Synthesis of Janus compounds for the recognition of G-U mismatched nucleobase pairs

The design and synthesis of two Janus-type heterocycles with the capacity to simultaneously recognize guanine and uracyl in G-U mismatched pairs through complementary hydrogen bond pairing is described. Both compounds were conveniently functionalized with a carboxylic function and efficiently attached to a tripeptide sequence by using solid-phase methodologies. Ligands based on the derivatization of such Janus compounds with a small aminoglycoside, neamine, and its guanidinylated analogue have been synthesized, and their interaction with Tau RNA has been investigated by using several biophysical techniques, including UV-monitored melting curves, fluorescence titration experiments, and 1H NMR. The overall results indicated that Janus-neamine/guanidinoneamine showed some preference for the +3 mutated RNA sequence associated with the development of some tauopathies, although preliminary NMR studies have not confirmed binding to G-U pairs. Moreover, a good correlation has been found between the RNA binding affinity of such Janus-containing ligands and their ability to stabilize this secondary structure upon complexation

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

A straightforward methodology for the synthesis of conjugates between a cytotoxic organometallic ruthenium(II) complex and amino- and guanidinoglycosides, as potential RNA-targeted anticancer compounds, is described. Under microwave irradiation, the imidazole ligand incorporated on the aminoglycoside moiety (neamine or neomycin) was found to replace one triphenylphosphine ligand from the ruthenium precursor [(η6-p-cym)RuCl(PPh3)2]+, allowing the assembly of the target conjugates. The guanidinylated analogue was easily prepared from the neomycin-ruthenium conjugate by reaction with N,N′-di-Boc-N″-triflylguanidine, a powerful guanidinylating reagent that was compatible with the integrity of the metal complex. All conjugates were purified by semipreparative high-performance liquid chromatography (HPLC) and characterized by electrospray ionization (ESI) and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and NMR spectroscopy. The cytotoxicity of the compounds was tested in MCF-7 (breast) and DU-145 (prostate) human cancer cells, as well as in the normal HEK293 (Human Embryonic Kidney) cell line, revealing a dependence on the nature of the glycoside moiety and the type of cell (cancer or healthy). Indeed, the neomycin-ruthenium conjugate (2) displayed moderate antiproliferative activity in both cancer cell lines (IC50 ≈ 80 μM), whereas the neamine conjugate (4) was inactive (IC50 ≈ 200 μM). However, the guanidinylated analogue of the neomycin-ruthenium conjugate (3) required much lower concentrations than the parent conjugate for equal effect (IC50 = 7.17 μM in DU-145 and IC50 = 11.33 μM in MCF-7). Although the same ranking in antiproliferative activity was found in the nontumorigenic cell line (3 2 > 4), IC50 values indicate that aminoglycoside-containing conjugates are about 2-fold more cytotoxic in normal cells (e.g., IC50 = 49.4 μM for 2) than in cancer cells, whereas an opposite tendency was found with the guanidinylated conjugate, since its cytotoxicity in the normal cell line (IC50 = 12.75 μM for 3) was similar or even lower than that found in MCF-7 and DU-145 cancer cell lines, respectively. Cell uptake studies performed by ICP-MS with conjugates 2 and 3 revealed that guanidinylation of the neomycin moiety had a positive effect on accumulation (about 3-fold higher in DU-145 and 4-fold higher in HEK293), which correlates well with the higher antiproliferative activity of 3. Interestingly, despite the slightly higher accumulation in the normal cell than in the cancer cell line (about 1.4-fold), guanidinoneomycin-ruthenium conjugate (3) was more cytotoxic to cancer cells (about 1.8-fold), whereas the opposite tendency applied for neomycin-ruthenium conjugate (2). Such differences in cytotoxic activity and cellular accumulation between cancer and normal cells open the way to the creation of more selective, less toxic anticancer metallodrugs by conjugating cytotoxic metal-based complexes such as ruthenium(II) arene derivatives to guanidinoglycosides

Atmospheric pressure plasma surface treatment of thermoplastic composites for bonded joints

Glass fiber reinforced polypropylene samples were treated by an atmospheric pressure plasma jet using a rotary nozzle, in order to improve adhesive properties of the material surface. Thereby, the influence of the most significant operational parameters of the plasma treatment was studied. These parameters are e.g. the distance between the nozzle and the treated substrate, and the total plasma exposure time, varied by the axial velocity of the plasma jet. Two different parameter sets were selected to be compared in the present study. The surface properties after the plasma treatment were investigated by atomic force microscopy in combination with the contact angle measurements followed by the surface free energy calculation according to the OWRK method. The results were compared with those of the untreated samples to evaluate the induced effects. The surface free energy and hence the wettability were found to be increased significantly by both treatments. The surface topography was changed also in both cases, whereas one of the used parameter sets resulted in a higher roughness comparing to the untreated reference sample, and another one reduced it. Moreover, the adhesion properties of the treated surfaces were evaluated by lap shear tests. All treated samples exhibit a significant increased bonding strength in comparison to the untreated substrates. This improvement can be related both to the changes of the surface topography, induced by the thermal component of the plasma, and the cleaning and activation effects caused by the reactive plasma species during the treatment. However, significant differences concerning the total bonding strength were found between the used process parameter sets. Thus, a higher intensity of the plasma treatment led to a lower resistance of the final bond. In this case, the polymer surface seems to be partly degraded, forming a weak boundary layer, which indicates an overtreatment of the material

Estudio de procesabilidad de composite CF-LMPAEK reciclado: inyección vs impresión 3D

El proyecto ECO-CLIP se basa en una combinación de actividades de innovación orientadas a lograr piezas estructurales más ligeras a partir de los residuos de fábrica de TPC´s (Thermoplastic Composites), para la próxima generación de demostradores de fuselaje de aviación, que se lleva a cabo como parte de Clean Sky 2. En el proyecto se ha desarrollado un material polimérico compuesto de LMPAEK reforzado con un 40% en peso de fibra de carbono corta para la producción de Brackets. Con el fin de seleccionar la tecnología más ventajosa para la fabricación de estos, se ha llevado a cabo la comparativa de un método de fabricación convencional, como es la inyección, con una tecnología emergente, como es el FGF (Fused Granulated Fabrication). Para su comparativa se han llevado a cabo estudios de longitud y distribución de fibra, caracterización térmica y ensayos mecánicos, tanto para las probetas de inyección como en FGF. En esta última tecnología, además se ha llevado a cabo un estudio de parametrización de diámetros de boquillas con el fin de obtener la influencia que tiene en la adhesión entre capas, la longitud de la fibra, la microestructura de la pieza y la calidad final de las piezas. Gracias a estos resultados se ha podido establecer una relación entre la naturaleza del refuerzo, las propiedades térmicas y los parámetros de fabricación, con las propiedades mecánicas en pieza final

Validation of the aberrant salience inventory in a general and clinical Spanish population.

The concept of aberrant salience is related to the onset of psychosis. Its study is important for early identification and possible intervention in processes activating later positive symptoms. This study validated the Spanish Aberrant Salience Inventory (ASI) for adult and clinical populations. The sample consisted of 6178 participants, of whom 4523 were adolescents, 1292 were general population adults and 363 were patients with a psychopathology. The evidence provided validates the instrument's structure. Invariance of measurement suggests that both men and women, patients and nonclinical population (adults and adolescents) interpreted the items on the ASI similarly. The distribution of scores by age also suggests stabilization of the trend at about 19 years of age, showing a developmental change in motivational response. The hypothesis that patients, and in particular, those diagnosed with schizophrenia and other psychotic disorders and bipolar disorders would have the highest average scores in aberrant salience was met. This is a valuable instrument for evaluating a complex process related to abnormal motivation in the development of schizophrenia

Validation of Spanish Language Evaluation Instruments for Body Dysmorphic Disorder and the Dysmorphic Concern Construct

Dysmorphic concern (DC) refers to excessive preoccupation with a slight or imagined defect in physical appearance with social avoidance and behavior directed at controlling the defect in appearance. This study attempted to adapt the factor structure of two instruments that cover the DC construct, the Dysmorphic Concern Questionnaire (DCQ) and the Body Dysmorphic Disorder Examination Self-Report (BDDE-SR), to Spanish and establish their psychometric properties. A total of 920 subjects (62.7% women, Mage = 32.44 years) participated. Exploratory and Confirmatory Factor Analysis of both scales found adequate goodness of fit indices. A one-dimensional structure was found for the DCQ and two first-order factors (dissatisfaction/preoccupation with body image (BI) and BI avoidance behavior) were identified for the BDDE-SR. The psychometric test–retest reliability and validity properties (content, convergent, and discriminant) were satisfactory. It is suggested that the DC construct includes both cognitive and behavioral aspects and may represent a continuum of severity with Body Dysmorphic Disorder at the end.Peer reviewe