Correlation of structure and function in oligonuclear zinc(II) model phosphatases

A series of pyrazolate-based dizinc(II) complexes has been synthesized and investigated as functional models for phosphoesterases, focusing on correlations between hydrolytic activity and molecular parameters of the bimetallic core. The Zn...Zn distance, the (bridging or nonbridging) position of the Zn-bound hydroxide nucleophile, and individual metal ion coordination numbers are controlled by the topology of the compartmental ligand scaffold. Species distributions of the various dizinc complexes in solution have been determined potentiometrically, and structures in the solid state have been elucidated by X-ray crystallography. The hydrolysis of bis(p-nitrophenyl)phosphate (BNPP) promoted by the dinuclear phosphoesterase model complexes has been investigated in DMSO/buffered water (1:1) at 50 degrees C as a function of complex concentration, substrate concentration, and pH. Coordination of the phosphodiester has been followed by ESI mass spectrometry, and bidentate binding could be verified crystallographically in two cases. Drastic differences in hydrolytic activity are observed and can be attributed to molecular properties. A significant decrease of the pK(a) of zinc-bound water is observed if the resulting hydroxide is involved in a strongly hydrogen-bonded intramolecular O(2)H(3) bridge, which can be even more pronounced than for a bridging hydroxide. Irrespective of the pK(a) of the Zn-bound water, a hydroxide in a bridging position evidently is a relatively poor nucleophile, while a nonbridging hydroxide position is more favorable for hydrolytic activity. Additionally, the metal array has to provide a sufficient number of coordination sites for activating both the substrate and the nucleophile, where phosphate diesters such as BNPP preferentially bind in a bidentate fashion, requiring a third site for water binding. Product inhibition of the active site by the liberated (p-nitrophenyl)phosphate is observed, and the product-inhibited complex could be characterized crystallographically. In that complex, the phosphate monoester is found to cap a rectangular array of four zinc ions composed of two bimetallic entities.     

Selective oxidation of a single primary alcohol function in oligopyridine frameworks

A variety of mono-oxidized pyridine, bipyridine, terpyridine, and pyridine/pyridazine are readily prepared under mild conditions using Pyrolusite MnO2. This phase has been characterized by means of X-ray powder diffraction and scanning electron microscopy. The oxidative activity is in keeping with the nature, morphology, and surface area of the MnO2 reagent.     

Insights into the structure and function of redox-active tyrosines from model compounds

Redox-active tyrosine residues play important roles in long distance electron-transfer reactions in enzymes, including prostaglandin H synthase, ribonucleotide reductase, and photosystem II. In cytochrome c oxidase, a cross-linked tyrosine-histidine cofactor has been proposed to play a role in proton and electron transfer reactions. Studies of tyrosyl radicals in model compounds, generated by UV photolysis, have recently provided new information about the structure and function of these redox-active species. The results of these studies, which combine magnetic resonance and optical spectroscopies, are described in this review.     

Numerical model of a large-scale oxygen consumption fire calorimeter

The present study introduces a volumetric heat and mass source model to investigate the flow field inside the hood and duct system and optimize the sampling technique in a large scale fire calorimeter. The model was validated using experimental measurements of the oxygen depletion factor, gas temperature and heat release rate. The calculated heat release rates determined using the CFD model were in good agreement with the experiments with the maximum discrepancy between the simulations and experiments being less than 5%. A series of CFD simulations were performed to examine the effects of sampling location, and the number of sampling points on the uncertainty of the heat release calculation. Detailed flow characteristics were analyzed to understand the complicated internal duct flow.     

Alveolar macrophages modulate allergic inflammation in a murine model of asthma

The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.     

Microstructured cocultures of cardiac myocytes and fibroblasts: a two-dimensional in vitro model of cardiac tissue.

Cardiac myocytes and fibroblasts are essential elements of myocardial tissue structure and function. In vivo, myocytes constitute the majority of cardiac tissue volume, whereas fibroblasts dominate in numbers. In vitro, cardiac cell cultures are usually designed to exclude fibroblasts, which, because of their maintained proliferative potential, tend to overgrow the myocytes. Recent advances in microstructuring of cultures and cell growth on elastic membranes have greatly enhanced in vitro preservation of tissue properties and offer a novel platform technology for producing more in vivo-like models of myocardium. We used microfluidic techniques to grow two-dimensional structured cardiac tissue models, containing both myocytes and fibroblasts, and characterized cell morphology, distribution, and coupling using immunohistochemical techniques. In vitro findings were compared with in vivo ventricular cyto-architecture. Cardiac myocytes and fibroblasts, cultured on intersecting 30-microm-wide collagen tracks, acquire an in vivo-like phenotype. Their spatial arrangement closely resembles that observed in native tissue: Strands of highly aligned myocytes are surrounded by parallel threads of fibroblasts. In this in vitro system, fibroblasts form contacts with other fibroblasts and myocytes, which can support homogeneous and heterogeneous gap junctional coupling, as observed in vivo. We conclude that structured cocultures of cardiomyocytes and fibroblasts mimic in vivo ventricular tissue organization and provide a novel tool for in vitro research into cardiac electromechanical function.     

Heat of transport of dilute adsorbable gases in single pores and model porous media as a function of pore structure

A previous theoretical study of the heat of transport of a dilute adsorbable gas in a model pore, based on a new, more rigorous approach, is here extended to confirm and amplify the general features of the behavior predicted by the new approach in contradistinction to conventional theory. A simple analytical semiquantitative treatment is developed for moderate to high heats of transport and the effects of the form of the adsorption potential and of pore shape are elucidated. Some important aspects of pore structure in real porous media are then simulated by means of suitable simple capillary models. The results obtained permit a significant advance in the interpretation of experimental results.     

On the structure of water—alcohol and ammonia—alcohol protonated clusters

Collision-induced dissociation (CID) of protonated ammonia-alcohol and water-alcohol heteroclusters was studied using a triple quadrupole mass spectrometer with a corona discharge atmospheric pressure ionization source. CID results suggested that the ammonia-alcohol clusters had NH: at the core of the cluster and that hydrogen-bonded alcohol molecules solvated this central ion. In contrast, CID results in water-alcohol clusters showed that water loss was strongly favored over alcohol loss and that there was a preference for the charge to reside on an alcohol molecule. The results also indicated that a loose chain of hydrogen-bonded molecules was formed in the water-alcohol clusters and that there appeared to be no rigid protonation site or a fixed central ion. (J Am Soc Mass     

The microwave spectrum and structure of allyl alcohol

The microwave spectrum of the normal species of the gauche, gauche isomer of allyl alcohol has been reassigned and rotational and centrifugal distortion constants have been determined. Rotational constants of nine deuterated species three carbon-13 species and the oxygen-18 species have also been obtained. These data were used to estimate structural parameters by least-squares fitting of the effective moments of inertia. Good agreement with an earlier electron diffraction and ab initio study was obtained. Unassigned transitions from another isomer were observed, presumably the cis, gauche conformer.     

Isolation and crystal structure of alcohol inclusion complexes

Some host compounds which include various kinds of alcohol were designed and X-ray crystal structures of their alcohol complexes were studied.     

Effects of ursodeoxycholic acid on photodynamic therapy in a murine tumor model

We previously reported that the efficacy of photodynamic therapy (PDT) in cell culture was enhanced by ursodeoxycholic acid (UDCA), a nontoxic bile acid. In this study, we examined the ability of UDCA to promote tumor control by PDT in the mouse, using the radiation-induced fibrosarcoma tumor and the photosensitizing agent tin etiopurpurin (SnET2). These experiments revealed that the addition of UDCA to a PDT protocol promoted inhibition of tumor growth, a phenomenon unrelated to either altered SnET2 biodistribution or the level of vascular shutdown during irradiation. These results indicate that UDCA acts solely by promoting direct tumor cell kill by PDT.     

Simultaneous determination of NNK and its metabolites in mouse tissue for evaluating the effects of chronic alcohol consumption on the metabolism of NNK in mouse liver and lung

A hydrophilic-interaction liquid chromatography–tandem mass spectrometry (HILIC–MS–MS) method was developed for the determination of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolites in mouse liver and lung. The limits of detection of all analytes were in the range 0.017–0.057 ng mL^?1, and recovery ranged from 88.4–119.8 % with intra and inter-day precision in the range 0.89–6.03 % and 1.01–6.97 %, respectively. This simple and accurate method was used to evaluate the effect of chronic alcohol consumption on NNK bioactivation in mouse tissue. Time-course curves for NNK and its metabolites were generated, and the areas under the curves (AUCs) were compared. It was found that target tissues of NNK carcinogenesis in C57BL/6 mice contained high levels of α-hydroxylation metabolites of NNK and its carbonyl reduction metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The most pronounced effect of alcohol was to enhance α-hydroxylation of NNK in mouse lung and liver, which suggests that chronic alcohol consumption may increase the risk of carcinogenicity associated with NNK in mice.

Forecasting China's natural gas consumption based on a combination model

Ensuring a sufficient energy supply is essential to a country. Natural gas constitutes a vital part in energy supply and therefore forecasting natural gas consumption reliably and accurately is an essential part of a country's energy policy. Over the years, studies have shown that a combinative model gives better projected results compared to a single model. In this study, we used Polynomial Curve and Moving Average Combination Projection (PCMACP) model to estimate the future natural gas consumption in China from 2009 to 2015. The new proposed PCMACP model shows more reliable and accurate results: its Mean Absolute Percentage Error (MAPE) is less than those of any previous models within the investigated range. According to the PCMACP model, the average annual growth rate will increase for the next 7 years and the amount of natural gas consumption will reach 171600 million cubic meters in 2015 in China.     

Micelle structure: a surfactant-block model

A structure of spheroidal micelles is developed by model building. It is a hybrid of two classical micelle models, the compact droplet and the bilayer fragment : droplet-like in overall shape and bilaver-like in local configuration. The micelle appears as a tiny isometric liquid crystal with particular architecture and dynamics.     

The evaluation of cardiac function and the effect of therapy in acute myocardial infarction--comparison by radio nuclide method in acute and chronic phase

The cardiac function and the effect of therapy in patients with acute myocardial infarction (AMI) were assessed in over 100 patients by analysis of 201Tl-scintigraphy and 99mTc-gated pool study in our ICU. The cardiac function and 201Tl-defect ratio were compared with the results obtained in chronic phase. Sixteen of them were treated with intravenous urokinase (UK) within 6 hours from onset. The other 18 patients without UK treatment served as a control group. Significant correlation was recognized between 201Tl-defect ratio and peak-CPK levels, peak-GOT levels, peak-LDH levels. Significant correlation (r = -0.655, r = -0.713) were found between 201Tl-defect ratio and LVEF in acute and chronic phase. The UK group showed a significant increase of LVEF as compared with the control group in patients with antero-septal (A/S) AMI. In inferior (INF) AMI, no significant differences were observed UK and control group in LVEF, RVEF and 201Tl-defect ratio. In chronic phase, improvements of LVEF and 201Tl-defect ratio were observed in patients with A/S AMI. But no significant differences of LVEF, RVEF and 201Tl-defect ratio were observed in A/S AMI in acute and chronic phase. The UK group showed a significant increase of LVEF (50.1%) as compared with the control group of A/S AMI in chronic phase. We have demonstrated that a combination of 201Tl-scintigraphy and 99mTc-gated pool study are useful techniques in ICU, to evaluate the cardiac function and the effect of thrombolysis therapy and thus greatly contribute to the primary care of AMI cases.     

The anatomic site of photodynamic therapy is a determinant for immunosuppression in a murine model

The role of the irradiation site in the induction of suppression of the contact hypersensitivity (CHS) response following photodynamic therapy (PDT) was examined in a murine model. Laser irradiation on the flanks of nontumor-bearing Photofrin-injected mice caused suppression of the CHS response. If the irradiation was conducted on a subcutaneously implanted foil disc on the flank no immunosuppression occurred, indicating that no suppressive factor(s) of sufficient quantity to cause suppression was released from the skin, but rather irradiation of internal organs was the cause. Irradiation of tumors implanted on the flanks of mice reduced the suppression, suggesting an immunopotentiating effect of PDT. Irradiation on the thigh in the presence or absence of a tumor gave no immunosuppression. These results suggest that the anatomic site of irradiation is one determinant for the elicitation of suppression of the CHS response.