Nitric oxide induces the alternative oxidase pathway in Arabidopsis seedlings deprived of inorganic phosphate

Phosphate starvation compromises electron fow through the cytochrome pathway of the mitochondrial electron transport chain, and plants commonly respond to phosphate deprivation by increasing fow through the alternative oxidase (AOX). To test whether this response is linked to the increase in nitric oxide (NO) production that also increases under phosphate starvation, Arabidopsis thaliana seedlings were grown for 15 d on media containing either 0 or 1 mM inorganic phosphate. The effects of the phosphate supply on growth, the production of NO, respiration, the AOX level and the production of superoxide were compared for wild-type (WT) seedlings and the nitrate reductase double mutant nia. Phosphate deprivation increased NO production in WT roots, and the AOX level and the capacity of the alternative pathway to consume electrons in WT seedlings; whereas the same treatment failed to stimulate NO production and AOX expression in the nia mutant, and the plants had an altered growth phenotype. The NO donor S-nitrosoglutathione rescued the growth phenotype of the nia mutants under phosphate deprivation to some extent, and it also increased the respiratory capacity of AOX. It is concluded that NO is required for the induction of the AOX pathway when seedlings are grown under phosphate-limiting conditions.This work was supported by research grants (AGL2010-16167; AGL2014-52396-P) from the Spanish Ministry of Economy and Competitiveness (MINECO) to JFM, an FPI fellowship from MINECO (BR), and a Marie Curie Intra-European Fellowship for Career Development within the 7th European Community Framework Programme (KJG and RGR).Peer Reviewe

Pembrolizumab as consolidation strategy in patients with multiple myeloma: Results of the GEM-Pembresid clinical trial

PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23

Simulador cardiovascular para ensayo de robots de navegación autónoma

[Resumen] Este artículo presenta un modelo de simulación del sistema cardiovascular en el entorno de Matlab/Simulink, más concretamente de la zona de mayor riesgo cardiovascular, la arteria carótida. Está basado en un modelo eléctrico del sistema que describe la dinámica de contracción del corazón, así como su carácter cíclico y autónomo. Como primer paso, este modelo se generaliza para contemplar también la dinámica de la arteria carótida izquierda. A partir de él, y haciendo una serie de equivalencias entre dominios, se obtiene un modelo hidráulico que emula el comportamiento del sistema cardiovascular en esa zona y que, a diferencia del anterior, no presenta carácter autónomo. Para el diseño del control, se hace uso de la estrategia de linealización por realimentaón. Se incluyen simulaciones, tanto del modelo eléctrico completo como del hidráulico propuesto, para demostrar el correcto funcionamiento del simulador desarrollado. El objetivo final de este trabajo es la construcción de una plataforma de ensayo para robots nadadores tipo flagelo eucariótico y bacteriano de pequeñas dimensiones a partir del modelo hidráulico desarrollado que permita emular las condiciones en las que se encontrarían estos robots navegando por el sistema circulatorio humano.Junta de Extremadura; GR15178Ministerio de Economía y Competitividad; DPI2016-80547-

New regulations regarding Postgraduate Medical Training in Spain: perception of the tutor's role in the Murcia Region

<p>Abstract</p> <p>Background</p> <p>Recently introduced regulatory changes have expanded the Tutor role to include their primary responsibility for Postgraduate Medical Training (PMT). However, accreditation and recognition of that role has been devolved to the autonomic regions. The opinions of the RT may be relevant to future decisions;</p> <p>Methods</p> <p>A comprehensive questionnaire, including demographic characteristics, academic and research achievement and personal views about their role, was sent to 201 RTs in the Murcia Region of Spain. The responses are described using median and interquartile ranges (IQR);</p> <p>Results</p> <p>There were 147 replies (response rate 73%), 69% male, mean age 45 ± 7 yrs. RTs perception of the residents' initial knowledge and commitment throughout the program was 5 (IQR 4-6) and 7 (IQR 5-8), respectively. As regards their impact on the PMT program, RTs considered that their own contribution was similar to that of senior residents. RTs perception of how their role was recognised was 5 (IQR 3-6). Only 16% did not encounter difficulties in accessing specific RT training programs. Regarding the RTs view of their various duties, supervision of patient care was accorded the greatest importance (64%) while the satisfactory completion of the PMT program and supervision of day-to-day activities were also considered important (61% and 59% respectively). The main RT requirements were: a greater professional recognition (97%), protected time (95%), specific RT training programs (95%) and financial recognition (86%);</p> <p>Conclusions</p> <p>This comprehensive study, reflecting the feelings of our RTs, provides a useful insight into the reality of their work and the findings ought to be taken into consideration in the imminent definitive regulatory document on PMT.</p

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

[EN]Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative, the Red Temática de Investigación Cooperativa en Cáncer (RTICC); grant SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain and; grant DTS15/00119 from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain

Unravelling Chemical Composition of Agave Spines: News from Agave fourcroydes Lem.

Spines are key plant modifications developed to deal against herbivores; however, its physical structure and chemical composition have been little explored in plant species. Here, we took advantage of high-throughput chromatography to characterize chemical composition of Agave fourcroydes Lem. spines, a species traditionally used for fiber extraction. Analyses of structural carbohydrate showed that spines have lower cellulose content than leaf fibers (52 and 72%, respectively) but contain more than 2-fold the hemicellulose and 1.5-fold pectin. Xylose and galacturonic acid were enriched in spines compared to fibers. The total lignin content in spines was 1.5-fold higher than those found in fibers, with elevated levels of syringyl (S) and guaiacyl (G) subunits but similar S/G ratios within tissues. Metabolomic profiling based on accurate mass spectrometry revealed the presence of phenolic compounds including quercetin, kaempferol, (+)-catechin, and (-)-epicatechin in A. fourcroydes spines, which were also detected in situ in spines tissues and could be implicated in the color of these plants' structures. Abundance of (+)-catechins could also explain proanthocyanidins found in spines. Agave spines may become a plant model to obtain more insights about cellulose and lignin interactions and condensed tannin deposition, which is valuable knowledge for the bioenergy industry and development of naturally dyed fibers, respectively

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

The use of scenarios and models to evaluate the future of nature values and ecosystem services in Mediterranean forests

Science and society are increasingly interested in predicting the effects of global change and socio-economic development on natural systems, to ensure maintenance of both ecosystems and human well-being. The Intergovernmental Platform on Biodiversity and Ecosystem Services has identified the combination of ecological modelling and scenario forecasting as key to improving our understanding of those effects, by evaluating the relationships and feedbacks between direct and indirect drivers of change, biodiversity, and ecosystem services. Using as case study the forests of the Mediterranean basin (complex socio-ecological systems of high social and conservation value), we reviewed the literature to assess (1) what are the modelling approaches most commonly used to predict the condition and trends of biodiversity and ecosystem services under future scenarios of global change, (2) what are the drivers of change considered in future scenarios and at what scales, and (3) what are the nature and ecosystem service indicators most commonly evaluated. Our review shows that forecasting studies make relatively little use of modelling approaches accounting for actual ecological processes and feedbacks between different socio-ecological sectors; predictions are generally made on the basis of a single (mainly climate) or a few drivers of change. In general, there is a bias in the set of nature and ecosystem service indicators assessed. In particular, cultural services and human well-being are greatly underrepresented in the literature. We argue that these shortfalls hamper our capacity to make the best use of predictive tools to inform decision-making in the context of global change.This work was supported by the Spanish Government through the INMODES project (grant number CGL2017-89999-C2-2-R), the ERA-NET FORESTERRA project INFORMED (grant number 29183), and the project Boscos Sans per a una Societat Saludable funded by Obra Social la Caixa (https://obrasociallacaixa.org/). AMO and AA were supported by Spanish Government through the “Juan de la Cierva” fellowship program (IJCI-2016-30349 and IJCI-2016-30049, respectively). JVRD was supported by the Government of Asturias and the FP7-Marie Curie-COFUND program of the European Commission (Grant “Clarín” ACA17-02)