Reversible Bulk Oxidation of Ni Foil During Oscillatory Catalytic Oxidation of Propane: A Novel Type of Spatiotemporal Self-Organization.

A novel type of temporal and spatial self-organization in a heterogeneous catalytic reaction is described for the first time. Using in situ x-ray photoelectron spectroscopy, gas chromatography, and mass spectrometry, we show that, under certain conditions, self-sustained reaction-rate oscillations arise in the oxidation of propane over Ni foil because of reversible bulk oxidation of Ni to NiO, which can be observed even with the naked eye as chemical waves propagating over the catalyst surface.

Adaptation of the gymnosperms to the conditions of irradiation in Chornobyl zone: from morphological anomalies to the molecular genetic consequences.

It is known that the most suitable plant indicator targets for radiation pollution biomonitoring are conifers, because they have high radiosensitivity. In this review are briefly considered previously accumulated information about the genetic nature of morphological abnormalities in gymnosperms, induced by acute and chronic irradiation in the exclusion zone of the Chornobyl nuclear power plant. Since in the last decade appeared additional number of important research results, dedicated to the analysis of molecular biological and molecular genetic effects of chronic irradiation on the coniferous plants growing in the exclusion zone of the Chornobyl disaster, all these results are also analyzed in current review.

In situ NAP-XPS spectroscopy during methane dry reforming on ZrO2/Pt(1 1 1) inverse model catalyst.

Due to the need of sustainable energy sources, methane dry reforming is a useful reaction for conversion of the greenhouse gases CH4 and CO2 to synthesis gas (CO + H2). Syngas is the basis for a wide range of commodity chemicals and can be utilized for fuel production via Fischer-Tropsch synthesis. The current study focuses on spectroscopic investigations of the surface and reaction properties of a ZrO2/Pt inverse model catalyst, i.e. ZrO2 particles (islands) grown on a Pt(1 1 1) single crystal, with emphasis on in situ near ambient pressure x-ray photoelectron spectroscopy (NAP-XPS) during MDR reaction. In comparison to technological systems, model catalysts facilitate characterization of the surface (oxidation) state, surface adsorbates, and the role of the metal-support interface. Using XPS and infrared reflection absorption spectroscopy we demonstrated that under reducing conditions (UHV or CH4) the ZrO2 particles transformed to an ultrathin ZrO2 film that started to cover (wet) the Pt surface in an SMSI-like fashion, paralleled by a decrease in surface/interface oxygen. In contrast, (more oxidizing) dry reforming conditions with a 1:1 ratio of CH4 and CO2 were stabilizing the ZrO2 particles on the model catalyst surface (or were even reversing the strong metal support interaction (SMSI) effect), as revealed by in situ XPS. Carbon deposits resulting from CH4 dissociation were easily removed by CO2 or by switching to dry reforming conditions (673-873 K). Thus, at these temperatures the active Pt surface remained free of carbon deposits, also preserving the ZrO2/Pt interface.

Characterization of a novel protein kinase C response element in the glucagon gene.

To maintain glucose levels in blood within narrow limits, the synthesis and secretion of pancreatic islet hormones are controlled by a variety of neural, hormonal, and metabolic messengers that act through multiple signal transduction pathways. Glucagon gene transcription is stimulated by cyclic AMP and depolarization-induced calcium influx. In this study, the effect of protein kinase C on glucagon gene transcription was investigated. After transient transfection of a glucagon-reporter fusion gene into the glucagon-producing islet cell line alphaTC2, activation of protein kinase C by 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated glucagon gene transcription. By 5' deletions, 3' deletions, internal deletion, and oligonucleotide cassette insertion, the TPA-responsive element was mapped to the G2 element (from -165 to -200). Like TPA, overexpression of oncogenic Ras (V-12 Ras) stimulated G2-mediated transcription whereas overexpression of a dominant negative Ras mutant (N-17 Ras) blocked the effect of TPA. A mutational analysis of G2 function and nuclear protein binding indicated that protein kinase C and Ras responsiveness is conferred to the glucagon gene by HNF-3beta functionally interacting with a protein that binds to a closely associated site with sequence similarity to binding sites of Ets family proteins. HNF-3beta belongs to the winged-helix family of transcription factors and has been implicated in the control of cell-specific and developmental gene expression. The results of the present study show that the cell lineage-specific transcription factor HNF-3beta is an essential component of a novel protein kinase C response element in the glucagon gene.

A new class of inhibitors for in vitro small intestinal transport of sugars and amino acids in the rat.

Polycationic compounds like polylysine, protamine or polyethylenimine may interfere with a cation-related membrane transport system depending on superficially accessible binding sites for particular cations. In vitro experiments were performed using either everted segments of rat small intestine to measure tissue accumulation or everted sacs to determine mucosal-to-serosal transport. The effect of polycations was also tested using brush-border membrane vesicles of rat jejunum. Polycations inhibited the tissue accumulation of methyl alpha-D-glucoside as well as binding of phlorizin. Inhibition of accumulation was increased by raising the polycation concentration and by preincubation of the tissue with the polycations. Kinetic experiments revealed a competitive type of inhibition for the uptake of neutral amino acids and actively transported sugars. Using everted sacs to compare the monomeric cations with their corresponding polymeric forms for their inhibitory effect, it was found that only polymers applied to the mucosal compartment impaired active transport. The passive diffusion of solutes, e.g. 2-deoxy-D-glucose or mannitol, was slightly increased by polycations. With some intermediate oligomers of lysine it could be shown that more than 20 cationic groups are required for approximate complete inhibition. That membrane-related events are responsible for the observed inhibition is suggested by the reduced uptake of D-glucose by brush-border membrane vesicles in the presence of polycations. Therefore an interaction with transport-related cation binding sites, i.e. anionic residues, at the mucosal surface may be assumed.

In vitro inhibition of rat small intestinal absorption by lipophilic organic cations.

Cationic, lipid-soluble organic compounds may interfere with cation-mediated membrane transport processes. Thus, small intestinal absorption may be influenced by lipophilic organic cations. Therefore a series of arylalkylamines was studied in the concentration range from 0.5 to 20 mmol/l for their effect on the transport of various monosaccharides and leucine in the rat small intestine in vitro by means of the tissue accumulation technique. Whereas the monophenyl substituted monoamines (e.g. benzylamine, 2-phenylethylamine, 3-phenylpropylamine) did not show a significant effect on the active transport, the corresponding omega,omega-diphenyl derivatives exhibited a strong inhibition of the active transport of the sugars and the amino acid. These monoamines and drugs of similar structure (e.g. benzoctamine, diphenydramine) exhibited a mixed or non-competitive type of inhibition which correlated quite well with their octanol-water partition coefficients. In contrast, di- or triamines (e.g. harmaline, imipramine, pyrilamine) revealed a rather pure competitive type of inhibition. These findings tentatively suggest a different mode of action on the active transport by lipid-soluble organic amines according to the molecular charge distribution. In addition, membrane vesicles were used to examine the effect of the different amines on the sucrase activity. Regarding the cation-dependent hydrolysis of sucrose, however, no distinct pattern developed.

Long-term feeding of unavailable carbohydrate gelling agents. Influence of dietary concentration and microbiological degradation on adaptive responses in the rat.

Guaran, tragacanth, gum arabic, carrageenan, gum karaya, and methylcellulose were used in a long-term feeding study to evaluate their effects upon adaptive responses of nutritionally controlled parameters in rats by feeding a fiber-free diet containing increasing additions of polysaccharides. In general, supplements reduced weight increases due to lower energy intakes. Only in the case of microbiologically inert polysaccharides the dilution of the the energy density was partially compensated by an increased food intake. Neither of the polysaccharides fed, however, decreased energy utilization. All polysaccharides similarily increased small intestinal length up to about 30% without grossly altering mucosal protein and DNA per unit of length. Concerning their effects on the colon and the cecum, polysaccharides behaved differentially according to their accessibility to microbiological degradation. Inert polysaccharides exerted a more pronounced effect on the colon whereas the others mainly increased cecum weight. Degree and locus of the observed changes are determined mainly by the dietary concentration of the polysaccharides and their accessibility to bacterial degradation within the intestinal tract.

Comparison of the effect of two different hypoglycemic agents, glibenclamide and HB 699, on the rat small intestinal absorption of sugars and amino acids.

4-(2-[5-Chloro-2-methoxy-benzamido]-ethyl)-benzoic acid (HB 699) belongs to the group of hypoglycemic benzoic acid derivatives. Although lacking the sulfonylurea group, the structure of HB 699 partly resembles that of glibenclamide which is known to impair small-intestinal glucose absorption in vitro at high concentrations. Whereas this intestinal effect of glibenclamide is unlikely to contribute to its blood-glucose lowering properties, extrapancreatic and particularly intestinal effects may be important for the antidiabetic action of HB 699. Thus, HB 699 was compared with glibenclamide for the effect on the small-intestinal absorption of sugars and amino acids in vitro (everted-sac and tissue-accumulation technique) and in vivo (single-pass perfusion of the jejunum). In vitro both drugs inhibited the active transport of sugars and amino acids in a dose dependent manner. At equieffective doses (HB 699, 4.5 mmol/l and glibenclamide, 1 mmol/l) the mode of inhibition by the two drugs was similar. A 30-min incubation period reduced the uptake of methyl alpha-D-glucoside by about 75%. The degree of inhibition depended on the time of exposure of the tissue to the drugs. In vitro kinetic studies revealed a mixed type of inhibition. The in vivo effect of the drugs was in accordance with the in vitro findings. Inhibition, as in vitro, was not reversible and even increased further after reinfusion of a drug-free perfusate. In vivo, the drugs inhibited the absorption of methyl alpha-D-glucoside and leucine only at low (less than 20 mmol/l) but not at high (greater than 30 mmol/l) solute concentrations. These results indicate that hypoglycemic benzoic acid derivatives may exert their blood-glucose lowering properties in part by impairing the small-intestinal active transport of glucose.

Hepatobiliary complications of polyarteritis nodosa.

Although polyarteritis nodosa (PAN) may result in thrombosis or aneurysm formation in any organ in the body, hepatobiliary complications are unusual. We reviewed seven cases that demonstrated the diagnostic difficulties and therapeutic options available in the management of hepatobiliary PAN. No consistent sign that indicated the severity of hepatobiliary PAN could be identified. In cases of thrombotic PAN, acalculus cholecystitis usually could be diagnosed preoperatively. Early tissue diagnosis and aggressive intervention are required for appropriate patient treatment. If the diagnosis is unclear, a preoperative muscle or skin biopsy specimen is often helpful in establishing a tissue diagnosis of PAN, even if no obvious pathologic condition is evident. Patients who undergo celiotomy for acalculus cholecystitis or peritoneal signs of an unclear origin should have tissue specimens (gallbladder wall, liver, or omentum) submitted for pathologic study. Angiography may be diagnostic preoperatively or when results of biopsies are equivocal. In addition, early angiography can define the extent of visceral involvement and permit control by embolization of hemorrhage secondary to aneurysm rupture. Awareness of the possibilities of thrombotic, ischemic, or bleeding complications from PAN allows more aggressive and rapid management of abdominal complaints, especially in patients who are receiving immunosuppressant therapy.

The immunosuppressive drugs cyclosporin A and FK506 inhibit calcineurin phosphatase activity and gene transcription mediated through the cAMP-responsive element in a nonimmune cell line.

Cyclosporin A and the macrolide tacrolimus (FK506) are powerful immunosuppressive drugs that in T cells inhibit the calcium/calmodulin-dependent phosphatase calcineurin thereby preventing the activation of T-cell-specific transcription factors, such as NF-AT, involved in lymphokine gene expression. While this may explain, at least in part, the mechanism of cyclosporin A/FK506 immunosuppression, additional mechanisms have to be invoked in order to explain the pharmacological properties and toxic effects of these drugs, such as nephrotoxicity and neurotoxicity. We have studied the effects of cyclosporin A and FK506 on calcineurin phosphatase activity and gene transcription mediated by the cAMP-responsive element (CRE), a binding site of the ubiquitous transcription factor CREB. A reporter gene was placed under the transcriptional control of the CRE of the rat glucagon gene and transiently transfected into the glucagon-expressing cell line alpha TC2. Cyclosporin A and FK506 inhibited depolarization-induced gene transcription in a concentration-dependent manner (IC50 of about 1 nM and 30 nM for FK506 and cyclosporin A, respectively). Both cyclosporin A and FK506 inhibited calcineurin phosphatase activity at drug concentrations that inhibited gene transcription. The FK506 analogue rapamycin had no effect on calcineurin activity and gene transcription, but excess concentrations of rapamycin prevented the effects of FK506 on both calcineurin activity and gene transcription. These results support the notion that the interaction of drug-immunophilin complexes with calcineurin may be the molecular basis of cyclosporin A/FK506-induced inhibition of CREB/CRE-mediated gene transcription. The ability to interfere with CREB/CRE-mediated gene transcription represents a novel mechanism of cyclosporin A/FK506 action which may underlie pharmacological effects and toxic manifestations of these potent immunuosuppressive drugs.

Inhibition of CREB- and cAMP response element-mediated gene transcription by the immunosuppressive drugs cyclosporin A and FK506 in T cells.

The clinically important immunosuppressant drugs cyclosporin A and FK506 (tacrolimus) inhibit in T-cells calcineurin phosphatase activity and nuclear translocation of the cytosolic component of the transcription factor nuclear factor of activated T-cells (NF-ATc) that is involved in the induction of early genes during T-cell activation. This effect has been proposed to explain at least part of the immunosuppressive effect of these drugs. Previous studies in pancreatic islet cell lines have shown that cyclosporin A and FK506 through inhibition of calcineurin interfere also with the function of the transcription factor cAMP response element binding protein (CREB) that is activated by cAMP and calcium signals and binds to cAMP/calcium response elements (CRE). By transient expression of CRE-reporter genes or GAL4-CREB fusion proteins, the present study shows that inhibition of CREB/CRE-directed transcription by cyclosporin A and FK506 occurs in a great variety of cell types including in cell lines derived from tissues in which adverse effects of the immunosuppressants develop. CREB activity and CRE-mediated transcription was blocked by these drugs also in Jurkat T-cells. When taken together with recent evidence for an essential role of CREB in T-cell activation and proliferation, the present results suggest that inhibition of CREB/CRE-directed transcription may be a molecular mechanism of the immunosuppressive effect of cyclosporin A and FK506.

Inhibition of human insulin gene transcription by peroxisome proliferator-activated receptor gamma and thiazolidinedione oral antidiabetic drugs.

BACKGROUND AND PURPOSE: The transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) is essential for glucose homeostasis. PPARgamma ligands reducing insulin levels in vivo are used as drugs to treat type 2 diabetes mellitus. Genes regulated by PPARgamma have been found in several tissues including insulin-producing pancreatic islet beta-cells. However, the role of PPARgamma at the insulin gene was unknown. Therefore, the effect of PPARgamma and PPARgamma ligands like rosiglitazone on insulin gene transcription was investigated. EXPERIMENTAL APPROACH: Reporter gene assays were used in the beta-cell line HIT and in primary mature pancreatic islets of transgenic mice. Mapping studies and internal mutations were carried out to locate PPARgamma-responsive promoter regions. KEY RESULTS: Rosiglitazone caused a PPARgamma-dependent inhibition of insulin gene transcription in a beta-cell line. This inhibition was concentration-dependent and had an EC(50) similar to that for the activation of a reporter gene under the control of multimerized PPAR binding sites. Also in normal primary pancreatic islets of transgenic mice, known to express high levels of PPARgamma, rosiglitazone inhibited glucose-stimulated insulin gene transcription. Transactivation and mapping experiments suggest that, in contrast to the rat glucagon gene, the inhibition of the human insulin gene promoter by PPARgamma/rosiglitazone does not depend on promoter-bound Pax6 and is attributable to the proximal insulin gene promoter region around the transcription start site from -56 to +18. CONCLUSIONS AND IMPLICATIONS: The human insulin gene represents a novel PPARgamma target that may contribute to the action of thiazolidinediones in type 2 diabetes mellitus.

Inhibition of MafA transcriptional activity and human insulin gene transcription by interleukin-1beta and mitogen-activated protein kinase kinase kinase in pancreatic islet beta cells.

AIMS/HYPOTHESIS: Inappropriate insulin secretion and biosynthesis are hallmarks of beta cell dysfunction and contribute to the progression from a prediabetic state to overt diabetes mellitus. During the prediabetic state, beta cells are exposed to elevated levels of proinflammatory cytokines. In the present study the effect of these cytokines and mitogen-activated protein kinase kinase kinase 1 (MEKK1), which is known to be activated by these cytokines, on human insulin gene (INS) transcription was investigated. METHODS: Biochemical methods and reporter gene assays were used in a beta cell line and in primary pancreatic islets from transgenic mice. RESULTS: IL-1beta and MEKK1 specifically inhibited basal and membrane depolarisation and cAMP-induced INS transcription in the beta cell line. Also, in primary islets of reporter gene mice, IL-1beta reduced glucose-stimulated INS transcription. A 5'- and 3'-deletion and internal mutation analysis revealed the rat insulin promoter element 3b (RIPE3b) to be a decisive MEKK1-responsive element of the INS. RIPE3b conferred strong transcriptional activity to a heterologous promoter, and this activity was markedly inhibited by MEKK1 and IL-1beta. RIPE3b is also known to recruit the transcription factor MafA. We found here that MafA transcription activity is markedly inhibited by MEKK1 and IL-1beta. CONCLUSIONS/INTERPRETATION: These data suggest that IL-1beta through MEKK1 inhibits INS transcription and does so, at least in part, by decreasing MafA transcriptional activity at the RIPE3b control element. Since inappropriate insulin biosynthesis contributes to beta cell dysfunction, inhibition of MEKK1 might decelerate or prevent progression from a prediabetic state to diabetes mellitus.