Protein degradation by E3 ubiquitin ligases in cancer stem cells

Review[Abstract] Cancer stem cells are a small subpopulation within the tumor with high capacity for self-renewal, differentiation and reconstitution of tumor heterogeneity. Cancer stem cells are major contributors of tumor initiation, metastasis and therapy resistance in cancer. Emerging evidence indicates that ubiquitination-mediated post-translational modification plays a fundamental role in the maintenance of cancer stem cell characteristics. In this review, we will discuss how protein degradation controlled by the E3 ubiquitin ligases plays a fundamental role in the self-renewal, maintenance and differentiation of cancer stem cells, highlighting the possibility to develop novel therapeutic strategies against E3 ubiquitin ligases targeting CSCs to fight cancer.Instituto de Salud Carlos III; PI18/00121Instituto de Salud Carlos III; PI21/00238Xunta de Galicia; IN607B2020/1

Peculiarities in the electrical and magnetic properties of cobalt perovskites Ln1−xMxCoO3 (Ln3+: La3+, M2+: Ca2+, Sr2+, Ba2+; Ln3+: Nd3+, M2+: Sr2+)

This is the accepted manuscript of the following article: Señarís-Rodríguez, M. et al. (1999). Peculiarities in the electrical and magnetic properties of cobalt perovskites Ln1−xMxCoO3 (Ln3+: La3+, M2+: Ca2+, Sr2+, Ba2+; Ln3+: Nd3+, M2+: Sr2+). International Journal Of Inorganic Materials, 1(3-4), 281-287. doi: 10.1016/s1466-6049(99)00042-2We refer here to the electrical and magnetic properties of the Ln1−xMxCoO3 systems (Ln3+: La3+, M2+: Ca2+, Sr2+, Ba2+; Ln3+: Nd3+, M2+: Sr2+), paying special attention to those ferromagnetic compounds that display M–I transitions as temperature rises: La1−xMxCoO3 (M2+: Ca2+, Sr2+, Ba2+) in the compositional interval x=0.2–0.3, and Nd1−xSrxCoO3, with x=0.40. The magneto-transport properties of such materials are peculiar and interesting: they show diodic behavior and large relaxation effects — these latter being specially important in the Nd compound — they display magnetoresistive effects specially at the M–I transition temperatures, and they age with time. All these results are discussed on the basis of the inhomogeneous electronic structure of these doped cobalt perovskites and taking into account the influence of the lanthanide ion on their magnetic and electrical propertiesWe thank the Spanish DGICYT for financial support under project MAT98-0416-C03-02S

El papel de la enseñanza de la historia en el desarrollo comunicativo del profesional de la salud / The Role of History teaching in the communicative development of the Health Professional

El presente trabajo introduce el tema en cuestión a partir del análisis de diferentes postulados teóricos sobre la comunicación y la importancia de la enseñanza de la Historia con estos propósitos, en el contexto de la formación médica, que sirvió de base para el análisis documental y la elaboración de dos instrumentos que se aplicaron corroborando la necesidad de crear vías para el desarrollo de la comunicación, y la efectividad de la experiencia aplicada desde el Programa de Historia de Cuba III en 4to año de la carrera de Medicina respectivamente. Para el desarrollo de estos propósitos se fundamentaron  teóricamente las potencialidades de la enseñanza de la asignatura y se ofreció un modelo recurrente que constituyó el estilo metodológico con que se impartieron las 16 actividades docentes  del programa para dar cumplimiento al objetivo propuesto, demostrando que el diseño de las estrategias de enseñanza aprendizaje debe estar encaminado a construir eslabones para el desarrollo de la comunicación, donde la enseñanza de la Historia constituya un fuerte puntal en este propósito, además de contribuir a solucionar los problemas de comunicación que afloren en el período de formación médica e incorpore habilidades, métodos y conocimientos al desarrollo del método clínico, cuyos resultados se evidenciaron en el análisis cualitativo y cuantitativo del instrumento aplicado .Palabras Clave: HISTORIA, ESTUDIANTES DE MEDICINA, COMUNICACIÓN, CUBA. ABSTRACT The present work is based on the teaching of History  from the analysis of different  theoretical postulates on communication  and the importance of  History teaching in the medical context,  which was used as a base  for the documented analysis and the creation of two instruments which were applied,  demonstrating the necessity of means  for the development of communication  and the effectiveness of the applied training  from the Cuban History III in the 4 academic year of Medical major. With these purposes the possibilities of the subject teaching were based theoretically  and it was offered a recurrent model which  constituted  the methodological style used for teaching 16 teaching activities of the program  fulfilling the proposed objective  which demonstrated  that the design of the teaching- learning strategies must be directed to create links  for the development of  communication  where the History teaching is a strong  support  and it also contributes to solve  the communication problems  which emerge in the medical formation period  and gives training , methods and knowledges of the clinical method development whose results  were evidenced in the qualitative and quantitative analysis of the applied instrument. Key words: HISTORY, MEDICAL STUDENTS, COMMUNICATION, CUBA

El papel de la enseñanza de la historia en el desarrollo comunicativo del profesional de la salud / The Role of History teaching in the communicative development of the Health Professional

El presente trabajo introduce el tema en cuestión a partir del análisis de diferentes postulados teóricos sobre la comunicación y la importancia de la enseñanza de la Historia con estos propósitos, en el contexto de la formación médica, que sirvió de base para el análisis documental y la elaboración de dos instrumentos que se aplicaron corroborando la necesidad de crear vías para el desarrollo de la comunicación, y la efectividad de la experiencia aplicada desde el Programa de Historia de Cuba III en 4to año de la carrera de Medicina respectivamente. Para el desarrollo de estos propósitos se fundamentaron  teóricamente las potencialidades de la enseñanza de la asignatura y se ofreció un modelo recurrente que constituyó el estilo metodológico con que se impartieron las 16 actividades docentes  del programa para dar cumplimiento al objetivo propuesto, demostrando que el diseño de las estrategias de enseñanza aprendizaje debe estar encaminado a construir eslabones para el desarrollo de la comunicación, donde la enseñanza de la Historia constituya un fuerte puntal en este propósito, además de contribuir a solucionar los problemas de comunicación que afloren en el período de formación médica e incorpore habilidades, métodos y conocimientos al desarrollo del método clínico, cuyos resultados se evidenciaron en el análisis cualitativo y cuantitativo del instrumento aplicado .Palabras Clave: HISTORIA, ESTUDIANTES DE MEDICINA, COMUNICACIÓN, CUBA. ABSTRACT The present work is based on the teaching of History  from the analysis of different  theoretical postulates on communication  and the importance of  History teaching in the medical context,  which was used as a base  for the documented analysis and the creation of two instruments which were applied,  demonstrating the necessity of means  for the development of communication  and the effectiveness of the applied training  from the Cuban History III in the 4 academic year of Medical major. With these purposes the possibilities of the subject teaching were based theoretically  and it was offered a recurrent model which  constituted  the methodological style used for teaching 16 teaching activities of the program  fulfilling the proposed objective  which demonstrated  that the design of the teaching- learning strategies must be directed to create links  for the development of  communication  where the History teaching is a strong  support  and it also contributes to solve  the communication problems  which emerge in the medical formation period  and gives training , methods and knowledges of the clinical method development whose results  were evidenced in the qualitative and quantitative analysis of the applied instrument. Key words: HISTORY, MEDICAL STUDENTS, COMMUNICATION, CUBA

Coexistence of different intrathalline symbiotic algae and bacterial biofilms in the foliose Canarian lichen Parmotrema pseudotinctorum

[EN] Parmotrema pseudotinctorum (des Abb.) Hale is a foliose lichen able to colonize large areas on rock surfaces in semiarid and warm localities in the Canary Islands. In this contribution, we investigate the phycobionts of this successful lichen under these extreme environmental conditions using ultrastructural and genetic methodologies. Two populations from La Gomera and La Palma islands were analyzed. After TEM analyses, three algal types were clearly distinguished in intrathalline symbiosis, provisionally named Ph1, Ph2, and Ph3. Two of them (Ph1 and Ph2) were Trebouxia showing a well visible pyrenoid corticolatype the chloroplast thylakoids being very different in both. The type Ph3 could be a taxon included in the genus Asterochloris. Our molecular approach consisted in sequencing two different DNA loci: a portion of the chloroplast psbA gene and nuclear ITS. Sequences of the psbA gene resulted in electrophoretograms showing double peaks when DNA extracted from the whole lichen thallus was used as template. Such double peaks were interpreted as single nucleotide polymorphisms (SNPs). This interpretation was confirmed by cloning. However, no intrathalline polymorphisms were detected among the nrITS sequences. Phylogenetic analyses on the basis of the psbA gene revealed three distinct clades. It is likely that these clades corresponded to the the three different morphotypes revealed by TEM. One of these clades, was closely related to T. corticola, other was related to Asterochloris glomerata and the third did not grouped with any specific taxa. These results are the first piece of evidence that algal coexistence may even be established between species of different genera of the Trebouxiophyceae (Asterochloris and Trebouxia at least). Moreover, the coexistence of several microalgal taxa evidenced in this study appears as a consistent character among the populations of this foliose lichen. Further isolation and cultivation of the three different algal types and physiological studies should shed light on the ecological plasticity of the entire holobiont. Along with such variety of intrathalline coexisting algae, another unexpected result was the observation of an almost continuous layer of bacterial-communities coating the lower cortex in all the studied samples of P. pseudotinctorum. The function of these biofilms in the lichen symbiosis remains to be elucidated. The existence of such particular symbiosis involving different algal species and bacteria could be explained by an increased fitness in particular habitats or under specific environmental conditions[ES] Parmotrema pseudotinctorum (des Abb.) Hale es un liquen foliáceo que coloniza roquedos volcánicos y es frecuente en localidades semiáridas y cálidas de las islas Canarias. En este trabajo, se investigan los ficobiontes de este liquen utilizando métodos ultraestructurales y genéticos. Se analizaron dos poblaciones de La Gomera y La Palma. Mediante análisis TEM, se han distinguido claramente tres tipos de algas en simbiosis intratalinas, llamados provisionalmente Ph1, Ph2 y Ph3. Dos de ellas (Ph1 y Ph2), pertenecientes al género Trebouxia, muestran un pirenoide bien visible del tipo corticola, pero los tilacoides del cloroplasto son muy diferentes en ambos. El tipo Ph3 podría ser un taxón incluido en el género Asterochloris. El enfoque molecular consistió en la secuenciación de dos loco diferentes de ADN: una porción del gen psbA del cloroplasto e ITS nuclear. Las secuencias del gen psbA proporcionaron electroforetogramas que mostraban dobles picos cuando se usó como patrón el ADN extraído de los talos completos. Estos dobles picos se interpretaron como polimorfismos de nucleótido simple (SNP). Esta interpretación se confirmó mediante técnicas de clonación. Sin embargo, no se detectaron polimorfismos intratalinos con las secuencias nrITS. Los análisis filogenéticos basados en las secuencias del gen psbA constataron la presencia de tres clados diferenciados. Es probable que éstos correspondan a los tres diferentes morfotipos puestos en evidencia por TEM. Uno de ellos está estrechamente relacionado con T. corticola, otro con Asterochloris glomerata, y el tercero no se agrupaba a ningún taxón especifico. Estos resultados son la primera evidencia de que en los líquenes la coexistencia de algas intratalinas se puede establecer incluso entre especies de difierentes géneros de Trebouxiophyceae (Asterochloris y Trebouxia al menos). Por otra parte, la coexistencia de varios taxones de microalgas, constatada en este estudio, puede considerarse como una sólida característica entre las poblaciones de este liquen foliáceo. Posteriores aislamientos y el cultivo de los tres tipos de algas, además de estudios fisiológicos, podrán explicar la plasticidad ecológica que muestra el holobionte. Otro resultado inesperado fue la observación de una capa casi continua de comunidades bacterianas que recubren el córtex inferior en todas las muestras estudiadas de P. pseudotinctorum. Está por determinar la función que estos biofilms puedan tener en las simbiosis liquénicas. La existencia de estos tipos de simbiosis tan particulares, que involucran tanto a diferentes especies de algas como a bacterias, podría explicarse por un incremento en la capacidad de colonizar hábitats peculiares o con condiciones ambientales específicasThis study was funded by the Spanish Ministry of Economy and Innovation (MINECO CGL2012-40058-C02-01/02), FEDER and the Generalitat Valenciana (PROMETEO 021/2013 GVA).Molins, A.; García-Breijo, F.; Reig Armiñana, J.; Del Campo, EM.; Casano, L.; Barreno Rodriguez, E. (2013). Coexistence of different intrathalline symbiotic algae and bacterial biofilms in the foliose Canarian lichen Parmotrema pseudotinctorum. Vieraea. Folia Scientarum Biologicarum Canariensium. 41:349-370. http://hdl.handle.net/10251/77348S3493704

Active flexible concentric ring electrode for non-invasive surface bioelectrical recordings

Bioelectrical surface recordings are usually performed by unipolar or bipolar disc electrodes even though they entail the serious disadvantage of having poor spatial resolution. Concentric ring electrodes give improved spatial resolution, although this type of electrode has so far only been implemented in rigid substrates and as they are not adapted to the curvature of the recording surface may provide discomfort to the patient. Moreover, the signals recorded by these electrodes are usually lower in amplitude than conventional disc electrodes. The aim of this work was thus to develop and test a new modular active sensor made up of concentric ring electrodes printed on a flexible substrate by thick-film technology together with a reusable battery-powered signal-conditioning circuit. Simultaneous ECG recording with both flexible and rigid concentric ring electrodes was carried out on ten healthy volunteers at rest and in motion. The results show that flexible concentric ring electrodes not only present lower skin electrode contact impedance and lower baseline wander than rigid electrodes but are also less sensitive to interference and motion artefacts. We believe these electrodes, which allow bioelectric signals to be acquired non-invasively with better spatial resolution than conventional disc electrodes, to be a step forward in the development of new monitoring systems based on Laplacian potential recordings.This research was supported in part by the Ministerio de Ciencia y Tecnologia de Espana (TEC2010-16945) and by the Universitat Politecnica de Valencia (PAID 2009/10-2298). The proof-reading of this paper was funded by the Universitat Politecnica de Valencia, Spain.Prats Boluda, G.; Ye Lin, Y.; García Breijo, E.; Ibáñez Civera, FJ.; Garcia Casado, FJ. (2012). Active flexible concentric ring electrode for non-invasive surface bioelectrical recordings. 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Role of the 4Kscore test as a predictor of reclassification in prostate cancer active surveillance

Background: Management of active surveillance (AS) in low-risk prostate cancer (PCa) patients could be improved with new biomarkers, such as the 4Kscore test. We analyze its ability to predict tumor reclassification by upgrading at the confirmatory biopsy at 6 months. Methods: Observational, prospective, blinded, and non-randomized study, within the Spanish National Registry on AS (AEU/PIEM/2014/0001; NCT02865330) with 181 patients included after initial Bx and inclusion criteria: PSA =10 ng/mL, cT1c-T2a, Grade group 1, =2 cores, and =5 mm/50% length core involved. Central pathological review of initial and confirmatory Bx was performed on all biopsy specimens. Plasma was collected 6 months after initial Bx and just before confirmatory Bx to determine 4Kscore result. In order to predict reclassification defined as Grade group =2, we analyzed 4Kscore, percent free to total (%f/t) PSA ratio, prostate volume, PSA density, family history, body mass index, initial Bx, total cores, initial Bx positive cores, initial Bx % of positive cores, initial Bx maximum cancer core length and initial Bx cancer % involvement. Wilcoxon rank-sum test, non-parametric trend test or Fisher’s exact test, as appropriate established differences between groups of reclassification. Results: A total of 137 patients met inclusion criteria. Eighteen patients (13.1%) were reclassified at confirmatory Bx. The %f/t PSA ratio and 4Kscore showed differences between the groups of reclassification (Yes/No). Using 7.5% as cutoff for the 4Kscore, we found a sensitivity of 89% and a specificity of 29%, with no reclassifications to Grade group 3 for patients with 4Kscore below 7.5% and 2 (6%) missed Grade group 2 reclassified patients. Using this threshold value there is a biopsy reduction of 27%. Additionally, 4Kscore was also associated with changes in tumor volume. Conclusions: Our preliminary findings suggest that the 4Kscore may be a useful tool in the decision-making process to perform a confirmatory Bx in active surveillance management