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Abstract Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric “RCR-complex”. We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called “R78C”, combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial.

Study region: The study uses 78 groundwater head time series across 10 European countries with various geological and hydrological settings. Study focus: The estimation of groundwater recharge using time series analysis and lumped modelling based on groundwater head time series is a low-cost and practical method. However, lumped recharge estimation models based on groundwater level variations are uncertain, and successful applications are known to depend on both climate and hydrogeological setting. Here, we assess the suitability of three different models to estimate recharge (Metran - Transfer Function-Noise model, AquiMod - groundwater level driven hydrological model, and GARDÉNIA - lumped catchment model). New hydrological insights: Results showed that while all three models generally did well during the modelling of groundwater heads, the resulting recharge estimations from the models were different. The analysis showed that the transfer-noise modelling of groundwater heads with recharge and evapotranspiration in Metran is not generally applicable for recharge estimation. The addition of physical information in AquiMod improved the recharge estimations, but the reliability was still limited without control of the water balance due to non-uniqueness. By adding discharge information to the modelling, GARDÉNIA can provide more reliable recharge values. Thus, recharge estimation from groundwater head time series without water balance information must be considered uncertain with low precision, but applicability can be improved when including knowledge of the local system.

Antibodies can have synergistic effects, but mechanisms are not well understood. Here, Ragotte et al. identify three antibodies that bind neighbouring epitopes on CyRPA, a malaria vaccine candidate, and show that lateral interactions between the antibodies slow dissociation and inhibit parasite growth synergistically.

The protection of groundwater resources in coastal aquifers is an increasingly important issue worldwide. To establish threshold values and remediation objectives, it is essential to know the natural background concentrations of relevant ions in groundwater. The rationale is to define the Natural Background Level (NBL) of chemical species determined by atmospheric and lithological forces. In many coastal aquifers, this evaluation worsens since atmospheric and lithological salinity combines with many other anthropogenic sources of salinity, including exogenous salinity induced by seawater intrusion (SWI). This paper presents a combination of six well-known statistical techniques and a new methodology (i.e., SITE index) in eight GWBs affected by SWI in Eastern Spain. The chloride ion was the selected conservative chemical specie to assess the qualitative status due to the variable SWI affection. The Natural Chloride Background (NCB) obtained from these methodologies at the GWB scale was compared with regional NCB data calculated with the Atmospheric Chloride Mass Balance (CMB) method in Continental Spain. The CMB method provides atmospherically derived NCB data that are not influenced by SWI or anthropogenic activities or lithological forces. This external evaluation can be considered the atmospheric fraction of NCB, which serves as a regional criterion to validate the more detailed statistical methodologies applied at the GWB scale. As a result, a conceptualization of NCB is obtained by means of a range of values between 115 mg L−1 and 261 mg L−1 in the studied coastal GWBs affected by SWI in Eastern Spain.

BackgroundRH5 is the leading vaccine candidate for the Plasmodium falciparum blood stage and has shown impact on parasite growth in the blood in a human clinical trial. RH5 binds to Ripr and CyRPA at the apical end of the invasive merozoite form, and this complex, designated RCR, is essential for entry into human erythrocytes. RH5 has advanced to human clinical trials, and the impact on parasite growth in the blood was encouraging but modest. This study assessed the potential of a protein-in-adjuvant blood stage malaria vaccine based on a combination of RH5, Ripr and CyRPA to provide improved neutralizing activity against P. falciparum in vitro.MethodsMice were immunized with the individual RCR antigens to down select the best performing adjuvant formulation and rats were immunized with the individual RCR antigens to select the correct antigen dose. A second cohort of rats were immunized with single, double and triple antigen combinations to assess immunogenicity and parasite neutralizing activity in growth inhibition assays.ResultsThe DPX® platform was identified as the best performing formulation in potentiating P. falciparum inhibitory antibody responses to these antigens. The three antigens derived from RH5, Ripr and CyRPA proteins formulated with DPX induced highly inhibitory parasite neutralising antibodies. Notably, RH5 either as a single antigen or in combination with Ripr and/or CyRPA, induced inhibitory antibodies that outperformed CyRPA, Ripr.ConclusionAn RCR combination vaccine may not induce substantially improved protective immunity as compared with RH5 as a single immunogen in a clinical setting and leaves the development pathway open for other antigens to be combined with RH5 as a next generation malaria vaccine.

Background Although recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, cases of coinfection with Streptococcus pneumoniae in patients with coronavirus disease 2019 (COVID-19) during hospitalization have been reported infrequently. This apparent contradiction may be explained by interactions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pneumococci in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses.Methods Here, we investigated the relationship of these 2 respiratory pathogens in 2 distinct cohorts of health care workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and patients with moderate to severe disease who presented to the hospital. We assessed the effect of coinfection on host antibody, cellular, and inflammatory responses to the virus.Results In both cohorts, pneumococcal colonization was associated with diminished antiviral immune responses, which primarily affected mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients.Conclusion Our findings suggest that S. pneumoniae impair host immunity to SARS-CoV-2 and raise the question of whether pneumococcal carriage also enables immune escape of other respiratory viruses and facilitates reinfection.Trial registration ISRCTN89159899 (FASTER study) and ClinicalTrials.gov NCT03502291 (LAIV study).

Summary: Background: There is an ongoing global effort to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations in key proteins. Methods: In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine (AZD2816) which expresses the spike protein of the Beta VoC (B.1.351). Findings: We demonstrate that AZD2816 is immunogenic after a single dose. When AZD2816 is used as a booster dose in animals primed with a vaccine encoding the original spike protein (ChAdOx1 nCoV-19/ [AZD1222]), an increase in binding and neutralising antibodies against Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) is observed following each additional dose. In addition, a strong and polyfunctional T cell response was measured all booster regimens. Interpretation: Real world data is demonstrating that one or more doses of licensed SARS-CoV-2 vaccines confer reduced protection against hospitalisation and deaths caused by divergent VoC, including Omicron. Our data support the ongoing clinical development and testing of booster vaccines to increase immunity against highly mutated VoC. Funding: This research was funded by AstraZeneca with supporting funds from MRC and BBSRC.

A significant number of investigations highlight that parents possess a great potential to influence positively or negatively the sport experience of their children. It is necessary to emphasize that they can also perform an astonishing number of inappropriate behaviours during the course of their sons’ sport events. In this investigation, the management, pressure, comprehension and active participation comments performed by parents in grassroots football matches have been analysed through the systematic observation. Twelve teams have been observed which belong to the 2nd division league of U-15 in the Balearic Islands (Spain) during 2016-17 season through 12 recordings. These comments were coded by trained observers using LINCE® recording software and POISE (Parents’ Observation Instrument at Sport Events) (Kidman and McKenzie, 1996). The results show that neutral comments are the most notorious followed by positives and negatives. In conclusion, it must be mentioned that the relevance of this study is double: (1) It provides objective data about comments done by parents-spectators during the matches of their children; (2) it adds necessary information to carry out a systematic observation of parents and spectators in grassroots sport from the grandstands.

Reducing the mortality and morbidity associated with COVID-19 remains a global health priority. Vaccines have proven highly effective at preventing infection and hospitalization, but efforts must continue to improve treatment options for those who still become seriously ill.

Aquifers are ubiquitous, and their water is easy to obtain with low extraction costs. On many occasions, these characteristics lead to overexploitation due to important water level declines, reduction of river base flows, enhanced seawater intrusion, and wetland affection. The forecasted increase in water demands and global warming will impact the future availability of water resources. Conjunctive use of surface and subsurface waters can help in mitigating these impacts. There are two main conjunctive use strategies: artificial recharge (AR) and alternate conjunctive use (ACU). AR stores waters that are not to be used directly in aquifers. ACU utilizes groundwater in dry periods, while surface waters are preferred in wet ones; this allows the increase of water supply with lower dam storage, economic gains, and environmental advantages. Efficient conjunctive use can prevent soil salinization and waterlogging problems in semiarid countries due to excessive recharge from irrigation return flows or other origins. Groundwater is a neglected and generally misused resource to maintain environmental conditions. When considering the solution to a water resources problem, groundwater should always be part of the design as an alternative or a complementary resource. Aquifers have large inertia, and changes in their volumes are only noticeable after years of observations. Unfortunately, groundwater observation networks are much poorer than surface ones, something that should be changed if groundwater is to come to the rescue in these times of climate change. Human and material resources should be made available to monitor, control, analyze, and forecast groundwater.

Climate change is expected to increase the occurrence of droughts, with the hydrology in alpine systems being largely determined by snow dynamics. In this paper, we propose a methodology to assess the impact of climate change on both meteorological and hydrological droughts, taking into account the dynamics of the snow cover area (SCA). We also analyze the correlation between these types of droughts. We generated ensembles of local climate scenarios based on regional climate models (RCMs) representative of potential future conditions. We considered several sources of uncertainty: different historical climate databases, simulations obtained with several RCMs, and some statistical downscaling techniques. We then used a stochastic weather generator (SWG) to generate multiple climatic series preserving the characteristics of the ensemble scenario. These were simulated within a cellular automata (CA) model to generate multiple SCA future series. They were used to calculate multiple series of meteorological drought indices, the Standardized Precipitation Index (SPI), Standardized Precipitation Evapotranspiration Index (SPEI), and a novel hydrological drought index (Standardized Snow Cover Index (SSCI)). Linear correlation analysis was applied to both types of drought to analyze how they propagate and the time delay between them. We applied the proposed methodology to the Sierra Nevada (southern Spain), where we estimated a general increase in meteorological and hydrological drought magnitude and duration for the horizon 2071–2100 under the RCP 8.5 emission scenario. The SCA droughts also revealed a significant increase in drought intensity. The meteorological drought propagation to SCA droughts was reflected in an immediate or short time (1 month), obtaining significant correlations in lower accumulation periods of drought indices (3 and 6 months). This allowed us to obtain information about meteorological drought from SCA deficits and vice versa.

Satellites produce valuable information for studying the surface water in wetlands, but in many cases the period covered, the spatial resolution and/or the revisit frequency is not enough to produce long historical series. In this paper we propose a novel method which uses regression models that include climatic and hydrological variables to complete the satellite information. We used this method in the Lagunas de Ruidera wetland (Spain). We approached the monthly dynamic of the surface water for a long period (1984–2015). Information from LANDSAT (30-m resolution) and MODIS (250-m resolution) satellites were tested but, due to the size of some lagoons, only the LANDSAT approach produced satisfactory results. An ensemble of regression models based on hydro-climatological explanatory variables was defined to complete the gaps in the monthly surface water. It showed a root mean squared error of around 476 pixels (0.4 Km2) in the cross-validation analysis. Our analysis showed that the explanatory variables with a more significant participation in the regression ensemble are the aquifer discharge, the effective precipitation and the surface water from the previous month. From January to June, the mean surface water in Lagunas de Ruidera is around 4.3 Km2. In summer a reduction of around 13% of the surface water can be observed, which is recovered during the autumn.

The development of novel treatment against tuberculosis is a priority global health challenge. Antimicrobial proteins and peptides offer a multifaceted mechanism suitable to fight bacterial resistance. Within the RNaseA superfamily there is a group of highly cationic proteins secreted by innate immune cells with anti-infective and immune-regulatory properties. In this work, we have tested the human canonical members of the RNase family using a spot-culture growth inhibition assay based mycobacteria-infected macrophage model for evaluating their anti-tubercular properties. Out of the seven tested recombinant human RNases, we have identified two members, RNase3 and RNase6, which were highly effective against Mycobacterium aurum extra- and intracellularly and induced an autophagy process. We observed the proteins internalization within macrophages and their capacity to eradicate the intracellular mycobacterial infection at a low micro-molar range. Contribution of the enzymatic activity was discarded by site-directed mutagenesis at the RNase catalytic site. The protein induction of autophagy was analyzed by RT-qPCR, western blot, immunofluorescence, and electron microscopy. Specific blockage of auto-phagosome formation and maturation reduced the protein's ability to eradicate the infection. In addition, we found that the M. aurum infection of human THP1 macrophages modulates the expression of endogenous RNase3 and RNase6, suggesting a function in vivo. Overall, our data anticipate a biological role for human antimicrobial RNases in host response to mycobacterial infections and set the basis for the design of novel anti-tubercular drugs.

An assessment of the risk for groundwater pollution and vulnerability to pumping can help identify strategic groundwater bodies to define sustainable management measures of groundwater resources. In this paper, we propose a new method to make a preliminary estimation of the risk for groundwater pollution at the aquifer scale through the lumped turnover time index (T index). A new lumped index (L-RISK index) was defined to assess the significance of the risk for pollution at the aquifer scale. Both L-RISK and T indices were employed to calibrate a linear regression model that showed a good inverse correlation in the eight aquifers of the Upper Guadiana Basin (Spain). This novel method can be applied to analyze a wide range of aquifers with limited information in order to identify potential strategic aquifers. It also allows one to make a preliminary assessment of the impacts of climate change on L-RISK. The results showed a high variability of the T index in the eight aquifers (8–76 years). Three of them had significant greater mean T values, which could be considered to be the main strategic groundwater resources. In the future, the T index will increase between 8 and 44%, and the L-RISK will decrease in all aquifers (1–18%).

The evaluation of aquifer recharge is essential to make a quantitative evaluation of renewable groundwater resources required to implement proper water policies aimed at maintaining stream–aquifer interactions, guaranteeing water supply to human activities, and preserving groundwater-dependent ecosystems at different spatial and temporal scales and climate conditions [...]

There is necessity of considering air temperature to simulate the hydrology and management within water resources systems. In many cases, a big issue is considering the scarcity of data due to poor accessibility and limited funds. This paper proposes a methodology to obtain high resolution air temperature fields by combining scarce point measurements with elevation data and land surface temperature (LST) data from remote sensing. The available station data (SNOTEL stations) are sparse at Rocky Mountain National Park, necessitating the inclusion of correlated and well-sampled variables to assess the spatial variability of air temperature. Different geostatistical approaches and weighted solutions thereof were employed to obtain air temperature fields. These estimates were compared with two relatively direct solutions, the LST (MODIS) and a lapse rate-based interpolation technique. The methodology was evaluated using data from different seasons. The performance of the techniques was assessed through a cross validation experiment. In both cases, the weighted kriging with external drift solution (considering LST and elevation) showed the best results, with a mean squared error of 3.7 and 3.6 °C2 for the application and validation, respectively.

The management of droughts is a challenging issue, especially in water scarcity areas, where this problem will be exacerbated in the future. The aim of this paper is to identify potential groundwater (GW) bodies with reduced vulnerability to pumping, which can be used as buffer values to define sustainable conjunctive use management during droughts. Assuming that the long term natural mean reserves are maintained, a preliminary assessment of GW vulnerability can be obtained by using the natural turnover time (T) index, defined in each GW body as the storage capacity (S) divided by the recharge (R). Aquifers where R is close to S are extremely vulnerable to exploitation. This approach will be applied in the 146 Spanish GW bodies at risk of not achieving the Water Framework Directive (WFD objectives, to maintain a good quantitative status. The analyses will be focused on the impacts of the climate drivers on the mean T value for Historical and potential future scenarios, assuming that the Land Use and Land Cover (LULC) changes and the management strategies will allow maintenance of the long term mean natural GW body reserves. Around 26.9% of these GW bodies show low vulnerability to pumping, when viewing historical T values over 100 years, this percentage growing to 33.1% in near future horizon values (until 2045). The results show a significant heterogeneity. The range of variability for the historical T values is around 3700 years, which also increases in the near future to 4200 years. These T indices will change in future horizons, and, therefore, the potential of GW resources to undergo sustainable strategies to adapt to climate change will also change accordingly, making it necessary to apply adaptive management strategies.

The DRASTIC (D: Depth to water; R: Net recharge; A: Aquifer media; S: Soil media; T: Topography; I: Impact of vadose zone; C: Hydraulic conductivity) index is usually applied to assess intrinsic vulnerability in detrital and carbonate aquifers, although it does not take into account the particularities of karst systems as the COP (C: Concentration of flow; O: Overlying layers above water table; P: precipitation) method does. In this paper we aim to find a reasonable correspondence between the vulnerability maps obtained using these two methods. We adapt the DRASTIC index in order to obtain reliable assessments in carbonate aquifers while maintaining its original conceptual formulation. This approach is analogous to the hypothesis of “equivalent porous medium”, which applies to karstic aquifers the numerical solution developed for detrital aquifers. We applied our novel method to the Upper Guadiana Basin, which contains both carbonate and detrital aquifers. Validation analysis demonstrated a higher confidence in the vulnerability assessment provided by the COP method in the carbonate aquifers. The proposed method solves an optimization problem to minimize the differences between the assessments provided by the modified DRASTIC and COP methods. Decision trees and spatial statistics analyses were combined to identify the ranges and weights of DRASTIC parameters to produce an optimal solution that matches the COP vulnerability classification for carbonate aquifers in 75% of the area, while maintaining a reliable assessment of the detrital aquifers in the Basin.

Gauges modify wind fields, producing important systematic errors (undercatching) in the measurement of solid precipitation (Ps), especially under windy conditions. A methodology that combines geostatistical techniques and hydrological models to perform a preliminary assessment of global undercatch and precipitation patterns in alpine regions is proposed. An assessment of temperature and precipitation fields is performed by applying geostatistical approaches assuming different hypothesis about the relationship between climatic fields and altitude. Several experiments using different approximations of climatic fields in different approaches to a hydrological model are evaluated. A new hydrological model, the Snow-Témez Model (STM), is developed including two parameters to correct the solid (Cs) and liquid precipitation (Cr). The procedure allows identifying the best combination of geostatistical approach and hydrological model for estimating streamflow in the Canales Basin, an alpine catchment of the Sierra Nevada (Spain). The sensitivity of the results to the correction of the precipitation fields is analyzed, revealing that the results of the streamflow simulation are improved when the precipitation is corrected considerably. High values of solid Cs are obtained, while Cr values, although smaller than the solid one, are also significant.

In this work, we developed a new method to assess the impact of climate change (CC) scenarios on land subsidence related to groundwater level depletion in detrital aquifers. The main goal of this work was to propose a parsimonious approach that could be applied for any case study. We also evaluated the methodology in a case study, the Vega de Granada aquifer (southern Spain). Historical subsidence rates were estimated using remote sensing techniques (differential interferometric synthetic aperture radar, DInSAR). Local CC scenarios were generated by applying a bias correction approach. An equifeasible ensemble of the generated projections from different climatic models was also proposed. A simple water balance approach was applied to assess CC impacts on lumped global drawdowns due to future potential rainfall recharge and pumping. CC impacts were propagated to drawdowns within piezometers by applying the global delta change observed with the lumped assessment. Regression models were employed to estimate the impacts of these drawdowns in terms of land subsidence, as well as to analyze the influence of the fine-grained material in the aquifer. The results showed that a more linear behavior was observed for the cases with lower percentage of fine-grained material. The mean increase of the maximum subsidence rates in the considered wells for the future horizon (2016−2045) and the Representative Concentration Pathway (RCP) scenario 8.5 was 54%. The main advantage of the proposed method is its applicability in cases with limited information. It is also appropriate for the study of wide areas to identify potential hot spots where more exhaustive analyses should be performed. The method will allow sustainable adaptation strategies in vulnerable areas during drought-critical periods to be assessed.

Tuberculosis (TB) continues to be a devastating infectious disease and remerges as a global health emergency due to an alarming rise of antimicrobial resistance to its treatment. Despite of the serious effort that has been applied to develop effective antitubercular chemotherapies, the potential of antimicrobial peptides (AMPs) remains underexploited. A large amount of literature is now accessible on the AMP mechanisms of action against a diversity of pathogens; nevertheless, research on their activity on mycobacteria is still scarce. In particular, there is an urgent need to integrate all available interdisciplinary strategies to eradicate extensively drug-resistant Mycobacterium tuberculosis strains. In this context, we should not underestimate our endogenous antimicrobial proteins and peptides as ancient players of the human host defense system. We are confident that novel antibiotics based on human AMPs displaying a rapid and multifaceted mechanism, with reduced toxicity, should significantly contribute to reverse the tide of antimycobacterial drug resistance. In this review, we have provided an up to date perspective of the current research on AMPs to be applied in the fight against TB. A better understanding on the mechanisms of action of human endogenous peptides should ensure the basis for the best guided design of novel antitubercular chemotherapeutics.

Candida albicans is a polymorphic fungus responsible for mucosal and skin infections. Candida cells establish themselves into biofilm communities resistant to most currently available antifungal agents. An increase of severe infections ensuing in fungal septic shock in elderly or immunosuppressed patients, along with the emergence of drug-resistant strains, urge the need for the development of alternative antifungal agents. In the search for novel antifungal drugs our laboratory demonstrated that two human ribonucleases from the vertebrate-specific RNaseA superfamily, hRNase3 and hRNase7, display a high anticandidal activity. In a previous work, we proved that the N-terminal region of the RNases was sufficient to reproduce most of the parental protein bactericidal activity. Next, we explored their potency against a fungal pathogen. Here, we have tested the N-terminal derived peptides that correspond to the eight human canonical RNases (RN1-8) against planktonic cells and biofilms of C. albicans. RN3 and RN7 peptides displayed the most potent inhibitory effect with a mechanism of action characterized by cell-wall binding, membrane permeabilization and biofilm eradication activities. Both peptides are able to eradicate planktonic and sessile cells, and to alter their gene expression, reinforcing its role as a lead candidate to develop novel antifungal and antibiofilm therapies.

Los esquistos de moscovita-cloritoide representan el metamorfi smo en bajo grado, facies esquisto verde, de sedimentos pelíticos en facies anfi bolita alta con relativas raras ocurrencias en la Cordillera Central de los Andes del Norte. Este litotipo se ha encontrado intercalado con metabasitas y migmatitas en facies anfi bolita alta de edad Triásica expuestas en los alrededores de El Retiro, Antioquia, han sido reportadas rocas en facies granulita. En este trabajo, se hace un análisis petrográfico detallado y de química mineral de estos esquistos expuestos en la región de El Retiro, con la intención de aplicar el geotermómetro cloritoide-clorita y entender las condiciones metamórfi cas e implicaciones geotectónica. Mediante la aplicación de este geotermómetro se obtuvieron temperaturas en el intervalo entre 520 y 600°C mostrando que esta asociación es estable en el bajo grado metamórfi co y que puede ser transicional para la facies anfi bolita, en su porción de más baja temperatura. En términos evolutivos, los datos obtenidos muestran que estas segmentos de esquistos de más bajo grado representan zonas de cizallamiento sobreimpuestas al metamorfi smo de alto grado expuesto en esta región. Al reconstruir la trayectoria retrograda regional de esta unidad metamórfi ca incluyendo resultados previamente publicados y aquellos incluidos en este trabajo, es posible sugerir que la generación de zonas de cizallamiento de más baja temperatura representan el proceso continuo de exhumación de las rocas estudiadas, pudiento dentro del contexto regional refl ejar el conjunto de rocas metamórfi cas de la región el segmento extensional que siguió a un orogeno colisional a ca. 230 Ma o la evolución de una zona de subducción con un importante componente extensional.

The objective of this paper is to investigate different methods to generate future potential climatic scenarios at monthly scale considering meteorological droughts. We assume that more reliable scenarios would be generated by using regional climatic models (RCMs) and statistical correction techniques that produce better approximations to the historical basic and drought statistics. A multi-objective analysis is proposed to identify the inferior approaches. Different ensembles (equifeasible and non-equifeasible) solutions are analysed, identifying their pros and cons. A sensitivity analysis of the method to spatial scale is also performed. The proposed methodology is applied in an alpine basin, the Alto Genil (southern Spain). The method requires historical climatic information and simulations provided by multiple RCMs (9 RCMs are considered in the proposed application) for a future period, assuming a potential emission scenario. We generate future series by applying two conceptual approaches, bias correction and delta change, using five statistical transformation techniques for each. The application shows that the method allows improvement of the definition of local climate scenarios from the RCM simulation considering drought statistics. The sensitivity of the results to the applied approach is analysed.

The availability of precipitation data is the key driver in the application of hydrological models when simulating streamflow. Ground weather stations are regularly used to measure precipitation. However, spatial coverage is often limited in low-population areas and mountain areas. To overcome this limitation, gridded datasets from remote sensing have been widely used. This study evaluates four widely used global precipitation datasets (GPDs): The Tropical Rainfall Measuring Mission (TRMM) 3B43, the Climate Forecast System Reanalysis (CFSR), the Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks (PERSIANN), and the Multi-Source Weighted-Ensemble Precipitation (MSWEP), against point gauge and gridded dataset observations using multiple monthly water balance models (MWBMs) in four different meso-scale basins that cover the main climatic zones of Peninsular Spain. The volumes of precipitation obtained from the GPDs tend to be smaller than those from the gauged data. Results underscore the superiority of the national gridded dataset, although the TRMM provides satisfactory results in simulating streamflow, reaching similar Nash-Sutcliffe values, between 0.70 and 0.95, and an average total volume error of 12% when using the GR2M model. The performance of GPDs highly depends on the climate, so that the more humid the watershed is, the better results can be achieved. The procedures used can be applied in regions with similar case studies to more accurately assess the resources within a system in which there is scarcity of recorded data available.

Streamflow data are of prime importance to water-resources planning and management, and the accuracy of their estimation is very important for decision making. The Soil and Water Assessment Tool (SWAT) and Artificial Neural Network (ANN) models have been evaluated and compared to find a method to improve streamflow estimation. For a more complete evaluation, the accuracy and ability of these streamflow estimation models was also established separately based on their performance during different periods of flows using regional flow duration curves (FDCs). Specifically, the FDCs were divided into five sectors: very low, low, medium, high and very high flow. This segmentation of flow allows analysis of the model performance for every important discharge event precisely. In this study, the models were applied in two catchments in Peninsular Spain with contrasting climatic conditions: Atlantic and Mediterranean climates. The results indicate that SWAT and ANNs were generally good tools in daily streamflow modelling. However, SWAT was found to be more successful in relation to better simulation of lower flows, while ANNs were superior at estimating higher flows in all cases.

The design of hydraulic structures and flood risk management is often based on instantaneous peak flow (IPF). However, available flow time series with high temporal resolution are scarce and of limited length. A correct estimation of the IPF is crucial to reducing the consequences derived from flash floods, especially in Mediterranean countries. In this study, empirical methods to estimate the IPF based on maximum mean daily flow (MMDF), artificial neural networks (ANN), and adaptive neuro-fuzzy inference system (ANFIS) have been compared. These methods have been applied in 14 different streamflow gauge stations covering the diversity of flashiness conditions found in Peninsular Spain. Root-mean-square error (RMSE), and coefficient of determination (R2) have been used as evaluation criteria. The results show that: (1) the Fuller equation and its regionalization is more accurate and has lower error compared with other empirical methods; and (2) ANFIS has demonstrated a superior ability to estimate IPF compared to any empirical formula.

Human Ribonuclease 6 is a secreted protein belonging to the ribonuclease A (RNaseA) superfamily, a vertebrate specific family suggested to arise with an ancestral host defense role. Tissue distribution analysis revealed its expression in innate cell types, showing abundance in monocytes and neutrophils. Recent evidence of induction of the protein expression by bacterial infection suggested an antipathogen function in vivo. In our laboratory, the antimicrobial properties of the protein have been evaluated against Gram-negative and Gram-positive species and its mechanism of action was characterized using a membrane model. Interestingly, our results indicate that RNase6, as previously reported for RNase3, is able to specifically agglutinate Gram-negative bacteria as a main trait of its antimicrobial activity. Moreover, a side by side comparative analysis with the RN6(1–45) derived peptide highlights that the antimicrobial activity is mostly retained at the protein N-terminus. Further work by site directed mutagenesis and structural analysis has identified two residues involved in the protein antimicrobial action (Trp1 and Ile13) that are essential for the cell agglutination properties. This is the first structure-functional characterization of RNase6 antimicrobial properties, supporting its contribution to the infection focus clearance.

Antimicrobial proteins and peptides (AMPs) are important effectors of the innate immune system that play a vital role in the prevention of infections. Recent advances have highlighted the similarity between AMPs and amyloid proteins. Using the Eosinophil Cationic Protein as a model, we have rationalized the structure-activity relationships between amyloid aggregation and antimicrobial activity. Our results show how protein aggregation can induce bacteria agglutination and cell death. Using confocal and total internal reflection fluorescence microscopy we have tracked the formation in situ of protein amyloid-like aggregates at the bacteria surface and on membrane models. In both cases, fibrillar aggregates able to bind to amyloid diagnostic dyes were detected. Additionally, a single point mutation (Ile13 to Ala) can suppress the protein amyloid behavior, abolishing the agglutinating activity and impairing the antimicrobial action. The mutant is also defective in triggering both leakage and lipid vesicle aggregation. We conclude that ECP aggregation at the bacterial surface is essential for its cytotoxicity. Hence, we propose here a new prospective biological function for amyloid-like aggregates with potential biological relevance.