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The long 5′ UTR of nrdAB modulates mRNA levels, stability, and virulence in Pseudomonas aeruginosa PAO1
(Nature Publishing Group, 2025-12-01) Martínez Mateos, Ángela; Rubio Canalejas, Alba; Pedraz López, Lucas; Torrents Serra, Eduard
The class Ia ribonucleotide reductase (RNR), encoded by the nrdAB operon in Pseudomonas aeruginosa, has a long 5’ untranslated region (5’ UTR) whose regulatory role remains poorly understood. In this study, we investigated the functional significance of the nrdAB 5’ UTR using a comprehensive set of bioinformatic and experimental approaches, including gene expression profiling, relative protein levels, and in vivo infection assays in the Galleria mellonella animal model. Our results demonstrate that the 5’ UTR negatively regulates nrdA expression by reducing transcript levels, decreasing mRNA stability and limiting protein abundance. Truncation of this region led to increased expression, particularly during the stationary phase, suggesting that this region may contribute to modulating RNR activity during the stationary phase, when dNTP demand is reduced. In vivo, the Δ5’ UTR mutant exhibited reduced virulence compared to the wild-type strain, accompanied by elevated nrdA mRNA levels and a modest decrease in nrdJ expression. Although these changes may contribute to altered RNR regulation during infection, they are unlikely to fully explain the observed phenotype, indicating that additional factors may be involved. Although no specific regulatory elements within or acting upon the 5’ UTR were probed under the tested conditions, the possibility of such mechanisms cannot be excluded, and further studies will be needed to elucidate the underlying molecular mechanisms. Overall, our findings demonstrate that the 5’ UTR plays a regulatory role in modulating nrdAB operon expression and contributes to maintaining RNR system homeostasis in P. aeruginosa.
Biofilm formation of Tenacibaculum maritimum, a fish pathogenic bacteria, to evaluate the antimicrobial activity of fish skin mucus
(Frontiers Media, 2025-10-13) Tejero, Marc; Sanahuja Piera, Ignasi; Balsalobre Parra, Carlos; Ibarz i Valls, Antoni; Madrid Xufré, Cristina; Fernández-Alacid, Laura
Biofilms, defined as aggregates of microorganisms embedded in a self-produced matrix of extracellular polymeric substances (EPS), are formed by most bacteria in both natural and pathogenic ecosystems. In aquaculture, biofilms pose a dual challenge: they confer recalcitrance to antimicrobials treatments and contribute to persistent infections by forming on facility surfaces such as tanks, nets, cages, and equipment. Tenacibaculum maritimum, the causative agent of tenacibaculosis, is responsible for significant economic losses in fish farming. Although the antibacterial activity of fish skin mucus against this pathogen has been evaluated in vitro, its effects on T. maritimum biofilms have not yet been determined. In this study, we provide a simple methodology for the in vitro formation and quantification of T. maritimum biofilms to monitor antibacterial properties of different compounds or substances, such as fish skin mucus. For this purpose, biofilm formation was assessed under varying culture volumes (200, 300, and 400 µL) and incubation times (24, 48, and 72 hours) in 48-well microplates. Then, the effects of gilthead seabream (Sparus aurata) skin mucus were evaluated on planktonic growth, biofilm formation, and biofilm dispersion, measuring both biomass and metabolic activity. Based on the tested volumes and incubation times, the optimal condition for biofilm formation was defined as 24 hours in MB at 25 ºC using 200 µL culture volume. These conditions supported the development of a biofilm (OD570>1.5 after crystal violet staining) while conserving time and mucus. Seabream mucus significantly impaired T. maritimum planktonic growth and biofilm formation in a concentration-dependent manner. Non-diluted mucus completely inhibited planktonic growth and biofilm metabolic activity, and reduced biofilm biomass by 81.16 ± 2.54%. In contrast, its effect on mature biofilms was limited, with reductions of approximately 50% in metabolic activity and 40% in biomass. This study provides a platform to assess how different fish culture conditions affect the host’s susceptibility to T. maritimum infections, which is crucial for preventing economic losses in fish farming. Additionally, it opens the door to studies analyzing the components of fish skin mucus responsible for its antibacterial activity, aiming to develop novel therapeutic compounds for targeting biofilms formed by this pathogen.
Optimized alveolar epithelial cell model for chronic Pseudomonas aeruginosa and Staphylococcus aureus coinfections
(Elsevier, 2025-11-21) Admella, Joana; Alcàcer Almansa, Júlia; Julian, Esther; Torrents Serra, Eduard
Pseudomonas aeruginosa is a relevant pathogen in chronic respiratory infections, which are usually associated with biofilm formation, complicating in vitro modeling and effective treatment strategies. While P. aeruginosa can coexist with several microorganisms, its association with Staphylococcus aureus is widespread in cystic fibrosis (CF) patients and other bronchiectasis. Finding a reliable and straightforward in vitro model to study long-term P. aeruginosa infections is extremely hard due to the secretion of highly virulent toxins that compromise the model within less than 10 h. Several optimizations, including the use of bovine serum albumin (BSA) and extracellular matrix proteins, led to enhanced A549 cell viability up to 30 h post-infection. Within this time frame, we developed P. aeruginosa biofilms, explored host-pathogen interactions, and delved deeper into the relationship between P. aeruginosa and S. aureus. Additionally, ciprofloxacin treatment was evaluated, revealing changes and differences in antibiotic susceptibility and underlying significant differences between bacterial strains
Characterizing decision-making and reward processing in bipolar disorder: A cluster analysis
(Elsevier B.V., 2018-07) Jiménez Martínez, Ester; Solé Cabezuelo, Brisa; Arias Sampériz, Bárbara; Mitjans Niubó, Marina; Varo, Cristina; Reinares, María; Bonnín Roig, Caterina del Mar; Salagre Muñoz, Estela; Ruíz, Victoria; Torres, Imma; Tomioka, Yoko; Sáiz Martínez, Pilar Alejandra; García-Portilla González, María Paz, 1962-; Burón, Patricia; Bobes García, Julio; Martínez-Arán, Anabel, 1971-; Torrent Font, Carla; Vieta i Pascual, Eduard, 1963-; Benabarre, Antonio
The presence of abnormalities in emotional decision-making and reward processing among bipolar patients (BP) has been well rehearsed. These disturbances are not limited to acute phases and are common even during remission. In recent years, the existence of discrete cognitive profiles in this psychiatric population has been replicated. However, emotional decision making and reward processing domains have barely been studied. Therefore, our aim was to explore the existence of different profiles on the aforementioned cognitive dimensions in BP. The sample consisted of 126 euthymic BP. Main sociodemographic, clinical, functioning, and neurocognitive variables were gathered. A hierarchical-clustering technique was used to identify discrete neurocognitive profiles based on the performance in the Iowa Gambling Task. Afterward, the resulting clusters were compared using ANOVA or Chi-squared Test, as appropriate. Evidence for the existence of three different profiles was provided. Cluster 1 was mainly characterized by poor decision ability. Cluster 2 presented the lowest sensitivity to punishment. Finally, cluster 3 presented the best decision-making ability and the highest levels of punishment sensitivity. Comparison between the three clusters indicated that cluster 2 was the most functionally impaired group. The poorest outcomes in attention, executive function domains, and social cognition were also observed within the same group. In conclusion, similarly to that observed in "cold cognitive" domains, our results suggest the existence of three discrete cognitive profiles concerning emotional decision making and reward processing. Amongst all the indexes explored, low punishment sensitivity emerge as a potential correlate of poorer cognitive and functional outcomes in bipolar disorder.
The hepatocyte traffic network in the human hepatitis A virus biological cyclefrom an evolutionary perspective
(Springer Nature, 2025-06-12) Carcereny, Albert; Arrebola, Alba; Chavarria Miró, Gemma; Castellarnau Serra, Montserrat de; Fuentes Pardo, Cristina; García-Pedemonte, David; Martínez-Velázquez, Adán; Ribes Mora, Enric; Bosch, Albert; Guix Arnau, Susana; Costafreda Salvany, M. Isabel (Maria Isabel); Pintó Solé, Rosa María
Hepatitis A virus (HAV) egresses from hepatocytes cloaked in exosomes (eHAV). However, the traffic network used for its release from polarized hepatocytes is not completely understood. We propose that eHAV biogenesis may follow not only an ESCRT-mediated pathway but also the syndecan-syntenin-ALIX pathway. The Bro1 and the V domains of ALIX bind to the pX extension of VP1 and the VP2-late domains of the unmature capsid, respectively. A Serine-to-Glycine replacement at position 134 of VP2, closely located with the first late domain, facilitates the interaction with ALIX promoting the syndecan-syntenin-ALIX pathway and improving the basolateral egress, preferentially using RAB35. This replacement is conserved in hepatoviruses infecting a wide range of mammalian species, but not in hepatoviruses infecting chimpanzees and humans. An inefficient basolateral egress could be a strategy to escape the antiviral cellular response in apes.
Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder
(Nature Publishing Group, 2024-04-03) Herrera Rivero, Marisol; Gutiérrez Fragoso, Karina; Kurtz, Joachim; Baune, Bernhard T.; Benabarre, Antonio; Jiménez Martínez, Ester; Reininghaus, Eva Z.; Arias Sampériz, Bárbara; Mitjans Niubó, Marina; Richard Lepouriel, Hélène; Vieta i Pascual, Eduard, 1963-; International Consortium on Lithium Genetics (ConLi+Gen)
The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we performed an exploratory study of the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. Overall, we observed relatively weak associations (p < 1 × 10−4) with BP phenotypes within immune-related genes. Network and functional enrichment analyses of the top findings from the association analyses of Li response variables showed an overrepresentation of pathways participating in cell adhesion and intercellular communication. These appeared to converge on the well-known Li-induced inhibition of GSK-3β. Association analyses of age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation suggested modest contributions of genes such as RTN4, XKR4, NRXN1, NRG1/3 and GRK5 to disease characteristics. PGS analyses returned weak associations (p < 0.05) between inflammation markers and the studied BP phenotypes. Our results suggest a modest relationship between immunity and clinical features in BP. More research is needed to assess the potential therapeutic relevance.
Detection and Quantification of Bacteriophages in Wastewater Samples by culture and molecular methods
(Springer Science + Business Media, 2023-11-16) Sala Comorera, Laura; Muniesa Pérez, Ma. Teresa; Rodríguez-Rubio, Lorena
Bacteriophages are promising tools for the detection of fecal pollution in water bodies and particularly for viral pathogen risk assessment. Having similar morphological and biological characteristics, bacteriophages are perfect surrogates for the study of the fate and transport of enteric viruses, generally better than any other group of indicators.Different groups of bacteriophages, such as somatic coliphages, F-specific RNA bacteriophages, and bacteriophages infecting selected strains of Bacteroides, have been comprehensively tested as indicators of fecal pollution. Somatic coliphages and F-specific RNA bacteriophages can be used as indicators of general fecal contamination, whereas Bacteroides phages can be used to detect a particular fecal source, for instance, human, bovine, porcine, or poultry fecal contamination.Feasible and cost-effective protocols standardized by the International Standardization Organization and the United States Environmental Protection Agency for the detection of infectious bacteriophages belonging to these three groups are available. Molecular methods for the detection of some particular phages have also been developed. Here we introduce those methods for the detection, enumeration, and isolation of bacteriophages in wastewater samples.
Metabolite Biomarkers Linking a High-Fiber Rye Intervention with Cardiometabolic Risk Factors: The RyeWeight Study.
(American Chemical Society, 2025-08-21) Unión-Caballero, Andrea; Meroño, Tomás; Åberg, Sebastian; Nordin, Elise; Dicksved, Johan; Sànchez, Àlex (Sànchez Pla); Cubedo Culleré, Marta; Carmona Pontaque, Francesc; Iversen, Kia No̷hr; Martínez Huélamo, Miriam; Guadall, Anna; Landberg, Rikard; Andrés Lacueva, Ma. Cristina
Wholegrain rye, considered one of the cereals with the highest content of dietary fiber and bioactive compounds, has been linked with reduced risk of cardiometabolic diseases. Thus, biomarkers reflecting its intake and/or the metabolic effect after consumption are essential to better elucidate its health effects. Our aim was to identify plasma metabolite biomarkers associated with a high-fiber rye intervention and to assess the associations between these metabolites, gut microbiota composition, and cardiometabolic risk factors in a 12-week randomized controlled trial comparing a hypocaloric diet with high-fiber rye (n = 108) or refined wheat (n = 99) in participants with obesity. Rye intervention increased plasma concentrations of benzoxazinoids (DIBOA-S) and phenylacetamides (2-HPA-S and 2-HHPA-S), gut microbial metabolites (indolepropionic acid, 2-aminophenol, enterolactone sulfate, and enterolactone glucuronide), betainized compounds (pipecolic-betaine), phenolic acids (2,6-DHBA and gallic acid-4- sulfate), and diverse endogenous metabolites. Microbiota composition changes were increased Eubacterium xylanophilum and Agathobacter and decreased Ruminococcus torques and Romboutsia. Moreover, the intervention effect was mostly captured by changes in metabolites and gut microbiota compared to clinical variables. Gallic acid-4-sulfate and phenylacetamides were associated with reductions in weight, fat mass, BMI, or fasting insulin levels even after adjusting for plasma alkylresorcinols, used as markers for rye intake compliance. Altogether, these metabolites may constitute biomarkers of wholegrain rye cardiometabolic effects.
New colonisers drive the increase of the emerging loggerhead turtle nesting in Western Mediterranean
(Nature Publishing Group, 2024-01-17) Luna Ortiz, Patricia Astrid; Marín Capuz, Gisela; Abella, Elena; Crespo Picazo, José Luis; Escribano, Fernando; Félix, Guillem; Giralt, Silvia; Tomás, Jesús; Pegueroles Queralt, Cinta; Pascual Damieta, Marta; Carreras Huergo, Carlos
The loggerhead sea turtle (Caretta caretta) is sensitive to climate change and is responding by colonising the Western Mediterranean. To understand the rapid nesting increase in recent years in Spain, we sampled 45 hatchlings from 8 nests between 2016 and 2019. We sequenced a mtDNA D‐loop region, genotyped 2291 SNPs using 2bRAD and collected data on clutch size, hatching success, and incubation duration. We confirmed that the colonisation has a Mediterranean and Atlantic mixed origin and we detected that these nests were laid by different females, except for two nests within the same season. Our results suggest that the recent increase in nesting is due to an increase in the number of colonising individuals rather than females born in the same area returning to breed. We hypothesize that this increase in the number of colonisers results from successful conservation efforts, feminisation of the populations of origin and earlier sexual maturation. However, the percentage of offspring females produced in Spain suggests that future returning individuals will aid to the settlement of the new population. These results allow defining the current status of this colonisation although future efforts are needed to detect remigrants to confirm the establishment of a resident population.
Structural and biochemical characterization of a new phage-encoded muramidase, KTN6 Gp46
(2024-06-21) Sanz-Gaitero, Marta; De Maesschalck, Vincent; Patel, Ankur; Longin, Hannelore; Van Noort, Vera; Rodríguez-Rubio, Lorena; van Ryne, Michael; Danis-Wlodarczyk, Katarzyna; Drulis-Kawa, Zuzanna; Mesnage, Stephane; van Raaij, Mark; Lavigne, Rob
Background: Endolysins are phage-encoded lytic enzymes that degrade bacterial peptidoglycan at the end of phage lytic cycles to release new phage particles. These enzymes are being explored as an alternative to small-molecule antibiotics. Methods: The crystal structure of KTN6 Gp46 was determined and compared with a ColabFold model. Cleavage specificity was examined using a peptidoglycan digest and reversed-phase high-performance liquid chromatography coupled to mass spectrometry (HPLC/MS). Results: The structure of KTN6 Gp46 could be determined at 1.4 Å resolution, and key differences in loops of the putative peptidoglycan binding domain were identified in comparison with its closest known homologue, the endolysin of phage SPN1S. Reversed-phase HPLC/MS analysis of the reaction products following peptidoglycan digestion confirmed the muramidase activity of Gp46, consistent with structural predictions. Conclusion: These insights into the structure and function of endolysins further expand the toolbox for endolysin engineering and explore their potential in enzyme-based antibacterial design strategies.
Clinical Burden and Costs of Anti-Neutrophil Cytoplasmic Antibody-ANCA-Associated Vasculitis: Main Findings from REDCap Registry of a University Hospital in Spain
(Dove Medical Press, 2025-08-01) Draibe, Juliana; Martinez Valenzuela, Laura; Gómez-Preciado, Francisco; Anton Pampols, Paula; Rau Lertora, Ana Melisa; Díaz-Cuervo, Helena; Crespo Palomo, Carlos; Cuervo, Jesús; Ramirez de Arellano, Antonio
Purpose: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) are rare chronic autoimmune diseases, potentially fatal, with frequent relapses. They are associated with vital organ damage, especially renal, often resulting in end-stage renal disease. While current standard of care with immunosuppressants has improved renal function and survival, the main risks for patients under life-long immunosuppression are infections and other concomitant diseases. This study evaluated the burden of AAV using patient-level data from a disease-specific registry. Patients and Methods: The cohort of incident AVV patients (2013– 2022) in the REDCap registry in a university hospital in Spain was studied. Patients with Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA) with at least one year of follow-up (or deceased during the period) were included. Clinical outcomes, including Birmingham Vasculitis Activity Score (BVAS) and healthcare resource consumption were analysed for the first year after diagnosis. Mean annual costs were calculated using unitary costs from the hospital accounting department. Results: Seventy-five patients (12% EGPA, 32% GPA, and 56% MPA) were included. Fifty-two percent were women. Mean age at diagnosis was 65.20± 14.70 years. At baseline, mean BVAS was 17.35± 5.70, 93.33% of patients showed renal affectation, mean estimated glomerular filtration rate was 33.32± 29.93mL/min/1.73m2. As induction treatment, 62.67% received methylprednisolone, 37.33% rituximab, 25.33% cyclophosphamide, 14.67% rituximab plus cyclophosphamide, 34.67% plasmapheresis. During the first year after diagnosis, 17.33% relapsed and 78.67% had at least 1 hospitalisation; 97.33% received steroids; 13.33% were on dialysis at some point; one patient received a kidney transplant; 46.67% presented infections and 28% suffered corticosteroid-associated complications; 4 patients died, being 50% of deaths treatment-related. The highest observed mean cost per patient for the first year was € 11,647.95 for hospital care. Conclusion: This study revealed a considerable burden of AAV, as evidenced by high rates of hospitalisation, relapses, and the need for intensive medical interventions.
A transient inflammatory response contributes to oxaliplatin neurotoxicity in mice
(American Neurological Association, 2022-11-11) Calls, Aina; Torres-Espin,Abel; Tormo, Marc; Martínez-Escardó, Laura; Bonet, Núria; Casals López, Ferran; Navarro, Xavier; Yuste, Victor J.; Udina, Esther; Bruna, Jordi
Objectives Peripheral neuropathy is a relevant dose-limiting adverse event that can affect up to 90% of oncologic patients with colorectal cancer receiving oxaliplatin treatment. The severity of neurotoxicity often leads to dose reduction or even premature cessation of chemotherapy. Unfortunately, the limited knowledge about the molecular mechanisms related to oxaliplatin neurotoxicity leads to a lack of effective treatments to prevent the development of this clinical condition. In this context, the present work aimed to determine the exact molecular mechanisms involved in the development of oxaliplatin neurotoxicity in a murine model to try to find new therapeutical targets. Methods By single-cell RNA sequencing (scRNA-seq), we studied the transcriptomic profile of sensory neurons and satellite glial cells (SGC) of the Dorsal Root Ganglia (DRG) from a well-characterized mouse model of oxaliplatin neurotoxicity. Results Analysis of scRNA-seq data pointed to modulation of inflammatory processes in response to oxaliplatin treatment. In this line, we observed increased levels of NF-kB p65 protein, pro-inflammatory cytokines, and immune cell infiltration in DRGs and peripheral nerves of oxaliplatin-treated mice, which was accompanied by mechanical allodynia and decrease in sensory nerve amplitudes. Interpretation Our data show that, in addition to the well-described DNA damage, oxaliplatin neurotoxicity is related to an exacerbated pro-inflammatory response in DRG and peripheral nerves, and open new insights in the development of anti-inflammatory strategies as a treatment for preventing peripheral neuropathy induced by oxaliplatin.
Sequential activation of transcription factors promotes liver regeneration through specific and developmental enhancers
(Elsevier, 2025-07-09) Llorens-Giralt, Palmira; Ruiz Romero, Marina; Nurtdinov, Ramil; Herranz Itúrbide, Macarena; Vicent, Guillermo Pablo; Serras Rigalt, Florenci; Fabregat Romero, Isabel; Corominas, Montserrat (Corominas Guiu)
The mammalian liver exhibits remarkable regenerative capabilities after injury or resection. Central to this process is the precise modulation of gene expression, driven by changes in chromatin structure and the temporal activation of distal regulatory elements. In this study, we integrated chromatin accessibility and transcriptomic data after partial hepatectomy in mice. We show that the expression of crucial regeneration genes is orchestrated by a diverse array of cis-regulatory elements, including regeneration-specific enhancers and enhancers repurposed from various developmental stages. These enhancers collaborate to activate the transcriptional programs required for hepatocyte priming and proliferation, with their activity initially regulated by the activator protein-1 (AP-1) complex and ATF3, and subsequently by nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2) during proliferation. Our results also indicate that hepatic regeneration involves the repression of enhancers regulating liver-specific metabolic functions, particularly those involved in lipid metabolism. This study provides a genome-wide atlas of enhancer-gene interactions, offering new insights into the regulatory mechanisms underlying liver regeneration.
Epithelial cells provide immunocompetence to the early embryo for bacterial clearance
(Elsevier, 2025-07-09) Roncero Carol, Joan; Olaizola-Muñoa, June; Arán, Begoña; Mularoni, Loris Sebastiano; Miret Cuesta, Marta; Blanco-Cabra, Núria; Casals, Marc; Rumbo, Mireia; Solé Inarejos, Miquel; Ojosnegros, Samuel; Alsina, Berta; Torrents Serra, Eduard; Veiga, Anna; Irimia Martínez, Manuel; Hoijman, Esteban
Early embryos are exposed to environmental perturbations that may influence their development, including bacteria. Despite lacking a proper immune system, the surface epithelium of early embryos (trophectoderm in mammals) can phagocytose defective pluripotent cells. Here, we explore the dynamic interactions between early embryos and bacteria. Quantitative live imaging of infection models developed in zebrafish embryos reveals the efficient phagocytic capability of surface epithelia in detecting, ingesting, and destroying infiltrated E. coli and S. aureus. In vivo single-cell interferences uncover actin-based epithelial zippering protrusions mediating bacterial phagocytosis, safeguarding developmental robustness upon infection. Transcriptomic and inter-scale dynamic analyses of phagocyte-bacteria interactions identify specific features of this epithelial phagocytic program. Notably, live imaging of mouse and human blastocysts supports a conserved role of the trophectoderm in bacterial phagocytosis. This defensive role of the surface epithelium against bacterial infection provides immunocompetence to early embryos, with relevant implications for understanding failures in human embryogenesis.
En recuerdo de José Luis Gómez Skarmeta (1966-2020)
(2021-03-01) Maeso, Ignacio; Casares, Fernando; Freitas, Renata; Irimia Martínez, Manuel; Tena, Juan J.
El pasado 16 de Septiembre, la prematura muerte de José Luis Gómez Skarmeta conmocionó duramente a la comunidad científica. La inmensa pasión y espíritu colaborativo de José Luis no sólo dejaron un gran legado científico, sino también grandes amistades que no conocieron fronteras, forjadas a lo largo de una vida que en sus primeros años fue casi nómada, desde su Chile natal, pasando por Puerto Rico, España y Colombia, hasta establecerse finalmente en Sevilla. Fue allí donde desarrolló la mayor parte de su carrera, impulsando desde su fundación el desarrollo de un centro de investigación al que se dedicó en cuerpo y alma, el Centro Andaluz de Biología del Desarrollo.
Decreased brain serotonin in rbfox1 mutant zebrafish and partial reversion of behavioural alterations by the SSRI fluoxetine
(MDPI, 2024-02-16) Adel, Maja R.; Antón Galindo, Ester; Gago-Garcia, Edurne; Arias-Dimas, Ángela; Arenas Solà, Concepción; Artuch, Rafael; Cormand Rifà, Bru; Fernàndez Castillo, Noèlia
RBFOX1 functions as a master regulator of thousands of genes, exerting a pleiotropic effect on numerous neurodevelopmental and psychiatric disorders. A potential mechanism by which RBFOX1 may impact these disorders is through its modulation of serotonergic neurotransmission, a common target for pharmacological intervention in psychiatric conditions linked to RBFOX1. However, the precise effects of RBFOX1 on the serotonergic system remain largely unexplored. Here we show that homozygous rbfox1sa15940 zebrafish, which express a shorter, aberrant rbfox1 mRNA, have significantly reduced serotonin levels in telencephalon and diencephalon. We observed that the acute administration of fluoxetine partially reverses the associated behavioural alterations. The hyperactive phenotype and altered shoaling behaviour of the rbfox1sa15940/sa15940 zebrafish could be reversed with acute fluoxetine exposure in the Open Field and the Shoaling test, respectively. However, in the other paradigms, hyperactivity was not diminished, suggesting a distinct intrinsic motivation for locomotion in the different paradigms. Acute fluoxetine exposure did not reverse the alterations observed in the aggression and social novelty tests, suggesting the involvement of other neurological mechanisms in these behaviours. These findings underscore the importance of investigating the intricate working mechanisms of RBFOX1 in neurodevelopmental and psychiatric disorders to gain a better understanding of the associated disorders along with their pharmacological treatment.
Intrinsic Information-Theoretic Models
(MDPI, 2024-04-28) Bernal-Casas, D.; Oller i Sala, Josep Maria
With this follow-up paper, we continue developing a mathematical framework based on information geometry for representing physical objects. The long-term goal is to lay down informational foundations for physics, especially quantum physics. We assume that we can now model information sources as univariate normal probability distributions ( , 0), as before, but with a constant 0 not necessarily equal to 1. Then, we also relaxed the independence condition when modeling m sources of information. Now, we model m sources with a multivariate normal probability distribution ( , 0) with a constant variance–covariance matrix 0 not necessarily diagonal, i.e., with covariance values different to 0, which leads to the concept of modes rather than sources. Invoking Schrödinger’s equation, we can still break the information into m quantum harmonic oscillators, one for each mode, and with energy levels independent of the values of 0, altogether leading to the concept of “intrinsic”. Similarly, as in our previous work with the estimator’s variance, we found that the expectation of the quadratic Mahalanobis distance to the sample mean equals the energy levels of the quantum harmonic oscillator, being the minimum quadratic Mahalanobis distance at the minimum energy level of the oscillator and reaching the “intrinsic” Cramér–Rao lower bound at the lowest energy level. Also, we demonstrate that the global probability density function of the collective mode of a set of m quantum harmonic oscillators at the lowest energy level still equals the posterior probability distribution calculated using Bayes’ theorem from the sources of information for all data values, taking as a prior the Riemannian volume of the informative metric. While these new assumptions certainly add complexity to the mathematical framework, the results proven are invariant under transformations, leading to the concept of “intrinsic” information-theoretic models, which are essential for developing physics.
CrAss-like phages are suitable indicators of antibiotic resistance genes found in abundance in fecally polluted samples
(Elsevier B.V., 2024-08-10) Morales-Cortés, Sara; Sala Comorera, Laura; Gómez-Gómez, Clara; Muniesa Pérez, Ma. Teresa; García Aljaro, Cristina
Antibiotic resistance genes (ARGs) have been extensively observed in bacterial DNA, and more recently, in phage particles from various water sources and food items. The pivotal role played by ARG transmission in the proliferation of antibiotic resistance and emergence of new resistant strains calls for a thorough understanding of the underlying mechanisms. The aim of this study was to assess the suitability of the prototypical p-crAssphage, a proposed indicator of human fecal contamination, and the recently isolated crAssBcn phages, both belonging to the Crassvirales group, as potential indicators of ARGs. These crAss-like phages were evaluated alongside specific ARGs (blaTEM, blaCTX-M-1, blaCTX-M-9, blaVIM, blaOXA-48, qnrA, qnrS, tetW and sul1) within the total DNA and phage DNA fractions in water and food samples containing different levels of fecal pollution. In samples with high fecal load (>103 CFU/g or ml of E. coli or somatic coliphages), such as wastewater and sludge, positive correlations were found between both types of crAss-like phages and ARGs in both DNA fractions. The strongest correlation was observed between sul1 and crAssBcn phages (rho = 0.90) in sludge samples, followed by blaCTX-M-9 and p-crAssphage (rho = 0.86) in sewage samples, both in the phage DNA fraction. The use of crAssphage and crAssBcn as indicators of ARGs, considered to be emerging environmental contaminants of anthropogenic origin, is supported by their close association with the human gut. Monitoring ARGs can help to mitigate their dissemination and prevent the emergence of new resistant bacterial strains, thus safeguarding public health.
Efficacy of Erwinia amylovora and Xanthomonas campestris pv campestris phages to control fire blight and black rot in vivo
(American Society for Microbiology, 2025-05-16) Vique, Gloria; Mendonza Barberá, Elena de; Ramos-Barbero, Maria Dolores; Blanco-Picazo, Pedro; Sala Comorera, Laura; Quirós, Pablo; Atares, Sergio; Salaet, Ignasi; Muniesa Pérez, Ma. Teresa; Rodríguez-Rubio, Lorena
Phytopathogens, such as Erwinia amylovora and Xanthomonas campestris, pose significant threats to agriculture, leading to substantial economic losses. Traditional chemical pesticides can harm soil fertility, contaminate water, and impact non-target organisms such as natural predators and pollinators, highlighting the need for sustainable pest control methods. This study explores the use of bacteriophages as biocontrol agents against E. amylovora, which causes fire blight, and X. campestris pv. campestris, responsible for black rot in cruciferous vegetables. Bacteriophages were isolated from urban wastewater and tested for their lytic activity against these pathogens. Three virulent phages were identified: ɸEF1 and ɸEF2 against E. amylovora and ɸXF1 against X. campestris pv. campestris. Genetic analysis confirmed the absence of known lysogeny-related genes, indicating that these phages are ideal candidates for biocontrol applications. In vitro assays demonstrated significant bacterial population reductions. Specifically, ɸEF1 killed 92.1% of the E. amylovora population at a multiplicity of infection (MOI) of 1 after 3 h, while ɸEF2 reduced the population by 98.1%. When combined in a 1:1 ratio, the two phages reduced E. amylovora populations by 99.7%, and no regrowth of resistant cells was observed, which was not the case when the phages were applied individually. ɸXF1 killed 99.9% of X. campestris pv. campestris populations at an MOI of 1 after 5 h. In vivo experiments using pears and kohlrabi as infection models further validated the phage effectiveness. Treated pears showed reduced fire blight symptoms, and kohlrabi plants exhibited markedly less necrosis from black rot compared to untreated controls.
Temporal and habitat adaptations in Drosophila subobscura populations: changes in chromosomal inversions
(Springer Science + Business Media, 2025-04-25) Zivanovic, Goran; Arenas Solà, Concepción; Mestres i Naval, Francesc
In insects, chromosomal inversion polymorphism has been related with different adaptations, including global warming. Regarding this environmental change, Drosophila subobscura stands out as a useful model species due to its rich inversion polymorphism covering the whole karyotype. The main aims of this research were to analyze the differentiation of this polymorphism in Jastrebac Mt. (Serbia) depending on the different habitats (beech and oak forests) and over time. These latter changes were studied in relation to climatic variables (mean, minimum and maximum temperatures, humidity and rainfall). Microdifferentiation was observed between beech and oak forests, mainly for the A and O chromosomes. However, the changes over time turned out to be larger than those due to habitat. In Jastrebac Mt., temperatures increased over time, with this increase being significant for mean and minimum one. The Multidimensional Scaling analysis showed a relation between chromosomal inversions and temperatures (mainly minimum) in Jastrebac Mt. and other Serbian populations of D. subobscura. In beech forest of Jastrebac Mt., the Chromosomal Thermal Index increased over time from 1990 to 1994, but showing a possible stabilization in 2023. This result was observed in other studied Serbian populations. Although those are preliminary results, it might hypothesize that there may be a threshold for the action of natural selection, increasing ‘warm’ adaptive inversions and decreasing ‘cold’ ones. The possible reasons for this hypothesis are also discussed.

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