Cancer is a complex disease that, despite advances in treatment and the greater understanding of the tumor biology until today, continues to be a prevalent and lethal disease. Chemotherapy, ...radiotherapy, and surgery are the conventional treatments, which have increased the survival for cancer patients. However, the complexity of this disease together with the persistent problems due to tumor progression and recurrence, drug resistance, or side effects of therapy make it necessary to explore new strategies that address the challenges to obtain a positive response. One important point is that tumor cells can interact with the microenvironment, promoting proliferation, dissemination, and immune evasion. Therefore, immunotherapy has emerged as a novel therapy based on the modulation of the immune system for combating cancer, as reflected in the promising results both in preclinical studies and clinical trials obtained. In order to enhance the immune response, the combination of immunotherapy with nanoparticles has been conducted, improving the access of immune cells to the tumor, antigen presentation, as well as the induction of persistent immune responses. Therefore, nanomedicine holds an enormous potential to enhance the efficacy of cancer immunotherapy. Here, we review the most recent advances in specific molecular and cellular immunotherapy and in nano-immunotherapy against cancer in the light of the latest published preclinical studies and clinical trials.
Mediterranean coastal aquatic ecosystems are heterogeneous systems covering a wide range of hydrological characteristics. Differences in the hydrological pattern determine the nutrient dynamics and ...microbial community composition of these habitats. We analysed the composition of the microbial community composition and the factors affecting the predominance of autotrophic (A) or heterotrophic (H) microorganisms in 17 coastal water bodies of the Empordà and Baix Ter wetlands (NE Iberian Peninsula) during mid-summer under severe drought conditions. We sampled three types of water bodies with differences in their water residence time: 6 isolated euhaline basins, 8 oligohaline basins and the estuaries of the three rivers that flood into the area. Our aim was to determine if differences exist in the microbial community structure in Mediterranean coastal water bodies with different residence time under conditions of severe drought or, on the other hand, if the lack of flooding during the summer makes isolated, choked and leaky ecosystems more similar. Isolated basins showed higher values than estuaries for temperature, conductivity and the proportion of nutrients in organic forms. Regarding microbial community composition, microphytoplankton (mainly dinoflagellates) dominated in isolated lagoons, while picoplankton dominated in estuaries. We found no significant differences between oligohaline basins and both estuaries and isolated basins for either physical and chemical variables or microbial community composition. Only the proportion between autotrophic and heterotrophic organisms was lower in oligohaline basins than in isolated ones. We conclude that the estuaries of rivers with measurable flow during the summer differ from lagoons long isolated from any surface water input; similarities that we expected to find between leaky and isolated ecosystems under drought conditions arise in only oligohaline waters with intermediate residence times.
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•Demographic trends resulted relevant for all the ecosystem services (ES) evaluated.•Contrasting ES supply due to land-use and population between natural highlands vs. agricultural ...lowlands.•Depopulation and rewilding increased regulating ES such as water regulation and soil retention in highlands.•Despite depopulation, agricultural intensification boosted food production in fertile accessible lowlands.•The response of provisioning and regulating ES to depopulation should be considered in rural land management.
Despite the exponential increase in human population at global scale, some rural areas have experienced a progressive abandonment over the last decades. Under particular socioecological and policy contexts, changes in demography may promote land-use changes and, consequently, alter ecosystem services (ES) supply. However, most studies on this topic have targeted urban population increase, whereas depopulation has been rarely addressed. Here, we examined how shifts in demographic variables (human population, population density, and number of villages) affect provisioning (water supply, food and biomass production) and regulating (soil retention, water and nutrient regulation) ES in Mediterranean rural areas with contrasting environmental, socioeconomic and land-use contexts. When depopulation results in underuse of socio-ecological systems, we expected a decrease of provisioning and an increase of regulating ES, whereas we expected the opposite pattern when it results in land-use intensification. To test this hypothesis, we compared demographic data and ES estimated with Soil and Water Assessment Tool (SWAT) linked to land-use changes between the 1950s and 2000s in three rural areas of Aragón (NE Spain). Generalized Additive Mixed Models and Linear Mixed-Effect Models were used to analyze demographic trends, ES changes and the relationship between them.
We found severe depopulation (−42% inhabitants) and associated land-use changes in the three areas, which was particularly evident in isolated mountainous zones (−63% inhabitants). Depopulation trends significantly affected land use and, consequently, all of the ES evaluated. In mountainous depopulated areas, land abandonment and rewilding resulted in the increase in water regulation (>1000%) and soil retention (>400%). In contrast, agriculture was intensified in more fertile and easy-to-access lowland areas, boosting the food production service (>600%). Accordingly, the interactions among depopulation, crop production and regulating ES should be considered in the management schemes and policies targeting rural areas for a balanced and sustainable supply of ES in the long term.
Feeding of the different developmental stages of Calanipeda aquaedulcis on natural particles (bacterio-, phyto- and microzooplankton) was measured in a Mediterranean salt marsh (Emporda wetlands, NE ...Iberian Peninsula). Bottle incubations were performed in the field both in autumn and spring. The results showed differences in the diet of the different developmental stages due to both prey type and size. In general, the size of the ingested prey increased with increasing size of the C. aquaedulcis stage. While C. aquaedulcis adults had high ingestion rates and selection coefficients for large prey (micro- and nanoplankton), nauplii preferentially consumed smaller prey items (picoplankton). Copepodites showed the widest prey size range, including pico-, nano- and microplankton. Nevertheless, the lower size limit for particle capture was similar for all stages, i.e. between 1.7 and 2.1 mum. Omnivory was observed in all stages of C. aquaedulcis. Heterotrophic prey (picoplankton, dinoflagellates and ciliates) were the most ingested items. The ability to partition the available food among the different developmental stages could represent an advantage in times of food scarcity because it may reduce intraspecific competition. This may explain how C. aquaedulcis is able to predominate in the zooplankton community for several weeks during spring and summer even in situations of low food availability.
Coastal wetlands, as transient links from terrestrial to marine environments, are important for nitrogen removal by denitrification. Denitrification strongly depends on both the presence of emergent ...plants and the denitrifier communities selected by different plant species. In this study, the effects of vegetation and habitat heterogeneity on the community of denitrifying bacteria were investigated in nine coastal wetlands in two preserved areas of Spain. Sampling locations were selected to cover a range of salinity (0.81 to 31.3 mS/cm) and nitrate concentrations (0.1 to 303 μM NO3-), allowing the evaluation of environmental variables that select for denitrifier communities in the rhizosphere of Phragmites sp., Ruppia sp., and Paspalum sp. Potential nitrate reduction rates were found to be dependent on the sampling time and plant species and related to the denitrifier community structure, which was assessed by terminal restriction fragment length polymorphism analysis of the functional genes nirS, nirK and nosZ. The results showed that denitrifier community structure was also governed by plant species and salinity, with significant influences of other variables, such as sampling time and location. Ruppia sp. and Phragmites sp. selected for certain communities, whereas this was not the case for Paspalum sp. The plant species effect was strongest on nirK-type denitrifiers, whereas water carbon content was a significant factor defining the structure of the nosZ-harboring community. The differences recognized using the three functional gene markers indicated that different drivers act on denitrifying populations capable of complete denitrification, compared to the overall denitrifier community. This finding may have implications for emissions of the greenhouse gas nitrous oxide.
In this study, performed in Mediterranean brackish ponds during spring season, we assessed the effects of biotic interactions and abiotic factors on the size and taxonomic structure of the ...phytoplankton and zooplankton. We used a taxonomic and a size diversity index as a descriptor of the community structure. We predicted that the size diversity of each trophic level would be mainly related to biotic interactions, such as size-based fish predation (in the case of zooplankton) and food resource availability (in the case of phytoplankton), whereas taxonomic diversity would be more affected by abiotic variables (e.g., conductivity, pond morphology). Our results showed a negative relationship between phytoplankton size diversity and food resource availability leading to low size diversities under food scarcity due to dominance of small species. Conductivity also negatively affected the phytoplankton size diversity, although slightly. Regarding zooplankton size diversity, none of predictors tested seemed to influence this index. Similar fish size diversities among ponds may prevent a significant effect of fish predation on size diversity of zooplankton. As expected, taxonomic diversity of phytoplankton and zooplankton was related to abiotic variables (specifically pond morphometry) rather than biotic interactions, which are usually body size dependent, especially in these species-poor brackish environments.
We investigated the composition of the microbial food web in the marshland of Doñana National Park (SW Spain). We analysed factors affecting the predominance of autotrophic (A) or heterotrophic (H) ...microorganisms in a set of 16 marshland water bodies that differ in their hydrological pattern. Autotrophic organisms were predominant in the Doñana marshland, with autotrophs between 0.3 and 25.3 times higher than heterotrophs in biomass. The variance partitioning analysis using the log A:H biomass ratio (A/H) as a response variable revealed that water body spatial position accounted for the largest portion of total variance (16% of unique effects), followed by environmental variables (13%), with a shared variation of 24%. Zooplankton biomass had no significant influence on A/H ratio. The two first axes of RDA analysis were related to soluble reactive phosphate (SRP) and dissolved inorganic nitrogen (DIN) concentrations respectively. Cyanobacteria were predominant in waters with high SRP, while other organisms were distributed in relation to DIN by their size, with small organisms predominating with low DIN and large ones with high DIN. Spatial effects reflect the importance of location with respect to the water source in this marshland, where flooding areas are very much dominated by autotrophs, while confined areas, which are a long way from nutrient sources, have a more balanced abundance of autotrophs and heterotrophs.
A method for the measurement of the size diversity based on the classical Shannon–Wiener expression was proposed as a proxy of the shape of the size distribution. The summatory of probabilities of a ...discrete variable (such as species relative abundances) in the original Shannon–Wiener expression was substituted by an integral of the probability density function of a continuous variable (such as body size). Here, we propose an update of this method by including the measurement of the size e‐evenness, just dividing the exponential of the size diversity by its possible maximum for a given size range. Assuming a domain of the size range of (0,∞), for a given logarithmic mean (
mln) and a logarithmic standard deviation
(σln), the distribution with the highest diversity is the Log‐Normal. The size e‐evenness ranges between 0 and 1 because of the division by the maximum exponential diversity. Size e‐evenness is useful to discriminate whether variations in size diversity are due to changes in the shape of the size distribution or caused by differences in size dispersion.
Mediterranean wetland communities are strongly constrained by hydrological perturbations and the water flow regime. Salinity and nutrient availability have often been considered the most important ...variables determining changes in the phytoplankton community of coastal wetlands. Ratios between the main environmental variables often have more relevance than the absolute values of each variable; however, in most cases ratios are not suitable for use in multivariate models commonly used by limnologists. The main objective of the present work was to identify the main variables or variable ratios that are the driving forces of the major phytoplankton taxonomic groups in Mediterranean coastal wetlands, using compositional data analysis techniques (CoDa). With this aim, eleven shallow wetlands (6 in Empordà, 5 in Doñana, NE and SW of Spain respectively) were sampled in winter and spring 2007. Two approaches were used: the first one using raw data and the second one using CoDa techniques to transform data. Our results show that differences in hydrological patterns led to three main community assemblages, ranging from communities dominated by typical marine taxa (diatoms and dinoflagellates) when the marine influence was high, to communities dominated by cyanobacteria during confinement and when inorganic nitrogen was scarce. In freshwaters with a high turnover rate, the community was dominated by opportunistic chlorophytes and cryptophytes that need inorganic nitrogen availability. When the raw data and CoDa approaches were compared, the CoDa approach permitted a better ecological interpretation of the phytoplankton community and the main ecological processes. Salinity was the main environmental determinant with both approaches, while the second CoDa RDA axis was related with the balance between the peptidase and phosphatase enzyme activities, confirming the relevance of nutrient retrieval processes in determining phytoplankton composition. We recommend the use of CoDa techniques for analyses of planktonic communities, such as the one presented here, in order to improve the interpretation of both existing and future datasets.
•CoDa analysis is based on a system of principles which prevent the inconsistency of results.•CoDa techniques facilitate the inclusion of ecologically relevant variable ratios.•The use of CoDa allows a more complete understanding of phytoplankton functioning.•Salinity and nutrient availability are the main factors driving phytoplankton communities.•The nutrient imbalance control is both supported by nutrient and enzyme activity ratios.
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