Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders
(Elsevier B.V., 2024-02-03) Koller, Dora; Mitjans Niubó, Marina; Kouakou, Manuela; Friligkou, Eleni; Cabrera-Mendoza, Brenda; Deak, Joseph; Llonga, Natalia; Pathak, Gita A.; Stiltner, Brendan; Lokhammer, Solveig; Levey, Daniel; Zhou, Hang; Hatoum, Alexander; Kember, Rachel; Kranzler, Henry; Stein, Murray; Corominas Castiñeira, Roser; Demontis, D.; Soler Artigas, María; Ramos Quiroga, Josep Antoni; Gelernter, Joel; Ribasés Haro, Marta; Cormand Rifà, Bru; Polimanti, Renato
We characterized the genetic architecture of the attention-deficit hyperactivity disorder-substance use disorder(ADHD-SUD) relationship by investigating genetic correlation, causality, pleiotropy, and common polygenic risk.Summary statistics from genome-wide association studies (GWAS) were used to investigate ADHD (Neff =51,568), cannabis use disorder (CanUD, Neff = 161,053), opioid use disorder (OUD, Neff = 57,120), problematicalcohol use (PAU, Neff = 502,272), and problematic tobacco use (PTU, Neff = 97,836). ADHD, CanUD, and OUDGWAS meta-analyses included cohorts with case definitions based on different diagnostic criteria. PAU GWAScombined information related to alcohol use disorder, alcohol dependence, and the items related to alcohol problematic consequences assessed by the alcohol use disorders identification test. PTU GWAS was generated amulti-trait analysis including information regarding Fagerstr¨om Test for Nicotine Dependence and cigarettes perday. Linkage disequilibrium score regression analyses indicated positive genetic correlation with CanUD, OUD,PAU, and PTU. Genomic structural equation modeling showed that these genetic correlations were related to twolatent factors: one including ADHD, CanUD, and PTU and the other with OUD and PAU. The evidence of a causaleffect of PAU and PTU on ADHD was stronger than the reverse in the two-sample Mendelian randomizationanalysis. Conversely, similar strength of evidence was found between ADHD and CanUD. CADM2 rs62250713was a pleiotropic SNP between ADHD and all SUDs. We found seven, one, and twenty-eight pleiotropic variantsbetween ADHD and CanUD, PAU, and PTU, respectively. Finally, OUD, CanUD, and PAU PRS were associatedwith increased odds of ADHD. Our findings demonstrated the contribution of multiple pleiotropic mechanisms tothe comorbidity between ADHD and SUDs.
Structure and mechanistic basis of NrdR, a bacterial master regulator of ribonucleotide reduction
(Elsevier B.V., 2026-02-04) Pedraz López, Lucas; Szura, Arkadiusz; Schmitz, Claus; Rubio Canalejas, Alba; Martínez Mateos, Ángela; Santella, Anthony; Gomila Lluch, Gabriel; Calò, Annalisa; Solà, Maria; Torrents Serra, Eduard
Ribonucleotide reductases (RNRs) are the essential enzymes responsible for synthesizing dNTPs, the building blocks of DNA. In bacteria, the entire RNR network is controlled by the master regulator NrdR. As a regulator of an essential pathway with no eukaryotic equivalent, NrdR is a promising antimicrobial target. Recent structural studies have outlined a mechanism of action for NrdR, in which ATP and dATP induce changes in the protein quaternary structure, regulating RNR repression. However, due to a lack of functional studies linking the known structures to their biological roles, the activation mechanism of NrdR is not yet fully understood. Here, we conducted a comprehensive study of NrdR in Escherichia coli and Pseudomonas aeruginosa. We delimited the NrdR regulon, combining transcriptomics and motif-based sequence analysis. We crystallized E. coli NrdR and identified the protein-protein interfaces involved in its oligomerization, including strong interactions between NrdR dimers to form tetramers, and less stable interfaces connecting such tetramers. We examined the variability of the quaternary structures of NrdR depending on the bound nucleotides by SEC-MALS and atomic force microscopy, and correlated structure to function using point mutations, EMSAs, and in vitro transcription assays. Overall, our results demonstrate the mechanism used by NrdR to modulate its quaternary structure and activity, deciphering essential interactions between subunits, and paving the way for targeted antimicrobial therapies.
Galleria mellonella as a simple yet reliable in vivo model for nanotoxicology: Techniques and applications
(John Wiley & Sons, 2025-09-01) Blanco-Cabra, Núria; Admella, Joana; Torrents Serra, Eduard
Nanomaterials are a rapidly advancing tool with applications across various scientific fields. However, their interactions with living organisms have raised numerous safety concerns, making it crucial to develop reliable models to predict and evaluate associated toxicity effects. Traditional in vitro assays fail to mimic the true physiological responses of living organisms to nanomaterials, whereas murine and other in vivo models are time-consuming, costly, and ethically controversial. The greater wax moth, Galleria mellonella, has emerged as a promising in vivo model for nanotoxicology, serving as an effective bridge between in vitro and in vivo mammalian testing. This model combines simplicity and ethical viability with a human-conserved innate immune system, making it ideal for immunotoxicity testing. While it cannot fully replace more complex animal models, G. mellonella represents a valuable alternative for early-stage nanotoxicology screening and deserves greater recognition and integration into toxicological research. In this review, we examine all the methodologies and applications of G. mellonella in nanotoxicological studies, highlighting its potential as a reliable and ethical model for assessing nanomaterial safety.
In Vitro Activity of Ampicillin Plus Ceftriaxone Against Non-faecalis and Non-faecium Enterococcal Isolates With/Without VanC Phenotype: Clinical Implications for Infective Endocarditis.
(MDPI, 2024-12-05) García González, Javier; Cañas, María Alexandra; Cuervo Requena, Guillermo; Hernández Meneses, Marta; Verdejo, Miguel Ángel; Bodro, Marta; Díez de los Ríos, Javier; Gasch, Oriol; Ribera, Alba; Falces Salvador, Carles; Perissinotti, Andrés; Vidal Hagemeijer, Bárbara; Quintana, Eduard; Moreno Camacho, Ma. Asunción; Piquet, Maria; Roca Subirà, Ignasi; Fernández Pittol, Mariana José; San José Villar, Sol María; García de la Mària, Cristina; Miró Meda, José M. (José María), 1956- ; Hospital Clínic Endocarditis Study Group
1) Background: Alternative antibiotics are needed to treat infective endocarditis (IE) caused by non-faecalis/non-faecium enterococci; we aimed to assess the in vitro activity of ampicillin plus ceftriaxone (AMP + CTR) against these enterococci and to describe its clinical efficacy in IE cases. (2) Methods: Time–kill curves with standard (ISI) and high (IHI) inocula were performed to test VanC isolates [3 E. casseliflavus (ECAS) and 1 E. gallinarum (EGALL)] and non-VanC isolates [1 E. durans (EDUR), 1 E. hirae (EHIR) and 1 E. raffinosus (ERAF)]. The narrative literature review of IE cases treated with AMP + CTR was analyzed alongside three study cases. Clinical outcomes were relapse and death. (3) Results: Ampicillin plus gentamicin (AMP + GEN) showed synergistic and bactericidal activity against most isolates. AMP + CTR was synergistic at ISI for EGALL, EDUR, and EHIR and bactericidal against EHIR. At IHI, indifferent activity was observed for all isolates. In IE cases treated with AMP + CTR, it was only effective for EDUR and EHIR. Clinical information for EGALL IE is lacking. For IE caused by ECAS and ERAF, AMP + CTR seems suboptimal or ineffective, respectively. (4) AMP + CTR cannot be recommended for treating IE due to ECAS/ERAF. In contrast, this combination was effective in IE caused by EDUR/EHIR and could be recommended.
Development of High-Level Daptomycin Resistance in Abiotrophia and Granulicatella Species Isolates from Patients with Infective Endocarditis
(American Society for Microbiology, 2021-09-17) Cañas, María Alexandra; Téllez, Adrián; García de la Mària, Cristina; Dahl, Anders; García González, Javier; Hernández Meneses, Marta; Almela, M. (Manel); Ambrosioni, Juan; Falces Salvador, Carles; Quintana, Eduard; Vidal, Bàrbara; Perissinotti, Andrés; Tolosana, José M. (José María); Sandoval, Elena; Pericàs, Juan M.; Moreno Camacho, Ma. Asunción; Miró Meda, José M. (José María), 1956- ; Hospital Clínic Endocarditis Team Investigator
Abiotrophia and Granulicatella species are fastidious organisms, representing the causative agents of ∼1% to 3% of cases of infective endocarditis (IE). Little is known about the optimal antibiotic treatment for these species, and daptomycin has been suggested as a therapeutic option. We describe the antimicrobial profiles of Abiotrophia and Granulicatella IE isolates, investigate high-level daptomycin resistance (HLDR) development, and evaluate daptomycin activity in combination therapy. In vitro studies with 16 IE strains (6 Abiotrophia defectiva strains, 9 Granulicatella adiacens strains, and 1 G. elegans strain) were performed using microdilution to determine MICs and time-kill methodology to evaluate combination therapy. Daptomycin nonsusceptibility (DNS) (MIC ≥ 2 mg/liter) and HLDR (MIC ≥ 256 mg/liter) were based on existing Clinical and Laboratory Standards Institute (CLSI) breakpoints for viridans group streptococci. All isolates were susceptible to vancomycin: G. adiacens was more susceptible to penicillin and ampicillin than A. defectiva (22% versus 0% and 67% versus 33%) but less susceptible to ceftriaxone and daptomycin (56% versus 83% and 11% versus 50%). HLDR developed in both A. defectiva (33%) and G. adiacens (78%) after 24 h of exposure to daptomycin. Combination therapy did not prevent the development of daptomycin resistance with ampicillin (2/3 strains), gentamicin (2/3 strains), ceftriaxone (2/3 strains), or ceftaroline (2/3 strains). Once developed, HLDR was stable for a prolonged time (>3 weeks) in G. adiacens, whereas in A. defectiva, HLDR reversed to the baseline MIC at day 10. This study is the first to demonstrate rapid HLDR development in Abiotrophia and Granulicatella species in vitro. Resistance was stable, and most combination therapies did not prevent it.
Active wetting of epithelial tissues
(Nature Publishing Group, 2019-01) Pérez González, Carlos; Alert Zenón, Ricard; Blanch Mercader, Carles; Gómez González, Manuel; Kolodziej, Tomasz; Bazellières, Elsa; Casademunt i Viader, Jaume; Trepat Guixer, Xavier
Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behaviour of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between two-dimensional epithelial monolayers and three-dimensional spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic length scale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting¿a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumour progression.
Two-layer elastographic 3-D traction force microscopy
(Nature Publishing Group, 2017-01-11) Álvarez-González, Begoña; Zhang, Shun; Gómez González, Manuel; Meili, Ruedi; Firtel, Richard A.; Lasheras, Juan C.; del Álamo, Juan C.
Cellular traction force microscopy (TFM) requires knowledge of the mechanical properties of the substratum where the cells adhere to calculate cell-generated forces from measurements of substratum deformation. Polymer-based hydrogels are broadly used for TFM due to their linearly elastic behavior in the range of measured deformations. However, the calculated stresses, particularly their spatial patterns, can be highly sensitive to the substratum’s Poisson’s ratio. We present two-layer elastographic TFM (2LETFM), a method that allows for simultaneously measuring the Poisson’s ratio of the substratum while also determining the cell-generated forces. The new method exploits the analytical solution of the elastostatic equation and deformation measurements from two layers of the substratum. We perform an in silico analysis of 2LETFM concluding that this technique is robust with respect to TFM experimental parameters, and remains accurate even for noisy measurement data. We also provide experimental proof of principle of 2LETFM by simultaneously measuring the stresses exerted by migrating Physarum amoeboae on the surface of polyacrylamide substrata, and the Poisson’s ratio of the substrata. The 2LETFM method could be generalized to concurrently determine the mechanical properties and cell-generated forces in more physiologically relevant extracellular environments, opening new possibilities to study cell-matrix interactions.
Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis.
(2024-02-17) Medina-Dols, Aina; Cañellas, Guillem; Capó, Toni; Solé, Montse; Mola Caminal, Marina; Cullell, Natalia; Jaume, Marina; Nadal-Salas, Laura; Llinàs, Jaume; Gómez, Lluís; Tur, Silvia; Jimenez, Carmen; Diaz-Navarro, Rosa M.; Carrera, Caty; Muiño Acuña, Elena; Gallego Fàbrega, Cristina; Soriano Tarraga, Carolina; Ruiz-Guerra, Laura; Pol-Fuster, Josep; Asensio, Víctor; Muncunill, Josep; Fleischer, Aarne; Iglesias, Amanda; Giralt Steinhauer, Eva; Lazcano, Uxue; Fernández-Pérez, Isabel; Jiménez-Balado, Joan; Gabriel-Salazar, Marina; Garcia-Gabilondo, Miguel; Lei, Ting; Torres Águila, Nuria Paz; Carcel-Marquez, Jara; Lladó, Jerònia; Olmos, Gabriel; Rosell, Anna; Montaner, Joan; Planas Obradors, Anna Maria; Rabionet Janssen, Raquel; Hernandez-Guillamon, Mar; Jiménez Conde, Jordi; Fernandez-Cadenas, Israel; Vives-Bauzà, Cristòfol
Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient’s blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) ≤2), compared to those patients with marked disability (mRS = 4–5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1α also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, β-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.
Two-point particle tracking microrheology of nematic complex fluids
(Royal Society of Chemistry, 2016-06) Gómez González, Manuel; del Álamo, Juan C.
Many biological and technological complex fluids exhibit tight microstructural alignment that confers them nematic mechanical properties. Among these we count liquid crystals and biopolymer networks, which are often available in microscopic amounts. However, current microrheological methods cannot measure the directional viscoelastic coefficients that appear in the constitutive relation of nematic complex fluids. This article presents directional two-point particle-tracking microrheology (D2PTM) – a novel microrheology technique to determine these coefficients. We establish the theoretical foundation for D2PTM by analyzing the motion of a probing microscopic particle embedded in a nematic complex fluid, and the mutual hydrodynamic interactions between pairs of distant particles. From this analysis, we generalize the formulation of two-point particle tracking microrheology for nematic complex fluids, and demonstrate that the new formulation provides sufficient information to fully characterize the anisotropic viscoelastic coefficients of such materials. We test D2PTM by simulating the Brownian motion of particles in nematic viscoelastic fluids with prescribed directional frequency-dependent shear moduli, showing that D2PTM accurately recovers the prescribed shear moduli. Furthermore, we experimentally validate D2PTM by applying it to a lyotropic nematic liquid crystal, and demonstrate that this new microrheology method provides results in agreement with dynamic light scattering measurements. Lastly, we illustrate the experimental application of the new technique to characterize nematic F-actin solutions. These experiments constitute the first microrheological measurement of the directional viscoelastic coefficients of an anisotropic soft material.
Evidence of viral dissemination and seasonality in a Mediterranean river catchment: implications for water pollution management
(Elsevier, 2015-08-15) Rusiñol Arantegui, Marta; Fernández Cassi, Xavier; Timoneda, N.; Carratalà Ripollès, Anna; Abril Ferrando, Josep Francesc, 1970-; Silvera, Carolina; Figueras Salvat, Maria Jose; Gelati, Emiliano; Rodo Lopez, Xavier; Kay, David; Wyn-Jones, A. Peter; Bofill Mas, Silvia; Gironès Llop, Rosina
Conventional wastewater treatment does not completely remove and/or inactive viruses; consequently, viruses excreted by the population can be detected in the environment. This study was undertaken to investigate the distribution and seasonality of human viruses and faecal indicator bacteria (FIB) in a river catchment located in a typical Mediterranean climate region and to discuss future trends in relation to climate change. Sample matrices included river water, untreated and treated wastewater from a wastewater treatment plant within the catchment area, and seawater from potentially impacted bathing water. Five viruses were analysed in the study. Human adenovirus (HAdV) and JC polyomavirus (JCPyV) were analysed as indicators of human faecal contamination of human pathogens; both were reported in urban wastewater (mean values of 106 and 105 GC/L, respectively), river water (103 and 102 GC/L) and seawater (102 and 101 GC/L). Human Merkel Cell polyomavirus (MCPyV), which is associated with Merkel Cell carcinoma, was detected in 75% of the raw wastewater samples (31/37) and quantified by a newly developed quantitative polymerase chain reaction (qPCR) assay with mean concentrations of 104 GC/L. This virus is related to skin cancer in susceptible individuals and was found in 29% and 18% of river water and seawater samples, respectively. Seasonality was only observed for norovirus genogroup II (NoV GGII), which was more abundant in cold months with levels up to 104 GC/L in river water. Human hepatitis E virus (HEV) was detected in 13.5% of the wastewater samples when analysed by nested PCR (nPCR). Secondary biological treatment (i.e., activated sludge) and tertiary sewage disinfection including chlorination, flocculation and UV radiation removed between 2.22 and 4.52 log10 of the viral concentrations. Climate projections for the Mediterranean climate areas and the selected river catchment estimate general warming and changes in precipitation distribution. Persistent decreases in precipitation during summer can lead to a higher presence of human viruses because river and sea water present the highest viral concentrations during warmer months. In a global context, wastewater management will be the key to preventing environmental dispersion of human faecal pathogens in future climate change scenarios.
Time to Reappraise the Antibiotic Treatment for Methicillin-Susceptible Staphylococcus aureus Infective Endocarditis: Data From the Experimental Model
(Oxford University Press, 2025-09-15) García de la Mària, Cristina; Gasch, Oriol; Cañas, María Alexandra; García González, Javier; Marco Reverté, Francesc; Hernández Meneses, Marta; Quintana, Eduard; Ambrosioni, Juan; Falces Salvador, Carles; Tolosana, José M. (José María); Vidal, Bàrbara; Pericàs, Juan M.; Perissinotti, Andrés; Llopis Pérez, Jaime; Moreno Camacho, Ma. Asunción; Cuervo Requena, Guillermo; Miró Meda, José M. (José María), 1956- ; Hospital Clinic Endocarditis Study Group
Background Traditional treatment of methicillin-susceptible Staphylococcus aureus (MSSA) native valve endocarditis is based on cloxacillin/cefazolin monotherapy. Antibiotics with high activity against MSSA, such as ceftaroline and daptomycin, have been marketed for years, but there are no clinical trials evaluating them as monotherapy or combination therapy in patients with MSSA endocarditis. The objective of this study was to compare the efficacy of cloxacillin, ceftaroline, and daptomycin monotherapies and daptomycin combinations with β-lactams in a rabbit model of MSSA endocarditis. Methods Endocarditis was induced in rabbits with 2 strains of MSSA. After 24 hours of infection, they received human-like doses of cloxacillin, ceftaroline, or daptomycin or combinations of daptomycin plus either cloxacillin or ceftaroline. Isolates recovered from vegetation, spleen, and kidney were retested for daptomycin nonsusceptibility (DNS) posttreatment. Results MSSA vancomycin minimum inhibitory concentration did not influence the efficacy of any antibiotic treatment. Cloxacillin, ceftaroline, and daptomycin had similar activity (25%–50%) in sterilizing vegetations. However, 13% of rabbits treated with daptomycin developed DNS. The addition of daptomycin to cloxacillin or ceftaroline was synergistic and bactericidal, showing significantly more activity and higher rates of sterile vegetations (≥90%) than any monotherapy. Combinations also showed better activity in spleens and kidneys as compared with daptomycin monotherapy and prevented the development of DNS in all tissues. There were no differences between the daptomycin combinations. Conclusions In the MSSA experimental endocarditis model, daptomycin combinations with β-lactams had significantly better activity than any of the monotherapies in sterilizing valve vegetations and preventing DNS development. These findings support their use in clinical practice and to perform clinical trials.
Unveiling the enterovirus diversity in Barcelona, Spain (2020-2024) through wastewater and clinical surveillance
(Taylor & Francis, 2025-12-14) García-Pedemonte, David; Carcereny, Albert; Andrés Gutiérrez, Claudia; Antón Pagarolas, Andrés, 1976-; Pérez, Ian; Blanco, Albert; Fuentes Moreno, Concha; Costafreda Salvany, M. Isabel (Maria Isabel) ; Nadal-Barón, Patricia; Galofré, Belén; Paraira, Miquel; Mendioroz, Jacobo; Pintó Solé, Rosa María; Bosch, Albert; Guix Arnau, Susana
Enterovirus (EV) infections are common and often mild or asymptomatic but can occasionally cause serious illness in children. Routine clinical surveillance typically underestimates the full spectrum of circulating EVs, whereas wastewater-based epidemiology captures a broader viral diversity and may serve as an early warning tool. We conducted a 5-year surveillance (2020-2024) in Barcelona, Spain, combining biweekly wastewater sampling with clinical EV reporting during the SARS-CoV-2 pandemic and subsequent relaxation of restrictions. We quantified EV genome copies in sewage by RT-qPCR and performed partial VP1 sequencing on wastewater concentrates and on clinical specimens. Over the study period, wastewater EV loads broadly paralleled reported case trends, with good correlations over the years except in 2022. A monotonic relationship was observed for certain EV type trends, including CVA6, CVB2, CVB3, E11, and EV-D68, but there was low robustness in their predictive capacity for clinical cases. Overall, deep sequencing revealed 122 distinct EV types in wastewater versus 92 types in clinical samples; 66 types were found in both sources, whereas 56 types appeared only in sewage. Sequences from wastewater and clinical sources showed high genetic similarity. Dominant EV types shifted over time highlighting the virus dynamics. These findings demonstrate that integrating WS with clinical surveillance yields a more comprehensive picture of EV circulation, uncovering hidden viral diversity and enabling early detection of emerging public health threats.
Assessing Viral Pollution in Seawater, Using Passive Samplers, Quantitative PCR and Target Enrichment Sequencing
(Springer Science + Business Media, 2026-01-16) Estarlich-Landajo, Ignasi; Tarradas-Alemany, Maria; Martínez-Puchol, Sandra; Mejías-Molina, Cristina; Verdaguer, Júlia; Bofill Mas, Silvia; Rusiñol Arantegui, Marta
Detecting pathogenic viruses in seawater presents significant challenges due to their typically low concentrations and the transient nature of contamination events. To address these challenges, this study evaluates passive sampling (PS) as a semiquantitative methodology for viral surveillance in seawater, focusing on human adenovirus (HAdV), norovirus GI (NoVGI) and GII (NoVGII). To optimize the approach, nylon and nitrocellulose membranes were compared, with nylon demonstrating greater consistency and reliability. In Barcelona, across 14 sampling events, 6 of them during combined sewer overflow (CSO) events, PS (n = 51) was assessed against grab sampling (n = 21) coupled with ultrafiltration (UF). Using PS, HAdV, NoVGI, and NoVGII were detected in 100%, 62.5%, and 75% of non-CSO events, respectively, outperforming UF, which detected these viruses in only 37.5%, 25%, and 37.5% of the same events. PS was applied during CSO events at both the CSO discharge point and at a nearby bathing site. As expected, the sampler deployed at the discharge point detected higher viral loads of HAdV, NoVGI, and NoVGII. However, viral genomes were also detected at the bathing site. Target enrichment sequencing of seawater vertebrate-infecting viruses conducted on PS samples, identified vertebrate viral pathogens, including members of the Circoviridae, Parvoviridae and Picornaviridae families, showcasing the extensive viral diversity in seawater due to fecal contamination. This study emphasizes the risk of viral exposure when seawater is impacted by CSO and the potential of PS as a robust tool for seawater viral surveillance, offering enhanced sensitivity and utility for quality management and public health risk assessment.
Polar flagellin glycan heterogeneity of Aeromonas hydrophila strain ATCC 7966T
(Elsevier, 2025-05-01) Fulton, Kelly M.; Mendoza-Barberá, Elena; Tomàs Magaña, Juan; Twine, Susan M.; Smith, Jeffrey C.; Merino Montero, Susana
Motile pathogens often rely upon flagellar motility as an essential virulence factor and in many species the structural flagellin protein is glycosylated. Flagellin glycosylation has been shown to be important for proper function of the flagellar filament in a number of bacterial species. Aeromonas hydrophila is a ubiquitous aquatic pathogen with a constitutively expressed polar flagellum. Using a suite of mass spectrometry techniques, the flagellin FlaA and FlaB structural proteins of A. hydrophila strain ATCC 7966T were shown to be glycosylated with significant microheterogeneity, macroheterogeneity, and metaheterogeneity. The primary linking sugar in this strain was a novel and previously unreported pseudaminic acid derivative with a mass of 422 Da. The pseudaminic acid derivative was followed in sequence by two hexoses, an N-acetylglucosamine (with additional variable secondary modification), and a deoxy N-acetylglucosamine derivative. These pentasaccharide glycans were observed modifying all eight modification sites. Hexasaccharides, which included an additional N-acetylhexosamine residue as the capping sugar, were observed exclusively modifying a pair of isobaric peptides from FlaA and FlaB. Interestingly, these isobaric peptides are immediately adjacent to a toll-like receptor 5 binding site in both protein sequences. Glycosylation status was also linked to motility, a critical bacterial virulence factor
RAB5A Promotes Active Fluid Wetting by Reprogramming Breast Cancer Spheroid Mechanics
(Wiley-VCH Verlag, 2025-09-11) Barnett, Samuel F.H.; Cartagena-Rivera, Alexander X.; Selhuber-Unkel, Christine; Prevedel, Robert; Trepat Guixer, Xavier; Spatz, Joachim P.; Ivaska, Johanna; Scita, Giorgio; Cavalcanti-Adam, Elisabetta A.; Lemahieu, Grégoire; Moreno-Layseca, Paulina; Hub, Tobias; Bevilacqua, Carlo; Gómez González, Manuel; Pennarola, Federica; Colombo, Ferran; Massey, Andrew E.; Barzaghi, Leonardo; Palamidessi, Andrea; Homagk, Leon-Luca
Unjamming transitions from a solid-like to a fluid-like state are a gateway to breast epithelial cancer invasion. However, the mechanical interplay between phase transitions and dimension transitions, in particular wetting, remains elusive, despite being critical for understanding the onset of metastatic dissemination. This study shows that unjamming, mediated by the RAB5A GTPase, alters carcinoma spheroid fluidity, rigidity, and rewires adhesion mechanics to drive supracellular active wetting as a new mode of tumor expansion. Spheroid fluidification enhances the selective expression of integrin subunits and increases focal adhesion dynamics, inducing a fluid-like spreading behavior on specific matrix ligands. Notably, nanoscale regulation of integrin clustering can select for distinct phase transitions at the collective scale upon wetting. In this framework, fluidized spheroids polarize into cohesive “supracells”, and maintain a stiff peripheral actin bundle as measured by nanomechanical mapping. Furthermore, a combination of Brillouin microscopy and 2.5D traction force analysis reveals a mechanical switch within the spheroid core, characterized by significant cell softening and a reduction in compressive forces exerted on the substrate, thereby mimicking the wetting of a liquid droplet. These findings establish unjamming-driven active wetting as a key mechanism to comprehend the molecular and biophysical underpinnings of solid tumor invasion.
Comparison of officacy and safety of preventive measures used against canine leishmaniasis in southern European countries:longitudinal retrospective study in 1647 client-owned dogs (2012-2016)
(Elsevier B.V., 2018-11-15) Fernandez, Mireia; Tabar, Maria Dolores; Arcas Pons, Antoni; Mateu, Cristina; Homedes, Josep; Roura, Xavier
The best preventive strategy for canine leishmaniosis is unknown. In the last few years, new preventive measures have become available in Europe, including vaccination against leishmaniosis and use of domperidone. The objective of the present study was to evaluate the efficacy, safety and use of different types of preventive measures against leishmaniosis in client-owned dogs. A database search of medical records was carried out in 52 private veterinary practices located in endemic areas of leishmaniosis in Spain, Italy and Portugal. Dogs recruited were initially healthy and seronegative. Dogs were retrospectively classified into healthy, infected or sick at the time of the final serology. A total of 1647 dogs were included in the study. The use of preventive measures in this population was widespread, although 10.7% did not have any preventive treatment applied. The single most utilized measure was repellents in 45.7% of dogs, followed by combination of repellents and vaccination in 23.0%, repellents and domperidone in 11.3%, vaccination in 4.2%, vaccination and domperidone in 2.7%, domperidone in 2.3%, and the combination of the three measures in 0.2% of dogs. Incidence of clinical leishmaniosis in the group with no preventive treatment applied was 12.5%. In the groups with prevention applied, the incidence was 10.1% for vaccination, 4.5% for repellents, 4.0% for repellents + vaccination, 0.5% for repellents + domperidone and no sick dogs were observed in the groups of domperidone, vaccination + domperidone, and combination of the three measures. All preventive measures resulted in a significant lower incidence of leishmaniosis compared with not applying any measure, except for vaccination alone. Overall, according to the statistical analysis, the group that performed significantly better was the combination of repellents and domperidone. Adverse events were reported in 5.2% of dogs and were significantly more common in dogs being vaccinated. However, most adverse events were mild and self-limiting. In conclusion, this is the first large-scale field study investigating the efficacy and safety of the preventive measures used routinely against leishmaniosis in client- owned dogs. Most preventive strategies used, with exception of vaccination alone, had some benefit over not applying any preventive. According to our results, the use of repellents is very important and, although lower numbers of dogs are included, use of domperidone seems to give additional benefits in preventing clinical leishmaniosis. The role of vaccination and its combination with other preventive strategies needs further study.
Who arrived first? Priority effects on Candida albicans and Pseudomonas aeruginosa dual biofilms
(Springer Nature, 2025-02-03) Arévalo Jaimes, Betsy Verónica; Admella, Joana; Torrents Serra, Eduard
Historical processes in community assembly, such as species arrival order, influence interactions, causing priority effects. Candida albicans and Pseudomonas aeruginosa often co-occur in biofilm-based infections of the skin, lungs, and medical devices. Their predominantly antagonistic relationship involves complex physical and chemical interactions. However, the presence and implications of priority effects among these microorganisms remain largely unexplored. Here, we investigate the presence and impact of priority effect in dual-species biofilms using clinical isolates. By varying inoculation order, we observe significant changes in biofilm composition, structure, virulence, and antimicrobial susceptibility. The first colonizer has an advantage for surface colonization. Consecutive colonization increases biofilm virulence and negates C. albicans' protective effect on P. aeruginosa PAET1 against meropenem treatment. Finally, we propose N-acetylcysteine as an adjuvant for treating C. albicans and P. aeruginosa interkingdom infections, working independently of priority effects.
Rare Variant Association Analysis Uncovers Involvement of VNN2 in Stroke Outcome
(American Heart Association, 2025-09-01) Jiménez Conde, Jordi; Balcells Comas, Susana; Rabionet Janssen, Raquel; Rodríguez Campello, Ana; Vallverdú-Prats, Marta; Medina-Dols, Aina; Jimenez, Carmen; Tur, Silvia; Diaz-Navarro, Rosa M.; Bruque, Carlos-David; Andreu-Somavilla, Nuria; González-Navarrete, Irene; Casals López, Ferran; Alcaide Consuegra, ESTEFANIA; Mola Caminal, Marina; Escaramís Babiano, Geòrgia; Lazcano, Uxue; Fernández-Pérez, Isabel; Reig-Palou, Jaume; Jiménez-Balado, Joan; Giralt Steinhauer, Eva; Cuadrado-Godia, Elisa; Ois, Angel; Vives-Bauzà, Cristòfol; Fernandez-Cadenas, Israel
BACKGROUND:
A stroke’s functional outcome presents vast variability among patients, which is influenced by age, sex, characteristics of the lesion, and genetic factors. However, there is little knowledge about stroke recovery genetics. Recently, some GWAS (Genome-Wide Association Studies) have highlighted the involvement of common or low-frequency variants near or within PATJ, PPP1R21, PTCH1, NTN4, and TEK genes, whereas the role of rare variants is still unclear. This study aims to identify the genetic contributions to differences in stroke outcomes by analyzing the effect of rare variants.
METHODS:
We performed a pilot study analyzing 90 exomes of extreme good and bad recovery (modified Rankin Scale score at 3 months, 0–1 versus 4–5) to select target genes involved in stroke recovery. To expand this study, 702 additional samples were sequenced by targeted next-generation sequencing capturing loci selected from the pilot study, GWASs, and literature input. Here, we performed continuous (modified Rankin Scale score, 0–6) and dichotomous (modified Rankin Scale score, 0–1 versus 3–6) analyses, yielding 1 candidate gene. All samples were selected by a retrospective cohort study from incidental stroke cases collected at Spanish Hospitals between 2000 and 2018. The identified VNN2 variants were assessed for protein structure and stability analysis, and an analysis of their effect on basal inflammation levels was performed using UK Biobank data.
RESULTS:
Our work identified rare coding variants in VNN2 associated with patients with better stroke recovery (∆ deviance information criterion >10, equivalent to P<0.001). Six rare variants were predicted to significantly affect protein stability (∆∆G >1.6 kcal/mol); meanwhile, another variant, located in the active site, could affect the electrostatic surface.
CONCLUSIONS:
We propose that VNN2 might play a role in stroke outcomes by modulating poststroke inflammation. A potentially affected function would be neutrophil cell adhesion and migration.
Microbial and physicochemical parameters associated with Legionella contamination in hot water recirculation systems
(Springer Verlag, 2013-02-23) Serrano Suárez, Alejandra; Dellundé, Jordi; Salvadó i Cabré, Humbert; Cervero Aragó, Sílvia; Méndez Viera, Javier; Canals, Oriol; Blanco, Silvia; Arcas Pons, Antoni; Araujo Boira, Rosa Ma.
Hot water recirculation systems (HWRS) in hotels and nursing homes, which are common in countries such as Spain, have been related to outbreaks of legionellosis. To establish the relationships of microbial and physicochemical parameters, especially protozoa, with the occurrence of Legionella in HWRS, 231 samples from hotels and nursing homes were analysed for Legionella, protozoa, heterotrophic plate counts (HPC) at 22 and 37 °C, Pseudomonas, metals, temperature and others. Legionella pneumophila was the dominant species isolated, and 22 % were sg. 1. The sampling method became particularly important in order to define which factors were involved on the occurrence of Legionella. Results showed that the bacteria and the accompanying microbiota were more abundant in the first flush water whose temperature was lower. The bacteria occurred in those samples with high HPC and were inversely correlated with high temperatures. Multivariate regression showed that a concentration above 1× 105CFU/100 mL of HPC at 37 °C, Fe above 0.095 ppm and the presence of protozoa increased significantly the risk of Legionella colonization, while univariant regression showed that the presence of Cu above 0.76 ppm and temperature above 55 °C diminished it. Therefore, to reduce the risk associated with Legionella occurrence in HWRS these parameters should be taken into consideration.
Comparative Study of Iron and Trace Element Mobilization during Fe-Oxide Bioreduction in Mine Tailings: a case study of Ensenada Chapaco (Chile) and Portman Bay (Spain)
((UB). (ICTJA). (IDEA). (UAB). (CSIC), 2025-02) Benaiges-Fernández, Robert; Palau, Jordi; Urmeneta, Jordi; Cama, Jordi; Soler, Josep M.; Dold, Bernhard
Bioreduction of Feoxides in mine tailings deposited under marine conditions releases Fe and associated trace elements (e.g. Ti, Ni, Cd, Pb), leading to contamination of the marine environment. Sea-Tailings Disposal (STD) along the northern coast of Chile (Ensenada Chapaco) and along the eastern coast of Spain (Portman Bay) results in an adverse impact on the environment. This paper focuses on bioreduction under marine conditions. To this end, two column experiments were carried out with samples from Portman Bay and Ensenada Chapaco. Lactate (i.e.organic matter source) was supplied during the experiments. The results obtained are compared with those from batch experiments performed under similar conditions.In the column filled with Portman Bay tailings, the high content of magnetite (15wt%) in contact with water gives rise to a large magnetite surface area and abundant Fe(III), which results in a high release of Fe(II) and Trace Elements (TE). Since Fe(II) adsorbs onto the magnetite surface reducing the availability of Fe(III), the magnetite bioreduction and the consequent TE release decrease after 2000h. By contrast, the magnetite bioreduction lasts longer (3000h) in the column with Ensenada Chapaco tailings. This is because a lower magnetite content in the tailings (1wt%) provides a smaller reactive surface area yielding less Fe(III). Consequently, the concentrations of Fe(II) and TE in the output solutions are lower, which slows down the Fe(II) adsorption onto magnetite. This results in a longer magnetite bioreduction. Bioreduction is regulated by the availability of Fe(III) in both columns. It is inferred that the bioreduction rate diminishes as a function of time and increases as a function of soluble Fe(II) concentration. Moreover, the concentrations of TE released from the two bioreduced tailings exceed the elemental concentrations under marine conditions.

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