Esta sección incluye una lista de los últimos artículos científicos del IPNA publicados en revistas incluidas en el Science Citation Index (SCI).
En DIGITAL.CSIC, repositorio institucional del CSIC, pueden encontrar el listado completo de artículos científicos desde 1962, así como otras colecciones de interés como congresos, tesis, libros, material divulgativo, etc. del centro. El objetivo de DIGITAL.CSIC es organizar, preservar y difundir en acceso abierto los resultados de nuestra investigación.
En el repositorio institucional del CSIC, pueden encontrar el listado completo de artículos científicos, así como otras colecciones de interés como congresos, tesis, libros, material divulgativo, etc.
Análisis de la Producción Científica del IPNA 2014-2019: análisis bibliométrico realizado a partir de datos recogidos en Scopus y Web of Science.
Antiamoeboid activity of squamins C–F, cyclooctapeptides from Annona globifora
Free-living amoebae of Acanthamoeba spp. are causative agents of human infections such as granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The exploration of innovative chemical entities from natural sources that induce intrinsic apoptotic pathway or a Programmed Cell Death (PCD) in Acanthamoeba protozoa is essential to develop new therapeutic strategies. In this work, the antiamoeboid activity of squamins C–F (1–4), four cyclooctapeptides isolated from Annona globiflora was tested in vitro against Acanthamoeba castellanii Neff, A. polyphaga, A. quina, and A. griffini, and a structure–activity relationship was also established. The most sensitive strain against all tested cyclooctapeptides was A. castellanii Neff being the R conformers of the S-oxo-methionine residue, squamins D (2) and F (4), the most active against the trophozoite stage. It is remarkable that all four peptides showed no cytotoxic effects against murine macrophages cell line J774A.1. The analysis of the mode of action of squamins C–F against A. castellanii indicate that these cyclopeptides induced the mechanisms of programmed cell death (PCD). All peptides trigger mitochondrial damages, significant inhibition of ATP production compared to the negative control, chromatin condensation and slight damages in membrane that affects its permeability despite it conserves integrity at the IC90 for 24 h. An increase in reactive oxygen species (ROS) was observed in all cases.
Rodríguez-Expósito, Rubén L.; Sosa-Rueda, Javier; Reyes-Batlle, María; Sifaoui, Inés; Cen-Pacheco, Francisco; Hernández Daranas, Antonio; Díaz-Marrero, Ana R.; Piñero, José E.; Fernández, José J.; Lorenzo-Morales, Jacob
Invasive snake causes massive reduction of all endemic herpetofauna on Gran Canaria
Invasive snakes represent a serious threat to island biodiversity, being responsible for far-reaching impacts that are noticeably understudied, particularly regarding native reptiles. We analysed the impact of the invasive California kingsnake, Lampropeltis californiae—recently introduced in the Canary Islands—on the abundance of all endemic herpetofauna of the island of Gran Canaria. We quantified the density in invaded and uninvaded sites for the Gran Canaria giant lizard, Gallotia stehlini, the Gran Canaria skink, Chalcides sexlineatus, and Boettger's wall gecko, Tarentola boettgeri. We used spatially explicit capture-recapture and distance-sampling methods for G. stehlini and active searches under rocks for the abundance of the other two reptiles. The abundance of all species was lower in invaded sites, with a reduction in the number of individuals greater than 90% for G. stehlini, greater than 80% for C. sexlineatus and greater than 50% for T. boettgeri in invaded sites. Our results illustrate the severe impact of L. californiae on the endemic herpetofauna of Gran Canaria and highlight the need for strengthened measures to manage this invasion. We also provide further evidence of the negative consequences of invasive snakes on island reptiles and emphasize the need for further research on this matter on islands worldwide.
Piquet, Julien C.; López-Darias, Marta
Site-selective modification of peptide backbones
The site-selective modification of peptide backbones allows an outstanding fine-tuning of peptide conformation, folding ability, and physico-chemical and biological properties. However, to achieve selectivity in the core of these biopolymers is challenging. In the last few years, many advances towards this goal have been developed. This review addresses the selective modification of Cα- and N-positions, from the use of “customizable units” to the residue-directed introduction of substituents. The site-selective modification of the peptide bond, i.e. the formation of thioamides or heterocycles, which alters backbone rigidity and ability to form hydrogen bonds or recognition by enzymes, is also described. Moreover, not only the modifications in internal backbone positions, but also in the N- and C-termini are discussed. In addition to chemical methodologies, the review addresses some reactions, catalyzed by natural or engineered enzymes, that afford unprecedent regio- and stereoselectivity in backbone modifications.
Boto, Alicia; González Martín, Concepción C.; Hernández, Dácil; Romero-Estudillo, Iván; Saavedra, Carlos J.
Relationship Between Exposure to Sulphur Dioxide Air Pollution, White Cell Inflammatory Biomarkers and Enzymatic Infarct Size in Patients With ST-segment Elevation Acute Coronary Syndromes
Aims: To analyse the relationship among air pollutants, markers of inflammation and infarct size in patients with acute coronary syndrome (ACS). Methods: This was a prospective analysis of consecutive patients admitted to hospital because of ACS. Cardiac biomarkers were drawn. The daily mean values of the air pollutants from the day before until 7 days before admission were analysed. The study population was stratified according to infarct size, based on median peak troponin value. Results: Patients were divided into two groups of 108 subjects each, according to median peak troponin value. Patients with extensive MIs had a higher neutrophil:lymphocyte ratio and leukocyte and neutrophil counts than patients with smaller MIs. In addition, they were exposed to higher concentrations of sulphur dioxide (9.7 ± 4.1 versus 8.4 ± 3.1 μg/m3 ; p=0.009) and lower concentrations of ozone (33.8 ± 13.7 versus 38.6 ± 14.5 μg/m3 ; p=0.014). Multivariate analysis showed that sulphur dioxide levels (OR 1.12; 95% CI [1.031–1.21]; p=0.007) and neutrophil/lymphocyte ratio (OR 1.08; 95% CI [1.011–1.17]; p=0.024) were independent predictors of infarct size. Conclusion: Patients with extensive MIs had higher white cell inflammatory levels and had been exposed to higher sulphur dioxide concentrations in the ambient air.
Díaz-Chirón, Laura; Negral, Luis; Megido, Laura; Suárez-Peña, Beatriz; Domínguez-Rodríguez, Alberto; Rodríguez, Sergio; Abreu-González, Pedro; Pascual, Isaac; Moris, César; Avanzas, Pablo
Intramolecular Metal-free C(sp3)-H Activation Enables a Selective Mono O-Debenzylation of Fully Protected Aminosugars
Carbamate-bearing benzylated aminosugars undergo an I2/I(III)-promoted intramolecular hydrogen atom transfer (IHAT) followed by a nucleophilic attack to provide polycyclic structures. Thus, suitably positioned benzyl ethers are surgically oxidized into the corresponding mixed N/O-benzylidene acetals, which can be conveniently deprotected under mild acidic conditions to grant access to selectively O-deprotected aminosugars amenable for further derivatization. The scope of this strategy has been proven with a battery of furanosic and pyranosic scaffolds. Preliminary mechanistic studies, including Hammett LFER and KIE analyses, support a reaction pathway with the nucleophilic cyclization as the rate-determining step.
Santana, Andrés G.; Herrera, Antonio J.; González Martín, Concepción C.
Dust and tropical PMx aerosols in Cape Verde: Sources, vertical distributions and stratified transport from North Africa
We investigated the sources and processes affecting the vertical distribution of tropical PMx aerosols (particulate matter -PM- smaller than 10, 2.5 and 1 μm, PM10, PM2.5 and PM1, respectively) in the low troposphere of Santo Antão and São Vicente islands, in Cape Verde archipelago, a region where a better understanding of aerosols is needed due to their involvement in tropical meteorology and their impact on air quality, ocean and climate. We found that local sources had a low-scale impact. From transect measurements at ground level, we found that PMx levels were predominantly low, except near to PMx sources, where distinctive PM1 / PM2.5 ratios were measured, linked to vehicle exhaust (0.96), biomass burning (0.67) and Cape Verdean dust (0.36) emissions. The depth of the marine boundary layer (MBL) and the vertical distributions of PMx showed wide variability prompted by meteorological conditions. The trade winds prevailed in the MBL, whereas other airflows were situated above it: North-Atlantic, African easterly airflow and Saharan Air Layer. Under North-Atlantic airflow conditions, the MBL extended to 1400 m above sea level (m.a.s.l.). Above this altitude, PMx concentrations decreased quickly (< 3 μg/m3) due to the free troposphere conditions. Under Saharan dust conditions, the MBL was confined to just 70 m.a.s.l., whereas a complex dust stratification was observed above, characterized by alternating dry air layers with high dust loads (PM10 ~ 100 μg/m3) and more humid air layers with lower aerosol loads (PM10 ~ 40 μg/m3). Within the dry easterly African airflow occurring above the marine stratocumulus typical of the MBL top (placed at 500 m.a.s.l.), we detected layers enriched in hydrophilic aerosols (PM10: ~ 8 μg/m3). These were imbedded in relatively humid air (RH ~48%), probably linked to secondary aerosol formation by in-cloud processes in the marine stratocumulus situated below. We found that PMx transport from North Africa, both under dust and dust-free conditions, is associated with complex vertical stratifications, even within the dusty Saharan Air Layer.
Rodríguez, Sergio; López-Darias, Jessica
Metapopulation structure modulates sexual antagonism
Despite the far-reaching evolutionary implications of sexual conflict, the effects of metapopulation structure, when populations are subdivided into several demes connected to some degree by migration, on sexual conflict dynamics are unknown. Here, we used experimental evolution in an insect model system, the seed beetle Callosobruchus maculatus, to assess the independent and interacting effects of selection histories associated with mating system (monogamy vs. polygamy) and population subdivision on sexual conflict evolution. We confirm traditional predictions from sexual conflict theory by revealing increased resistance to male harm in females from populations with a history of intense sexual selection (polygamous populations) compared to females from populations with a history of relaxed sexual selection (monogamous populations). However, selection arising from metapopulation structure reversed the classic pattern of sexually antagonistic coevolution and led to reduced resistance in females from polygamous populations. These results underscore that population spatial structure moderates sexual selection and sexual conflict, and more broadly, that the evolution of sexual conflict is contingent on ecological context. The findings also have implications for population dynamics, conservation biology, and biological control.
Rodríguez-Expósito, Eduardo; García-González, Francisco
The Bone Regeneration Capacity of BMP-2 + MMP-10 Loaded Scaffolds Depends on the Tissue Status
Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold’s slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.
García-García, Patricia; Reyes, Ricardo; Rodríguez, José Antonio; Martín, Tomás; Evora, Carmen; Díaz-Rodríguez, Patricia; Delgado, Araceli
Changes in the structure of seed dispersal networks when including interaction outcomes from both plant and animal perspectives
Interaction frequency is the most common currency in quantitative ecological networks, although interaction quality can also affect benefits provided by mutualisms. Here, we evaluate if interaction quality can modify network topology, species' role and whether such changes affect community vulnerability to species loss. We use a well-examined study system (bird–lizard and fleshy-fruited plants in the ‘thermophilous' woodland of the Canary Islands) to compare network and species-level metrics from a network based on fruit consumption rates (interaction frequency, IF), against networks reflecting functional outcomes: a seed dispersal effectiveness network (SDE) quantifying recruitment, and a fruit resource provisioning network (FRP), accounting for the nutrient supply of fruits. Nestedness decreased in the FRP and the SDE networks, due to the lack of association between fruit consumption rates and 1) nutrient content and; 2) recruitment at the seed deposition sites, respectively. The FRP network showed lower niche overlap due to resource use complementarity among frugivores. Interaction evenness was lower in the SDE network, in response to a higher dominance of lizards in the recruitment of heliophilous species. Such changes, however, did not result in enhanced vulnerability against extinctions. At the plant species level, strength changed in the FRP network in frequently consumed or highly nutritious species. The number of effective partners decreased for species whose seeds were deposited in unsuitable places for recruitment. In frugivores, strength was consistent across networks (SDE vs IF), showing that consumption rates outweighed differences in dispersal quality. In the case of lizards, the increased importance of nutrient-rich species resulted in a higher number of effective partners.
Our work shows that although frequency strongly impacts interaction effects, accounting for quality improves our inferences about interaction assembly and species role. Thus, future studies including interaction outcomes from both partners' perspectives will provide valuable insights about the net effects of mutualistic interactions.
González-Castro, Aaron; Morán-López, Teresa; Nogales, Manuel; Traveset, Anna
Acrylonitrile Derivatives against Trypanosoma cruzi: In Vitro Activity and Programmed Cell Death Study
The neglected infection known as Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, results in more than 7000 deaths per year, with an increasing number of cases in non-endemic areas such as Europe or the United States. Moreover, with the current available therapy, only two compounds which are active against the acute phase of the disease are readily available. In addition, these therapeutic agents display multiple undesired side effects such as high toxicity, they are expensive, the treatment is lengthy and the resistant strain has emerged. Therefore, there is a need to find new compounds against Chagas disease which should be active against the parasite but also cause low toxicity to the patients. In the present work, the activity of novel acrylonitriles against Trypanosoma cruzi was evaluated as well as the analysis of the physiological events induced in the treated parasites related to the cell death process. Hence, the characteristic features of an apoptosis-like process such as chromatin condensation and mitochondrial membrane potential, among others, were studied. From the 32 compounds tested against the epimastigote stage of T. cruzi, 11 were selected based on their selectivity index to determine if these compounds were able to induce programmed cell death (PCD) in the treated parasites. Furthermore, acrylonitriles Q5, Q7, Q19, Q27 and Q29 were shown to trigger physiological events related in the PCD. Therefore, this study highlights the therapeutic potential of acrylonitriles as novel trypanocidal agents.
Bethencourt-Estrella, Carlos J.; Delgado-Hernández, Samuel; López-Arencibia, Atteneri; San Nicolás-Hernández, Desirée; Sifaoui, Ines; Tejedor, David; García-Tellado, Fernando; Lorenzo-Morales, Jacob; Piñero, José E.
Dynamic Nucleophilic Aromatic Substitution of Tetrazines
A dynamic nucleophilic aromatic substitution of tetrazines (SNTz) is presented herein. It combines all the advantages of dynamic covalent chemistry with the versatility of the tetrazine moiety. Indeed, libraries of compounds or sophisticated molecular structures can be easily obtained, which are susceptible to post-functionalization by inverse electron demand Diels–Alder (IEDDA) reaction, which also locks the exchange. Additionally, the structures obtained can be disassembled upon the application of the right stimulus, either UV irradiation or a suitable chemical reagent. Moreover, SNTz is compatible with the imine chemistry of anilines. The high potential of this methodology has been proved by building two responsive supramolecular systems: A macrocycle that displays a light-induced release of acetylcholine; and a truncated [4+6] tetrahedral shape-persistent fluorescent cage, which is disassembled by thiols unless it is post-stabilized by IEDDA.
Santos, Tanausú; Rivero, David S.; Pérez-Pérez, Yaiza; Martín-Encinas, Endika; Pasán, Jorge; Hernández Daranas, Antonio; Carillo, Romen
Evaluating species origins within tropical sky-islands arthropod communities
Aim: To (a) evaluate if colonization of newly emerged high-elevation habitats occurred from neighbouring highlands (allopatric divergence and niche conservatism) or from within the same mountain (peripatric or parapatric divergence and niche shift), and (b) test for the effect of past landscape configurations in geographically structuring biodiversity (a West-East structure spanning the central part of the Transmexican Volcanic Belt).Location: Transmexican Volcanic Belt, Mexico. Taxa: Coleoptera and Araneae. Methods: Coleoptera and Araneae communities were collected in a comparative sampling framework. Seven sky-islands were sampled within two high-elevation habitats separated by altitude. Samples were individually sequenced for a region of the mtDNA COI gene to delimit Operational Taxonomic Units (OTUs) and haplotypes within them. Richness was estimated at the community level, as well as genetic diversity within and among mountains and habitats. The West East structure was tested with a null model and an analysis of variance with permutations. Results: Few OTUs were shared between the Abies forests and alpine grasslands. High beta diversity was found across mountains. Beta diversity between the West – East grouping is higher than expected by chance. Main conclusions: Our results indicate that colonization from other mountains followed by allopatric divergence dominates as a source of OTU formation, and that despite some probable connectivity during glacial periods existed, ancient communities and genetic structures persist.
Uscanga-Castillo, Adriana; López, Heriberto; Piñero, Daniel; Emerson, Brent C.; Mastretta-Yanes, Alicia
The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies
Living species are continuously subjected to all extrinsic forms of reactive oxidants and others that are produced endogenously. There is extensive literature on the generation and effects of reactive oxygen species (ROS) in biological processes, both in terms of alteration and their role in cellular signaling and regulatory pathways. Cells produce ROS as a controlled physiological process, but increasing ROS becomes pathological and leads to oxidative stress and disease. The induction of oxidative stress is an imbalance between the production of radical species and the antioxidant defense systems, which can cause damage to cellular biomolecules, including lipids, proteins and DNA. Cellular and biochemical experiments have been complemented in various ways to explain the biological chemistry of ROS oxidants. However, it is often unclear how this translates into chemical reactions involving redox changes. This review addresses this question and includes a robust mechanistic explanation of the chemical reactions of ROS and oxidative stress.
Andrés Juan, Celia; Pérez de Lastra, José Manuel; Plou Gasca, Francisco José; Pérez-Lebeña, Euardo
Biodiversity monitoring using environmental DNA
Monitoring biodiversity is essential to protect, preserve and restore ecosystems, particularly in the context of current challenges such as climate change, habitat destruction and globalization (Baird & Hajibabaei, 2012). Biomonitoring is needed for developing biotic indices for assessing ecological status, measuring impacts of anthropogenic activities in natural ecosystems, evaluating biodiversity loss, surveying nonindigenous species, conservation, and identifying cryptic species (Balvanera et al., 2006; Fišer et al., 2018). Thus, spatially and temporally structured biomonitoring activities provide a powerful tool for the implementation of regional, national and international regulations, directives and policies for nature conservation. However substantial impediments exist including access to remote locations, limited specialist taxonomic knowledge, cost, slow pace of human-driven data analyses, and typically low sensitivity for detection of rare and elusive species (Zinger et al., 2020). These drawbacks are often translated into expensive monitoring activities with limited spatial, temporal and taxonomic coverage. In this context, new approaches for biomonitoring are being explored, among which advanced DNA-based technologies are emerging (Kissling et al., 2018). The field of biodiversity monitoring through the analysis of the pool of DNA isolated from environmental samples, referred to as environmental DNA or eDNA (Pawlowski et al., 2020; Taberlet et al., 2012), is rapidly growing. This growth is being driven through improved approaches for sampling, data generation and analyses, and with recent advances on how eDNA should be interpreted for biodiversity assessments (Bohmann et al., 2014). The success of eDNA-based biomonitoring is reflected in exponential growth of publications within this area and increasing submissions to Molecular Ecology Resources in particular (Figure 1). Molecular Ecology Resources aims to publish high quality eDNA studies that serve as broad resources, including innovative methodologies for DNA sampling, enhanced laboratory protocols for data generation, or new computer programs and statistical advances for data analyses. Thus, the aim of this editorial is to contribute to producing good quality DNA data-derived essential biodiversity variables (EBVs) (Kissling et al., 2018) by providing guidance to the community submitting articles on the subject. For that purpose, we have summarized best practices established in published literature related to the different phases involved in the process, namely sampling, laboratory work, bioinformatic analyses and data interpretation (Figure 2).
Rodríguez-Ezpeleta, Naiara; Zinger, Lucie; Kinziger, Andrew; Bik, Holly M.; Bonin, Aurélie; Coissac, Eric; Emerson, Brent C. ; Martins Lopes, Carla; Pelletier, Tara A.; Taberlet, Pierre; Narum, Shawn
FLTX2: A Novel Tamoxifen Derivative Endowed with Antiestrogenic, Fluorescent, and Photosensitizer Properties
Tamoxifen is the most widely used selective modulator of estrogen receptors (SERM) and the first strategy as coadjuvant therapy for the treatment of estrogen-receptor (ER) positive breast cancer worldwide. In spite of such success, tamoxifen is not devoid of undesirable effects, the most life-threatening reported so far affecting uterine tissues. Indeed, tamoxifen treatment is discouraged in women under risk of uterine cancers. Recent molecular design efforts have endeavoured the development of tamoxifen derivatives with antiestrogen properties but lacking agonistic uterine tropism. One of this is FLTX2, formed by the covalent binding of tamoxifen as ER binding core, 7-nitrobenzofurazan (NBD) as the florescent dye, and Rose Bengal (RB) as source for reactive oxygen species. Our analyses demonstrate (1) FLTX2 is endowed with similar antiestrogen potency as tamoxifen and its predecessor FLTX1, (2) shows a strong absorption in the blue spectral range, associated to the NBD moiety, which efficiently transfers the excitation energy to RB through intramolecular FRET mechanism, (3) generates superoxide anions in a concentration- and irradiation time-dependent process, and (4) Induces concentration- and time-dependent MCF7 apoptotic cell death. These properties make FLTX2 a very promising candidate to lead a novel generation of SERMs with the endogenous capacity to promote breast tumour cell death in situ by photosensitization.
Díaz, Mario; Lobo, Fernando; Hernández, Dácil; Amesty, Ángel; Valdés-Baizabal, Catalina; Canerina-Amaro, Ana; Mesa-Herrera, Fátima; Soler, Kevin; Boto, Alicia; Marín, Raquel; Estévez-Braun, Ana; Lahoz, Fernando
Diet of the black rat (Rattus rattus) in a Canary laurel forest: species identification based on morphological markers and DNA sequences
The black rat (Rattus rattus) is an alien species that causes severe 10 impact on island ecosystems, floras and faunas. The main aim of this study was to determine the plant and animal contributions to black rat diet in a pristine misty laurel forest area on La Palma (Canary Islands). Our working hypothesis was that this rat equally consumes plants and animals (fully omnivorous animal) wherever it is intro- 15 duced, including pristine habitats. A total of 483 droppings collected from the terrain were first morphologically examined using a stereomicroscope, which showed high plant consumption (presence in 92.4% of droppings), followed by invertebrates (46.0%) and vertebrates (31.2%). DNA-based analyses revealed even higher pro- 20 portions of plants (97%) and invertebrates (79%), while fine-scale sequence searches (DNA barcoding) in the GenBank (BLAST tool) provided a preliminary identification of 44 plants and 12 invertebrate taxa. To gain more in-depth insight into plant identification, we built up a local DNA reference collection (58 species), improving accuracy 25 (30 species confirmed) compared to GenBank searches (25 species). Contingency analyses (chisquare and G-test) only showed significant differences in droppings between plant sequences and toxic plant presence. This study confirms that the black rat is here an omnivorous animal but with a strong plant diet component, including an intrigu- 30 ingly high number of toxic plants. Interestingly, despite rodents chewing on fruits and usually crushing seeds, 66 intact Rubus seeds (Rosaceae) were found in 15 droppings (3.1%). All these results suggest that black rats consume any plant types, including fruits and seeds that can be locally dispersed such as native brambles.
Pomeda-Gutiérrez, Fernando; Medina, Félix M.; Nogales, Manuel; Vargas, Pablo