Influence of data sources and processing methods on theoretical river network quality

ABSTRACT: Stream ecosystem research and water resource management need to be considered over broad spatial scales. Moreover, the investigation of the spatial configuration and habitat characteristics of streams requires an accurate and precise spatial framework to reflect a catchment's physical reality that can successfully explain observed patterns at smaller scales. In this sense, geographic information systems represent an essential tool to satisfy the needs of researchers and managers. Specifically, theoretical river networks (TRNs) extracted from digital elevation models (DEMs) have become much more common in recent years, as they can provide a suitable spatial network and hierarchical organisation to sort out river ecosystem information from reach to catchment levels. Nevertheless, the quality of the extracted TRN depends greatly on the spatial resolution of the DEM and the methodology used in the network extraction processes. In this study, we compare the quality of 9 TRNs extracted from DEMs with different spatial resolutions ranging from regional (5 m) to national (25 m) and global scales (90 m) using the ArcHydro, Hec-GeoHMS and Netstream software packages. To achieve our goal, we compared (i) the DEM-derived slope; (ii) the spatial accuracy of the TRNs in relation to a control river network; (iii) the structure of the TRNs through analysis of the number of river segments, average river segment length and total river length by stream order, drainage density and the mean upstream slope throughout the TRN; and (iv) the ability of variables derived from TRNs to discriminate among stream types classified according to flow type and substrate composition. We demonstrated that not only DEM spatial resolution but also the DEM data source and raster creation process exert an important influence on terrain characteristics derived from DEMs and TRN properties. Moreover, TRNs extracted with NetStream generally showed better performance than those extracted with ArchHydro and HecGeoHMS. Nevertheless, river network extraction quality, DEM spatial resolution and extraction algorithms exhibit complex relationships due to the large number of interacting factors.The work described in this paper is part of a research project financed by the National Plan (2008-2011) for Research in Science & Technology of the Spanish Government (Project CTM2009-07447). The authors appreciate the valuable suggestions of anonymous reviewers that greatly improvement the document

Desarrollo de snacks a partir bienes agroalimentarios de la cuenca media del río otún

Inmersas en la cuenca media del rio Otún Risaralda – Colombia están las Escuelas Agroecológicas ECAS, con una población mayoritariamente campesina, la cual presenta un alto riesgo de vulnerabilidad en aspectos nutricionales, esta condición permite plantear estrategias alimentarias que subsanen algunos de estos requerimientos y por ende se aprovechen al máximo los recursos agroalimentarios con los que cuenta la comunidad en su entorno. En Colombia y en especial en la zona cafetera se vienen implementando políticas que permitan adquirir unos niveles fundamentales en la seguridad alimentaria de comunidades potencialmente afectadas por la dificultad en la disponibilidad, el acceso, la cantidad, la calidad e inocuidad de alimentos, dentro de esta perspectiva el objetivo del estudio se enfoca en la elaboración de un producto que pueda tener un alto valor nutricional, que sea aceptado organolépticamente por los niños y adolescentes de las ECAS, pero que a su vez permita revalorizar o repotenciar los bienes agroalimentarios autóctonos de la zona de estudio, en el marco de los productos agrícolas reconocidos por los campesinos se destacaron 3 después de los análisis bromatológicos y microbiológicos: el maíz, la yuca y el fríjol petaco; estos presentaron un valor nutricional significativo; con ellos se desarrolló una alternativa gastronómica tipo Snacks dulces (galletas), utilizando mezclas de 2 de los 3 bienes escogidos en proporciones 25% - 75%, 50% -50% y 75%- 25% (frijol-maíz y frijol-yuca) en cada uno de los ensayos realizados. El proyecto se basa en una investigación aplicada implementado una metodología exploratoria y descriptiva la cual consta de un enfoque mixto (cualitativo – cuantitativo). Los análisis y la recolección de los datos, permitieron obtener los siguientes resultados: los mejores productos para la elaboración del Snack son frijol-yuca (25% - 75%) y frijol-maíz (25%-75%), dadas las condiciones nutrimentales de los componentes, organolépticamente la mezcla mejor aceptada fue frijol-yuca (25%-75%)

Response to Bile Salts in Clinical Strains of Acinetobacter baumannii Lacking the AdeABC Efflux Pump: Virulence Associated with Quorum Sensing

Introduction:Acinetobacter baumannii is an opportunistic nosocomial pathogen associated with multiple infections. This pathogen usually colonizes (first stage of microbial infection) host tissues that are in contact with the external environment. As one of the sites of entry in human hosts is the gastrointestinal tract, the pathogen must be capable of tolerating bile salts. However, studies analyzing the molecular characteristics involved in the response to bile salts in clinical strains of A. baumannii are scarce.Material and Methods: Microbiological and transcriptional studies (arrays and RT-PCR) in the response to bile salts were carried out in isogenic (A. baumanni ΔadeB ATCC 17978 and A. baumannii ΔadeL ATCC 17978) and clinical strains from clone ST79/PFGE-HUI-1 which is characterized by lacking the AdeABC efflux pump and by overexpression the AdeFGH efflux pump.Results and Discussion: In presence of bile salts, in addition to the glutamate/aspartate transporter were found overexpressed in A. baumannii ΔadeB ATCC 17978, the virulence factors (surface motility, biofilm, and Type VI Secretion System) which are associated with activation of the Quorum Sensing system. Overexpression of these factors was confirmed in clinical strains of clone ST79/PFGE-HUI-1.Conclusions: This the first study about the adaptive response to bile salts investigating the molecular and microbiological characteristics in response to bile salts of an isogenic model of A. baumannii ATCC 17978 and clinical isolates of A. baumannii (clinical strains of ST79/PFGE-HUI-1) lacking the main RND efflux pump (AdeABC). Clinical isolates of A. baumannii lacking the AdeABC efflux pump (clone ST79/PFGE-HUI-1) displayed a new clinical profile (increased invasiveness) possibly associated with the response to stress conditions (such as the presence of bile salts)

Genetic variation of cork oak a tool for improving regeneration of cork oak woodlands

The European Academies' Science Advisory Council (2017) reports that the Mediterranean forest is already being affected by climate change (IPCC, 2014) and cork oak woodlands are particularly vulnerable to high-end climate scenarios that go above the Paris Agreement 2° C increase in temperature. Since longer, more frequent, and more intense drought periods are expected, stress caused by the expansion of arid and semi-arid climate will affect the species distribution. Consequently, not only established stands may be prone to tree mortality, but also the current reforestation effort may be jeopardized by low survival rates attributed to the use of unsuitable genetic material. It is expected that, through genetic adaptation and/or phenotypic plasticity, cork oak populations may have developed significant differences in fitness and the traits related to it. In this context, provenance and progeny trials are the best resource of material to assess the variability between and within populations from seed sources sampled in a wide range of locations (stands) covering the geographical distribution of the species. Profiting from the multi-locality provenance and progeny trials belonging to a Network, established in 1998, in the initiative frame of FAIR I CT 0202 for the evaluation of genetic resources of cork oak for appropriate use in breeding and gene conservation strategies”, where 35 cork oak populations covering all the natural distribution area are represented. The provenance trials that where set up in different countries are entering now the age of first debarking and this should allow to have first data about the influence of genetics on production by different site qualities. INCREDIBLE project should document this knowledgeFAIR I CT 0202info:eu-repo/semantics/publishedVersio

Assessment of Multilocus Sequence Analysis (MLSA) for Identification of Candidatus Liberibacter Solanacearum from Different Host Plants in Spain

[EN] Liberibacteris a bacterial group causing different diseases and disorders in plants. Among liberibacters,CandidatusLiberibacter solanaceraum (CLso) produces disorders in several species mainly within Apiaceae and Solanaceae families. CLso isolates are usually grouped in defined haplotypes according to single nucleotide polymorphisms in genes associated with ribosomal elements. In order to characterize more precisely isolates of CLso identified in potato in Spain, a Multilocus Sequence Analysis (MLSA) was applied. This methodology was validated by a complete analysis of ten housekeeping genes that showed an absence of positive selection and a nearly neutral mechanism for their evolution. Most of the analysis performed with single housekeeping genes, as well as MLSA, grouped together isolates of CLso detected in potato crops in Spain within the haplotype E, undistinguishable from those infecting carrots, parsnips or celery. Moreover, the information from these housekeeping genes was used to estimate the evolutionary divergence among the different CLso by using the concatenated sequences of the genes assayed. Data obtained on the divergence among CLso haplotypes support the hypothesis of evolutionary events connected with different hosts, in different geographic areas, and possibly associated with different vectors. Our results demonstrate the absence in Spain of CLso isolates molecularly classified as haplotypes A and B, traditionally considered causal agents of zebra chip in potato, as well as the uncertain possibility of the present haplotype to produce major disease outbreaks in potato that may depend on many factors that should be further evaluated in future worksThis research was funded by Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria (INIA), grant numbers AT2016-007 and RTA2014-00008-C04-03-E, co-financed by FEDER.Ruiz-Padilla, A.; Redondo, C.; Asensio, A.; Garita-Cambronero, J.; Martinez, C.; Perez-Padilla, V.; Marquinez, R.... (2020). Assessment of Multilocus Sequence Analysis (MLSA) for Identification of Candidatus Liberibacter Solanacearum from Different Host Plants in Spain. Microorganisms. 8(9):1-19. https://doi.org/10.3390/microorganisms8091446S11989Haapalainen, M. (2014). Biology and epidemics ofCandidatusLiberibacter species, psyllid-transmitted plant-pathogenic bacteria. Annals of Applied Biology, 165(2), 172-198. doi:10.1111/aab.12149Raddadi, N., Gonella, E., Camerota, C., Pizzinat, A., Tedeschi, R., Crotti, E., … Alma, A. (2010). ‘Candidatus Liberibacter europaeus’ sp. nov. that is associated with and transmitted by the psyllid Cacopsylla pyri apparently behaves as an endophyte rather than a pathogen. Environmental Microbiology, 13(2), 414-426. doi:10.1111/j.1462-2920.2010.02347.xWang, N., Pierson, E. A., Setubal, J. C., Xu, J., Levy, J. G., Zhang, Y., … Martins, J. (2017). The Candidatus Liberibacter–Host Interface: Insights into Pathogenesis Mechanisms and Disease Control. Annual Review of Phytopathology, 55(1), 451-482. doi:10.1146/annurev-phyto-080516-035513Morris, J., Shiller, J., Mann, R., Smith, G., Yen, A., & Rodoni, B. (2017). Novel ‘Candidatus Liberibacter’ species identified in the Australian eggplant psyllid, Acizzia solanicola. Microbial Biotechnology, 10(4), 833-844. doi:10.1111/1751-7915.12707Alfaro-Fernández, A., Hernández-Llopis, D., & Font, M. I. (2017). Haplotypes of ‘Candidatus Liberibacter solanacearum’ identified in Umbeliferous crops in Spain. European Journal of Plant Pathology, 149(1), 127-131. doi:10.1007/s10658-017-1172-2Haapalainen, M., Wang, J., Latvala, S., Lehtonen, M. T., Pirhonen, M., & Nissinen, A. I. (2018). Genetic Variation of ‘Candidatus Liberibacter solanacearum’ Haplotype C and Identification of a Novel Haplotype from Trioza urticae and Stinging Nettle. Phytopathology®, 108(8), 925-934. doi:10.1094/phyto-12-17-0410-rHaapalainen, M., Latvala, S., Wickström, A., Wang, J., Pirhonen, M., & Nissinen, A. I. (2019). A novel haplotype of ‘Candidatus Liberibacter solanacearum’ found in Apiaceae and Polygonaceae family plants. European Journal of Plant Pathology, 156(2), 413-423. doi:10.1007/s10658-019-01890-0Mauck, K. E., Sun, P., Meduri, V. R., & Hansen, A. K. (2019). New Ca. 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Identification of a New Haplotype of ‘CandidatusLiberibacter solanacearum’ inSolanum tuberosum. Plant Disease, 103(3), 468-474. doi:10.1094/pdis-06-18-0937-reLin, H., Lou, B., Glynn, J. M., Doddapaneni, H., Civerolo, E. L., Chen, C., … Vahling, C. M. (2011). The Complete Genome Sequence of ‘Candidatus Liberibacter solanacearum’, the Bacterium Associated with Potato Zebra Chip Disease. PLoS ONE, 6(4), e19135. doi:10.1371/journal.pone.0019135Thompson, S. M., Johnson, C. P., Lu, A. Y., Frampton, R. A., Sullivan, K. L., Fiers, M. W. E. J., … Smith, G. R. (2015). Genomes of ‘Candidatus Liberibacter solanacearum’ Haplotype A from New Zealand and the United States Suggest Significant Genome Plasticity in the Species. Phytopathology®, 105(7), 863-871. doi:10.1094/phyto-12-14-0363-fiLin, H., Pietersen, G., Han, C., Read, D. A., Lou, B., Gupta, G., & Civerolo, E. L. (2015). Complete Genome Sequence of « Candidatus Liberibacter africanus,» a Bacterium Associated with Citrus Huanglongbing. Genome Announcements, 3(4). doi:10.1128/genomea.00733-15Wulff, N. A., Zhang, S., Setubal, J. C., Almeida, N. F., Martins, E. C., Harakava, R., … Gabriel, D. W. (2014). The Complete Genome Sequence of ‘Candidatus Liberibacter americanus’, Associated with Citrus Huanglongbing. Molecular Plant-Microbe Interactions®, 27(2), 163-176. doi:10.1094/mpmi-09-13-0292-rDuan, Y., Zhou, L., Hall, D. G., Li, W., Doddapaneni, H., Lin, H., … Gottwald, T. (2009). Complete Genome Sequence of Citrus Huanglongbing Bacterium, ‘CandidatusLiberibacter asiaticus’ Obtained Through Metagenomics. Molecular Plant-Microbe Interactions®, 22(8), 1011-1020. doi:10.1094/mpmi-22-8-1011Katoh, H., Miyata, S., Inoue, H., & Iwanami, T. (2014). Unique Features of a Japanese ‘Candidatus Liberibacter asiaticus’ Strain Revealed by Whole Genome Sequencing. PLoS ONE, 9(9), e106109. doi:10.1371/journal.pone.0106109Leonard, M. T., Fagen, J. R., Davis-Richardson, A. G., Davis, M. J., & Triplett, E. W. (2012). Complete genome sequence of Liberibacter crescens BT-1. Standards in Genomic Sciences, 7(2), 271-283. doi:10.4056/sigs.3326772Teresani, G. R., Bertolini, E., Alfaro-Fernández, A., Martínez, C., Tanaka, F. A. O., Kitajima, E. W., … Font, M. I. (2014). Association of ‘Candidatus Liberibacter solanacearum’ with a Vegetative Disorder of Celery in Spain and Development of a Real-Time PCR Method for Its Detection. Phytopathology®, 104(8), 804-811. doi:10.1094/phyto-07-13-0182-rLi, W., Hartung, J. S., & Levy, L. (2006). Quantitative real-time PCR for detection and identification of Candidatus Liberibacter species associated with citrus huanglongbing. Journal of Microbiological Methods, 66(1), 104-115. doi:10.1016/j.mimet.2005.10.018Munyaneza, J. E., Sengoda, V. G., Crosslin, J. M., De la Rosa-Lozano, G., & Sanchez, A. (2009). First Report of ‘Candidatus Liberibacter psyllaurous’ in Potato Tubers with Zebra Chip Disease in Mexico. Plant Disease, 93(5), 552-552. doi:10.1094/pdis-93-5-0552aPhillips, J. L., & Gnanakaran, S. (2014). A data-driven approach to modeling the tripartite structure of multidrug resistance efflux pumps. Proteins: Structure, Function, and Bioinformatics, 83(1), 46-65. doi:10.1002/prot.24632Kumar, S., Stecher, G., Li, M., Knyaz, C., & Tamura, K. (2018). MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Molecular Biology and Evolution, 35(6), 1547-1549. doi:10.1093/molbev/msy096Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. (1993). Molecular Biology and Evolution. doi:10.1093/oxfordjournals.molbev.a040023Rozas, J., Ferrer-Mata, A., Sánchez-DelBarrio, J. C., Guirao-Rico, S., Librado, P., Ramos-Onsins, S. E., & Sánchez-Gracia, A. (2017). DnaSP 6: DNA Sequence Polymorphism Analysis of Large Data Sets. Molecular Biology and Evolution, 34(12), 3299-3302. doi:10.1093/molbev/msx248Liao, J., Wiedmann, M., & Kovac, J. (2017). Genetic Stability and Evolution of the sigB Allele, Used for Listeria Sensu Stricto Subtyping and Phylogenetic Inference. Applied and Environmental Microbiology, 83(12). doi:10.1128/aem.00306-17Tamura, K., Battistuzzi, F. U., Billing-Ross, P., Murillo, O., Filipski, A., & Kumar, S. (2012). Estimating divergence times in large molecular phylogenies. Proceedings of the National Academy of Sciences, 109(47), 19333-19338. doi:10.1073/pnas.1213199109Tamura, K., Tao, Q., & Kumar, S. (2018). Theoretical Foundation of the RelTime Method for Estimating Divergence Times from Variable Evolutionary Rates. Molecular Biology and Evolution, 35(7), 1770-1782. doi:10.1093/molbev/msy044López-Hermoso, C., de la Haba, R. R., Sánchez-Porro, C., Papke, R. T., & Ventosa, A. (2017). Assessment of MultiLocus Sequence Analysis As a Valuable Tool for the Classification of the Genus Salinivibrio. Frontiers in Microbiology, 8. doi:10.3389/fmicb.2017.01107Hajri, A., Loiseau, M., Cousseau-Suhard, P., Renaudin, I., & Gentit, P. (2017). Genetic Characterization of ‘Candidatus Liberibacter solanacearum’ Haplotypes Associated with Apiaceous Crops in France. Plant Disease, 101(8), 1383-1390. doi:10.1094/pdis-11-16-1686-reFang, Y., Wang, Y., Liu, Z., Dai, H., Cai, H., Li, Z., … Wang, D. (2019). Multilocus Sequence Analysis, a Rapid and Accurate Tool for Taxonomic Classification, Evolutionary Relationship Determination, and Population Biology Studies of the Genus Shewanella. Applied and Environmental Microbiology, 85(11). doi:10.1128/aem.03126-18Konstantinidis, K. T., Ramette, A., & Tiedje, J. M. (2006). Toward a More Robust Assessment of IntraspeciesDiversity, Using Fewer GeneticMarkers. Applied and Environmental Microbiology, 72(11), 7286-7293. doi:10.1128/aem.01398-06Ajene, I. J., Khamis, F., Ballo, S., Pietersen, G., van Asch, B., Seid, N., … Mohamed, S. (2020). Detection of Asian Citrus Psyllid (Hemiptera: Psyllidae) in Ethiopia: A New Haplotype and its Implication to the Proliferation of Huanglongbing. Journal of Economic Entomology, 113(4), 1640-1647. doi:10.1093/jee/toaa113Thapa, S. P., De Francesco, A., Trinh, J., Gurung, F. B., Pang, Z., Vidalakis, G., … Coaker, G. (2020). Genome‐wide analyses of Liberibacter species provides insights into evolution, phylogenetic relationships, and virulence factors. Molecular Plant Pathology, 21(5), 716-731. doi:10.1111/mpp.12925Antolinez, C. A., Fereres, A., & Moreno, A. (2017). Risk assessment of ‘Candidatus Liberibacter solanacearum’ transmission by the psyllids Bactericera trigonica and B. tremblayi from Apiaceae crops to potato. 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The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study

Background: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU. Methods: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group. Results: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). Kaplan‒Meier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways. Conclusions: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.11 página

Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine

BACKGROUND: The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. RESULTS: Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. CONCLUSIONS: We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles.This study was supported by grants FIS PI050265, FIS PI040503, FIS PI070291, FIS Intrasalud 080752, FIS PS09/01297, FIS PI10/02984, SAF2006-26667-E, FIT 09-010-205-9, FIPSE 36780/08, Fundación Mútua Madrileña, TRA-094, EC10-153, ISCIII-RETIC RD06/0006, HIVACAT–HIV Development Program in Catalonia, FIPSE 36630/07, UE Program Health 2009 CHAARM. Spanish Health Institute Carlos III (ISCIII) and the Health Department of the Catalan Government (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S