bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of complementary pathway blockade on efficacy of combination enzastaurin and rapamycin
Authors: Liu Jing , Kuo Wen‐Liang , Seiwert Tanguy Y. , Lingen Mark , Ciaccio Mark F. , Jones Richard B. , Rosner Marsha Rich , Cohen Ezra Eddy Wyssam 
Published: March 2011

AbstractBackgroundRapamycin is an mTOR inhibitor with preclinical efficacy in squamous cell carcinoma of the head and neck (SCCHN). However, mTOR inhibitors also increase Akt activity in SCCHN cell lines, which would promote survival and oncogenesis. Enzastaurin is an AGC kinase inhibitor with nanomolar inhibitory concentrations for Akt and protein kinase C (PKC). Moreover, Akt and PKC inhibitors have demonstrated efficacy in SCCHN.MethodsWe hypothesized that the combination of rapamycin and enzastaurin would be more effective than either agent alone.ResultsRapamycin and enzastaurin generally inhibited putative targets in SCCHN cell lines in culture. In mice xenografted with CAL27 cells, rapamycin and enzastaurin produced growth delay. In contrast, the combination of rapamycin and enzastaurin caused regression of CAL27 tumors with evidence of inhibition of putative targets, survival, angiogenesis and proliferation.ConclusionThese data demonstrate that the combination of rapamycin and enzastaurin disrupts critical oncogenic pathways in SCCHN and has efficacy in preclinical models. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Problems faced when evaluating the bioaccumulation potential of substances under REACH
Authors: Ehrlich Gunnar , Jöhncke Ulrich , Drost Wiebke , Schulte Christoph 
Published: March 2011

Abstract
The identification and regulation of substances that combine persistence, bioaccumulation potential, and toxicity (“PBT” substances) is one central aspect of the European chemical legislation REACH (Registration, Evaluation, Authorisation, and Restriction of Chemicals), because these substances may elicit adverse long-term effects after release to the environment. The determination of a substance that has persistence, bioaccumulation potential, and toxicity is based on a set of distinct cutoff criteria identified in Annex XIII of the REACH regulation. Regarding the bioaccumulation potential, the evaluation is focused on the substance's bioconcentration factor as single decisive criterion. In addition, the REACH guidelines provide a selection of standardized test procedures for measuring bioconcentration factor and guidance in appraising test results. However, alternative test results like bioaccumulation factors and biomagnification as well as additional indications for a bioaccumulation potential such as trophic magnification are only allowed for supporting evidence. The currently used test systems with aquatic exposure have been demonstrated to generate reliable results for the majority of neutral, lipophilic organic substances, which facilitate clear decision-making by means of the crucial bioconcentration factor cutoff criteria of Annex XIII. However, certain substance groups such as highly hydrophobic organic substances and amphiphilic and nonlipophilic compounds are difficult to evaluate with common test strategies due to inappropriate test systems or accumulation mechanisms not based on lipophilicity. Recent scientific progress has already been made to establish alternative test systems and to refine the bioaccumulation assessment by consideration of additive accumulation mechanisms and indications. This article gives an overview on actual shortcomings in the current bioaccumulation assessment under REACH and also provides suggestions for a refinement of evaluation. Integr Environ Assess Manag 2011;7:550–558. © 2011 SETAC
Use of Bayesian belief networks for dealing with ambiguity in integrated groundwater management
Authors: Henriksen Hans Jørgen , Zorrilla-Miras Pedro , de la Hera Africa , Brugnach Marcella 
Published: March 2011

Abstract
In integrated groundwater management, different knowledge frames and uncertainties need to be communicated and handled explicitly. This is necessary in order to select efficient adaptive groundwater management strategies. In this connection, Bayesian belief networks allow for integration of knowledge, for engaging stakeholders and for dealing with multiple knowledge frame uncertainties. This is illustrated for the case of the Upper Guadiana Basin, Spain, where Bayesian belief networks with stakeholder involvement were used for dealing with the ambiguities related to sustainable groundwater exploitation. Integr Environ Assess Manag 2012; 8: 430–444. © SETAC
Protease‐activated receptors and myocardial infarction
Authors: Antoniak Silvio , Pawlinski Rafal , Mackman Nigel 
Published: March 2011

AbstractProtease‐activated receptors (PARs) are widely expressed within the heart. They are activated by a myriad of proteases, including coagulation proteases. In vitro studies showed that activation of PAR‐1 and PAR‐2 on cardiomyocytes induced hypertrophy. In addition, PAR‐1 stimulation on cardiac fibroblasts induced proliferation. Genetic and pharmacologic approaches have been used to investigate the role of the different PARs in cardiac ischemia/reperfusion (I/R) injury. In mice and rats, PAR‐1 is reported to play a role in inflammation, infarct size, and remodeling after cardiac I/R injury. However, there are notable differences between the effect of a deficiency in PAR‐1 and inhibition of PAR‐1. For instance, inhibition of PAR‐1 reduced infarct size whereas there was no effect of a deficiency of PAR‐1. These differences maybe due to off‐target effects of the inhibitor or PAR‐4 compensation of PAR‐1 deficiency. Similarly, a deficiency of PAR‐2 was associated with reduced cardiac inflammation and improved heart function after I/R injury, whereas pharmacologic activation of PAR‐2 was found to be protective due to increased vasodilatation. These differences maybe due to different signaling responses induced by an endogenous protease versus an exogenous agonist peptide. Surprisingly, PAR‐4 deficiency resulted in increased cardiac injury and increased mortality after I/R injury. In contrast, a pharmacological study indicated that inhibition of PAR‐4 was cardioprotective. It is possible that the major cellular target of the PAR‐4 inhibitor is platelets, which have been shown to contribute to inflammation in the injured heart, whereas PAR‐4 signaling in cardiomyocytes may be protective. These discrepant results between genetic and pharmacological approaches indicate that further studies are needed to determine the role of different PARs in the injured heart. © 2011 IUBMB IUBMB Life, 63(6): 383–389, 2011
Regulation of protease‐activated receptor signaling by post‐translational modifications
Authors: Grimsey Neil , Soto Antonio G. , Trejo JoAnn 
Published: March 2011

AbstractProtease‐activated receptors (PARs) are a unique family of G‐protein‐coupled receptors (GPCRs) that are irreversibly activated following proteolytic cleavage of their extracellular N‐terminus. PARs play critical functions in hemostasis, thrombosis, inflammation, embryonic development, and cancer progression. Because of the irreversible proteolytic nature of PAR activation, signaling by the receptors is tightly regulated. Three distinct processes including desensitization, internalization, and lysosomal degradation, regulate the temporal and spatial aspects of activated PAR signaling. Post‐translational modifications play a critical role in regulating each of these processes and here we review the nature of PAR post‐translational modifications and their importance in signal regulation. The PARs are activated by numerous proteases, and some can elicit distinct cellular responses, how this biased agonism is determined is unknown. Further study of the function of post‐translational modifications of the PARs will lead to a greater understanding of the physiological regulation of baised agonism and how PAR signaling is precisely controlled in different cellular contexts. © 2011 IUBMB IUBMB Life, 63(6): 403–411, 2011
Cell damage through pentose phosphate pathway in fetus fibroblast cells exposed to methyl mercury
Authors: Amoli Jamileh Salar , Barin Abbas , Ebrahimi‐Rad Mina , Sadighara Parisa 
Published: March 2011

ABSTRACTMethylmercury (MeHg) is a global pollutant that causes malformations. There has been no direct evidence for the effect of MeHg on pentose phosphate pathway (PPP). In embryonic development, PPP is much more active. This pathway produces ribose for DNA/RNA production. It is possible that one of teratogenicity mechanisms of MeHg is through PPP. The fetus fibroblast cells were incubated with different concentrations of MeHg (0.1–100 μm). A dose–response dependence was observed in MTT assay. Transketolase activity and DNA content were determined in cell exposed to MeHg. A defect at the level of DNA content was observed. This amount of DNA was highly correlated with transketolase activity (r = 0.76). This study has demonstrated that the potential teratogenic action of MeHg is through PPP. To assess the protective effects of thiamin, the infected cells were incubated with different concentrations of thiamin. The obtained results show that thiamin pyrophosphate supplementation correlated with the toxicity. This finding confirms that thiamin therapy is suitable for the prevention of MeHg toxicity. Our study provides basic data for prevention and treatment of MeHg toxicity via boosting PPP. Copyright © 2011 John Wiley & Sons, Ltd.
Proteomics in Ménière disease
Authors: Chiarella Giuseppe , Saccomanno Milena , Scumaci Domenica , Gaspari Marco , Faniello Maria Concetta , Quaresima Barbara , Di Domenico Marina , Ricciardi Carmela , Petrolo Claudio , Cassandro Claudia , Costanzo Francesco Saverio , Cuda Giovanni , Cassandro Ettore 
Published: March 2011

AbstractMénière's disease (MD) is a disorder of the inner ear characterized by an insidious onset and aspecific symptoms, such as dizziness, vertigo, tinnitus, and hearing loss, that may become very debilitating. The presence of endolymphatic hydrops is a common feature in MD patients, but the pathophysiology is still largely unknown. In this study, we have used a proteomics‐driven approach to identify potential biomarkers of MD. To this end, plasma was obtained from whole blood of 16 individuals previously diagnosed as suffering from MD and compared to plasma from healthy donors. A depletion of the highly abundant proteins (i.e., albumin, IgG, transferrin, etc.) was performed in order to enhance the chance of detection of the less represented ones, therefore reducing the noise‐background. Two‐dimensional gel electrophoresis, followed by in‐gel tryptic digestion of the selected spots and LC‐MS/MS analysis, allowed us to identify a set of proteins whose expression appears to be differentially modulated in patients versus controls. In particular: complement factor H and B, fibrinogen alpha and gamma chains, beta‐actin and pigment epithelium derived factor are over expressed; on the other hand, the levels of beta‐2 glycoprotein‐1, vitamin D binding protein and apolipoprotein‐1 are significantly decreased in the plasma of MD‐affected individuals. Even though preliminary and not necessarily linked directly to the molecular pathogenesis of the disease, our original findings suggest that a molecular signature, represented by the plasma protein profile previously described, might represent a potentially powerful, innovative and not invasive tool for early diagnosis and clinical management of MD patients. J. Cell. Physiol. 227: 308–312, 2012. © 2011 Wiley Periodicals, Inc.
Three dimensional cultures of rat liver cells using a natural self‐assembling nanoscaffold in a clinically relevant bioreactor for bioartificial liver construction
Authors: Giri Shibashish , Acikgöz Ali , Pathak Priya , Gutschker Sylvia , Kürsten Anne , Nieber Karen , Bader Augustinus 
Published: March 2011

AbstractTill date, no bioartificial liver (BAL) procedure has obtained FDA approval or widespread clinical acceptance, mainly because of multifactorial limitations such as the use of microscale or undefined biomaterials, indirect and lower oxygenation levels in liver cells, short‐term undesirable functions, and a lack of 3D interaction of growth factor/cytokine signaling in liver cells. To overcome preclinical limitations, primary rat liver cells were cultured on a naturally self‐assembling peptide nanoscaffold (SAPN) in a clinically relevant bioreactor for up to 35 days, under 3D interaction with suitable growth factors and cytokine signaling agents, alone or combination (e.g., Group I: EPO, Group II: Activin A, Group III: IL‐6, Group IV: BMP‐4, Group V: BMP4 + EPO, Group VI: EPO + IL‐6, Group VII: BMP4 + IL‐6, Group VIII: Activin A + EPO, Group IX: IL‐6 + Activin A, Group X: Activin A + BMP4, Group XI: EPO + Activin A + BMP‐4 + IL‐6 + HGF, and Group XII: Control). Major liver specific functions such as albumin secretion, urea metabolism, ammonia detoxification, phase contrast microscopy, immunofluorescence of liver specific markers (Albumin and CYP3A1), mitochondrial status, glutamic oxaloacetic transaminase (GOT) activity, glutamic pyruvic transaminase (GPT) activity, and cell membrane stability by the lactate dehydrogenase (LDH) test were also examined and compared with the control over time. In addition, we examined the drug biotransformation potential of a diazepam drug in a two‐compartment model (cell matrix phase and supernatant), which is clinically important. This present study demonstrates an optimized 3D signaling/scaffolding in a preclinical BAL model, as well as preclinical drug screening for better drug development. J. Cell. Physiol. 227: 313–327, 2012. © 2011 Wiley Periodicals, Inc.
The complexity of ERK1 and ERK2 MAPKs in multiple hepatocyte fate responses
Authors: Frémin Christophe , Ezan Frédéric , Guegan Jean‐Philippe , Gailhouste Luc , Trotard Maud , Le Seyec Jacques , Rageul Julie , Theret Nathalie , Langouët Sophie , Baffet Georges 
Published: March 2011

AbstractRecent reports suggest that extracellular signal‐regulated kinase (ERK1) and ERK2 mitogen‐activated protein kinases (MAPK) may direct specific biological functions under certain contexts. In this study, we investigated the role of early and sustained epidermal growth factor (EGF) stimulation on long‐term hepatocyte differentiation and the possible role of ERK1 and ERK2 in this process. We demonstrate a long‐term survival and an elevated level of differentiation up to 3 weeks. The differentiation state of hepatocytes is supported by sustained expression of aldolase B, albumin, and the detoxifying enzymes CYP1A2, 2B2, and 3A23. Similarly to freshly isolated cells, cultured hepatocytes also retain the ability to respond to 3‐methylcholanthrene (3MC) and phenobarbital (PB), two known CYP inducers. In addition, we show evidence that continuous MAPK/ERK kinase (MEK) inhibition enhances the level of differentiation. Using RNA interference approaches against ERK1 and ERK2, we demonstrate that this effect requires both ERK1 and ERK2 activity, whereas the specific ERK1 knockdown promotes cell survival and the specific ERK2 knockdown regulates cell proliferation. In conclusion, we demonstrate that early and sustained EGF stimulation greatly extends long‐term hepatocyte survival and differentiation, and that inhibition of the ERK1/2 MAPK pathway potentiates these pro‐survival/pro‐differentiation phenotypes. We clearly attest that specific ERK1 and ERK2 MAPKs determine hepatocyte survival and proliferation, respectively, whereas dual inhibition is required to stabilize a highly differentiated state. J. Cell. Physiol. 227: 59–69, 2012. © 2011 Wiley Periodicals, Inc.
Chemicals from biomass: synthesis of lactic acid by alkaline hydrothermal conversion of sorbitol
Authors: Ramírez‐López Camilo A. , Ochoa‐Gómez José R. , Gil‐Río Silvia , Gómez‐Jiménez‐Aberasturi Olga , Torrecilla‐Soria Jesús 
Published: March 2011

AbstractBACKGROUND: Currently, the ‘green chemistry’ philosophy is being increasingly adopted by the chemical industry and, therefore, new production procedures of valuable chemicals from biomass‐derived raw materials are being sought. In this work, the synthesis of lactic acid from sorbitol under alkaline hydrothermal conditions is investigated by analyzing the influence on conversions and yields of temperature, NaOH/sorbitol molar ratio (MR), initial sorbitol concentration (SC) and reaction time.RESULTS: A 100% sorbitol conversion and a maximum 39.5% yield of lactic acid on a carbon basis are obtained at 280 °C, 50 min, 1.0 mol L−1 SC and 2.0 MR. Glyceraldehyde was the only identified intermediate while formic acid, acrylic acid, acetic acid, oxalic acid and sodium carbonate were identified as over‐oxidation products, all of them in very low yields with the exception of formic acid (16% yield at a MR of 4 and 280 °C). Several plausible conversion routes of sorbitol involving dehydrations, keto‐enol tautomerisms, reverse aldol condensations, aldol condensations, Cannizzaro reactions and oxidations are proposed.CONCLUSIONS: Considering the high number of parallel conversion routes as a consequence of high functionality of sorbitol, the 39.5% lactic acid yield obtained is a good result. Total carbon mass in all identified products only justifies, at most, 50% of that in sorbitol due to the coexistence of several conversion routes resulting in a large number of products other than lactic acid. Copyright © 2011 Society of Chemical Industry
Degradation of C.I. Acid Orange 7 by heterogeneous Fenton oxidation in combination with ultrasonic irradiation
Authors: Zhong Xin , Xiang Luojing , Royer Sebastien , Valange Sabine , Barrault Joel , Zhang Hui 
Published: March 2011

AbstractBACKGROUND: A mesoporous alumina supported nanosized Fe2O3 was prepared through an original synthesis procedure and used as a heterogeneous catalyst for the Fenton process degradation of the model azo dye C.I. Acid Orange 7 enhanced by ultrasound irradiation (US/Fe2O3‐Al2O3‐meso/H2O2 system). The effect of various operating conditions was investigated, namely hydrogen peroxide concentration, initial pH, ultrasonic power and catalyst loading.RESULTS: The results indicated that the degradation of C.I. Acid Orange 7 followed a pseudo‐first‐order kinetic model. There exists an optimal hydrogen peroxide concentration, initial pH, ultrasonic power and catalyst loading for decolorization. The aggregate size of the spent catalyst was reduced after dispersion in water by ultrasonic irradiation. A very low level of iron leaching was observed ranging from < 0.1 to 0.23 mg L−1. The intermediate products of C.I. Acid Orange 7 degradation were identified using gas chromatography–mass spectrometry (GC‐MS).CONCLUSION: The optimal conditions for efficient C.I. Acid Orange 7 degradation were pH close to 3, hydrogen peroxide concentration 4 mmol L−1, catalyst loading 0.3 g L−1, and ultrasonic power 80 W. Copyright © 2011 Society of Chemical Industry
Contaminants abatement by ozone in secondary effluents. Evaluation of second‐order rate constants
Authors: Javier Rivas F. , Sagasti Jose , Encinas Angel , Gimeno Olga 
Published: March 2011

AbstractBACKGROUND: The ozonation of a mixture of contaminants commonly found in secondary effluents has been carried out in an artificially contaminated secondary effluent. Competitive ozonation experiments in heterogeneous and homogeneous mode have also been carried out to determine the second‐order direct ozonation rate constants.RESULTS: Inlet ozone concentration, alkaline conditions and addition of 10−3 mol L−1 of H2O2 positively affected the degree of mineralization and the disappearance of chemical oxygen demand of the mixture. Reaction rates depend on pH; at pH 7 the following direct ozone rate constants were obtained: 2.7 × 105, 2.5 × 103, 2.5 × 104, 6.2 × 105, 3.2 × 105, 3.4 × 105, 8.0 × 105 and 4.6 × 105 mol−1 L1 s−1 for acetaminophen, metoprolol, caffeine, antipyrine, norfloxacin, ketorolac, doxycycline, hydroxybiphenyl, and diclofenac, respectively.CONCLUSIONS: The positive effect on TOC and COD removal that ozone dosage exerts is not applicable to individual contaminants. An optimum ozone concentration can be found with no further improvement of the depletion rate of organics as the ozone inlet concentration is increased. Carbonates affect the oxidation of recalcitrant compounds like atrazine. Carbonate concentration must be considered when dealing with real effluents. Addition of hydrogen peroxide can increase the mineralization level obtained, however the increase in complexity and costs does not justify its addition. Copyright © 2011 Society of Chemical Industry
Activated sludge process coupled with intermittent ozonation for sludge yield reduction and effluent water quality control
Authors: Järvik Oliver , Viiroja Andres , Kamenev Sven , Kamenev Inna 
Published: March 2011

AbstractBACKGROUND: Ozone is applied in wastewater treatment for effluent water quality improvement (post‐ozonation) as well as for excess sludge reduction (in the recirculation line). There is some evidence that ozone dosed directly to aerobic biooxidation (ABO) process enhances degradation of recalcitrant compounds into intermediates, following their biodegradation in the same reactor. However, no information regarding the influence of ozone on sludge yield in this system was found. Therefore, the current work aimed to evaluate the effect of ozone on the sludge yield when ozone is dosed directly to the ABO process. In addition, batch and continuous treatment schemes for phenolic wastewater treatment are compared.RESULTS: The results revealed that an optimal ozone dose of ∼30 mgO3 L−1 day−1 reduced the sludge yield by ∼50%, while effluent water quality in terms of total chemical oxygen demand (TCOD), compared with a conventional ABO process, was improved by 35.5 ± 3.6%. Slight improvement in soluble COD removal at the same ozone dose was also detected. The toxicity of effluent water was reduced as the ozone dose was increased.CONCLUSIONS: In an integrated ozonation‐ABO process it is possible to simultaneously reduce sludge yield and to improve effluent water quality, as COD and toxicity are reduced. Copyright © 2011 Society of Chemical Industry
Effect of B‐site cation on the catalytic activity of La1−xCaxBO3 (B = Fe, Ni) perovskite‐type oxides for toluene combustion
Authors: Pecchi G. , Jiliberto M.G. , Delgado E.J. , Cadús L.E. , Fierro J.L.G. 
Published: March 2011

AbstractBackground The effect of the B cation on the surface properties and catalytic activity in the total combustion of toluene over La1−xCaxBO3 (B = Fe,Ni) perovskite‐type oxides was studied.Result For the La1−xCaxFeO3 series, the perovskite structure was maintained in the range of substitution studied. A completely different behaviour was observed for the La1−xCaxNiO3 series. A Brownmillerite‐type structure (La2Ni2O5) with a large degree of phase segregation as well dispersed mixed oxides was observed upon the substitution of La for Ca. In the Fe series, the catalytic activity in the total combustion of toluene showed that the insertion of calcium ions into the perovskite lattice resulted in higher activity relative to the unsubstituted LaFeO3 perovskite. In contrast, for the Ni series, substitution results in solids with lower activity than the pure LaNiO3 perovskite.Conclusion For the Fe series, higher activity and stability are attributed to a synergy between Fe4+/Fe3+ and the oxygen vacancies generated by the calcium substitution. For the Ni counterpart, the structural modification leads to a lower activity of substituted solids compared with the pure LaNiO3 perovskite, indicating that Ni3+ ions are the active sites for toluene oxidation. Copyright © 2011 Society of Chemical Industry