Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

Effect of hot strip processing during direct charging of thin slabs on the properties of cold strip of LC-steel

Direct charging of thin slabs of low carbon steel (0.05%C) was investigated by using laboratory tests on a thin-slab-casting Simulator linked with the hot deformation Simulator (Wumsi). Starting with a different initial thickness of simulated thin slabs (45 down to 25 mm) the total strain ?∑ was varied. Hot deformation schedules (with and without roughing) with different finishing temperatures T_F lead to some differences in the hot strip microstructure. Nevertheless, after cold rolling and batch annealing, a rather uniform pancake-structure and a pronounced {111}-texture were achieved in the cold strip without any significant relation to the processing routs. The measurement of final mechanical properties proved that a good deep drawability of cold strip can be achieved with direct charging of thin slabs, well comparable to that after a conventional cold charging of thick slabs.     

Age Differences in Everyday Problem-Solving and Decision-Making Effectiveness: A Meta-Analytic Review.

The authors report a meta-analysis of age differences in everyday problem-solving/decision-making effectiveness (EPSE). Effect sizes were calculated to reflect 3 age group comparisons: old versus young, young versus middle-aged, and middle-aged versus old. Findings from the meta-analysis of 28 separate studies with an aggregate of 4,482 participants do not support theories of preserved EPSE in late adulthood. Although significant age differences of moderate magnitude persisted across methodological and theoretical domains, rating criteria (experimenter vs. participant) emerged as a significant moderator of the effect magnitude and direction. In addition, EPSE in older adults was bolstered when problem content was interpersonal and when samples were highly educated. Finally, the current results support the conceptual integration of findings from the everyday problem-solving and everyday decision-making literatures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social comparison and affiliation under threat: Going beyond the affiliate-choice paradigm.

Examined the emotional similarity hypothesis, a derivation from social comparison theory, which predicts that increasing fear should lead to greater affiliation with someone who is awaiting the same threat (and who therefore is of relatively similar emotional status) relative to someone who has already experienced the threat (and who therefore is of relatively dissimilar emotional status). Results failed to support the emotional similarity hypothesis and in so doing challenged the importance of emotional comparison as a determinant of verbal affiliation under threat. Cognitive clarity concerns instead seemed to account better for the observed effects on verbal affiliation. Supplementary analyses of nonverbal affiliation (facial glances) likewise ran counter to an emotional similarity prediction. Effects of affiliation on anxiety were also examined. Previous conclusions regarding the pattern and causes of affiliation under threat that have relied on the affiliate-choice paradigm are considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microstructural Aspects and Optimization of Thin Slab Direct Rolling of Steels

By using a thin slab casting simulator combined with the hot deformation simulator WUMSI, laboratory tests were performed to investigate the microstructure processes and mechanical properties in the process of thin slab direct rolling (TSDR). The paper shows the possibilities to improve the initial as‐cast state of microstructure prior to hot rolling (microvoids, dendritic structure, austenite grain size, state of precipitation). The main part of the study is dedicated to the role of microalloying and sulphur for the austenite grain control and for the precipitation hardening in the final structure. On examples of selected low carbon steel grades the effect of the variation of the process parameters of hot rolling and cooling on the microstructure and mechanical properties is presented.     

Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential.     

TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts

TRPM7 plays an important role in cellular Ca²⁺, Zn²⁺ and Mg²⁺ homeostasis. TRPM7 channels are abundantly expressed in ameloblasts and, in the absence of TRPM7, dental enamel is hypomineralized. The potential role of TRPM7 channels in Ca²⁺ transport during amelogenesis was investigated in the HAT-7 rat ameloblast cell line. The cells showed strong TRPM7 mRNA and protein expression. Characteristic TRPM7 transmembrane currents were observed, which increased in the absence of intracellular Mg²⁺ ([Mg²⁺]_i), were reduced by elevated [Mg²⁺]_i, and were inhibited by the TRPM7 inhibitors NS8593 and FTY720. Mibefradil evoked similar currents, which were suppressed by elevated [Mg²⁺]_i, reducing extracellular pH stimulated transmembrane currents, which were inhibited by FTY720. Naltriben and mibefradil both evoked Ca²⁺ influx, which was further enhanced by the acidic intracellular conditions. The SOCE inhibitor BTP2 blocked Ca²⁺ entry induced by naltriben but not by mibefradil. Thus, in HAT-7 cells, TRPM7 may serves both as a potential modulator of Orai-dependent Ca²⁺ uptake and as an independent Ca²⁺ entry pathway sensitive to pH. Therefore, TRPM7 may contribute directly to transepithelial Ca²⁺ transport in amelogenesis.