Fludarabine inhibits KV1.3 currents in human B lymphocytes

Fludarabine (F-ara-A) is a purine analog commonly used in the treatment of indolent B cell malignancies that interferes with different aspects of DNA and RNA synthesis. KV1.3 K+ channels are membrane proteins involved in the maintenance of K+ homeostasis and the resting potential of the cell, thus controlling signaling events, proliferation and apoptosis in lymphocytes. Here we show that F-ara-A inhibits KV currents in human B lymphocytes. Our data indicate that KV1.3 is expressed in both BL2 and Dana B cell lines, although total KV1.3 levels were higher in BL2 than in Dana cells. However, KV currents in the plasma membrane were similar in both cell lines and were abrogated by the specific KV1.3 channel inhibitor PAP-1, indicating that KV1.3 accounts for most of the KV currents in these cell lines. F-ara-A, at a concentration (3.5 μM) similar to that achieved in the plasma of fludarabine phosphate-treated patients (3 μM), inhibited KV1.3 currents by 61 ± 6.3% and 52.3 ± 6.3% in BL2 and Dana B cells, respectively. The inhibitory effect of F-ara-A was concentration-dependent and showed an IC50 value of 0.36 ± 0.04 μM and a nH value of 1.07 ± 0.15 in BL2 cells and 0.34 ± 0.13 μM (IC50) and 0.77 ± 0.11 (nH) in Dana cells. F-ara-A inhibition of plasma membrane KV1.3 was observed irrespective of its cytotoxic effect on the cells, BL2 cells being sensitive and Dana cells resistant to F-ara-A cytotoxicity. Interestingly, PAP-1, at concentrations as high as 10 μM, did not affect the viability of BL2 and Dana cells, indicating that blockage of KV1.3 in these cells is not toxic. Finally, F-ara-A had no effect on ectopically expressed KV1.3 channels, suggesting an indirect mechanism of current inhibition. In summary, our results describe the inhibitory effect of F-ara-A on the activity of KV1.3 channel. Although KV1.3 inhibition is not sufficient to induce cell death, further research is needed to determine whether it might still contribute to F-ara-A cytotoxicity in sensitive cells or be accountable for some of the clinical side effects of the drug.This study was supported by MINECO (SAF2013-45800-R, SAF2016-75021-R, RD12/0042/0019, CB/11/00222) and ISCIII (PI12/01135 and PI16/00895). The cost of this publication was paid in part by funds from the European Fund for Economic and Regional Development (FEDER). TG is supported by the Ramón y Cajal Program.Peer reviewedPeer Reviewe

A glucuronoxylan-specific xylanase from a new Paenibacillus favisporus strain isolated from tropical soil of Brazil

A new xylanolytic strain, Paenibacillus favisporus CC02-N2, was isolated from sugarcane plantation fi elds in Brazil. The strain had a xylan-degrading system with multiple enzymes, one of which, xylanase Xyn30A, was identifi ed and characterized. The enzyme is a single-domain xylanase belonging to family 30 of the glycosyl hydrolases (GH30). Xyn30A shows high activity on glucuronoxylans, with a Vmax of 267.2 U mg1, a Km of 4.0 mg/ml, and a kcat of 13,333 min1 on beechwood xylan, but it does not hydrolyze arabinoxylans. The three- dimensional structure of Xyn30A consists of a common (β/α)8 barrel linked to a side-chain-associated β-structure, similar to previously characterized GH30 xylanases. The hydrolysis products from glucuronoxylan were methylglucuronic-acid-substituted xylooligomers (acidic xylooligosaccharides). The enzyme bound to insoluble xylan but not to crystalline cellulose. Our results suggest a specifi c role for Xyn30A in xylan biodegradation in natural habitats. The enzyme is a good candidate for the production of tailored xylooligosaccharides for use in the food industry and in the biotechnological transformation of biomass. [Int Microbiol 2014; 17(3):175-184

Small Molecules as Dream Modulators: New Avenues for the Search of Drugs for Neurodegenerative Diseases

Trabajo presentado en el 9th drug Design and Medicinal Chemistry, celebrado en Berlín (Alemania) del 05 al 06 de mayo de 2015.Altered neuronal calcium homeostasis and early compensatory changes in transcriptional programs are common features of many neurodegenerative pathologies including Alzheimer¿s disease, Down syndrome and Huntington¿s disease. DREAM (Downstream Regulatory Element Antagonist Modulator), also known as calsenilin or KChIP-3 (potassium channel interacting protein-3), is a multifunctional calcium binding protein that controls the expression level and/or the activity of several proteins related to calcium homeostasis, neuronal excitability and neuronal survival. This protein is widely expressed in the brain and, depending on the cell type and physiological conditions, shows multiple subcellular localizations, in the nucleus, cytosol or cell membrane. The interest in DREAM is based on its key role in the regulation of intracellular calcium levels. As a calcium-dependent transcriptional repressor, DREAM is a master regulator of activity-dependent gene expression and controls genes important for calcium homeostasis such as the sodium/calcium exchanger-3 (NCX3), IP3R and L-type calcium channels. As an auxiliary protein in the plasma membrane, DREAM interacts with and regulates the gating of Kv4 potassium channels, L- and T-type voltage-dependent calcium channels and NMDA receptors. These findings suggest that DREAM could be a novel and versatile target for therapeutic intervention in neurodegeneration and that molecules able to bind to DREAM and block its physiological functions could be candidates for drugs to treat neurodegenerative diseases. Moreover, up to now, only two DREAM-binding molecules have been identified. In this communication we report the rational design and the synthesis of novel DREAM-binding molecules and their effects on the modulation of DREAM/protein interactions

Influence of gaseous pollutants and their synergistic effects on the aging of reflector materials for concentrating solar thermal technologies

ABSTRACT: Concentrating solar thermal technologies have experienced an important boost in the last few years. Besides the production of electricity, they are particularly useful for the supply of industrial process heat. The industrial atmospheres affecting these solar plants typically contain gaseous pollutants that are likely to promote corrosion on the components of the solar facility, specifically solar reflectors, thereby compromising their optimal performance and the overall system efficiency. Seven accelerated aging tests were designed to study the effects of three air pollutants (H2S, SO2 and NO2) on the durability of two commercially available reflector types (silvered glass and aluminum), both in single-gas tests and in multicomponent gas mixtures. Additionally, the same material types were exposed outdoors at five representative polluted sites, including industrial, urban and coastal environments. Reflectance and optical microscope monitoring corroborated which degree of corrosion was developed on a specific type of reflector in the different tests with gaseous pollutants, as well as the synergistic effects of gas combinations. For example, tests with sulfur were harmful for silvered-glass reflectors (up to a total of 16 corrosion spots), whereas aluminum was particularly affected by tests with NO2 (numerous micro spots of around 50 pm size). Moreover, comparisons of the corrosion patterns found in accelerated-aging and outdoor exposures revealed which laboratory test reproduced the different real polluted atmospheres in the most realistic way, which is the main goal of this work. For instance, the degradation found at Site 2 was reproduced by Test NO2+SO2, with an acceleration factor of 27.info:eu-repo/semantics/publishedVersio

Laccase/TEMPO-mediated bacterial cellulose functionalization: production of paper-silver nanoparticles composite with antimicrobial activity

Bacterial cellulose (BC) was functionalized applying the Laccase/TEMPO oxidative treatment, leading to a five-fold increase of the concentration of carboxyl groups. Paper produced with this cellulose showed improved mechanical properties while maintaining barrier function against water and greases as compared to paper produced with non-oxidized BC. Also, the negative charge provided by the carboxyl groups on functionalized BC was used to generate silver nanoparticles (AgNPs), obtaining a BC paper and Ag composite. The presence of AgNPs in the composites was validated by SEM, EDS and ICP analysis, showing spherical, uniformly sized particles stabilized in the BC nanofibers matrix. Additionally, antimicrobial property of composites containing AgNPs was tested. The results showed the strong antimicrobial activity of the composites against Gram-positive and Gram-negative bacteria and fungi. The generation of Ag nanoparticles in a matrix that combine the physical characteristics of the BC nanofibers with the stiffness and the mechanical properties of paper produced composites that may have applicability in technological and biomedical uses

Bacterial cellulose for increasing barrier properties of paper products

Bacterial cellulose was combined with wood cellulose papers in order to obtain biomaterials with increased barrier properties. For this purpose, different parameters were assessed: two producing bacterial strains (Komagataeibacter xylinus and Gluconacetobacter sucrofermentans), two paper supports to hold bacterial cellulose (filter paper and eucalyptus paper), two kinds of combined biomaterials (composite and bilayer) and two drying temperatures (90ºC and room temperature). Papers with increased barrier properties (100º of water contact angle, 1220s of water drop test and air permeability ˂1µm (Pa·s)-1) were obtained by the addition of bacterial cellulose to each paper support. However, due to the lower initial barrier properties of filter paper, higher improvements were produced with this paper. In addition, bacterial cellulose provided smoother surfaces with higher gloss without a detrimental effect on physical properties. Higher resistance to water absorption was obtained with K. xylinus possibly explained by its longer size fibers than G. sucrofermentans, as analysed by SEM. Smoothness and gloss were specially increased in the bilayer biomaterial although resistance to air and water were further improved in the composite. In this biomaterial drying at high temperature had a detrimental effect. SEM analysis of the products obtained showed the intimate contact among fibers of bacterial cellulose and wood paper. Results obtained show the contribution of bacterial cellulose to improve the properties of paper and its potential for the design of new added value paper products from biomass

Laccase/TEMPO-mediated bacterial cellulose functionalization: production of paper-silver nanoparticles composite with antimicrobial activity

“This is a post-peer-review, pre-copyedit version of an article published in Cellulose. The final authenticated version is available online at: https://doi.org/10.1007/s10570-019-02678-5Bacterial cellulose (BC) was functionalized applying the Laccase/TEMPO oxidative treatment, leading to a five-fold increase of the concentration of carboxyl groups. Paper produced with this cellulose showed improved mechanical properties while maintaining barrier function against water and greases as compared to paper produced with non-oxidized BC. Also, the negative charge provided by the carboxyl groups on functionalized BC was used to generate silver nanoparticles (AgNPs), obtaining a BC paper and Ag composite. The presence of AgNPs in the composites was validated by SEM, EDS and ICP analysis, showing spherical, uniformly sized particles stabilized in the BC nanofibers matrix. Additionally, antimicrobial property of composites containing AgNPs was tested. The results showed the strong antimicrobial activity of the composites against Gram-positive and Gram-negative bacteria and fungi. The generation of Ag nanoparticles in a matrix that combine the physical characteristics of the BC nanofibers with the stiffness and the mechanical properties of paper produced composites that may have applicability in technological and biomedical usesPeer ReviewedPostprint (author's final draft

Bacterial cellulose for increasing barrier properties of paper products

Bacterial cellulose was combined with wood cellulose papers in order to obtain biomaterials with increased barrier properties. For this purpose, different parameters were assessed: two producing bacterial strains (Komagataeibacter xylinus and Gluconacetobacter sucrofermentans), two paper supports to hold bacterial cellulose (filter paper and eucalyptus paper), two kinds of combined biomaterials (composite and bilayer) and two drying temperatures (90 °C and room temperature). Papers with increased barrier properties (100° of water contact angle, 1220 s of water drop test and air permeability < 1 µm (Pa s)-1) were obtained by the addition of bacterial cellulose to each paper support. However, due to the lower initial barrier properties of filter paper, higher improvements were produced with this paper. In addition, bacterial cellulose provided smoother surfaces with higher gloss without a detrimental effect on physical properties. Higher resistance to water absorption was obtained with K. xylinus possibly explained by its longer size fibers than G. sucrofermentans, as analysed by SEM. Smoothness and gloss were specially increased in the bilayer biomaterial although resistance to air and water were further improved in the composite. In this biomaterial drying at high temperature had a detrimental effect. SEM analysis of the products obtained showed the intimate contact among fibers of bacterial cellulose and wood paper. Results obtained show the contribution of bacterial cellulose to improve the properties of paper and its potential for the design of new added value paper products from biomassPostprint (author's final draft