El ratolí com a sistema model en biologia

Des de l'establiment de les primeres soques de laboratori al començament del segle xx, el ratolí s'ha convertit en una eina fonamental en la recerca en biologia. Múltiples models experimentals han permès ampliar el nostre coneixement en camps com l'embriogènesi, la fisiologia o la biomedicina, entre d'altres. El desenvolupament de les tecnologies de modificació genètica ha consolidat definitivament el ratolí com el mamífer d'elecció a l'hora de caracteritzar patrons d'expressió, funcions i interaccions entre gens, així com en la modelització de malalties humanes i l'assaig de nous fàrmacs. Aquest capítol pretén oferir una visió general de les àmplies possibilitats que es deriven de l'ús del ratolí en el laboratori i inclou exemples que demostren per què és un element clau en la recerca en biologia actualment.The mouse as a model system in biology. Since the beginning of the 20th century, when the first laboratory strains were developed, the mouse has become a central tool in biological research. Many experimental models have allowed the broadening of our knowledge in scientific fields such as embryogenesis, physiology or biomedicine. Development of genetic modification techniques has definitely established the mouse as the mammal organism of choice for the characterization of gene expression patterns, functions and interactions among genes as well as for the modeling of human diseases and drug testing. This chapter wants to offer a general view on the possibilities derived from the use of the mouse in the laboratory, and includes examples showing why it has become a key element in biological research

Disturbances in metabolic, transport and structural genes in experimental colonic inflammation in the rat: a longitudinal genomic analysis

Background: Trinitrobenzenesulphonic acid (TNBS) induced rat colitis is one of the most widely used models of inflammatory bowel disease (IBD), a condition whose aetiology and pathophysiology are incompletely understood. We have characterized this model at the genomic level using a longitudinal approach. Six control rats were compared with colitic animals at 2, 5, 7 and 14 days after TNBS administration (n = 3). The Affymetrix Rat Expression Array 230 2.0 system was used. Results: TNBS-induced colitis had a profound impact on the gene expression profile, which was maximal 5 and 7 days post-induction. Most genes were affected at more than one time point. They were related to a number of biological functions, not only inflammation/immunity but also transport, metabolism, signal transduction, tissue remodeling and angiogenesis. Gene changes generally correlated with the severity of colitis. The results were successfully validated in a subset of genes by real-time PCR. Conclusion: The TNBS model of rat colitis has been described in detail at the transcriptome level. The changes observed correlate with pathophysiological disturbances such as tissue remodelling and alterations in ion transport, which are characteristic of both this model and IBD.This study was supported by the Instituto de Investigación Carlos III (PI051651, PI051625), the Spanish Junta de Andalucía (ARM/LD 43035), the Ministry of Industry, and Fundación Genoma España

A genome editing approach to study cancer stem cells in human tumors

The analysis of stem cell hierarchies in human cancers has been hampered by the impossibility of identifying or tracking tumor cell populations in an intact environment. To overcome this limitation, we devised a strategy based on editing the genomes of patient-derived tumor organoids using CRISPR/Cas9 technology to integrate reporter cassettes at desired marker genes. As proof of concept, we engineered human colorectal cancer (CRC) organoids that carry EGFP and lineage-tracing cassettes knocked in the LGR5 locus. Analysis of LGR5-EGFP+ cells isolated from organoid-derived xenografts demonstrated that these cells express a gene program similar to that of normal intestinal stem cells and that they propagate the disease to recipient mice very efficiently. Lineage-tracing experiments showed that LGR5+ CRC cells self-renew and generate progeny over long time periods that undergo differentiation toward mucosecreting- and absorptive-like phenotypes. These genetic experiments confirm that human CRCs adopt a hierarchical organization reminiscent of that of the normal colonic epithelium. The strategy described herein may have broad applications to study cell heterogeneity in human tumors

L'avaluació continuada i la millora en el rendiment acadèmic: el cas de de la Farmacologia i Toxicologia en R+D+i del Grau de Farmàcia

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524Des de la implantació de Espai Europeu d’Educació Superior i l’adopció per part de les universitats de l’avaluació continuada (AC) com a sistema d’acreditació del aprenentatges, existeix la preocupació tant per part dels estudiants com dels professors, que l’AC, entesa com la suma de proves i/o evidències parcials d’avaluació, ens porta a una disminució de notes en la franja alta de qualificació..

A systematic review on the use of action research methods in mental health nursing care

Aims: To identify and synthesize evidence on the use of action research methods in mental health nursing care. Design: Systematic review. Data sources: CINAHL, Web of Science, PubMed and Scopus databases were searched in January 2021. Review methods: Data were selected using the updated Preferred Reporting Items for Systematic Reviews and Meta-Analysis framework. Two reviewers independently conducted the study selection, and quality appraisal using Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research, data extraction and data analysis procedures. Results: Sixteen studies, half of which used participatory action research, were included in this review. Nurses, along with other stakeholders, were an active part of the action research process. The main topics of interest addressed were categorized as improving the adoption of a person-centred approach to care and improving decision-making procedures. The use of action research helped the participants to identify the meaning they attached to the topic of interest to be improved. Moreover, this method helped to identify needs and strategies for improving care. The studies concurred that the use of action research enabled participants to gain awareness, improve attitudes and acquire knowledge. In addition, it enabled participants to gain confidence and security in the group context, as key aspects of their empowerment. Conclusion: This review shows the usefulness of action research in any mental health nursing context, contributing to the improvement of care at both the individual and collective levels. Impact: This paper demonstrates the use of the action research method in the field of mental health nursing. Its use has improved the clinical practice of nurses as well as that of teams in both community and hospital settings, addressing issues of the person-centred approach to care and decision-making procedures

Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer

Colorectal cancers (CRCs) are composed of an amalgam of cells with distinct genotypes and phenotypes. Here, we reveal a previously unappreciated heterogeneity in the biosynthetic capacities of CRC cells. We discover that the majority of ribosomal DNA transcription and protein synthesis in CRCs occurs in a limited subset of tumor cells that localize in defined niches. The rest of the tumor cells undergo an irreversible loss of their biosynthetic capacities as a consequence of differentiation. Cancer cells within the biosynthetic domains are characterized by elevated levels of the RNA polymerase I subunit A (POLR1A). Genetic ablation of POLR1A-high cell population imposes an irreversible growth arrest on CRCs. We show that elevated biosynthesis defines stemness in both LGR5+ and LGR5− tumor cells. Therefore, a common architecture in CRCs is a simple cell hierarchy based on the differential capacity to transcribe ribosomal DNA and synthesize proteins

Evaluation of the Adenocarcinoma-Associated Gene AGR2 and the Intestinal Stem Cell Marker LGR5 as Biomarkers in Colorectal Cancer

We aim to estimate the diagnostic performances of anterior gradient homolog-2 (AGR2) and Leucine-rich repeat-containing-G-protein-coupled receptor 5 (LGR5) in peripheral blood (PB) as mRNA biomarkers in colorectal cancer (CRC) and to explore their prognostic significance. Real-time PCR was used to analyze AGR2 and LGR5 in 54 stages I-IV CRC patients and 19 controls. Both mRNAs were significantly increased in PB from CRC patients compared to controls. The area under the receiver-operating characteristic curves were 0.722 (p = 0.006), 0.376 (p = 0.123) and 0.767 (p = 0.001) for AGR2, LGR5 and combined AGR2/LGR5, respectively. The AGR2/LGR5 assay resulted in 67.4% sensitivity and 94.7% specificity. AGR2 correlated with pT3–pT4 and high-grade tumors. LGR5 correlated with metastasis, R2 resections and high-grade. The progression-free survival (PFS) of patients with high AGR2 was reduced (p = 0.037; HR, 2.32), also in the stage I-III subgroup (p = 0.046). LGR5 indicated a poor prognosis regarding both PFS (p = 0.007; HR, 1.013) and overall survival (p = 0.045; HR, 1.01). High AGR2/LGR5 was associated with poor PFS (p = 0.014; HR, 2.8) by multivariate analysis. Our findings indicate that the assessment of AGR2 and LGR5 in PB might reflect the presence of circulating tumor cells (CTC) and stem cell like CTC in CRC. Increased AGR2 and LGR5 are associated with poor outcomes

Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism

Ephexin4 is a RhoG-specific guanine nucleotide exchange factor that interacts with the EphA2 receptor in breast cancer cells

Genealogies. Rescatar penyores

[ca] Com a «penyores»... coneixem aquells objectes que es deixen en poder d’algú, com a prova de retorn o com a promesa de record. Penyores són també aquells estris oblidats en espais en desús, peces descartades, de manera conscient o involuntària —descuidar-se, fugir. Els espais que ens envolten, on diàriament vivim i treballem, acumulen artefactes carregats de vivències, històries i faules de qui abans els ha emprat. Narren èxits, fracassos, formes de viure; si més no, la màgia de la quotidianitat. Independentment de l’estadi vital on s’estigui —joventut o senectut—, s’entén la importància i el potencial de reutilitzar el que s’ha llegat: per acostar-se a la memòria, rellegir-la, fer-ne crida, furgar-hi, reivindicar i, siguin els que siguin, propiciar canvis a situacions actuals. A «Genealogies. Rescatar penyores», artistes novells, artistes convidats i professorat de la Facultat de Belles Arts de la Universitat de Barcelona, amb la complicitat del públic assistent, miren d’aportar noves visions sobre els objectes i els temps pignorats que contenen, com a punt de partida per encetar un diàleg narratiu de tint feminista, econòmic, de cura, de sostenibilitat emocional

Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche

Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps