Experimentando con las redes sociales en la enseñanza universitaria en ciencias

This paper describes the results obtained by applying a Web 2.0-based social networking to the field of high education. In particular, we have analysed the experience achieved by combining "GNOSS Universidad 2.0" networking and the subject "Experimentación en Química Física", which corresponds to the 4th year of the Degree in Chemistry (Universidad de La Rioja). "University GNOSS2.0" provides a clear opportunity to develop teaching-learning methodologies based on collaborative work and allows the generation of shared-knowledge through different communities. As a result, this novel methodology improves, enhances and accelerates the learning process. During the four months that this experience has lasted, the students have compiled a large number of attractive scientific resources related to “Molecular Cuisine” topic. Notably, The platform allows the teacher to monitor students participation and to evaluate their resources. In addition, both the resources and comments have been evaluated by the entire community by positive or negative votes. Finally, the survey conducted at the end of the activity showed that, in general, the students value positively this novel teaching-learning methodology.En este trabajo se describen los resultados obtenidos en la aplicación de herramientas Web 2.0 basadas en redes sociales en el ámbito de la enseñanza universitaria. En concreto, se analiza la experiencia de uso de la plataforma “GNOSS Universidad 2.0” en la asignatura “Experimentación en Química Física” de 4º curso de la Licenciatura de Química de la Universidad de La Rioja. “GNOSS Universidad 2.0” ofrece la posibilidad de aplicar metodologías de enseñanza-aprendizaje fundamentadas en el trabajo colaborativo y la generación de conocimiento compartido a través de comunidades de conocimiento. Esta novedosa metodología mejora, enriquece y acelera el aprendizaje. De este modo, los alumnos han aportado un gran número de recursos de carácter científico relacionados con el tema Cocina Molecular durante los 4 meses que ha durado la experiencia. La plataforma permite el seguimiento de la participación de los alumnos por parte del profesor, así como la evaluación de los recursos aportados por estos. Adicionalmente, cada recurso y comentario ha sido evaluado por toda la comunidad a través de votos positivos y negativos. Las encuestas realizadas al final de la experiencia muestran el alto grado de aceptación por parte de los alumnos de esta novedosa metodología de enseñanza-aprendizaje.Palabras clave: Web 2.0; GNOSS; comunidades del conocimiento; aprendizaje colaborativo; conocimiento compartido.Experimenting with social networks in university science teachingThis paper describes the results obtained by applying a Web 2.0-based social networking to the field of high education. In particular, we have analysed the experience achieved by combining "GNOSS Universidad 2.0" networking and the subject "Experimentación en Química Física", which corresponds to the 4th year of the Degree in Chemistry (Universidad de La Rioja). "GNOSS 2.0 Universidad" provides a clear opportunity to develop teaching-learning methodologies based on collaborative work and allows the generation of sharedknowledge through different communities. As a result, this novel methodology improves, enhances and accelerates the learning process. During the four months that this experience has lasted, the students have compiled a large number of attractive scientific resources related to “Molecular Cuisine” topic. Notably, the platform allows the teacher to monitor students participation and to evaluate their resources. In addition, both the resources and comments have been evaluated by the entire community by positive or negative votes. Finally, the survey conducted at the end of the activity showed that, in general, the students value positively this novel teaching-learning methodology.Keywords: Web 2.0; GNOSS; knowledge communities; collaborative learning; shared-knowledge

Molecular Recognition of GalNAc in Mucin-Type O-Glycosylation

N-Acetylgalactosamine (GalNAc)-type O-glycosylation is an essential posttranslational modification (PTM) that plays fundamental roles in biology. Malfunction of this PTM is exemplified by the presence of truncated O-glycans in cancer. For instance, the glycoprotein MUC1 is overexpressed in many tumor tissues and tends to carry simple oligosaccharides that allow for the presentation of different tumor-associated antigens, such as the Tn or sTn antigens (GalNAc-α-1-O-Thr/Ser and Neu5Acα2-6GalNAcα1-O-Ser/Thr, respectively). In other cases, such as tumoral calcinosis associated with O-glycosylation of the fibroblast growth factor 23, O-glycans are absent or less abundant. Significant progress has been made in determining the three-dimensional structures of biomolecules that recognize GalNAc, such as antibodies, lectins, mucinases, GalNAc-transferases, and other glycosyltransferases. Analysis of the complexes between these entities and GalNAc-containing glycopeptides, in most cases derived from crystallographic or NMR analysis, provides an understanding of the key structural elements that control molecular recognition of these glycopeptides. Here, we describe and compare the binding sites of these proteins in detail, focusing on how the GalNAc moieties interact selectively with them. We also summarize the differences and similarities in GalNAc recognition. In general, the recognition of GalNAc-containing glycopeptides is determined by hydrogen bonds between hydroxyl groups and the N-acetyl group of GalNAc with proteins, as well as CH-π contacts in which the hydrophobic α-face of the sugar and the methyl group of NHAc can be involved. The latter interaction usually provides the basis for selectivity. It is worth noting that binding of these glycopeptides depends primarily on recognition of the sugar moiety, with some exceptions such as a few anti-MUC1 antibodies that primarily recognize the peptide backbone and use the sugar to facilitate shape complementarity or to establish a limited number of interactions with the protein. Focusing specifically on the GalNAc moiety, we can observe that there is some degeneracy of interactions within the same protein families, likely due to substrate flexibility. However, when all studied proteins are considered together, despite the commonalities within each protein family, no pattern can be discerned between the different families, apart from the presence of common residues such as Tyr, His, or Asp, which are responsible for hydrogen bonds. The lack of a pattern can be anticipated, given the diverse functions of mucinases, glycosyltransferases, antibodies, and lectins. Finally, it is important to point out that the conformational differences observed in solution in glycopeptides bearing GalNAc-α-1-O-Ser or GalNAc-α-1-O-Thr also can be found in the bound state. This unique characteristic is exploited, for instance, by the enzyme C1GalT1 to broadly glycosylate both acceptor substrates. The findings summarized in this review may contribute to the rational structure-guided development of therapeutic vaccines, novel diagnostic tools for early cancer detection, and new cancer treatments for cancer with tailored anti-Tn or anti-STn antibodies or new drugs to inhibit GalNAc-T isoenzymes

Experimenting with social networks in university science teaching

En este trabajo se describen los resultados obtenidos en la aplicación de herramientas Web 2.0 basadas en redes sociales en el ámbito de la enseñanza universitaria. En concreto, se analiza la experiencia de uso de la plataforma “GNOSS Universidad 2.0” en la asignatura “Experimentación en Química Física” de 4º curso de la Licenciatura de Química de la Universidad de La Rioja. “GNOSS Universidad 2.0” ofrece la posibilidad de aplicar metodologías de enseñanza-aprendizaje fundamentadas en el trabajo colaborativo y la generación de conocimiento compartido a través de comunidades de conocimiento. Esta novedosa metodología mejora, enriquece y acelera el aprendizaje. De este modo, los alumnos han aportado un gran número de recursos de carácter científico relacionados con el tema Cocina Molecular durante los 4 meses que ha durado la experiencia. La plataforma permite el seguimiento de la participación de los alumnos por parte del profesor, así como la evaluación de los recursos aportados por estos. Adicionalmente, cada recurso y comentario ha sido evaluado por toda la comunidad a través de votos positivos y negativos. Las encuestas realizadas al final de la experiencia muestran el alto grado de aceptación por parte de los alumnos de esta novedosa metodología de enseñanzaaprendizaje.This paper describes the results obtained by applying a Web 2.0-based social networking to the field of high education. In particular, we have analysed the experience achieved by combining "GNOSS Universidad 2.0" networking and the subject "Experimentación en Química Física", which corresponds to the 4th year of the Degree in Chemistry (Universidad de La Rioja). "University GNOSS2.0" provides a clear opportunity to develop teaching-learning methodologies based on collaborative work and allows the generation of shared-knowledge through different communities. As a result, this novel methodology improves, enhances and accelerates the learning process. During the four months that this experience has lasted, the students have compiled a large number of attractive scientific resources related to “Molecular Cuisine” topic. Notably, The platform allows the teacher to monitor students participation and to evaluate their resources. In addition, both the resources and comments have been evaluated by the entire community by positive or negative votes. Finally, the survey conducted at the end of the activity showed that, in general, the students value positively this novel teachinglearning methodology.12 página

Chondroitin Sulfate Tetrasaccharides: Synthesis, Three-Dimensional Structure and Interaction with Midkine

The biological activity of midkine, a cytokine implicated in neuro- and tumourigenesis, is regulated by its binding to glycosaminoglycans (GAGs), such as heparin and chondroitin sulfate (CS). To better understand the molecular recognition of GAG sequences by this growth factor, the interactions between synthetic chondroitin sulfate-like tetrasaccharides and midkine were studied by using different techniques. Firstly, a synthetic approach for the preparation of CS-like oligosaccharides in the sequence GalNAc-GlcA was developed. A fluorescence polarisation competition assay was then employed to analyse the relative binding affinities of the synthetic compounds and revealed that midkine interacted with CS-like tetrasaccharides in the micromolar range. The 3D structure of these tetramers was studied in detail by a combination of NMR spectroscopy experiments and molecular dynamics simulations. Saturation transfer difference (STD) NMR spectroscopy experiments indicate that the CS tetrasaccharides bind to midkine in an extended conformation, with similar saturation effects along the entire sugar chain. These results are compatible with docking studies that suggest an interaction of the tetrasaccharide with midkine in a folded structure. Overall, this study provides valuable information on the interaction between midkine and well-defined, chemically synthesised CS oligosaccharides and these data can be useful for the design of more active compounds that modulate the biological function of this protein.Peer Reviewe

Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen

12/IA/1398 16/IA/4419 GOIPG/2016/858 IF/00780/2015 PTDC/BIA-MIB/31028/2017 UIDB/04378/2020 PD/BD/142847/2018 RTI2018-094751-B-C22 RTI2018-099592-B-C2.The human macrophage galactose lectin (MGL) is an endocytic type II transmembrane receptor expressed on immature monocyte-derived dendritic cells and activated macrophages and plays a role in modulating the immune system in response to infections and cancer. MGL contains an extracellular calcium-dependent (C-type) carbohydrate recognition domain (CRD) that specifically binds terminal N-acetylgalactosamine glycan residues such as the Tn and sialyl-Tn antigens found on tumor cells, as well as other N- and O-glycans displayed on certain viruses and parasites. Even though the glycan specificity of MGL is known and several binding glycoproteins have been identified, the molecular basis for substrate recognition has remained elusive due to the lack of high-resolution structures. Here we present crystal structures of the MGL CRD at near endosomal pH and in several complexes, which reveal details of the interactions with the natural ligand, GalNAc, the cancer-associated Tn-Ser antigen, and a synthetic GalNAc mimetic ligand. Like the asialoglycoprotein receptor, additional calcium atoms are present and contribute to stabilization of the MGL CRD fold. The structure provides the molecular basis for preferential binding of N-acetylgalactosamine over galactose and prompted the re-evaluation of the binding modes previously proposed in solution. Saturation transfer difference nuclear magnetic resonance data acquired using the MGL CRD and interpreted using the crystal structure indicate a single binding mode for GalNAc in solution. Models of MGL1 and MGL2, the mouse homologues of MGL, explain how these proteins might recognize LewisX and GalNAc, respectively.publishersversionpublishe

Exploiting structure-activity relationships of QS-21 in the design and synthesis of streamlined saponin vaccine adjuvants

We report the design, synthesis, immunological evaluation, and conformational analysis of new saponin variants as promising vaccine adjuvants. These studies have provided expedient synthetic access to streamlined adjuvant-active saponins and yielded molecularlevel insights into saponin conformation that correlated with their in vivo adjuvant activities

Bifunctional chiral dehydroalanines for peptide coupling and stereoselective <i>S</i>-Michael addition

A second generation of chiral bicyclic dehydroalanines easily accessible from serine has been developed. These scaffolds behaved as excellent S-Michael acceptors when tri-O-acetyl-2-acetamido-2-deoxy-1-thio-α-d-galactopyranose (abbreviated as GalNAc-α-SH) was used as a nucleophile. This addition proceeds with total chemo- and stereoselectivity, complete atom economy, quickly, and at room temperature, making it a true click reaction. The Michael adducts were easily transformed into S-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l- and -d-cysteines, which can be regarded as mimics of the Tn antigen derived from l-Ser (α-d-GalNAc-l-Ser) and d-Ser (α-d-GalNAc-d-Ser), respectively.Peer Reviewe

Fucosyltransferase-specific inhibitionvianext generation of fucose mimetics

The ability to custom-modify cell surface glycans holds great promise for treatment of a variety of diseases. We propose a glycomimetic ofl-fucose that markedly inhibits the creation of sLeby FTVI and FTVII, but has no effect on creation of Leby FTIX. Our findings thus indicate that selective suppression of sLex display can be achieved, and STD-NMR studies surprisingly reveal that the mimetic does not compete with GDP-fucose at the enzymatic binding site