Amaia Agirre

A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool

BACKGROUND Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is contraindicated or biopsy results are inconclusive. Recent findings show that GBM cells release microvesicles that contain a select subset of cellular proteins and RNA. The aim of this hypothesis-generating study was to assess the diagnostic potential of miRNAs found in microvesicles isolated from the serum of GBM patients. METHODS To control disease heterogeneity, we used patients with newly diagnosed GBM. In the discovery stage, PCR-based TaqMan Low Density Arrays followed by individual quantitative reverse transcriptase polymerase chain reaction were used to test the differences in the miRNA expression levels of serum microvesicles among 25 GBM patients and healthy controls paired by age and sex. The detected noncoding RNAs were then validated in another 50 GBM patients. RESULTS We found that the expression levels of 1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p) were significantly associated with a GBM diagnosis. In addition, RNU6-1 was consistently an independent predictor of a GBM diagnosis. CONCLUSIONS Altogether our results uncovered a small noncoding RNA signature in microvesicles isolated from GBM patient serum that could be used as a fast and reliable differential diagnostic biomarker.

Waterborne, Semicrystalline, Pressure-Sensitive Adhesives with Temperature-Responsiveness and Optimum Properties

The synthesis and resulting temperature-responsive properties of semicrystalline waterborne pressure-sensitive adhesives (PSAs) were investigated. A crystalline polymer fraction was produced in situ within waterborne particles by miniemulsion polymerization of non-branched long chain acrylates. The degree of crystallinity was controlled by copolymerization with a short chain acrylate. The polymerization strategy determined the polymer architecture and film structure, which then influenced the adhesion properties. The high sensitivity of the adhesion strength of these PSAs to temperature, in the range around the crystal melting point, opens up the possibility of designing temperature-responsive adhesives. With the right distribution and concentration of crystalline polymers, a simultaneous increase in both the peel strength and the shear resistance was obtained, which is a combination that is often not found when optimizing adhesive properties.

Polymerization of n-butyl acrylate with high concentration of a chain transfer agent (CBr4): detailed characterization and impact on branching

Poly(n-butyl acrylate) (polyn-BA) polymers synthesized by radical bulk polymerization in the presence and absence of a high concentration (0.4 mol L−1) of carbon tetrabromide (CBr4) as a chain transfer agent at nominal temperatures of 60, 100 and 140 °C were fully characterized by 1D and 2D NMR, SEC/MALS and MALDI-TOF mass spectrometry. The structures generated by chain transfer to CBr4 in secondary chain-end radicals and reinitiation of polymer chains by CBr3 radicals formed by chain transfer to CBr4 reactions were identified by MALDI-TOF and NMR analysis. The potential structures that might have been created by chain-transfer to tertiary radicals (quaternary carbons with a Br unit) formed by backbiting or intermolecular chain transfer to polymer could not be detected and hence their abundance was not important. The branching density (BD) of the polymers synthesized in the presence and absence of CBr4 was also determined. The BD increases with temperature in both cases, and for each temperature the branching density considerably reduced when CBr4 was employed in the polymerization as found for other transfer agents and controlled radical mediated polymerizations. However, the explanation that patching on the tertiary radicals was the cause of reduction of the branching in the polyn-BA was discarded in this case because the resulting structures could not be identified.

Determining the effect of side reactions on product distributions in RAFT polymerization by MALDI-TOF MS

Reversible Addition–Fragmentation chain Transfer (RAFT) polymerization has emerged as one of the most versatile reversible deactivation radical polymerization techniques and is capable of polymerizing a wide range of monomers under various conditions. One of the most important factors governing the success of a RAFT polymerization is the fraction of living chains at the end of the reaction, which can be maximized by using a low amount of initiator. From the point of view of the process, it is tempting to perform the polymerization in solution, which allows a better mixing. However, in this work it is shown that this choice may be negative for the quality of the polymer. Detailed analysis using Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) of poly(n-butyl acrylate) (pBA) obtained at high conversion in the RAFT solution polymerization revealed that in addition to the polymer chains, formed by the RAFT mechanism, there were two distinct populations resulting from chain transfer to solvent and transfer to polymer followed by β-scission. Complementary results from Size Exclusion Chromatography coupled with Multi Angle Light Scattering detector (SEC/MALS), quantum chemical calculations, and a mathematical model that predicts product distributions, were also used to further confirm the assigned structures. The results highlight the scope and limitation on the living fraction of chains due to chain transfer events using RAFT polymerization and reversible deactivation radical polymerizations in general, and furthermore, yielded information about the fate of midchain radicals formed by intramolecular transfer to polymer.

Role of Grafting on Particle and Film Morphology and Film Properties of Zero VOC Polyurethane/Poly(meth)acrylate Hybrid Dispersions

Dr. S. Mehravar, Dr. N. Ballard, Dr. A. Agirre, Prof. R. Tomovska, Prof. J. M. Asua POLYMAT and Departamento de Química Aplicada University of the Basque Country UPV/EHU Joxe Mari Korta Zentroa Tolosa Hiribidea 72, Donostia-San Sebastian 20018, Spain E-mail: jm.asua@ehu.es Prof. R. Tomovska IKERBASQUE Basque Foundation for Science 48011 Bilbao, Spain The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/mame.201800532.