The effect of the neutral cytidine protonated analogue pseudoisocytidine on the stability of i-motif structures

Incorporation of pseudoisocytidine (psC), a neutral analogue of protonated cytidine, in i-motifs has been studied by spectroscopic methods. Our results show that neutral psC:C base pairs can stabilize i-motifs at neutral pH, but the stabilization only occurs when psC:C base pairs are located at the ends of intercalated C:C+ stacks. When psC occupies central positions, the resulting i-motifs are only observed at low pH and psC:C+ or psC:psC+ hemiprotonated base pairs are formed instead of their neutral analogs. Overall, our results suggest that positively charged base pairs are necessary to stabilize this non-canonical DNA structure

Ametantrone-based compounds as potential regulators of Tau pre-mRNA alternative splicing

We describe the synthesis and characterization of ametantrone-containing RNA ligands based on the derivatization of this intercalator with two neamine moieties (Amt-Nea,Nea) or with one azaquinolone heterocycle and one neamine (Amt-Nea,Azq) as well as its combination with guanidinoneamine (Amt-NeaG4). Biophysical studies revealed that guanidinylation of the parent ligand (Amt-Nea) had a positive effect on the binding of the resulting compound for Tau pre-mRNA target as well as on the stabilization upon complexation of some of the mutated RNA sequences associated with the development of tauopathies. Further studies by NMR revealed the existence of a preferred binding site in the stem-loop structure, in which ametantrone intercalates in the characteristic bulged region. Regarding doubly-functionalized ligands, binding affinity and stabilizing ability of Amt-Nea,Nea were similar to those of the guanidinylated ligand, but the two aminoglycoside fragments seem to interfere with its accommodation in a single binding site. However, Amt-Nea,Azq binds at the bulged region in a similar way than Amt-NeaG4. Overall, these results provide new insights on fine-tuning RNA binding properties of ametantrone by single or double derivatization with other RNA recognition motifs, which could help in the future design of new ligands with improved selectivity for disease-causing RNA molecules

Self-association of short DNA loops through minor groove C:G:G:C tetrads

In addition to the better known guanine-quadruplex, four-stranded nucleic acid structures can be formed by tetrads resulting from the association of Watson-Crick base pairs. When such association occurs through the minor groove side of the base pairs, the resulting structure presents distinctive features, clearly different from quadruplex structures containing planar G-tetrads. Although we have found this unusual DNA motif in a number of cyclic oligonucleotides, this is the first time that this DNA motif is found in linear oligonucleotides in solution, demonstrating that cyclization is not required to stabilize minor groove tetrads in solution. In this article, we have determined the solution structure of two linear octamers of sequence d(TGCTTCGT) and d(TCGTTGCT), and their cyclic analogue d, utilizing 2D NMR spectroscopy and restrained molecular dynamics. These three molecules self-associate forming symmetric dimers stabilized by a novel kind of minor groove C:G:G:C tetrad, in which the pattern of hydrogen bonds differs from previously reported ones. We hypothesize that these quadruplex structures can be formed by many different DNA sequences, but its observation in linear oligonucleotides is usually hampered by competing Watson-Crick duplexes

Prevalent sequences in the Human Genome Can Form Mini i-Motif Structures at Physiological pH

We report here the solution structure of several repetitive DNA sequences containing d(TCGTTCCGT) and related repeats. At physiological pH, these sequences fold into i-motif like quadruplexes in which every two repeats a globular structure is stabilized by two hemiprotonated C:C+ base pairs, flanked by two minor groove tetrads resulting from the association of G:C or G:T base pairs. The interaction between the minor groove tetrads and the nearby C:C+ base pairs affords a strong stabilization, which results in effective pHT values above 7.5. Longer sequences with more than two repeats are able to fold in tandem, forming a rosary bead-like structure. Bioinformatics analysis shows that these sequences are prevalent in the human genome, and are present in development-related genes

The Bi-Loop, a new general four-stranded DNA motif

The crystal structure of the cyclic octanucleotide d contains two independent molecules that form a novel quadruplex by means of intermolecular Watson-Crick A.T pairs and base stacking. A virtually identical quadruplex composed of G.C pairs was found by earlier x-ray analysis of the linear heptamer d(GCATGCT), when the DNA was looped in the crystal. The close correspondence between these two structures of markedly dissimilar oligonucleotides suggests that they are both examples of a previously unrecognized motif. Their nucleotide sequences have little in common except for two separated 5'-purine-pyrimidine dinucleotides forming the quadruplex, and by implication these so-called 'bi-loops' could occur widely in natural DNA. Such structures provide a mechanism for noncovalent linking of polynucleotides in vivo. Their capacity to associate by base stacking, demonstrated in the crystal structure of d(GCATGCT), creates a compact molecular framework made up of four DNA chains within which strand exchange could take place

El paper dels sistemes de gestió en el desenvolupament de competències transversals en els estudiants

S’ha treballat la formació competencial dels estudiants mitjançant la realització d’activitats relacionades amb la implementació de sistemes de gestió (qualitat, medi ambient i seguretat). A l’assignatura “Qualitat i Prevenció” (Grau Química), els alumnes han fet auditories de medi ambient i seguretat als laboratoris de pràctiques de la Facultat de Química. Els alumnes de l’assignatura “Direcció d’operacions en el sector químic” (màster Enginyeria Química) han treballat la implementació del sistemes de gestió mitjançant un joc de rol. Finalment, a “Anàlisi i estimació del risc” (màster Enginyeria Química) s’ha treballat una part concreta del sistema de gestió de la seguretat mitjançant l’anàlisi de risc d’una pràctica de laboratori. Els estudiants han treballat competències relacionades amb l’ètica, capacitat d’expressió oral i escrita, capacitat de diàleg, capacitat de lideratge, gestió de la qualitat, el medi ambient i la seguretat. Els resultats de les actuacions han posat de manifest mancances i problemes als laboratoris i als sistemes de gestió, l’anàlisi del quals ha de permetre millorar la qualitat de les pràctiques i dels ensenyaments. Finalment, les enquestes fetes a alguns dels grups implicats han reflectit un alt grau de satisfacció amb la feina feta i la manera de fer-la

Les competències transversals i les auditories als laboratoris de pràctiques de la Facultat de Química: desenvolupament i anàlisi

S’ha treballat la formació competencial dels estudiants mitjançant la realització d’auditories del sistema de gestió de la qualitat dels laboratoris de practiques de la Facultat de Química. Per fer aquesta tasca, s’ha seleccionat com auditors a 102 estudiants de l’assignatura “Qualitat i Prevenció” del Grau de Química, els quals, després d’una breu formació, han actuat com auditors en 49 auditories, la qual cosa ha implicat també la participació de 99 estudiants i 49 professors com a interlocutors en els laboratoris auditats. En total han estat auditats 49 torns de pràctiques relacionats amb els diferents tipus d’assignatures pràctiques impartides per tots els departaments de la Facultat i corresponents als tres graus que s’imparteixen (Química, Enginyeria Química i Enginyeria de Materials), havent estat auditats pràcticament tots els laboratoris docents de la Facultat. Seguint els objectius del projecte, els estudiants han pogut treballar competències transversals relacionades amb l’ètica, la capacitat d’expressió oral i escrita, la capacitat de diàleg, la capacitat de lideratge, l’anàlisi i la interpretació de dades, la gestió de la qualitat, el treball respectuós amb el medi ambient, la seguretat, etc. Per tant, aquest projecte ha sigut una eina important en la seva formació. D’altra banda, dels resultats dels informes d’auditoria realitzats pels estudiants, s’han posat de manifest una sèrie de mancances i problemes als laboratoris que estan sent analitzats per tal de millorar la qualitat de les pràctiques. Finalment, s’han realitzat enquestes de satisfacció a tots els grups implicats (estudiants auditors, estudiants auditats, professors auditats) i els resultats de les mateixes han posat de manifest un alt grau de satisfacció amb la feina feta i la manera de fer-la.PMI

The surveys to the companies: a tool for the improvement of degrees

In scientific and technical degrees, the opinion of the final employers on the given subjects is really important. For this reason, the Quality Committee (CQ) of the Faculty of Chemistry of the University of Barcelona prepared a survey for chemical, engineering and pharmaceutical companies asking about the academic training required by the companies. The survey consists of nine sections including items related to laboratory operations, chemical processes, calculation methods, management systems (quality, environment and safety) or general management information. In addition, at the end of each section, a question inquires the companies about the competences shown by students in the items of the section. The results were compared with that of a similar survey carried out in 2007. The scores obtained, between 2 and 3, for all the items (score: 1, not important; 2, unimportant; 3, important; 4, very important), show that companies accept the training given to our students and the competences achieved by them. However, according to their opinion, it is possible to improve this training, especially in the subjects related to management (time, information, environment, quality, safety, etc.). Therefore, surveys are a good tool for the evaluation of the training achieved in our degrees and, consequently, for improving degrees and the teaching task, according the Quality Management System implemented in the Faculty of Chemistry

Formación competencial de los estudiantes de la Facultad de Química de la Universidad de Barcelona mediante la realización de auditorías internas

Se ha trabajado la formación competencial de los estudiantes de la Facultad de Química de la Universidad de Barcelona (UB) mediante su participación en auditorías a diferentes laboratorios de prácticas y diferentes tipos de asignaturas prácticas. Los estudiantes han podido trabajar competencias transversales relacionadas con la ética, la capacidad de expresión oral y escrita, la capacidad de diálogo, la capacidad de liderazgo, el trabajo en equipo, el análisis y la interpretación de datos, etc

Competency training of students of the Faculty of Chemistry of the University of Barcelona by conducting internal audits

This work deals with the competences and skills training of the students of the Faculty of Chemistry of the University of Barcelona (UB) through participation in internal audits at different laboratories in which different experimental subjects are taught. Students have been able to work cross competences related to ethics, the ability on oral and written expression, the ability to dialogue, the ability to leadership, the teamwork, the analysis and the data interpretation, among others