Autocrítica de la conquista de las Indicas desde la perspectiva de los Derechos humanos

El objetivo de este artículo es analizar el proceso de autocrítica que la Corona hispánica fue capaz de desarrollar en tiempos tempranos, comienzos del XVI, cuando ni siquiera se había acometido la conquista clásica de las altas culturas incaica y azteca. ¿Por qué pesó más el drama de la guerra que el valor de la diplomacia si Fernando el Católico, responsable último de las incipientes decisiones, era propuesto como arquetipo de príncipe? ¿Cuáles fueron los factores que impulsaron a ocultar el diálogo bajo las armas? ¿Qué actitud adoptó la Corte cuando fue informada de que, tras la sorpresa del descubrimiento, se precipitaba la destrucción de las Indias?. Frente a la retórica expansionista y falaz, que reflexionaba sobre el comportamiento ante sujetos a los que su propia naturaleza había hecho esclavos, al tiempo que se fraguaba el Imperio español constituyó todo un acierto, innovador en el contexto, que aflorara la idea de que la humanidad es una y, así, la Escuela de Salamanca pasó a ser la precursora del Derecho de Gentes y, por ende, de los Derechos Humano

The multifaceted roles of gasdermins in cancer biology and oncologic therapies

The involvement of the Gasdermin (GSDM) protein family in cancer and other pathologies is one of the hottest topics in biomedical research. There are six GSDMs in humans (GSDMA, B, C, D, GSDME/DFNA5 and PJVK/DFNB59) and, except PJVK, they can trigger cell death mostly by pyroptosis (a form of lytic and pro-inflammatory cell death) but also other mechanisms. The exact role of GSDMs in cancer is intricate, since depending on the biological context, these proteins have diverse cell-death dependent and independent functions, exhibit either pro-tumor or anti-tumor functions, and promote either sensitization or resistance to oncologic treatments. In this review we provide a comprehensive overview on the multifaceted roles of the GSDMs in cancer, and we critically discuss the possibilities of exploiting GSDM functions as determinants of anti-cancer treatment and as novel therapeutic targets, with special emphasis on innovative GSDM-directed nano-therapies. Finally, we discuss the issues to be resolved before GSDM-mediated oncologic therapies became a reality at the clinical levelThis study was supported by the Ministerio de Ciencia e Innovaci´on (PID2019-104644RB-I00 -GMB-), the Instituto de Salud Carlos III (CIBERONC, CB16/12/00295 –GMB-; partly supported by FEDER funds) and by the Fundaci´on Científica de la AECC (FC_AECC PROYE19036MOR -GMB-

DNA methylation-associated dysregulation of transfer RNA expression in human cancer

The human cytoplasmatic pool of tRNA for the 20 proteinogenic amino acids and selenocysteine is composed of 48 isoacceptor families -those tRNA with different anticodons- divided into 253 different isodecoder species -those tRNAs that share the same anticodon but present sequence variations in other positions [1, 2]. All these molecules cooperate to translate the genetic information encoded in mRNA to enable protein synthesis. For many years, tRNAs have been considered as housekeeping molecules without any additional regulatory function, but compelling recent evidence of the intricacy of tRNA biology have proven that this initial misconception was far from reality. In fact, tRNAs actively engage in protein synthesis regulation and in additional molecular processes that are unrelated to translation, like apoptosis prevention and the generation of small derivative non-coding RNAs that perform further cellular function

qPCR multiplex para la detección de polimorfismos de la hemocromatosis hereditaria

La hemocromatosis hereditaria (HH) es una enfermedad genética autosómica recesiva que afecta a la absorción de hierro (Fe) en el intestino y que está caracterizada por el incremento de los depósitos de Fe en células y de Fe libre que va a pasar a las células de diversos órganos, principalmente, el hígado. En función del gen afectado existen 5 tipos de HH, siendo la HH de tipo 1 la más frecuente. Este tipo de hemocromatosis se ocasiona por mutaciones en el gen HFE, especialmente las mutaciones C282Y y H63D. La HH puede ser difícil de diagnosticar. Muchas personas que tienen esta afección no presentan signos ni síntomas aparte de niveles elevados de Fe en la sangre. La HH y sin tratamiento puede causar varias complicaciones. Por ello, dada la importancia de un diagnóstico precoz para prevenir el desarrollo de lesiones asociadas a la hemosiderosis y a la elevada frecuencia de las mutaciones es esencial determinar con mayor exactitud las implicaciones derivadas de la presencia de los dos polimorfismos mayoritarios, C282Y y H63D. La empresa Blackhills Diagnostic Resources (BDR) dispone de kits para la determinación singleplex de las mutaciones H63D, S65C y C282Y de asociación a la HH. Teniendo en cuenta las ventajas que ofrece la multiplexación, varios clientes de la empresa han sugerido un formato multiplex de detección de HFE que permiten detectar 4 fluoróforos (2 polimorfismos de único nucleótido, SNPs, por pocillo) para determinar las 2 mutaciones más relevantes, C282Y y H63D. El kit Genvinset® H63D-C282Y multiplex permite determinar de forma específica y eficaz las dos mutaciones más relevantes lo que facilita mucho el tratamiento y mejora la esperanza de vida. Es imprescindible que todo el proceso de diseño del producto vaya acompañado por un sistema de calidad que permita organizarlo y minimice los riesgos que puedan surgir.<br /

Minimal Dose of Resistance Exercise Required to Induce Immediate Hypotension Effect in Older Adults with Hypertension:Randomized Cross-Over Controlled Trial

To determine the optimal exercise volume to generate a hypotension response after the execution of a single strength exercise in elderly subjects with hypertension (HT), a randomized crossover design was performed. A total of 19 elderly subjects with HT performed one control session and three experimental sessions of resistance training with different volumes in a randomized order: three, six, and nine sets of 20 repetitions maximum (RM) of a single elbow flexion exercise with elastic bands. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean heart rate (MHR) were tested at the beginning and immediately afterwards, at 30 and 60 min, and at 4, 5, and 6 h after the resistance exercise. The results show that the volumes of six and nine sets of 20 RM obtained statistically significant differences in the SBP at 30 and 60 min post-exercise (p &lt; 0.05); in the DBP at 30 min after exercise (p &lt; 0.05); and in the MHR immediately after exercise at 30 and 60 min (p &lt; 0.05), compared to a control session. A single resistance exercise with a minimum volume of six sets of 20 RM generated an acute post-exercise antihypertensive response that was maintained for 60 min in elderly people with controlled HT

Importance of frequency and intensity of strength training for work ability among physical therapists

The aim of the study was to evaluate the association between frequency and intensity of strength training participation and work ability among physical therapists (PTs). The Work Ability Index questionnaire (WAI) and a questionnaire about participation in strength training during leisure time were administered to a sample of Spanish PTs. In addition, participants provided information on gender, age, body mass index, education, substance use, working experience and working hours per week. The odds for having excellent WAI (score 44–49) as a function of intensity or frequency of strength training participation were determined using binary logistic regression controlled for various confounders. Data from 981 PTs were analysed. High-intensity strength training (&gt; 80% 1 RM) showed strong associations with excellent WAI (odds ratio = 9.7; 95% confidence interval, 2.9–31.6). In addition, performing strength training more than 3 times per week was associated with excellent WAI (odds ratio = 1.79; 95% confidence interval, 1.24–2.59), however, no significant associations were found with lower levels of frequency and intensities. High-intensity strength training 3 times per week is associated with excellent WAI among PTs. Training programs meeting these features may importantly contribute to maintain or improve WAI

The microbiome of the uropygial secretion in hoopoes is shaped along the nesting phase

Microbial symbiont acquisition by hosts may determine the effectiveness of the mutualistic relationships. A mix of vertical and horizontal transmission may be advantageous for hosts by allowing plastic changes of microbial communities depending on environmental conditions. Plasticity is well known for gut microbiota but is poorly understood for other symbionts of wild animals. We here explore the importance of environmental conditions experienced by nestling hoopoes (Upupa epops) during the late nesting phase determining microbiota in their uropygial gland. In cross-fostering experiments of 8 days old nestlings, “sibling-sibling” and “mother-offspring” comparisons were used to explore whether the bacterial community naturally established in the uropygial gland of nestlings could change depending on experimental environmental conditions (i.e., new nest environment). We found that the final microbiome of nestlings was mainly explained by nest of origin. Moreover, cross-fostered nestlings were more similar to their siblings and mothers than to their stepsiblings and stepmothers. We also detected a significant effect of nest of rearing, suggesting that nestling hoopoes acquire most bacterial symbionts during the first days of life but that the microbiome is dynamic and can be modified along the nestling period depending on environmental conditions. Estimated effects of nest of rearing, but also most of those of nest of origin are associated to environmental characteristics of nests, which are extended phenotypes of parents. Thus, natural selection may favor the acquisition of appropriated microbial symbionts for particular environmental conditions found in nests.Support by funding was provided by Spanish Ministerio de Economía y Competitividad, European funds (FEDER) (CGL2013-48193-C3-1-P, CGL2013-48193-C3-2-P), and Junta de Andalucía (P09-RNM-4557). AM-G had a predoctoral grant from the Junta de Andalucía (P09-RNM-4557).Peer reviewe

Special structures of hoopoe eggshells enhance the adhesion of symbionts-carrying uropygial secretion to prevent embryo infection

This is the pre-peer-reviewed version of the following article: Martín-Vivaldi, M.; et al. Special structures of hoopoe eggshells enhance the adhesion of symbionts-carrying uropygial secretion to prevent embryo infection. Journal of Animal Ecology, (2014). which has been published in final form at: http://onlinelibrary.wiley.com/doi/10.1111/1365-2656.12243/abstract1. Animals live in a bacterial world, and detecting and exploring adaptations favouring mutualistic relationships with antibiotic-producing bacteria as a strategy to fight pathogens are of prime importance for evolutionary ecologists. 2. Uropygial secretion of European hoopoes (Upupa epops, Linnaeus) contains antimicrobials from mutualistic bacteria that may be used to prevent embryo infection. Here, we investigated the microscopic structure of hoopoe eggshells looking for special features favouring the adhesion of antimicrobial uropygial secretions. 3. We impeded female access to the uropygial gland and compared microscopic characteristics of eggshells, bacterial loads of eggs and of uropygial secretion, and hatching success of experimental and control females. Then, we explored the link between microbiological characteristics of uropygial secretion and these of eggs of hoopoes, as well as possible fitness benefits. 4. The microscopic study revealed special structures in hoopoes' eggshells (crypts). The experimental prevention of females' gland access demonstrated that crypts are filled with uropygial secretion and that symbiotic enterococci bacteria on the eggshells come, at least partially, from those in the female's uropygial gland. Moreover, the experiment resulted in a higher permeability of eggshells by several groups of bacteria and in elimination of the positive relationships detected for control nests between hatching success and density of symbiotic bacteria, either in the uropygial secretion of females or on the eggshell. 5. The findings of specialized crypts on the eggshells of hoopoes, and of video-recorded females smearing secretion containing symbiotic bacteria at a high density onto the eggshells strongly support a link between secretion and bacteria on eggs. Moreover, the detected associations between bacteria and hatching success suggest that crypts enhancing the adhesion of symbiont-carrying uropygial secretion likely protect embryos against infections.Support by funding was provided by Spanish Ministerio de Ciencia e Innovación, European funds (FEDER) (CGL2009-14006, CGL2010-19233-C03-01 and CGL2010-19233-C03-03) and Junta de Andalucía (P09-RNM-4557)

Efecto de la sinucleína en la fisiología de células neuronales cultivadas en 3D en la enfermedad del Parkinson

La enfermedad del Parkinson (EP) es el trastorno neurológico degenerativo más común, después de la enfermedad del Alzheimer, cuya principal característica anatomopatológica es la presencia de agregados de α-sinucleína (aSyn), una proteína intrínsecamente desordenada presináptica, que desencadenará en la formación de fibrillas dando lugar a los cuerpos de Lewy (CL). La etiología y mecanismos patogénicos de la EP siguen sin comprenderse. Por tal motivo, resulta importante mejorar su conocimiento a partir de ensayos in vitro. Dado que las neuronas dopaminérgicas humanas son difíciles de obtener y mantener como células primarias, la investigación se realiza con modelos de células neuronales establecidos, como la línea celular SH-SY5Y. Las plataformas para cultivo celular bidimensional no recapitulan eficazmente los requerimientos espaciales esenciales para la organización e interacciones celulares que ocurren entre las células in vivo. La limitación del contacto célula-célula y la alteración de la señalización celular que ocurren in vitro puede resultar en grandes discrepancias entre la información obtenida en investigaciones in vivo e in vitro. Por tanto, el desarrollo de andamios tridimensionales puede facilitar el crecimiento celular en un macro y microambiente adecuados. En el presente trabajo, se procura comparar los resultados obtenidos en base a la diferenciación y comportamiento de la línea modelo en el cultivo en monocapa y tridimensional para determinar las condiciones óptimas de crecimiento de las SH-SY5Y cultivadas en 3D. Así, para ello, se cultiva la línea en dispositivos, como chips de microfluídica y µ-slides, que permiten el estudio del efecto en la viabilidad, diferenciación y contactos célula-célula de la adición de fibras de α-sinucleína. Esto posibilita que las células se comporten de la manera en que lo harían en la porción compacta de la sustancia negra (SNpc) del mesencéfalo pudiendo determinar así, los efectos de la adición α-sinucleína de forma similar a la que ocurre in vivo. <br /

Physical and Quality of Life Changes in Elderly Patients after Laparoscopic Surgery for Colorectal Cancer-A Prospective Cohort Study

Background—The incidence of colorectal cancer is increasing among elderly people, where postoperative complications are frequent. Methods—We evaluated postoperative physical and quality of life changes in elderly patients undergoing laparoscopic surgery for colorectal cancer. A prospective cohort study was performed in 31 colorectal cancer patients ≥60 years who were scheduled for laparoscopic surgery due to colorectal cancer. Outcomes were measured one month preoperative (T1), three days postoperative (T2) and one month postoperative (T3). Results—The largest early postoperative (from T1 to T2) declines were observed for isometric knee extension strength (33.1%), 30 s Chair Stand Test (27.9%) and handgrip strength (16.9%). Significant reductions in quality of life measured with the QLQ-C30 summary score and the EQ 5D index score were found between T1–T3 and T1–T2, respectively. Conclusions—A decline in isometric knee extension strength, 30 s Chair Stand Test, handgrip strength and quality of life is evident in elderly patients in the days following laparoscopic surgery for colorectal cancer. Preoperative values are recovered one month after surgery for all the outcomes, except for isometric knee extension, which should receive especial attention