were functional with respect to oxygen consumption but no increase in bioluminescence was observed in vivo, and only minimal bone was produced. Proliferating MSCs are likely required for initiation of bone formation in tissue engineered constructs in vivo. Bioluminescence is a useful tool to monitor cellular responses and predict bone formation in vivo. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:901–909, 2008
EWS/FLI1 suppresses retinoblastoma protein function and senescence in Ewing's sarcoma cells
Authors: Hu Hsien‐Ming , Zielinska‐Kwiatkowska Anna , Munro Karen , Wilcox Jason , Wu Daniel Y. , Yang Liu , Chansky Howard A. 
Published: February 2008

AbstractEwing's Family Tumors (EFTs) most commonly harbor a specific t(11;22) translocation that generates the EWS/FLI1 fusion protein responsible for malignant transformation. Many potential downstream targets of EWS/FLI1 have been identified but a detailed mechanism by which the fusion protein brings about transformation remains unknown. In this report, we show that depletion of EWS/FLI1 in Ewing's cell lines results in a senescence phenotype, a marked increase in expression of the G1/S regulatory proteins p27kip1 and p57kip2, and a significant decrease in cyclin D1 and CDK2. We also demonstrate for the first time, to our knowledge, that knockdown of EWS/FLI1 leads to hypophosphorylation and functional activation of the retinoblastoma (pRb) family of proteins. Consistent with activation of the pRb proteins, E2F‐responsive genes such as cyclin A are repressed in EWS/FLI1‐depleted cells. Together, these results support the role of EWS/LI1 as an inhibitor of cellular senescence and implicate the retinoblastoma family of proteins as key mediators of this inhibition. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:886–893, 2008