Present i futur de les cèl·lules dendrítiques

El sistema immunitari és una de les estructures més complexes del cos. Aquesta complexitat no és supèrflua, sinó que és totalment necessària per fer totes les tasques complicades a les quals fa front, com és el reconeixement i eliminació d'un ampli espectre de microorganismes i patògens, la detecció i destrucció de lesions oncològiques en un ampli rang de teixits i, mentre porta a terme aquestes tasques, el manteniment de la tolerància perifèrica per mitjà de la supressió de respostes perjudicials autoreactives dirigides contra teixits sans. Des del seu descobriment, fet per R. Steinman i col·laboradors fa uns quaranta anys, les cèl·lules dendrítiques (CD) s'han situat com uns elements clau en la direcció del sistema immunitari per portar a terme les seves tasques. En aquesta revisió mostrem una visió general sobre la biologia de les CD, els coneixements que se'n tenen fins al moment, les seves possibles aplicacions terapèutiques per al tractament de malalties i les incògnites que encara queden per respondre en investigacions futures.The immune system is probably one of the most complex cellular organisations in the body. Its complexity is not superfluous; rather, it is necessary to fulfil the complicated purpose of the immune system, namely: recognition of the diverse repertoire of microorganisms and pathogens; the detection of neoplastic lesions originating from a range of tissues; and, while executing these tasks, the maintenance of peripheral tolerance by suppressing detrimental responses against healthy tissues. Since they were discovered by R. Steinman and co. nearly forty years ago, dendritic cells (DCs) have emerged to be critical players in conducting the immune response to fulfil these roles. Here, we provide a general overview of DCs, what we currently know, their possible therapeutic applications and the questions that remain unanswered for future research

Aplicabilidad de la goniometría mediante videografía en el seguimiento de programas de flexibilidad

El objetivo del siguiente trabajo es el de evaluar los efectos de un programa específico de la mejora de la flexibilidad isquiotibial, utilizando la videografía como metodología para el cálculo del ángulo de extensión de rodilla. La muestra ha estado formada por 75 deportistas escolares con un rango de edad de entre 7 y 16 años. Los resultados nos muestran como antes de la intervención sólo un 5% de los casos era considerado flexible (ángulo<20º). Después de la intervención, el porcentaje de flexibles fue del 21% (p=0,002). No obstante, el 47% de los casos había mejorado su flexibilidad. Esta mejora estaba asociada al género (OR niños vs. niñas 3,7 (IC95% 1,04–13,16)), y a la edad (OR 0,78 por año (IC95% 0,62–0,97)), no observándose asociación con las características antropométricas. La intervención practicada fue efectiva, tanto en relación al aumento de casos considerados flexibles, como al número de casos que habían mejorado su flexibilidad. La posibilidad de mejora de la flexibilidad es mayor en los niños y disminuye con la edad. La videografía es un método objetivo para el cálculo del rango de movimiento, hace posible la comparación visual entre dos tests realizados y permite dar un feedback al deportista.The purpose of this study was to investigate the influence of a hamstring stretching program, using videography as the methodology to calculate knee extension range of motion. 75 scholar football players, between 7 and 16 years old, were evaluated. 5% (angle <20º) of the subjects had hamstrings flexibility limitation before the stretching program and 21% (p=0,002) of the total population had flexibility limitations after the program conclude. Nevertheless, 47% of subjects showed increases in their flexibility between first and second assessment. The improvement of flexibility is gender (OR boys vs. girls 3,7 (IC95% 1,04–13,16)) and age (OR 0,78 per year (IC95% 0,62–0,97)) correlated. No association was found with anthropometric characteristics. The stretching program was successful for the improvement of hamstrings flexibility. Boys have greater possibility to improve flexibility and it decreases in relation with age. Videography is an objective methodology to analyze range of movement, allows the visual comparison between tests and gives a feedback to the subject

Comparación entre la videografía y el método Sit and Reach para la valoración de la flexibilidad isquiotibial en deportistas escolares

Existen diferentes test para evaluar la flexibilidad articular. El objetivo de nuestro estudio era el de comparar el test de sit and reach y el de goniometría de la rodilla en extensión, mediante videografía para la valoración de la flexibilidad isquiotibial en una muestra de 139 deportistas escolares, de edades comprendidas entre los 7 y los 16 años. El coeficiente de Kappa muestra una concordancia muy débil entre las dos pruebas (0,022 (I.C. 95% -0,07 – 0,12)). Demostrando que el sit and reach no es un test válido para la evaluación de la flexibilidad isquiotibial.There are different test to evaluate flexibility of human movement. The comparison of sit and reach test and videogaphy measurement of hamstrings flexibility was the purpose of this study. 139 scholar football players, between 7 and 16 years old, were evaluated. Kappa coefficient shows little concordance between the two tests (0,022 (I.C. 95% -0,07 – 0,12)) which demonstrates that sit and reach test is not valid enough for hamstrings flexibility evaluation

Therapeutic potential of extracellular vesicles

Extracellular vesicles (EV) have emerged as important mediators of intercellular communication. By their origin, we can find vesicles derived from plasma membrane such as microvesicles, ectosomes, and membrane particles or exosomes, which originate in the endosomal membrane compartment. They contain numerous proteins, lipids, and even nucleic acids like mRNA and miRNA that can affect the cells that encounter these structures in complex ways. The EV have recently gained interest for their therapeutic potential both as a treatment itself and as a biomarker of several pathologies. The research lines involving EV cover a wide range of aspects from basic research on the EV biology to the manipulation or monitoring of EV for therapeutic purposes

Selective Enzymatic Oxidation of Silanes to Silanols

Compared to the biological world's rich chemistry for functionalizing carbon, enzymatic transformations of the heavier homologue silicon are rare. We report that a wild‐type cytochrome P450 monooxygenase (P450_(BM3) from Bacillus megaterium, CYP102A1) has promiscuous activity for oxidation of hydrosilanes to give silanols. Directed evolution was applied to enhance this non‐native activity and create a highly efficient catalyst for selective silane oxidation under mild conditions with oxygen as the terminal oxidant. The evolved enzyme leaves C−H bonds present in the silane substrates untouched, and this biotransformation does not lead to disiloxane formation, a common problem in silanol syntheses. Computational studies reveal that catalysis proceeds through hydrogen atom abstraction followed by radical rebound, as observed in the native C−H hydroxylation mechanism of the P450 enzyme. This enzymatic silane oxidation extends nature's impressive catalytic repertoire

Immunomodulatory effect of MSC on B cells is independent of secreted extracellular vesicles

Altres ajuts: this work was supported in part by Fundació La Marató de TV3 (201516-10, 201502-30). MM-T is sponsored by the PERIS (SLT002/16/00234) from the Generalitat de Catalunya; FB is a researcher from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, supported by the Health Department of the Catalan Government (Direcció General de Recerca i Innovació, Department Salut, Generalitat de Catalunya) and MF is funded by the Catalan Health Department (Generalitat de Catalunya) contract PERIS (SLT002/16/00069).Mesenchymal stem or stromal cells (MSC) have proven immunomodulatory properties toward B cell activation and induce regulatory B cells (Breg), through a dual mechanism of action that relies both on cell contact and secreted factors. One of them are MSC-derived extracellular vesicles (EVs), membrane nanovesicles that mediate cell communication and typically reflect the phenotype of the cell of origin. MSC-EVs could resemble MSC functions, and are being contemplated as an improved alternative to the MSC-based immunomodulatory therapy. In the present work, we focused on the factors secreted by MSC and aimed to elucidate the putative role of MSC-EVs in the immunomodulation of B cells. EVs and soluble protein-enriched fractions (PF) were isolated from MSC-conditioned medium (CM) using size-exclusion chromatography (SEC) and their capacity to modulate B cell activation, induction of Breg and B cell proliferation was compared to that of the whole MSCs. Co-culture with MSC or unfractionated CM induced naïve and CD24hiCD38hi, IL-10 producing (Breg) phenotypes on B cells while not affecting proliferation. MSC-PF had a comparable effect to MSCs, inducing a naïve phenotype, and even though they did not induce the shift toward a CD24hiCD38hi population, MSC-PF fostered IL-10 production by B cells. Conversely, MSC-EVs failed to promote naïve B cells and to reduce memory B cells. MSC-EVs induced CD24hiCD38hi B cells to a similar extent of that of MSC, but not bona fide Bregs since they did not produce IL-10. Our results show that B cell modulation by MSC is partially mediated by soluble factors other than EVs

Comprehensive proteomic profiling of plasma-derived Extracellular Vesicles from dementia with Lewy Bodies patients

Altres ajuts: Grant 201405/10 from Fundació La Marató TV3Proteins and nucleic acids contained in extracellular vesicles (EVs) are considered a feasible source of putative biomarkers for physiological and pathological conditions. Within the nervous system, not only neurons but also other brain cells are able to produce EVs, which have been involved in their physiological processes and also in the development and course of several neurodegenerative diseases. Among these, dementia with Lewy bodies (DLB) is the second cause of dementia worldwide, though most cases are missed or misdiagnosed as Alzheimer's disease (AD) due to the important clinical and pathological overlap between both diseases. In an attempt to find reliable biomarkers for DLB diagnosis, our group characterized the proteome of plasma-derived EVs from DLB patients compared to aged-matched healthy controls (HCs) using two different proteomic LC-MS/MS approaches. Remarkably, we found that gelsolin and butyrylcholinesterase were differentially identified between DLB and HCs. Further validation of these results using conventional ELISA techniques, and including an additional group of AD patients, pointed to decreased levels of gelsolin in plasma-EVs from DLB compared to HCs and to AD samples. Thus, gelsolin may be considered a possible biomarker for the differentiation between DLB and AD

Lung cancer mortality in European regions (1955-1997)

Background: The different spread of tobacco smoking across European countries has caused a substantial variability in lung cancer mortality. The objective of this investigation was to analyse the trends in lung cancer mortality rates in three broad European regions (Northern and Western countries, Eastern countries, and Mediterranean countries) during the second half of the 20th century. Patients and methods: Mortality data were obtained from the World Health Organisation database. Lung cancer mortality rates were age-standardised by the direct method to the world standard population. Trends from 1955 to 1997 were assessed by means of joinpoint regression analysis. Results: In men, rates in Eastern Europe increased to reach in the 1990s the highest values ever registered, while downward trends were observed in Northern and Western Europe since 1979, and in Mediterranean countries since the 1990s. In women, upward trends were observed in the three regions considered for the whole period. Conclusions: Different smoking prevalences over time explain the shift of almost one decade in the trends in Mediterranean men as compared with Northern and other Western European men. The persisting upward trends in women in the three regions are of concer

Size-Exclusion Chromatography-based isolation minimally alters Extracellular Vesicles' characteristics compared to precipitating agents

Extracellular vesicles (EVs) have become an attractive field among the scientific community. Yet, a major challenge is to define a consensus method for EVs isolation. Ultracentrifugation has been the most widely used methodology but rapid methods, including Size Exclusion Chromatography (SEC) and/or precipitating agents such as Polyethylene glycol (PEG) or PRotein Organic Solvent PRecipitation (PROSPR) have emerged. To evaluate the impact of these different methods on the resulting EV preparations, plasma EVs were isolated using SEC, PEG and PROSPR, and their total protein content, NTA and Cryo-electron microscopy profiles, and EV-markers were compared. Also, their effect on recipient cells was tested. Low protein content and Cryo-EM analysis showed that SEC removed most of the overabundant soluble plasma proteins, which were not removed using PEG and partially by PROSPR. Moreover, only SEC allowed the detection of the EV-markers CD9, CD63 and CD81, LGALS3BP and CD5L, suggesting a putative interference of the precipitating agents in the structure/composition of the EVs. Furthermore, PEG and PROSPR-based EV isolation resulted in reduced cell viability in vitro. These results stress that appropriate EV-isolation method should be considered depending on the forthcoming application of the purified EVs

Growth-promoting effects of sustained swimming in fingerlings of gilthead sea bream (Sparus aurata L.)

Fish growth is strongly influenced by environmental and nutritional factors and changing culture conditions can help optimize it. The importance of early-life experience on the muscle phenotype later in life is well known. Here, we study the effects of 5 weeks of moderate and sustained swimming activity (5 BL s) in gilthead sea bream during early development. We analysed growth and body indexes, plasma IGF-I and GH levels, feed conversion, composition [proximate and isotopic (N/C)] and metabolic key enzymes (COX, CS, LDH, HOAD, HK, ALAT, ASAT) of white muscle. Moderate and continuous exercise in fingerlings of gilthead sea bream increased plasma IGF-I, whereas it reduced plasma GH. Under these conditions, growth rate improved without any modification to feed intake through an increase in muscle mass and a reduction in mesenteric fat deposits. There were no changes in the content and turnover of muscle proteins and lipid reserves. Glycogen stores were maintained, but glycogen turnover was higher in white muscle of exercised fish. A lower LDH/CS ratio demonstrated an improvement in the aerobic capacity of white muscle, while a reduction in the COX/CS ratio possibly indicated a functional adaptation of mitochondria to adjust to the tissue-specific energy demand and metabolic fuel availability in exercised fish. We discuss the synergistic effects of dietary nutrients and sustained exercise on the different mitochondrial responses.A.M.C and E.J.V. are supported by a predoctoral fellowship from the “Ministerio de Ciencia e Innovación” (MICINN) and A.M.P. by a fellowship from the University of Barcelona (APIF-2012). This study was supported by the projects from the MICINN AGL2012-39768, and the “Xarxa de Refèrencia d’R+D+I en Aqüicultura” and the SGR2009-00402 from the “Generalitat de Catalunya”.Peer Reviewe