An experience beyond continuous assessment activities: virtual tour to the medieval medicinal plant garden of the Pedralbes monastery

El grupo de innovación docente integrado por profesores del área de Botánica (GIBAF) de la Universidad de Barcelona (UB) se plantea cada curso el diseño de nuevas actividades acreditativas en el marco de la evaluación continuada. Se presenta la experiencia llevada a cabo durante el curso 2008- 09 en la asignatura Botánica Farmacéutica. El objetivo ha sido implicar durante un semestre a los estudiantes en la autoría de un proyecto tutorizado de inmediata utilidad y clara perdurabilidad, más allá de su utilidad acreditativa. Como recurso se ha utilizado el Jardín de Plantas Medicinales del Monasterio de Pedralbes y se ha firmado un convenio de colaboración docente entre la UB y el Instituto de Cultura de Barcelona. Los estudiantes han realizado el trabajo utilizando la plataforma Moodle del Campus virtual de la UB en cinco etapas que han incluido la confección de unas fichas que se han ido modificando en función de las diversas retroacciones de los profesores. Al inicio de la actividad, se facilitó a los estudiantes el cronograma completo de la actividad, la pauta para su realización, así como un total de 18 recursos bibliográficos de uso obligado. Finalmente, a través de GoogleSites, se ha realizado una web que permite realizar un paseo virtual por el jardín, documentando de forma referenciada para las 50 plantas medicinales su nomenclatura, descripción botánica, distribución, usos (históricos, actuales y futuros) y toxicidad. El resultado de la actividad fue presentado en un acto público en el Monasterio de Pedralbes y puede consultarse en: http://sites.google.com/site/jardimedievalpedralbes/The group of teaching innovation in the area of Botany (GIBAF), University of Barcelona (UB), is raised each year to design new accreditation activities under continuous evaluation framework. We present the experience carried out during the academic year 2008-09 in the course of Pharmaceutical Botany. The aim has been to involve students for a semester in the authorship of a tutored project immediately useful and of easy permanence, beyond its assessment proving usefulness. The Medicinal Plants Garden of the Monastery of Pedralbes has been used as a resource and a collaboration agreement has been signed between the UB faculty and the Institute of Culture of Barcelona. The students have developed the work using the Moodle platform CampusvirtualUB into five stages which included preparation of files by students that have been modified in some steps following the various feedbacks from teachers. At the beginning of the activity, students were provided with a complete schedule of activities, the schedule for its implementation, and a total of 18 forced-use library resources. Finally, through Google sites, a website has been implemented, allowing for a virtual tour of the garden, documenting by referenced literature 50 medicinal plants for their nomenclature, botanical description, distribution, uses (historical, current and future) and toxicity. The result of the activity was presented at a public ceremony in the Monastery of Pedralbes and is available at: http://sites.google.com/site/jardimedievalpedralbes/Este trabajo ha sido parcialmente financiado con un Ajut per a Projectes d'Innovació Docent (2006PID-UB/11) de la Universidad de Barcelona

A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers

HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism

Structure-Based Analysis of Five Novel Disease-Causing Mutations in 21-Hydroxylase-Deficient Patients

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent inborn error of metabolism, and accounts for 90–95% of CAH cases. The affected enzyme, P450C21, is encoded by the CYP21A2 gene, located together with a 98% nucleotide sequence identity CYP21A1P pseudogene, on chromosome 6p21.3. Even though most patients carry CYP21A1P-derived mutations, an increasing number of novel and rare mutations in disease causing alleles were found in the last years. In the present work, we describe five CYP21A2 novel mutations, p.R132C, p.149C, p.M283V, p.E431K and a frameshift g.2511_2512delGG, in four non-classical and one salt wasting patients from Argentina. All novel point mutations are located in CYP21 protein residues that are conserved throughout mammalian species, and none of them were found in control individuals. The putative pathogenic mechanisms of the novel variants were analyzed in silico. A three-dimensional CYP21 structure was generated by homology modeling and the protein design algorithm FoldX was used to calculate changes in stability of CYP21A2 protein. Our analysis revealed changes in protein stability or in the surface charge of the mutant enzymes, which could be related to the clinical manifestation found in patients

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

A meta-analysis of genome-wide association studies identifies multiple longevity genes

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity

A meta-analysis of genome-wide association studies identifies multiple longevity genes

Publisher's version (útgefin grein).Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.Alexander von Humboldt-StiftungPeer Reviewe