L’ús educatiu de l’hort escolar La gestió de la participació, espai i conreu de l’hort, treball educatiu i rol del professorat

Curs 2012-2013En el present treball s’aprofundeix en l’ús educatiu que es fa de l’hort a partir d’una recerca bibliogràfica sobre el tema i, també, a partir d’una recollida dades feta a dues escoles situades en contextos diferents: una pertany a un ambient rural amb només 21 alumnes en tota l’escola i l’altra a un ambient més urbà amb uns 200 infants només a parvulari. Per tal de dur a terme la teoria del treball i poder-la relacionar amb la pràctica, s’han utilitzat quatre àmbits que es creuen importants per tal que l’hort de l’escola funcioni correctament: gestió de la participació, l’hort: espais i cultiu, treball educatiu i paper del mestre. A partir d’aquesta relació s’han extret uns resultats i unes conclusions, de les quals les més rellevants són les següents: la gestió de l’hort no l’ha de portar a terme una sola persona sinó vàries, que aquest espai ha de servir per poder treballar la majoria d’àrees del currículum i que cada escola hauria d’adaptar l’hort segons les seves necessitats i interessos.This document deepens to the educational use of the school orchard. The information has been extracted from a bibliographic research and from two schools’ fieldwork located in different contexts: one of these schools is located in a rural setting and there are 21 students; the other one is located in an urban context with about 200 children in kindergarten. To carry out the theory of this document and be able to relate to the practice were been used four areas, which are important for correct use of school orchard: participation management, orchard: spaces and cultivation, educational work and the teacher role. From this relation have been extracted results and conclusions The most relevant are: the orchard management should not made a single person but more people, this space should be used to work most curriculum areas and each school should adapt the orchard according to their needs and interests

A hybrid approach to assess the structural impact of long noncoding RNA mutations uncovers key NEAT1 interactions in colorectal cancer

Long noncoding RNAs (lncRNAs) are emerging players in cancer and they entail potential as prognostic biomarkers or therapeutic targets. Earlier studies have identified somatic mutations in lncRNAs that are associated with tumor relapse after therapy, but the underlying mechanisms behind these associations remain unknown. Given the relevance of secondary structure for the function of some lncRNAs, some of these mutations may have a functional impact through structural disturbance. Here, we examined the potential structural and functional impact of a novel A > G point mutation in NEAT1 that has been recurrently observed in tumors of colorectal cancer patients experiencing relapse after treatment. Here, we used the nextPARS structural probing approach to provide first empirical evidence that this mutation alters NEAT1 structure. We further evaluated the potential effects of this structural alteration using computational tools and found that this mutation likely alters the binding propensities of several NEAT1-interacting miRNAs. Differential expression analysis on these miRNA networks shows upregulation of Vimentin, consistent with previous findings. We propose a hybrid pipeline that can be used to explore the potential functional effects of lncRNA somatic mutations.Funding information H2020 European Research Council, Grant/Award Number: 724173Peer ReviewedPostprint (published version

Discovery and validation of clinically relevant long non-coding RNAs in colorectal cancer

Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with nearly two million newly diagnosed cases each year. The survival of patients with CRC greatly depends on the cancer stage at the time of diagnosis, with worse prognosis for more advanced cases. Consequently, considerable effort has been directed towards improving population screening programs for early diagnosis and identifying prognostic markers that can better inform treatment strategies. In recent years, long non-coding RNAs (lncRNAs) have been recognized as promising molecules, with diagnostic and prognostic potential in many cancers, including CRC. Although large-scale genome and transcriptome sequencing surveys have identified many lncRNAs that are altered in CRC, most of their roles in disease onset and progression remain poorly understood. Here, we critically review the variety of detection methods and types of supporting evidence for the involvement of lncRNAs in CRC. In addition, we provide a reference catalog that features the most clinically relevant lncRNAs in CRC. These lncRNAs were selected based on recent studies sorted by stringent criteria for both supporting experimental evidence and reproducibility.This research was funded by the Spanish Ministry of Science and Innovation with grant PGC2018-099921-B-I00, cofounded by European Regional Development Fund (ERDF); by the Catalan Research Agency (AGAUR) SGR423; by the European Union’s Horizon 2020 research and innovation programme (Grant ERC-2016-724173); by TRANSCOLONCAN COST action network (CA17118); by the Gordon and Betty Moore Foundation (Grant GBMF9742); by the “La Caixa” foundation (Grant LCF/PR/HR21/00737), and by the Instituto de Salud Carlos III (IMPACT grant IMP/00019) and CIBERINFEC (grant CB21/13/00061-ISCIII-SGEFI/ERDF). This research was made possible by the Fulbright U.S. Student Grant Program, sponsored by the U.S. Department of State, Bureau of Education and Cultural Affairs.Peer ReviewedPostprint (published version

Multiplexed target enrichment of coding and non-coding transcriptomes enables studying Candida spp. infections from human derived samples

The study of transcriptomic interactions between host and pathogens in in vivo conditions is challenged by the low relative amounts of the pathogen RNA. Yeast opportunistic pathogens of the genus Candida can cause life-threatening systemic infections in immunocompromised patients, and are of growing medical concern. Four phylogenetically diverse species account for over 90% of Candida infections, and their specific interactions with various human tissues are still poorly understood. To enable in vivo transcriptomic analysis in these species, we designed and validated pan-Candida target capture probes to enrich protein-coding and non-coding transcriptomes. The probe-based enrichment approach outperformed enrichment based on differential lysis of host cells, and showed similar enrichment performance as an existing capture design, yet achieving better fidelity of expression levels, enabling species multiplexing and capturing of lncRNAs. In addition, we show that our probe-based enrichment strategy allows robust genotype-based identification of the infecting strain present in the sample.TG group acknowledges support from the Spanish Ministry of Science and Innovation for grants ‘Centro de Excelencia Severo Ochoa’ and PGC2018-099921-B-I00, cofounded by European Regional Development Fund (ERDF); from the CERCA Programme/Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR423, and grants from the European Union’s Horizon 2020 research and innovation programme under the grant agreement ERC-2016-724173, and the Marie Sklodowska-Curie grant agreement No. 642095. The group also receives support from an INB Grant (PT17/0009/0023 - ISCIII-SGEFI/ERDF). AR was also supported by the Marie Sklodowska-Curie grant agreement No. 642095.Peer ReviewedPostprint (published version

Microbiome and colorectal cancer : Roles in carcinogenesis and clinical potential

Altres ajuts: Instituto Nacional de Bioinformatica (INB, grant PT17/0009/0023 - ISCIII-SGEFI/ERDF)The gastrointestinal tract harbors most of the microbiota associated with humans. In recent years, there has been a surge of interest in assessing the relationships between the gut microbiota and several gut alterations, including colorectal cancer. Changes in the gut microbiota in patients suffering colorectal cancer suggest a possible role of host-microbe interactions in the origin and development of this malignancy and, at the same time, open the door for novel ways of preventing, diagnosing, or treating this disease. In this review we survey current knowledge on the healthy microbiome of the gut and how it is altered in colorectal cancer and other related disease conditions. In describing past studies we will critically assess technical limitations of different approaches and point to existing challenges in microbiome research. We will have a special focus on host-microbiome interaction mechanisms that may be important to explain how dysbiosis can lead to chronic inflammation and drive processes that influence carcinogenesis and tumor progression in colon cancer. Finally, we will discuss the potential of recent developments of novel microbiota-based therapeutics and diagnostic tools for colorectal cancer

Citizen-science reveals changes in the oral microbiome in Spain through age and lifestyle factors

The relevance of the human oral microbiome to our understanding of human health has grown in recent years as microbiome studies continue to develop. Given the links of the oral cavity with the digestive, respiratory and circulatory systems, the composition of the oral microbiome is relevant beyond just oral health, impacting systemic processes across the body. However, we still have a very limited understanding about intrinsic and extrinsic factors that shape the composition of the healthy oral microbiome. Here, we followed a citizen-science approach to assess the relative impact on the oral microbiome of selected biological, social, and lifestyle factors in 1648 Spanish individuals. We found that the oral microbiome changes across age, with middle ages showing a more homogeneous composition, and older ages showing more diverse microbiomes with increased representation of typically low abundance taxa. By measuring differences within and between groups of individuals sharing a given parameter, we were able to assess the relative impact of different factors in driving specific microbial compositions. Chronic health disorders present in the analyzed population were the most impactful factors, followed by smoking and the presence of yeasts in the oral cavity. Finally, we corroborate findings in the literature that relatives tend to have more similar oral microbiomes, and show for the first time a similar effect for classmates. Multiple intrinsic and extrinsic factors jointly shape the oral microbiome. Comparative analysis of metabarcoding data from a large sample set allows us to disentangle the individual effects.We are thankful to all citizens that participated in the second edition of the “Saca La Lengua” project by contributing samples and sharing ideas (see more details here www.sacalalengua.org). In particular, for the work described here we are extremely thankful to all the students and teachers of the schools that we have visited, for their enthusiasm and questions, which helped to expand our hypotheses, to those responsible for civic centers, libraries, museums, bars, for giving us their spaces and giving us the possibility of organizing all events, and to the following national associations: Spanish Federation of Cystic Fibrosis (www.fibrosisquistica.org), Down España (www.sindromedown.net), and Federación de Asociaciones de Celíacos de España (www.celiacos.org); and local associations: Asociación Madrileña de Fibrosis Quística, Associació Catalana de Fibrosi Quística, Cocemfe Cantabria, Down Lleida, Down Bilbao, Down Vigo, Down Málaga, Associació Celíacs de Catalunya, Celíacos Euskadi, Federación de Asociaciones Celíacos Andalucía, and Asojum Murcia. Only with their effort are studies like this possible. The authors acknowledge the CRG Genomics Core Facility, CRG Bioinformatics Core Facility, CRG Biomolecular Screening and Protein Technologies Unit, CRG Communication and Public Relationships Department, and UCT ICTS High Performance Computing unit for providing access to the computing facilities. CRG authors acknowledge the Spanish Ministry for Economy, Industry and Competitiveness (MEIC) for the EMBL partnership, and Centro de Excelencia Severo Ochoa. The following reagents were obtained through BEI Resources, NIAID, NIH as part of the Human Microbiome Project: (1) Genomic DNA from Microbial Mock Community B (Even, Low Concentration), v5.1 L, for 16 S rRNA Gene Sequencing, HM-782D, and (2) Genomic DNA from Microbial Mock Community B (Staggered, Low Concentration), v5.2 L, for 16 S rRNA Gene Sequencing, HM-783D. The project was financed by the CRG through Genomics and Bioinformatics Core Facilities funds, and by the EduCaixa program through funds from the Fundación Bancaria “La Caixa”, with the participation of the Center for Research into Environmental Epidemiology (CREAL), and the “Centre d’Excellència Severo Ochoa 2013–2017” program (SEV-2012-02-08) of the Ministry of Economy and Competitiveness. Eppendorf, Illumina, and ThermoFisher sponsored the research by donating some materials and reagents. TG group acknowledges support from the Spanish Ministry of Science and Innovation for grant PGC2018-099921-B-I00, cofounded by European Regional Development Fund (ERDF); from the CERCA Program / Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR423; from the European Union’s Horizon 2020 research and innovation program under the grant agreement ERC-2016-724173; from Instituto de Salud Carlos III (INB Grant PT17/0009/0023 - ISCIII-SGEFI/ERDF).Peer Reviewed"Article signat per 15 autors/es: Jesse R. Willis, Ester Saus, Susana Iraola-Guzmán, Ewa Ksiezopolska, Luca Cozzuto, Luis A. Bejarano, Nuria Andreu-Somavilla, Miriam Alloza-Trabado, Andrea Blanco, Anna Puig-Sola, Elisabetta Broglio, Carlo Carolis, Julia Ponomarenko, Jochen Hecht & Toni Gabaldón"Postprint (published version

Long Non-Coding RNAs As Potential Novel Prognostic Biomarkers in Colorectal Cancer

Colorectal cancer (CRC) is the fourth most common cause of death worldwide. Surgery is usually the first line of treatment for patients with CRC but many tumors with similar histopathological features show significantly different clinical outcomes. The discovery of robust prognostic biomarkers in patients with CRC is imperative to achieve more effective treatment strategies and improve patient's care. Recent progress in next generation sequencing methods and transcriptome analysis has revealed that a much larger part of the genome is transcribed into RNA than previously assumed. Collectively referred to as non-coding RNAs (ncRNAs), some of these RNA molecules such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been shown to be altered and to play critical roles in tumor biology. This discovery leads to exciting possibilities for personalized cancer diagnosis, and therapy. Many lncRNAs are tissue and cancer-type specific and have already revealed to be useful as prognostic markers. In this review, we focus on recent findings concerning aberrant expression of lncRNAs in CRC tumors and emphasize their prognostic potential in CRC. Further studies focused on the mechanisms of action of lncRNAs will contribute to the development of novel biomarkers for diagnosis and disease progression

Chromosome-level assemblies from diverse clades reveal limited structural and gene content variation in the genome of Candida glabrata

Background Candida glabrata is an opportunistic yeast pathogen thought to have a large genetic and phenotypic diversity and a highly plastic genome. However, the lack of chromosome-level genome assemblies representing this diversity limits our ability to accurately establish how chromosomal structure and gene content vary across strains. Results Here, we expanded publicly available assemblies by using long-read sequencing technologies in twelve diverse strains, obtaining a final set of twenty-one chromosome-level genomes spanning the known C. glabrata diversity. Using comparative approaches, we inferred variation in chromosome structure and determined the pan-genome, including an analysis of the adhesin gene repertoire. Our analysis uncovered four new adhesin orthogroups and inferred a rich ancestral adhesion repertoire, which was subsequently shaped through a still ongoing process of gene loss, gene duplication, and gene conversion. Conclusions C. glabrata has a largely stable pan-genome except for a highly variable subset of genes encoding cell wall-associated functions. Adhesin repertoire was established for each strain and showed variability among clades.TG group acknowledges support from the Spanish Ministry of Science and Innovation (MCIN) for grant PGC2018-099921-B-I00, cofounded by European Regional Development Fund (ERDF); from the Catalan Research Agency (AGAUR) SGR423; from the European Union’s Horizon 2020 research and innovation programme (ERC-2016-724173); from the Gordon and Betty Moore Foundation (Grant GBMF9742); from the “La Caixa” foundation (Grant LCF/PR/HR21/00737), and from the Instituto de Salud Carlos III (IMPACT Grant IMP/00019 and CIBERINFEC CB21/13/00061- ISCIII-SGEFI/ERDF). PWJG acknowledges support by grants SBPLY/19/180501/000114 and SBPLY/19/180501/000356 funded by the Regional government of Castilla-La Mancha and grants SAF2013-47570-P and PID2020-117983RB-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF a way of making Europe.Peer ReviewedPostprint (author's final draft

Genome analysis of five recently described species of the CUG-Ser clade uncovers Candida theae as a new hybrid lineage with pathogenic potential in the Candida parapsilosis species complex

Candida parapsilosis species complex comprises three important pathogenic species: Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis. The majority of C. orthopsilosis and all C. metapsilosis isolates sequenced thus far are hybrids, and most of the parental lineages remain unidentified. This led to the hypothesis that hybrids with pathogenic potential were formed by the hybridization of non-pathogenic lineages that thrive in the environment. In a search for the missing hybrid parentals, and aiming to get a better understanding of the evolution of the species complex, we sequenced, assembled and analysed the genome of five close relatives isolated from the environment: Candida jiufengensis, Candida pseudojiufengensis, Candida oxycetoniae, Candida margitis and Candida theae. We found that the linear conformation of mitochondrial genomes in Candida species emerged multiple times independently. Furthermore, our analyses discarded the possible involvement of these species in the mentioned hybridizations, but identified C. theae as an additional hybrid in the species complex. Importantly, C. theae was recently associated with a case of infection, and we also uncovered the hybrid nature of this clinical isolate. Altogether, our results reinforce the hypothesis that hybridization is widespread among Candida species, and potentially contributes to the emergence of lineages with opportunistic pathogenic behaviour.This work received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie Grant Agreement No. H2020-MSCA-ITN-2014-642095. T.G. group also acknowledges support from the Spanish Ministry of Science and Innovation for grant PGC2018-099921-B-I00, cofounded by European Regional Development Fund (ERDF); from the Catalan Research Agency (AGAUR) SGR423; from the European Union’s Horizon 2020 research and innovation programme (ERC-2016-724173); from the Gordon and Betty Moore Foundation (Grant GBMF9742) and from the Instituto de Salud Carlos III (INB Grant PT17/0009/0023—ISCIII-SGEFI/ERDF). J.N. group was supported by the Slovak Research and Development Agency (APVV-18-0239, APVV-20-0166) and the Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic (VEGA 1/0027/19).Peer ReviewedPostprint (published version

Evolution of loss of heterozygosity patterns in hybrid genomes of Candida yeast pathogens

Background Hybrids are chimeric organisms with highly plastic heterozygous genomes that may confer unique traits enabling the adaptation to new environments. However, most evolutionary theory frameworks predict that the high levels of genetic heterozygosity present in hybrids from divergent parents are likely to result in numerous deleterious epistatic interactions. Under this scenario, selection is expected to favor recombination events resulting in loss of heterozygosity (LOH) affecting genes involved in such negative interactions. Nevertheless, it is so far unknown whether this phenomenon actually drives genomic evolution in natural populations of hybrids. To determine the balance between selection and drift in the evolution of LOH patterns in natural yeast hybrids, we analyzed the genomic sequences from fifty-five hybrid strains of the pathogenic yeasts Candida orthopsilosis and Candida metapsilosis, which derived from at least six distinct natural hybridization events. Results We found that, although LOH patterns in independent hybrid clades share some level of convergence that would not be expected from random occurrence, there is an apparent lack of strong functional selection. Moreover, while mitosis is associated with a limited number of inter-homeologous chromosome recombinations in these genomes, induced DNA breaks seem to increase the LOH rate. We also found that LOH does not accumulate linearly with time in these hybrids. Furthermore, some C. orthopsilosis hybrids present LOH patterns compatible with footprints of meiotic recombination. These meiotic-like patterns are at odds with a lack of evidence of sexual recombination and with our inability to experimentally induce sporulation in these hybrids. Conclusions Our results suggest that genetic drift is the prevailing force shaping LOH patterns in these hybrid genomes. Moreover, the observed LOH patterns suggest that these are likely not the result of continuous accumulation of sporadic events—as expected by mitotic repair of rare chromosomal breaks—but rather of acute episodes involving many LOH events in a short period of time.This work was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. H2020-MSCA-ITN-2014-642095. The TG group also acknowledges the support from the Spanish Ministry of Economy, Industry, and Competitiveness (MEIC) for the EMBL partnership and grants “Centro de Excelencia Severo Ochoa 2013-2017” SEV-2012-0208 and BFU2015-67107 co-founded by the European Regional Development Fund (ERDF); from the CERCA Programme/Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR857 and grants from the European Union’s Horizon 2020 research and innovation program under the grant agreement ERC-2016-724173. TG also receives support from an INB Grant (PT17/0009/0023—ISCIII-SGEFI/ERDF). The authors thank Dr. Powel Golik’s guidance in the identification of PPR proteins, Simone Mozzachiodi and Dr. Gianni Liti for the helpful discussions on the analysis of meiotic patterns, and all Gabaldón lab members for the helpful discussions and comments on this work, especially Marina Marcet-Houben.Peer ReviewedPostprint (author's final draft