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    Autobiografías drogadas : texto drogado y escritura autobiográfica en la literatura hispánica del XXI : de Levrero a Escohotado
    (Nueva Revista del Pacífico, 2024) Luque Amo, Álvaro
    RESUMEN: Este trabajo analiza obras literarias de carácter autobiográfico producidas en el ámbito hispánico y en cuyo desarrollo temático tiene relevancia la droga y la relación del autor con la sustancia. Partiendo de los estudios de Castoldi y Labrador sobre los vínculos entre literatura y droga, y los sintagmas de «texto drogado» y «literatura drogada», respectivamente, se pretende rastrear una temática arraigada en otras tradiciones literarias y que tiene una aparición reciente en el contexto hispánico. Se examinan seis obras de cinco escritores: el uruguayo Mario Levrero, los mexicanos Julián Herbert y Carlos Velázquez, así como los españoles Daniel Jiménez y Antonio Escohotado. El objetivo principal es ofrecer una panorámica amplia del surgimiento de estas «autobiografías drogadas» en la narrativa hispánica del siglo XXI.
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    Mariana Reis de Castro: contrabando e contrabandistas: Elvas na Primeira Guerra Mundial, Lisboa, Imprensa de Ciências Sociais, 2019, 243 págs.
    (Historia y política: ideas, procesos y movimientos sociales, 2021) Vaquero Martínez, Sergio
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    Gamma-irradiated janus electrospun nanofiber membranes for desalination and nuclear wastewater treatment
    (Journal of Membrane Science, 2024) Essalhi, Mohamed; Afsar, Noor Ul; Bouyer, Denis; Sundman, Ola; Holmboe, Michael; Khayet Souhaimi, Mohamed; Jonsson, Mats; Tavajohi, Naser
    This study presents the fabrication of double-layer electrospun nanofibrous membranes (DL-ENMs) using polyvinylidene fluoride (PVDF) and polyether sulfone (PES) based polymers with different degrees of hydrophilicity (PES, sulfonated PES, and PES with hydroxyl terminals). A comparative analysis was carried out with single-layer electrospun nanofiber membranes (SL-ENM) with a total thickness of about 375 mu m. Using feed solutions, including sodium chloride, sodium nitrate, and simulated nuclear wastewater (SNWW), the performance of DL-ENMs was evaluated for desalination and radionuclide decontamination by direct contact membrane distillation (DCMD) and air gap membrane distillation (AGMD) techniques. The results showed that DL-ENMs, especially those incorporating a sulfonated PES-based hydrophilic layer, exhibited superior permeate fluxes, reaching values of 72.72 kg/m(2)h and 73.27 kg/m(2)h in the DCMD using aqueous feed solutions of NaCl and NaNO3, respectively, and 70.80 kg/m(2)h and 41.96 kg/m(2)h using aqueous feed solutions of SNWW in DCMD and AGMD, respectively. Both SL-ENMs and DL-ENMs exhibited high rejection efficiencies and decontamination factors for the feed solutions (>99.9%). In addition, the prepared ENMs were exposed to gamma radiation to evaluate their applicability in real-life applications. The result of irradiation revealed the negative impact of gamma radiation on the fluorine content of PVDF which could be a critical point in using PVDF as a hydrophobic material for decontaminating nuclear wastewater by membrane distillation.
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    Ovine macrophage identity and plasticity: novel insights into CSF-driven polarization and species-specific responses
    (Frontiers in Immunology, 2025) Hecker, Yanina P.; Coronado, Montserrat; Hurtado Morillas, Clara; Arranz Solís, David; Sánchez Sánchez, Roberto; Corbí, Ángel; Ortega Mora, Luis Miguel
    Macrophages (MØs) are pivotal immune cells exhibiting significant plasticity that has been widely studied in human and murine models. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are key regulators of macrophage differentiation from monocytes. In this study, we comprehensively investigated the immunophenotypic, functional, and transcriptomic profiles of ovine MØs differentiated with GM-CSF (GM-oMØs) or M-CSF (M-oMØs) to provide a more nuanced understanding of their activation states. After 7 days, GM-oMØs displayed a smaller, more varied morphology with lower cell yields compared to the larger, uniformly amoeboid M-oMØs. Immunophenotypically, M-oMØs showed significantly higher CD163 expression, consistent with human M-MØs, while CLEC5A was uninformative for differentiation. Transcriptomic analysis, complemented by qPCR and ELISA, revealed clearly distinct profiles, with GM-oMØs exhibiting a pronounced pro-inflammatory phenotype and showing significantly higher expression of 408 genes, mostly associated with interferon and inflammatory response pathways, a feature that aligns with the functional and phenotypic characteristics of human and mouse GM-MØ. Conversely, M-oMØs displayed a regulatory and anti-inflammatory profile, marked by a significantly higher expression of IL-10 and a set of 248 genes involved in cellular homeostasis. Notably, LPS stimulation dramatically shifted the M-oMØ phenotype toward a pro-inflammatory state, unequivocally demonstrating their substantial plasticity, and mirroring human M-CSF-polarized monocytes. Our findings fundamentally challenge the prevailing M1/M2 simplification in ovine macrophage biology and provide a robust foundation for selecting appropriate in vitro macrophage models for future investigations into ovine host defense and disease pathogenesis. This study demonstrated that M-oMØs exhibit greater plasticity, making them more suitable for pathogen-host interaction studies. Unlike GM macrophages, which already have a defined phenotype, M-oMØs more accurately reflect the dynamic immune response induced by a pathogen in the host
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    Viral Distribution of Wild Boar Exposed to Low (Vaccine Candidate) and High Virulence African Swine Fever Virus Isolates: Immunohistochemical Characterization
    (Transboundary and Emerging Diseases, 2025) Porras, Néstor; Rodríguez Bertos, Antonio Manuel; Barroso Arévalo, Sandra; Kosowska, Aleksandra; Díaz De Frutos, Marta; Pablo-Moreno, Javier M. De; Sánchez-Segovia, Mónica; Barasona García-Arévalo, José Ángel
    Although several biosecurity and control measures are currently in place to mitigate the African swine fever (ASF) epidemic, vaccination is being explored as a potential long‐term strategy. However, standardized guidelines for evaluating the safety and efficacy of ASF vaccines are not yet fully established. Understanding infection dynamics in wild boar is crucial, as they play a key role in the spread and persistence of the virus. This work aims to provide comprehensive information on viral distribution through immunohistochemical analysis (p72) with histopathologic assessment in wild boar. The study design comprises animals: (i) intramuscular infected with the high‐virulence genotype II isolate Arm07 (highly virulent isolate [HVI]; n = 6); (ii) orally vaccinated with the low virulence isolate Lv17/WB/Rie1‐ΔCD (low virulent isolate [LVI]; n = 6); and (iii) orally vaccinated with Lv17/WB/Rie1‐ΔCD, either with a single dose (LVI‐HVI1; n = 6) or repeated doses (LVI‐HVI2; n = 6), followed by intramuscular challenge with Arm07. Clinical monitoring, viral load quantification in blood and tissues via real‐time quantitative PCR, and virus viability in tissue cultures using peripheral blood mononuclear cells were performed. HVI animals had hemorrhagic and inflammatory lesions, along with generalized lymphoid depletion, correlated with widespread viral dissemination. LVI animals rarely showed mild lymphoid depletion of the lymph nodes; minimal immunostaining was observed in macrophages of the tonsils and lymph nodes, typically restricted to the oral entry point. A few LVI–HVI1 cases had infected resident sinus macrophages related to necrotic lesions at tonsils and lymph nodes, preventing the virus from disseminating to vital organs. No viral immunostaining or associated histopathologic lesions were observed in LVI–HVI2 animals, indicating that revaccination enhances safety against virulent challenges. Observed changes following vaccination do not reflect chronic infection but rather a transient one, followed by lymphoid system recovery. Immunohistochemical and histological evaluation has proven valuable in advancing our understanding of ASF pathogenesis in wild boar, contributing to improved vaccination safety and disease management strategies
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    Evaluation of the safety and immunogenicity of a peptide vaccine against canine leishmaniosis: a double-blind, multicenter, controlled clinical trial in dogs
    (Veterinary Quarterly, 2025) Hurtado Morillas, Clara; Mas Zubiri, Alicia; Orden Gutiérrez, José Antonio; de Urbina-Fuentes, Laura; Blanco Gutiérrez, María Del Mar; Domínguez Bernal, Gustavo Ramón; Martínez Rodrigo, Abel
    Current vaccines for canine leishmaniosis (CanL) provide limited protection, underscoring the need for improved immunization strategies. Multi-epitope peptide vaccine delivered via nanoparticle systems represents a promising alternative but remains underexplored in canine clinical trials. Here, we report the results of a double-blind clinical trial (499/ECV) evaluating the safety and immunogenicity of HisDTC, a peptide vaccine targeting Leishmania infantum, encapsulated in poly(lactic-co-glycolic acid) PLGA nanoparticles and adjuvanted with Toll-like receptor 2 (TLR2) and TLR3 ligands. Forty healthy dogs were immunized with different vaccine formulations and monitored over 12 months. Immune responses were assessed by flow cytometry, ELISA, and in vitro macrophage infection assays, while safety was evaluated through clinical follow-up. Vaccination with HisDTC elicited a protective cellular response, including sustained IFN-γ production by CD4+ and CD8+ T cells, an IgG2a-skewed humoral response, and expansion of CD4+CD8α+ double-positive memory T cells. Notably, only HisDTC-vaccinated dogs exhibited a >80% reduction in in vitro macrophage infection, with protective effects persisting for up to 8 months post-immunization. Importantly, the formulation was well tolerated, with no adverse effects reported. These findings demonstrate that HisDTC delivered via PLGA nanoparticles induces durable, protective immunity against L. infantum in dogs and supports its further evaluation under natural exposure conditions.
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    Fluidity as a key determinant of stability in PEGylated lipid nanoparticles loaded with a TLR7 agonist
    (International Journal of Pharmaceutics, 2026) Palomino-Cano, Carmen; Mera-Delgado, M.Carmen; Pons, Ramon; Moreno, Esther; Larrea, Esther; Aguirre, Lecnia; Mamani, Elisa; Martínez-Ohárriz, M.Cristina; Irache, Juan M.; Carrión Herrero, Francisco Javier; Espuelas, Socorro
    TLR7 agonists are low molecular weight immunomodulators that can rapidly diffuse from the site of administration, often leading to undesired systemic inflammatory effects. To mitigate toxicity and broaden therapeutic applicability, imiquimod (IMQ), a widely used TLR7 agonist, was encapsulated in lipid-based nanocarriers (LNCs). A fractional factorial design (24−1) was employed to examine the influence of formulation variables—liquid lipid (LL), solid lipid (SL), lipid molar ratio, and surfactant—on particle size, encapsulation efficiency, colloidal stability, and cytotoxicity in bone marrow-derived macrophages (BMDMs) and erythrocytes. Screening indicated that LL type and SL/LL ratio were the most critical factors affecting both physicochemical and biological properties. Based on these insights, a refined study focused on C10–C18 triglycerides as SL and PEG40-stearate as surfactant, while varying LL (oleic acid or isostearic acid) at two SL/LL molar ratios (2.5:1 and 1:2.5). Structural and biophysical analyses (DSC, SAXS, DPH and Laurdan fluorescence) showed that lipid shell fluidity dictated PEG conformation at the particle surface: rigid shells promoted a hydrated brush-like PEG layer, whereas fluid shells yielded a collapsed, less stable arrangement. The optimal formulation (triglycerides: oleic acid, 2.5:1) generated nanoparticles of 45 nm with efficient IMQ encapsulation and low cytotoxicity. This system effectively reprogrammed BMDMs toward a pro-inflammatory (M1) phenotype, confirmed by gene and cytokine expression. Altogether, these results highlight the importance of formulation design and nanostructural characterization in developing nanocarrier systems that enable safer and more versatile delivery of potent immunotherapeutics such as IMQ
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    Hepatitis E virus in pigs at the moment of slaughter in Spain, 2015 and 2017
    (Food Microbiology, 2026) García Benzaquén, Nerea; Hernández, Marta; Santamaría-Palacios, Jorge; Martínez Alares, Irene; Navarro Gómez, Alejandro; Muñoz-Chimeno, Milagros; Escobar, Franco; Fongaro, Gislaine; Yeramian, Nadine; Trząskowska, Monika; Avellón, Ana; Eiros, José María; Domínguez Rodríguez, Lucas José; Valero, Antonio; Goyache Goñi, Joaquín; Rodríguez-Lázaro, David
    We investigated the presence of hepatitis E virus (HEV) in pigs at the moment of slaughter in Spain in years 2015 and 2017. A total of 1786 caecal content, liver, and serum samples from animals at slaughterhouses were tested by reverse transcription real-time quantitative PCR (RT-qPCR) and anti-HEV antibodies were evaluated in 623 serum samples by an ELISA test. The overall seroprevalence obtained was 70.9 %. A total of 398 RT-qPCR positive samples were identified in caecal content (26.8 %; 156/583), serum (21.8 %; 136/623) and liver (18.3 %; 106/580). A total of 32 RT-qPCR positive samples were genotyped; 3f (84.4 %) and the 3c (9.4 %) being the most prevalent subgenotypes. This is the first report on detection of HEV in pigs at the moment of slaughter with a Spain nation-wide representation. The data show a large high seroprevalence (70.9 %) in pigs, while the presence of the virus (HEV RNA) was significantly lower. HEV RNA detection varied markedly between matrices, with caecal samples showing higher positivity (30–50 %) than serum (5–25 %); both simple and interaction GEE models confirmed strong effects of sample type and its interaction with year on prevalence estimates. However, the percentage of positive liver samples (18.3 %) and the concurrence between the HEV 3 subtypes identified (3f, 3m and 3c) and those identified in human patients in Spain, underscores the possibility of foodborne zoonosis. It can represent a real risk for consumers if pork products are not cooked adequately. A holistic One-Health approach, including a better understanding of HEV prevalence in the swine population, would allow implementation of control measures in the meat chain to mitigate the main transmission routes for humans.
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    Characteristics of widespread extreme precipitation events in Peninsular Spain and the Balearic Islands: spatio-temporal dynamics and driving mechanisms
    (Climate Dynamics, 2025) Vicente-Serrano, Sergio M.; Garrido Pérez, José Manuel; Fernández-Álvarez, José Carlos; Gimeno-Sotelo, Luis; Beguería, Santiago; Halifa-Marín, Amar; Latorre, Borja; El Kenawy, Ahmed M.; Franquesa, Magí; Adell-Michavila, María; Domínguez-Castro, Fernando; Barriopedro Cepero, David; Gimeno-Presa, Luis; Nieto, Raquel; Azorin-Molina, Cesar; Andres-Martin, Miguel; Gutiérrez, Jose Manuel; García Herrera, Ricardo Francisco
    This study analysed widespread extreme precipitation events (WEPEs) across Spain using a high-density network of daily precipitation records, aiming to clarify their spatiotemporal trends and drivers. The findings reveal that WEPEs in Spain show a non-significant trend in either frequency or intensity since 1961, despite the prevailing trend of global warming. Nevertheless, atmospheric circulation plays a key role in shaping WEPEs in Spain, with five distinct synoptic patterns driving extreme precipitation across different regions. Westerly flows associated with Atlantic lows lead to widespread precipitation in northern and western Spain, while cut-off lows generate intense but more localized events, particularly in the east. Jet stream anomalies and moisture transport patterns, particularly from the Mediterranean and Atlantic, further modulate the spatial distribution and intensity of WEPEs, highlighting the interaction between regional and large-scale climatic drivers. These findings highlight the importance of distinguishing between widespread and localized EPEs and the associated atmospheric mechanisms.
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    A Morbillivirus Infection Shifts DC Maturation Toward a Tolerogenic Phenotype to Suppress T Cell Activation
    (Journal of Virology, 2022) Rodríguez-Martín, Daniel; García García, Isabel; Martín, Verónica; Rojas, José Manuel; Sevilla, Noemí
    Viruses have evolved numerous strategies to impair immunity so that they can replicate more efficiently. Among those, the immunosuppressive effects of morbillivirus infection can be particularly problematic, as they allow secondary infections to take hold in the host, worsening disease prognosis. In the present work, we hypothesized that the highly contagious morbillivirus peste des petits ruminants virus (PPRV) could target monocytes and dendritic cells (DC) to contribute to the immunosuppressive effects produced by the infection. Monocytes isolated from healthy sheep, a natural host of the disease, were able be infected by PPRV and this impaired the differentiation and phagocytic ability of immature monocyte-derived DC (MoDC). We also assessed PPRV capacity to infect differentiated MoDC. Ovine MoDC could be productively infected by PPRV, and this drastically reduced MoDC capacity to activate allogeneic T cell responses. Transcriptomic analysis of infected MoDC indicated that several tolerogenic DC signature genes were upregulated upon PPRV infection. Furthermore, PPRV-infected MoDC could impair the proliferative response of autologous CD4+ and CD8+ T cell to the mitogen concanavalin A (ConA), which indicated that DC targeting by the virus could promote immunosuppression. These results shed new light on the mechanisms employed by morbillivirus to suppress the host immune responses. IMPORTANCE Morbilliviruses pose a threat to global health given their high infectivity. The morbillivirus peste des petits ruminants virus (PPRV) severely affects small-ruminant-productivity and leads to important economic losses in communities that rely on these animals for subsistence. PPRV produces in the infected host a period of severe immunosuppression that opportunistic pathogens exploit, which worsens the course of the infection. The mechanisms of PPRV immunosuppression are not fully understood. In the present work, we demonstrate that PPRV can infect professional antigen-presenting cells called dendritic cells (DC) and disrupt their capacity to elicit an immune response. PPRV infection promoted a DC activation profile that favored the induction of tolerance instead of the activation of an antiviral immune response. These results shed new light on the mechanisms employed by morbilliviruses to suppress the immune responses.
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    Co-expression of environmental extremophilic genes strongly enhances Escherichia coli cross-protection to abiotic stress
    (Extremophiles, 2025) Loera, Melany Yalibeth; de Figueras, Carolina González; Sánchez Costa, Mercedes; Martínez Rodríguez, Pablo; Mirete, Salvador; Lamprecht Grandío, María; Díaz Del Toro, Silvia; González Pastor, José Eduardo; Díaz Rullo, Jorge
    Nature is home to a wide range of species that thrive in extreme conditions. Despite the identification and study of many extremophilic organisms, significant questions remain regarding the limits of life and the potential for enhancing, combining, or transferring extreme characteristics to other organisms. In previous works of our group, several genes retrieved from environmental extremophiles using functional metagenomics were shown to increase the tolerance of the model bacterium Escherichia coli towards different stress conditions. Here, we proposed to evaluate whether the rational combination of those resistance genes isolated from environmental extremophiles and involved in different molecular mechanisms enhanced the cross-protection of E. coli to extreme conditions. Data revealed that the simultaneous introduction in E. coli of environmental extremophilic resistance genes involved in protein degradation, biofilm formation, oxidative stress, and DNA protection resulted in strongly enhanced, non-additive effects, significantly increasing survival rate under perchlorate exposure, UV radiation, and low pH compared to the individual introduction of these genes. Our findings supports that the introduction of multiple resistance genes isolated from environmental extremophiles that belong to diverse biological processes of stress adaptation may be crucial for engineering of multi-resistant species of interest in biomanufacturing and astrobiology.
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    Basis of genetic adaptation to heavy metal stress in the acidophilic green alga Chlamydomonas acidophila
    (Aquatic Toxicology, 2018) Puente-Sánchez, Fernando; Díaz Del Toro, Silvia; Penacho, Vanessa; Aguilera, Angeles; Olsson, Sanna
    To better understand heavy metal tolerance in Chlamydomonas acidophila, an extremophilic green alga, we assembled its transcriptome and measured transcriptomic expression before and after Cd exposure in this and the neutrophilic model microalga Chlamydomonas reinhardtii. Genes possibly related to heavy metal tolerance and detoxification were identified and analyzed as potential key innovations that enable this species to live in an extremely acid habitat with high levels of heavy metals. In addition we provide a data set of single orthologous genes from eight green algal species as a valuable resource for comparative studies including eukaryotic extremophiles. Our results based on differential gene expression, detection of unique genes and analyses of codon usage all indicate that there are important genetic differences in C. acidophila compared to C. reinhardtii. Several efflux family proteins were identified as candidate key genes for adaptation to acid environments. This study suggests for the first time that exposure to cadmium strongly increases transposon expression in green algae, and that oil biosynthesis genes are induced in Chlamydomonas under heavy metal stress. Finally, the comparison of the transcriptomes of several acidophilic and non-acidophilic algae showed that the Chlamydomonas genus is polyphyletic and that acidophilic algae have distinctive aminoacid usage patterns.
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    Monoolein/phytantriol-enriched lipid-based nanocarriers loaded with resveratrol as topical ophthalmic vehicles: effect of PEGylation and incorporation in ophthalmic hydrogels and soft contact lenses
    (Journal of Drug Delivery Science and Technology, 2025) Faria, Maria João; Romaguera, Maria; Gonçalves, Hugo; Ribeiro, Artur; Ribeiro, Clarisse; Lira, Madalena; Real Oliveira, M. Elisabete; Carracedo Rodríguez, Juan Gonzalo; Lúcio, Marlene
    Most topical ophthalmic solutions to treat posterior eye disorders demonstrate low therapeutic bioavailability. This results in poor medical outcomes and underlines the need for innovative non-invasive approaches. In this study, lipid-based nanocarriers (LN) of dioctadecyldimethylammonium bromide (DODAB) enriched with monoolein (MO@LN) or phytantriol (PHY@LN) were loaded with resveratrol (RSV-MO@LN/-PHY@LN) and functionalized with poly(ethylene glycol)2000–distearoyl-phosphatidylethanolamine (DSPE–PEG(2000)). PEGylated RSV-MO@LN/-PHY@LN exhibited favorable physicochemical properties for prolonged interaction with the ocular surface (>+30 mV) and enhanced permeation through ocular membrane barriers (76.3–113.8 nm; <0.3 polydispersity index). They also showed high RSV encapsulation efficiencies (92.1 ± 3.7–98.1 ± 0.7 %). Moreover, PEGylated RSV-MO@LN/-PHY@LN were incorporated in ophthalmic hydrogels (HG) and soft contact lenses (CL), and their influence on the vehicle's main parameters was assessed. HG exhibited non-Newtonian pseudoplastic rheological behavior, and the transmittance remained near 90 % in HG and almost all CL. Additionally, CL were characterized regarding their refractive index, equilibrium water content, central thickness, and power profiles, and did not show clinically relevant alterations. Furthermore, CL wettability and mechanical properties were studied, and the presence of PEGylated RSV-MO@LN/-PHY@LN within CL matrix was confirmed using ATR-FTIR and fluorescence microscopy. Finally, release studies highlighted the potential of PEGylated MO@LN/PHY@LN and HG/CL to enhance RSV release and promote its continuous delivery to the ocular cavity for several hours, compared to its non-encapsulated form. Altogether, PEGylated RSV-PHY@LN, incorporated either in HG or silicone hydrogel CL, seems to be a promising and innovative delivery strategy for ophthalmic applications.
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    La huella microbiológica del "terroir"
    (La Semana Vitivinícola, 2016) Belda Aguilar, Ignacio; Zarraonaindia, Iratxe; Palacios, Antonio; Acedo, Alberto
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    Effects of landscape fragmentation at a fine scale on Mediterranean mountain grassland plant diversity
    (Ecosphere : an ESA open access journal, 2025) Sánchez-Dávila, Jesús; Gavilán García, Rosario Gloria; Sánchez Mata, Daniel Pablo De La Cruz
    European mountain grasslands are affected by abandonment and are being colo-nized by shrubs and forest. Grassland fragmentation is caused when the forest matrix grows, and surrounding grassland is split into fragments. Multiple studies have been done on grassland fragmentation but in anthropic matrices. Grassland isolation would not be a constraint for plant dispersion since the dis-tance between grassland fragments is usually short. However, when they are abandoned, the surrounding forest can change the environmental characteristics and small fragments can disappear. We studied abandoned Mediterranean mountain grasslands in an oak forest matrix. We surveyed the grassland com-munities and their soil properties in multiple fragments of different sizes and isolation distances. We classified the grassland species into different groups by habitat preference and life form and calculated the landscape fragmentation var-iables. We analyzed the effect of fragmentation on the richness of the grassland groups and communities. Results showed that the fragmentation variables did not have any effect on the grasslands, except at the extreme ends of the gradient of the vegetation succession. The smallest grasslands favored perennial and wet-ter species over annual or drier species due to wetter soil conditions and less availability of light. Annual species are more abundant in southern aspect frag-ments with drier conditions across the fragments. The lack of connectivity among fragments is not a problem for grassland communities at a fine scale. Annual and drier grassland species remain even in the smallest fragments, but their conservation requires maintaining a minimum fragment size more than it does landscape connectivity.
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    New Biomarkers in the Diagnosis and Prognosis of Dilated Cardiomyopathy: Pro-Resolving Lipids and miRNAs
    (Cells, 2025) Rafael I. Jaén; Sergio Sánchez-García; María Fernández-Velasco; Cuadrado Berrocal, Irene; Heras Polo, Beatriz De Las; Bosca Gomar, Lisardo; Prieto Chinchilla, Patricia
    Dilated cardiomyopathy is a major cause of heart failure and is one of the most common forms of cardiomyopathy worldwide. Although there has been significant progress in its clinical management, early diagnosis and precise prognosis remain challenging due to the lack of specificity in current biomarkers. As inflammation plays a key role in DCM, we determined the levels of systemic inflammatory markers and specific pro-resolving lipid mediators (SPMs) in a cohort of DCM patients. Our data show that the levels of lipoxin A4 significantly increased in DCM patients (343 + 75.1 pg/mL in controls vs. 482.2 ± 159.1 pg/mL in DCM patients), whereas the opposite was observed for resolving D1 (57.18 ± 32.68 pg/mL in controls vs. 38.55 ± 25.13 pg/mL in DCM patients). These results may indicate that SPMs could be considered new biomarkers related to the progression of this pathology. Moreover, since microRNAs (miRNAs) are also considered potential biomarkers at the molecular level, we conducted comprehensive miRNA expression profiling using a high-throughput array platform in our cohort. Of the differentially expressed miRNAs identified, we chose to focus on two that were significantly upregulated (miR378-3p and miR486-5p; more than two-folds) or downregulated (miR142-3p and miR328-3p < 20% and 40% vs. the control, respectively) in DCM patients, all of them strongly associated with inflammatory pathways. The selected miRNAs showed considerable potential as biomarkers, exhibiting statistical significance after ROC analysis. In fact, improved performance was observed when combining both miR142-3p and miR328-3p, using a LASSO regression model. However, we found no correlation between miRNAs and traditional inflammatory markers or SPMs ruling out the possibility to proposing them as combined biomarkers in this case. The heterogeneity of DCM leads to the need to identify new biomarkers that, either individually or in combination, may improve the prognosis of affected individuals. In our study, we have identified that some of the main SPMs can provide valuable information about disease progression, in addition to the combination of certain circulating miRNAs, which show promising prognostic values in our cohort. Thus, we have identified novel biomarkers that integrate inflammatory profiles with specific circulating miRNA expression patterns is an important step towards more targeted patient stratification in DCM. This approach can improve DCM diagnosis and prognosis, supporting the development of personalized treatments through a multi-parameter panel of biomarkers that can be measured in peripheral blood and used in routine clinical practice. Such a strategy can enable earlier treatment, resulting in better patient outcomes and quality of life.
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    Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn's disease
    (Nature Microbiology, 2021) Doron, Itai; Mesko, Marissa; Li, Xin V.; Kusakabe, Takato; Leonardi, Irina; Shaw, Dustin G.; Fiers, William D.; Lin, Woan-Yu; Bialt-DeCelie, Meghan; Román González, Elvira; Longman, Randy S.; Pla Alonso, Jesús; Wilson, Patrick C.; Iliev, Iliyan D.
    Secretory immunoglobulin A (sIgA) plays an important role in gut barrier protection by shaping the resident microbiota community, restricting the growth of bacterial pathogens and enhancing host protective immunity via immunological exclusion. Here, we found that a portion of the microbiota-driven sIgA response is induced by and directed towards intestinal fungi. Analysis of the human gut mycobiota bound by sIgA revealed a preference for hyphae, a fungal morphotype associated with virulence. Candida albicans was a potent inducer of IgA class-switch recombination among plasma cells, via an interaction dependent on intestinal phagocytes and hyphal programming. Characterization of sIgA affinity and polyreactivity showed that hyphae-associated virulence factors were bound by these antibodies and that sIgA influenced C. albicans morphotypes in the murine gut. Furthermore, an increase in granular hyphal morphologies in patients with Crohn's disease compared with healthy controls correlated with a decrease in antifungal sIgA antibody titre with affinity to two hyphae-associated virulence factors. Thus, in addition to its importance in gut bacterial regulation, sIgA targets the uniquely fungal phenomenon of hyphal formation. Our findings indicate that antifungal sIgA produced in the gut can play a role in regulating intestinal fungal commensalism by coating fungal morphotypes linked to virulence, thereby providing a protective mechanism that might be dysregulated in patients with Crohn's disease.
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    Global changes in synthesis rates and mRNA stabilities during adaptive responses to cell wall stress in yeast
    (Scientific Reports, 2025) García-Martínez, José; Rodríguez Peña, José Manuel; Pérez-Ortín, Jose E.; Arroyo Nombela, Francisco Javier; García Sánchez, Raúl
    Eukaryotic cells respond to stress through complex transcriptional and post-transcriptional mechanisms. While various environmental stress responses are well studied in yeast, the effects of cell wall stress, primarily mediated by the Cell Wall Integrity (CWI) pathway, on mRNA dynamics remain less understood. This study employed the Genomic Run-On (GRO) method to analyse genome-wide changes in mRNA synthesis rates and stability in Saccharomyces cerevisiae exposed to Congo Red, a cell wall stress-inducing agent. We found a moderate global decrease in mRNA levels, mainly due to reduced synthesis rates, with overall mRNA stability largely unchanged. This contrasts with other stress conditions, where altered mRNA stability plays a prominent role. Additionally, Congo Red elicited a weaker activation of environmental stress response (ESR-up) genes than other stressors. However, cluster analysis revealed that about 15% of transcripts showed significant changes in stability, a novel finding for cell wall stress. Thus, many CWI-dependent genes showed mRNA accumulation resulting from both increased synthesis and enhanced stability. We also identified genes with increased synthesis but unchanged mRNA levels, revealing post-transcriptional buffering. Finally, we uncovered novel Congo Red-responsive genes and suggested that transcription factors Met32 and Rpn4, along with RNA-binding proteins Nab2 and Hrp1, may participate in the regulation of CWI-dependent genes. These findings advance our understanding of the transcriptional and post-transcriptional control of the cell wall stress response.
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    Sexualidad marginal a través de la poesía de Catulo, Marcial y Juvenal
    (Signos históricos, 2021) Pérez Carrandi, Juan
    En este artículo se analizan algunos aspectos de las relaciones mascu-linas en la antigua Roma, a través de las obras de tres importantes poetas latinos: Catulo, Marcial y Juvenal. Por medio de estas fuentes, comprobamos que las relaciones masculinas de los romanos tendieron a ser frecuentes, si bien mayor-mente a través de esclavos, como lo prueba el monopolio del homoerotismo en la poesía representativa del periodo. En cambio, la censura moral se mantuvo constante, pero no hasta el punto de permitir una reprobación legal efectiva.