Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia

The calcium-binding proteins S100A4, S100A8, and S100A9 are upregulated in chronic lymphocytic leukemia (CLL), while the S100A9 promotes NF-κB activity during disease progression. The S100-protein family has been involved in several malignancies as mediators of inflammation and proliferation. The hypothesis of our study is that S100A proteins are mediators in signaling pathways associated with inflammation-induced proliferation, such as NF-κB, PI3K/AKT, and JAK/STAT. The mononuclear cells (MNCs) of CLL were treated with proinflammatory IL-6, anti-inflammatory IL-10 cytokines, inhibitors of JAK1/2, NF-κB, and PI3K signaling pathways, to evaluate S100A4, S100A8, S100A9, and S100A12 expression as well as NF-κB activation by qRT-PCR, immunocytochemistry, and immunoblotting. The quantity of S100A4, S100A8, and S100A9 positive cells (p < 0.05) and their protein expression (p < 0.01) were significantly decreased in MNCs of CLL patients compared to healthy controls. The S100A levels were generally increased in CD19⁺ cells compared to MNCs of CLL. The S100A4 gene expression was significantly stimulated (p < 0.05) by the inhibition of the PI3K/AKT signaling pathway in MNCs. IL-6 stimulated S100A4 and S100A8 protein expression, prevented by the NF-κB and JAK1/2 inhibitors. In contrast, IL-10 reduced S100A8, S100A9, and S100A12 protein expressions in MNCs of CLL. Moreover, IL-10 inhibited activation of NF-κB signaling (4-fold, p < 0.05). In conclusion, inflammation stimulated the S100A protein expression mediated via the proliferation-related signaling and balanced by the cytokines in CLL.     

Cellular mechanism for the improvement of multiple stress tolerance in brewer's yeast by potassium ion supplementation

The ethanol fermentation efficiency was affected by multiple stress tolerance of yeast during brewing and bioethanol industry. The effect of KCl on the multiple stress tolerance of yeast cells was examined. Results showed that KCl addition significantly enhanced the tolerance of yeast cells to osmotic and ethanol stress, which correlated with the decreased membrane permeability, the increased intracellular ergosterol and ATP content, and the improved activity of complex II and complex III in yeast cells. Biomass and viability of yeast cells under osmotic and ethanol stress were increased significantly by KCl addition. Supplementation of 4 and 10 g L⁻¹ KCl exhibited the best promotion activity for yeast cells present in medium with 500 g L⁻¹ sucrose and 10% (v v⁻¹) ethanol, respectively. These results suggested that exogenous potassium addition might be an effective strategy to improve yeast tolerance and fermentation efficiency during industrial very-high-gravity (VHG) fermentation.     

Hydrolysis of fatty acid esters in subcritical water

Hydrolysis of esters of higher fatty acids by subcritical water, performed in a flow‐through tubular reactor, was investigated at temperatures from 280 up to 340 °C and pressures exceeding 12 MPa, using an ester/water ratio of 1 : 2 or 1 : 4 (vol/vol). The kinetics of the hydrolysis of both the triacylglycerols and the methyl esters obeyed the rate equation valid for first‐order reactions. Conversion of the esters to free fatty acids exceeding 95% was reached at the temperature of 340 °C during 12 min. IR spectroscopy revealed structural changes in the chains of the unsaturated fatty acids and their partial polymerization during the hydrolysis.     

Synthesis,post‐modification and characterization of linear polystyrene‐based supports for interaction with immobilized biocatalysts

A series of linear polystyrene‐based supports has been synthesized using conventional or controlled (reversible addition fragmentation chain transfer or nitroxide‐mediated) free radical polymerizations, in order to modulate their molecular weight characteristics. Polymer post‐modification via esterification of the primary hydroxyl alcohol functionalities, pendant from the polymer backbone, with a mandelic acid derivative introduces efficiently (>85% yield) racemic, enzyme‐cleavable moieties. A study of the interactions of these polymeric substrates with immobilized penicillin G acylase, in mixed organic/aqueous buffer solvent systems, results in a modest enantioselectivity (comparable with that of racemic mandelic acid methyl ester), but reveals that the biocatalytically active moieties on the linear polymers can be cleaved with first‐order rate kinetics, as observed with small molecules in solution; the reaction rates (which can differ by more than one order of magnitude) are influenced both by the synthetic polymer length and by the polymer structure resulting from the method of polymerization used. Copyright © 2012 Society of Chemical Industry     

The bivariate Shepard operator of Bernoulli type

Abstract The method of Shepard is an efficient method for interpolation of very large scattered data sets; unfortunately, it has poor reproduction qualities and high computational cost. In this paper we introduce a new operator which diminishes these drawbacks. This operator results from the combination of the Shepard operator with a new interpolation operator, recently proposed by Costabile and Dell’Accio, and generalizes to two variate functions the Shepard-Bernoulli operator introduced in [2]. We study this combined operator and give error bounds in terms of the modulus of continuity of high order and of the mesh length. We improve the accuracy and computational efficiency using a method introduced by Franke and Nielson. Keywords: Shepard operator, Bernoulli operator, interpolation of scattered data, error estimations. Mathematics Subject Classification (2000): 41A05, 41A25, 41A80.     

Synthesis and electronic spectra of 3-hetaryl substituted coumarin derivatives 7-hydroxy-2H-chromen-2-on and 9-hydroxy-2H-benzo(f)chromen-2-on

The synthesis of 3-hetaryl substituted coumarin derivatives [7-hydroxy-2H-chromen-2-on and 9-hydroxy-2H-benzo(f)chromen-2-on] containing a hydroxyl group by reacting 2,4-dihydroxybenzaldehyde and 2,4-dihydroxynaphtaldehydes with 2-cyanomethylbenzothiazole, 2-cyanomethylbenzimidazole, 1-methyl-2-cyanomethylbenzimidazole and 2-cyanomethyl-4-phenylthiazole is presented. The absorption and steady-state fluorescence characteristics of the synthesised 3-hetaryl substituted 7-hydroxy-2H-chromen-2-on and 9-hydroxy-2H-benzo(f)chromen-2-on in a solution of ethanol and at different pH values are studied to assess their possible application as fluorescent probes for use in molecular biology and medicine.     

The role of reactive oxygen species in the induction of Ty1 retrotransposition in Saccharomyces cerevisiae

Here we provide evidence for a dependence between the increased production of reactive oxygen species and the activation of Ty1 retrotransposition. We have found that the strong activator of Ty1 mobility, methylmethane sulphonate, can not induce Ty1 retrotransposition in cells with compromised mitochondrial oxidative phosphorylation (rho^?; sco1Δ), which is the major source for production of reactive oxygen species (ROS) in Saccharomyces cerevisiae. The quantitative estimation of superoxide anions in living cells showed that rho⁺ cells exposed to methylmethane sulphonate increase Ty1 retrotransposition and superoxide levels. The increase of superoxide anions by the superoxide generator menadione is accompanied by induction of Ty1 mobility without any treatment with a DNA‐damaging agent. Higher frequencies of retrotransposition were found in rho⁺ and rho^? cells treated with exogenously added hydrogen peroxide or in cells with disrupted YAP1 gene characterized by increased intracellular levels of hydrogen peroxide. These data indicate that increased levels of ROS may have an independent and key role in the induction of Ty1 retrotransposition. Copyright © 2010 John Wiley & Sons, Ltd.     

Knowledge networks across Europe: which distance matters?

In this paper, we address the manifold nature of knowledge through the analysis of four distinct but complementary phenomena (Internet hyperlinks, EPO co-patent applications, Erasmus students mobility and European research networks) which characterise knowledge as an intrinsic relational structure (directly) connecting people, institutions and (indirectly) regions across five European countries. We study the structure (in terms of density, centralisation, clustering, assortativity, centre-periphery and resilience) of these international knowledge flows through network analysis techniques and we test the influence of geographical distance as opposed to sectoral (based on the industrial distribution of innovative activity) and functional (based on the value of the European technological index) distances in shaping the strength of knowledge relations through a gravitational model. Network Analysis techniques applied to the configuration of international knowledge flows between European regions highlight the existence of a polarised hierarchical structure. By estimating a “gravity equation” model we demonstrate that, far from the claim of the “death of distance”, geographic distance is still relevant for determining the structure of inter-regional knowledge flows. Functional and, above all, sectoral distances play also a relevant role suggesting that knowledge flows easier between similar regions (according to their technological level and the industrial distribution of their innovation system).     

A Learning Community of University Freshman Design,Freshman Graphics,and High School Technology Students: Description,Projects, and Assessment

A learning community was developed to enhance the teamwork and communication components of a freshman design course. The learning community was comprised of students from a freshman design course, a freshman graphics course, and a high school technology course. Design teams were formed by combining three to four students from each of these courses. These teams were required to research, design, build, and test a specified product. The high school and university students communicated only using e‐mails and Internet conferencing. This paper outlines how the learning community is implemented, describes three design projects, and presents the assessment methods. Assessment reveals that university students who participate in the learning community have a better understanding and confidence in the technical aspects of the design project than the students who do not participate in the learning community. It also reveals that high school participants display notable interest in the engineering design process.     

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach.