The flavonoid tangeretin activates the unfolded protein response and synergizes with imatinib in the erythroleukemia cell line K562

We explored the mechanism of cell death of the polymethoxyflavone tangeretin (TAN) in K562 breakpoint cluster region‐abelson murine leukemia (Bcr‐Abl+) cells. Flow cytometric analysis showed that TAN arrested the cells in the G₂/M phase and stimulated an accumulation of the cells in the sub‐G₀ phase. TAN‐induced cell death was evidenced by poly(ADP)‐ribose polymerase cleavage, DNA laddering fragmentation, activation of the caspase cascade and downregulation of the antiapoptotic proteins Mcl‐1 and Bcl‐x_L. Pretreatment with the pancaspase inhibitor Z‐VAD‐FMK_blocked caspase activation and cell cycle arrest but did not inhibit apoptosis which suggest that other cell killing mechanisms like endoplasmic reticulum (ER)‐associated cell death pathways could be involved. We demonstrated that TAN‐induced apoptosis was preceded by a rapid activation of the proapoptotic arm of the unfolded protein response, namely PKR‐like ER kinase. This was accompanied by enhanced levels of glucose‐regulated protein of 78 kDa and of spliced X‐box binding protein 1. Furthermore, TAN sensitized K562 cells to the cell killing effects of imatinib via an apoptotic mechanism. In conclusion, our results suggest that TAN is able to induce apoptosis in Bcr‐Abl+ cells via cell cycle arrest and the induction of the unfolded protein response, and has synergistic cytotoxicity with imatinib.     

Mechanism for SOFC anode degradation from hydrogen sulfide exposure

Recent results on solid oxide fuel cells with Ni/YSZ and Ni/GDC anodes reveal a mechanism for permanent performance degradation due to hydrogen sulfide exposure. Our results confirm the temporary performance decline observed by others but also reveal a mechanism for the long term permanent degradation. We find that hydrogen sulfide leads to nickel migration and depletion in the anode, thereby compromising electrical conductivity and cell performance.     

Exopolysaccharide Carbohydrate Structure and Biofilm Formation by Rhizobium leguminosarum bv. trifolii Strains Inhabiting Nodules of Trifolium repens Growing on an Old Zn–Pb–Cd-Polluted Waste Heap Area

Heavy metals polluting the 100-year-old waste heap in Bolesław (Poland) are acting as a natural selection factor and may contribute to adaptations of organisms living in this area, including Trifolium repens and its root nodule microsymbionts—rhizobia. Exopolysaccharides (EPS), exuded extracellularly and associated with bacterial cell walls, possess variable structures depending on environmental conditions; they can bind metals and are involved in biofilm formation. In order to examine the effects of long-term exposure to metal pollution on EPS structure and biofilm formation of rhizobia, Rhizobium leguminosarum bv. trifolii strains originating from the waste heap area and a non-polluted reference site were investigated for the characteristics of the sugar fraction of their EPS using gas chromatography mass-spectrometry and also for biofilm formation and structural characteristics using confocal laser scanning microscopy under control conditions as well as when exposed to toxic concentrations of zinc, lead, and cadmium. Significant differences in EPS structure, biofilm thickness, and ratio of living/dead bacteria in the biofilm were found between strains originating from the waste heap and from the reference site, both without exposure to metals and under metal exposure. Received results indicate that studied rhizobia can be assumed as potentially useful in remediation processes.     

Affinity and Specificity for Binding to Glycosaminoglycans Can Be Tuned by Adapting Peptide Length and Sequence

Although glycosaminoglycan (GAG)–protein interactions are important in many physiological and pathological processes, the structural requirements for binding are poorly defined. Starting with GAG-binding peptide CXCL9(74-103), peptides were designed to elucidate the contribution to the GAG-binding affinity of different: (1) GAG-binding motifs (i.e., BBXB and BBBXXB); (2) amino acids in GAG-binding motifs and linker sequences; and (3) numbers of GAG-binding motifs. The affinity of eight chemically synthesized peptides for various GAGs was determined by isothermal fluorescence titration (IFT). Moreover, the binding of peptides to cellular GAGs on Chinese hamster ovary (CHO) cells was assessed using flow cytometry with and without soluble GAGs. The repetition of GAG-binding motifs in the peptides contributed to a higher affinity for heparan sulfate (HS) in the IFT measurements. Furthermore, the presence of Gln residues in both GAG-binding motifs and linker sequences increased the affinity of trimer peptides for low-molecular-weight heparin (LMWH), partially desulfated (ds)LMWH and HS, but not for hyaluronic acid. In addition, the peptides bound to cellular GAGs with differential affinity, and the addition of soluble HS or heparin reduced the binding of CXCL9(74-103) to cellular GAGs. These results indicate that the affinity and specificity of peptides for GAGs can be tuned by adapting their amino acid sequence and their number of GAG-binding motifs.     

Characterisation of activated nanoporous carbon for supercapacitor electrode materials

Commercial nanoporous carbon RP-20 was activated with water vapor in the temperature range from 950 °C to 1150 °C. The XRD analysis was carried out on nanoporous carbon powder samples to investigate the structural changes (graphitisation) in modified carbon that occurred at activation temperatures T ? 1150 °C. The first-order Raman spectra showed the absorption peak at 1582 cm⁻¹ and the disorder (D) peak at 1350 cm⁻¹. The low-temperature N₂ adsorption experiments were performed at −196 °C and a specific surface area up to 2240 m²g⁻¹ for carbon activated at T = 1050 °C was measured. The cell capacitance for two electrode activated nanoporous carbon system advanced up to 60 F g⁻¹ giving the specific capacitance ∼240 F g⁻¹ to one electrode nanoporous carbon ∣1.2 M (C₂H₅)₃CH₃NBF₄ + acetonitrile solution interface. A very wide region of ideal polarisability for two electrode system (∼3.2 V) was achieved. The low frequency limiting specific capacitance very weakly increases with the rise of specific area explained by the mass transfer limitations in the nanoporous carbon electrodes. The electrochemical characteristics obtained show that some of these materials under discussion can be used for compilation of high energy density and power density non-aqueous electrolyte supercapacitors with higher power densities than aqueous supercapacitors.     

Adsorption of camphor and 2,2′-bipyridine on Bi(1 1 1) electrode surface

Impedance spectroscopy and in situ STM methods have been used for investigation of the camphor and 2,2′-bipyridine (2,2′-BP) adsorption at the electrochemically polished Bi(1 1 1) electrode from weakly acidified Na₂SO₄ supporting electrolyte solution. The influence of electrode potential on the adsorption kinetics of camphor and 2,2′-BP on Bi(1 1 1) has been demonstrated. In the region of maximal adsorption, i.e. capacitance pit in the differential capacitance versus electrode potential curve, the heterogeneous adsorption and diffusion steps are the rate determining stages for camphor and 2,2′-BP adsorption at the Bi(1 1 1) electrode. It was found that for camphor | Bi(1 1 1) interface the stable adsorbate adlayer detectable by using the in situ STM method has been observed only at the positively charged electrode surface, where the weak co-adsorption of SO₄²⁻ anions and camphor molecules is possible. At the weakly negatively charged Bi(1 1 1) electrode surface there are only physically adsorbed camphor molecules forming the compact adsorption layer. The in situ STM data in a good agreement with impedance data indicate that a very well detectable 2,2′-BP adsorption layer is formed at Bi(1 1 1) electrode in the wide region of charge densities around the zero charge potential.     

Effects of alcohol sensitivity on P3 event-related potential reactivity to alcohol cues.

Although alcoholics and individuals at risk for alcoholism often show smaller amplitude of the P3 event-related brain potential (ERP), recent data (K. Namkoong, E. Lee, C. H. Lee, B. O. Lee, & S. K. An, 2004) indicate that alcohol-related cues elicit larger P3 amplitude in alcoholics than in controls. Little is known concerning the ERP profiles or alcohol cue reactivity of social drinkers at risk for alcoholism due to low sensitivity to alcohol's effects. Participants differing in alcohol sensitivity viewed images of alcoholic and nonalcoholic beverages while ERPs were recorded and provided information about their alcohol use patterns at baseline and 4 months later. Compared to high-sensitivity participants, those low in sensitivity showed larger P3s to alcohol cues, even when recent alcohol use was statistically controlled for. Moreover, the P3 elicited by alcohol cues predicted alcohol use at follow-up, a finding supporting the idea that P3 amplitude reflects the motivational significance of substance-related cues. These findings point to risk status, not consumption history, as an important predictor of cue reactivity effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Substrates of energy metabolism attenuate methamphetamine-induced neurotoxicity in striatum

High doses of methamphetamine (METH) produce a long-term depletion in striatal tissue dopamine content. The mechanism mediating this toxicity has been associated with increased concentrations of dopamine and glutamate and altered energy metabolism. In vivo microdialysis was used to assess and alter the metabolic environment of the brain during high doses of METH. METH significantly increased extracellular concentrations of lactate in striatum and prefrontal cortex. This increase was significantly greater in striatum and coincided with the greater vulnerability of this brain region to the toxic effects of METH. To examine the effect of supplementing energy metabolism on METH-induced dopamine content depletions, the striatum was perfused directly with decylubiquinone or nicotinamide to enhance the energetic capacity of the tissue during or after a neurotoxic dosing regimen of METH. When decylubiquinone or nicotinamide was perfused into striatum during the administration of METH, there was no significant effect on METH-induced striatal dopamine efflux, glutamate efflux, or the long-term dopamine depletions measured 7 days later. However, a delayed perfusion with decylubiquinone or nicotinamide for 6 h beginning immediately after the last METH injection attenuated the METH-induced striatal dopamine depletions measured 1 week later. These results support the hypothesis that the compromised metabolic state produced by METH administration predisposes dopamine terminals to the neurotoxic effects of glutamate, dopamine, and/or free radicals.     

Tool-use in a blended undergraduate course: In Search of user profiles

The popularity of today’s blended courses in higher education is driven by the assumption that students are provided with a rich toolset that supports them in their learning process. However, little is known on how students actually use these tools and how this affects their performance for the course. The current study investigates how students use the entire toolset at their disposal, whether tool-use patterns can be found and if these patterns affect performance for the course. Logging students (n = 156) actions throughout the content management system and registering students’ use of the face-to-face support in an undergraduate course, the study reveals large student differences and an underuse for some tool-types. Further to this, K-means cluster analysis reveals three distinct tool-use patterns or user profiles: the no-users, the intensive users and the incoherent users. These patterns are characterized by different tool-choices and even different use intensity among students. Evidence is retrieved that these tool-use differences are problematic since multivariate analysis of variance reveals significant performance effects. Hence, these results imply that not all students seem to profit from the learning affordances that are provided. Similar as evidence in controlled settings, the results suggest that learner control in using tools cannot be taken for granted. Consequently, this study legitimates more research into the influencing (student and context) variables that can explain these differences.     

Wheat Variety and Barley Malt Properties: Influence on Haze Intensity and Foam Stability of Wheat Beer

Laboratory wheat beers were brewed with different wheat varieties of different protein content (8.7–14.4%) and with five different barley malts, varying in degree of modification (soluble protein: 3.9–6.9%). In a first series of experiments, it was investigated whether wheat positively influences the foam stability, a major characteristic of wheat beers. NIBEM and Rudin (CO₂) foam analyses revealed that the effect of wheat on foam stability depended on the barley malt used for brewing. When using malt with high foaming potential, wheat exerts a negative influence. However, wheat added to over‐modified malt with less foam promoting factors, ameliorates beer foaming characteristics proving that wheat contains foam active compounds. In addition, Rudin (N₂) values suggested that wheat positively influences foam stability by decreasing liquid drainage, probably caused by a higher beer viscosity and/or a finer foam bubble size distribution. Furthermore, the haze in wheat beers, which is another important quality characteristic of these beers, was investigated. Permanent haze readings of the 40% wheat beers were lower than 1.5 EBC haze units. For 20% wheat beers, an inverse relation between the permanent haze (9.4–19.3 EBC haze units) and the protein content of the wheat was established. The barley malt used for brewing also influenced permanent haze readings. A positive correlation between the modification degree of the malt and the permanent haze intensity was found. It was concluded that the choice of raw materials for wheat beer brewing considerably influences the visual properties of the beer.