Síntesis, caracterización y aplicaciones de nanotransportadores formados por tensioactivos derivados de (Ru(bpy)3)2+.

En la presente Tesis Doctoral se han sintetizado cuatro metalosurfactantes derivados del Ru(bpy)3 2+, donde se han variado el número de cadenas hidrofóbicas y la longitud de las mismas. Se han caracterizado los tensioactivos y se ha estudiado su proceso de agregación. Posteriormente se ha investigado la interacción entre los monómeros y los agregados de los metalosurfactantes con el ADN, al que compactan, pasando de una conformación elongada a una forma de ovillo. Se han determinado las constantes de interacción entre los metalosurfactantes y las α-, β., y -ciclodextrinas. Se observa la formación de complejos de inclusión estables, lo que permitiría usar las ciclodextrinas para decompactar el ADN. Se han preparado también metaloliposomas y se han caracterizado los complejos liposoma/ADN o lipoplejos, en los que el polinucleótido está compactado. Los estudios de viabilidad celular realizados confirman que los etalosurfactantes tienen propiedades antineoplásicas. Como monómeros, presentan baja toxicidad a concentraciones bajas, mientras que las micelas presentan citotoxicidad elevada. Sólo en el caso de los metaloliposomas se encuentra, a concentraciones intermedias, que las células sanas prácticamente no se ven afectadas, mientras que para las líneas celulares cancerígenas son citotóxicos. Estudios de internalización celular indican una elevada internalización de las metalomicelas. Por último, las metalomicelas y los metaloliposomas se han usado como nanotransportadores de un agente antineoplásico como la doxorrubicina, observándose altos porcentajes de encapsulación de este fármaco, especialmente en los liposomas

Preparation and Characterization of New Liposomes. Bactericidal Activity of Cefepime Encapsulated into Cationic Liposomes

Cefepime is an antibiotic with a broad spectrum of antimicrobial activity. However, this antibiotic has several side effects and a high degradation rate. For this reason, the preparation and characterization of new liposomes that are able to encapsulate this antibiotic seem to be an important research line in the pharmaceutical industry. Anionic and cationic liposomes were prepared and characterized. All cationic structures contained the same cationic surfactant, N,N,N-triethyl-N-(12-naphthoxydodecyl)ammonium. Results showed a better encapsulation-efficiency percentage (EE%) of cefepime in liposomes with phosphatidylcholine and cholesterol than with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The presence of cholesterol and the quantity of egg-yolk phospholipid in the liposome increased the encapsulation percentage. The bactericidal activity against Escherichia coli of cefepime loaded into liposomes with phosphatidylcholine was measured. The inhibitory zone in an agar plate for free cefepime was similar to that obtained for loaded cefepime. The growth-rate constant of E. coli culture was also measured in working conditions. The liposome without any antibiotic exerted no influence in such a rate constant. All obtained results suggest that PC:CH:12NBr liposomes are biocompatible nanocarriers of cefepime that can be used in bacterial infections against Escherichia coli with high inhibitory activity

A logic-algebraic tool for reasoning with Knowledge-Based Systems

A detailed exposition of foundations of a logic-algebraic model for reasoning with knowledge bases speci ed by propositional (Boolean) logic is presented. The model is conceived from the logical translation of usual derivatives on polynomials (on residue rings) which is used to design a new inference rule of algebro-geometric inspiration. Soundness and (refutational) completeness of the rule are proved. Some applications of the tools introduced in the paper are shown.Ministerio de Economía y Competitividad TIN2013-41086-

Binding of DNA by a dinitro-diester calix[4]arene: Denaturation and condensation of DNA

A study of a dinitro-diester calix[4]arene (5,17-(3-nitrobenzylideneamino)-11,23-di-tert-butyl-25,27-diethoxycarbonyl methyleneoxy-26,28-dihydroxycalix[4]arene) interaction with calf-thymus DNA was carried out using several techniques. The measurements were done at various molar ratios X=[calixarene]/[DNA]. Results show diverse changes in the DNA conformation depending on the X value. Thus, at low macrocycle concentrations, the calixarene binds to the polynucleotide. This interaction, mainly in groove mode, weakens the hydrogen bonds between base pairs of the helix inducing denaturation of the double strands, as well as condensation of the macromolecule, from an extended coil state to a globular state. An opposite effect is observed at X molar ratios higher than 0.07. The de-condensation of DNA happens, that is, the transition from a compact state to a more extended conformation, probably due to the stacking of calixarene molecules in the solution. Results also show the importance of making a proper choice of the system under consideration.Junta de Andalucía P08-FQM-03623, P12-FQM-110

Extending Attribute Exploration by Means of Boolean Derivatives

We present a translation of problems of Formal Context Analysis into ideals problems in F2[x] through the Boolean derivatives. The Boolean derivatives are introduced as a kind of operators on propositional formulas which provide a complete calculus. They are useful to refine stem basis as well as for extending attribute exploration

Fluorescent Calixarene-Schiff as a Nanovehicle with Biomedical Purposes

Gene therapy is a technique that is currently under expansion and development. Recent advances in genetic medicine have paved the way for a broader range of therapies and laid the groundwork for next-generation technologies. A terminally substituted difluorene-diester Schiff Base calix[4]arene has been studied in this work as possible nanovector to be used in gene therapy. Changes to luminescent behavior of the calixarene macrocycle are reported in the presence of ct-DNA. The calixarene macrocycle interacts with calf thymus DNA (ct-DNA), generating changes in its conformation. Partial double-strand denaturation is induced at low concentrations of the calixarene, resulting in compaction of the ct-DNA. However, interaction between calixarene molecules themselves takes place at high calixarene concentrations, favoring the decompaction of the polynucleotide. Based on cytotoxicity studies, the calixarene macrocycle investigated has the potential to be used as a nanovehicle and improve the therapeutic efficacy of pharmacological agents against tumors

In vitro supporting diagnostic tools in plant‐food allergy.

Funding for open access charge: Universidad de Málaga / CBU

Potentiometric study of carbon nanotube/surfactant interactions by ion-selective electrodes. Driving forces in the adsorption and dispersion processes

The interaction (adsorption process) of commercial ionic surfactants with non-functionalized and functionalized carbon nanotubes (CNTs) has been studied by potentiometric measurements based on the use of ion-selective electrodes. The goal of this work was to investigate the role of the CNTs' charge and structure in the CNT/surfactant interactions. Non-functionalized single- (SWCNT) and multi-walled carbon nanotubes (MWCNT), and amine functionalized SWCNT were used. The influence of the surfactant architecture on the CNT/surfactant interactions was also studied. Surfactants with different charge and hydrophobic tail length (sodium dodecyl sulfate (SDS), octyltrimethyl ammonium bromide (OTAB), dodecyltrimethyl ammonium bromide (DoTAB) and hexadecyltrimethyl ammonium bromide (CTAB)) were studied. According to the results, the adsorption process shows a cooperative character, with the hydrophobic interaction contribution playing a key role. This is made evident by the correlation between the free surfactant concentration (at a fixed [CNT]) and the critical micellar concentration, cmc, found for all the CNTs and surfactants investigated. The electrostatic interactions mainly determine the CNT dispersion, although hydrophobic interactions also contribute to this process.Fil: Ostos, Francisco José. Universidad de Sevilla; EspañaFil: Lebrón, José Antonio. Universidad de Sevilla; EspañaFil: Moyá, María Luisa. Universidad de Sevilla; EspañaFil: Bernal, Eva. Universidad de Sevilla; EspañaFil: Flores, Ana. Universidad de Huelva; EspañaFil: Lépori, Cristian Marcelo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Maestre, Ángeles. Universidad de Huelva; EspañaFil: Sánchez, Francisco. Universidad de Sevilla; EspañaFil: López Cornejo, Pilar. Universidad de Sevilla; EspañaFil: López López, Manuel Carlos. Universidad de Huelva; Españ

sRNAbench and sRNAtoolbox 2019: intuitive fast small RNA profiling and differential expression

Since the original publication of sRNAtoolbox in 2015, small RNA research experienced notable advances in different directions. New protocols for small RNA sequencing have become available to address important issues such as adapter ligation bias, PCR amplification artefacts or to include internal controls such as spike-in sequences. New microRNA reference databases were developed with different foci, either prioritizing accuracy (low number of false positives) or completeness (low number of false negatives). Additionally, other small RNA molecules as well asmicroRNA sequence and length variants (isomiRs) have continued to gain importance. Finally, the number of microRNA sequencing studies deposited in GEO nearly triplicated from 2014 (280) to 2018 (764). These developments imply that fast and easy-to-use tools for expression profiling and subsequent downstream analysis of miRNAseq data are essential to many researchers. Key features in this sRNAtoolbox release include addition of all major RNA library preparation protocols to sRNAbench and improvements in sRNAde, a tool that summarizes several aspects of small RNA sequencing studies including the detection of consensus differential expression. A special emphasis was put on the user-friendliness of the tools, for instance sRNAbench now supports parallel launching of several jobs to improve reproducibility and user time efficiency.European Union [765492 to M.H.]; Spanish Government [AGL2017-88702-C2-2-R to M.H., J.L.O.]; Instituto de Salud Carlos III, FEDER funds [PIE16/00045 to J.A.M.]; Chair ‘Doctors Galera-Requena in cancer stem cell research’ to JMA and by the Ministry of Education of Spain [FPU13/05662 to R.L., IFI16/00041 to E.A.]; Strategic Research Area (SFO) program of the Swedish Research Council (to V.R.) through Stockholm University (to B.F.). Funding for open access charge: SpanishGovernment [AGL2017-88702-C2-2-R]

Metallo-Liposomes Derived from the [Ru(bpy)3]2+ Complex as Nanocarriers of Therapeutic Agents

The obtaining of nanocarriers of gene material and small drugs is still an interesting research line. Side-effects produced by the toxicity of several pharmaceutics, the high concentrations needed to get therapeutic effects, or their excessive use by patients have motivated the search for new nanostructures. For these reasons, cationic metallo-liposomes composed by phosphatidylcholine (PC), cholesterol (CHO) and RuC1C19 (a surfactant derived from the metallic complex [Ru(bpy)3]2+) were prepared and characterized by using diverse techniques (zeta potential, dynamic light scattering and electronic transmission microscopy –TEM-). Unimodal or bimodal populations of spherical aggregates with small sizes were obtained depending on the composition of the liposomes. The presence of cholesterol favored the formation of small aggregates. ct-DNA was condensed in the presence of the liposomes investigated. In-vitro assays demonstrated the ability of these nanoaggregates to internalize into different cell lines. A positive gene transfection into human bone osteosarcoma epithelial cells (U2OS) was also observed. The RuC1C19 surfactant was used as sensor to quantify the binding of DNA to the liposomes. Doxorubicin was encapsulated into the metallo-liposomes, demonstrating their ability to be also used as nanocarriers of drugs. A relationship between then encapsulation percentage of the antibiotic and the composition of the aggregates has been established.Junta de Andalucía 2019/FQM-206, 2019/FQM-274Ministerio de Ciencia e Innovación RTI2018-100692-BI00, PI-0005-2018, P18-RT-127