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Trusting the forces of our cell lines
(Elsevier, 2024-09-01) Moro López, Marina; Farré Ventura, Ramon; Otero Diaz, Jorge; Sunyer Borrell, Raimon
Cells isolated from their native tissues and cultured in vitro face different selection pressures than those cultured in vivo. These pressures induce a profound transformation that reshapes the cell, alters its genome, and transforms the way it senses and generates forces. In this perspective, we focus on the evidence that cells cultured on conventional polystyrene substrates display a fundamentally different mechanobiology than their in vivo counterparts. We explore the role of adhesion reinforcement in this transformation and to what extent it is reversible. We argue that this mechanoadaptation is often understood as a mechanical memory. We propose some strategies to mitigate the effects of on-plastic culture on mechanobiology, such as organoid-inspired protocols or mechanical priming. While isolating cells from their native tissues and culturing them on artificial substrates has revolutionized biomedical research, it has also transformed cellular forces. Only by understanding and controlling them, we can improve their truthfulness and validity.
Bladder EpiCheck clinical utility to predict BCG response in non-muscle-invasive bladder cancer
(Wiley, 2025-10-01) Roldán, Fiorella L.; Ingelmo-Torres, Mercedes; Mercader Barrull, Clàudia; Figueras Torras, Marcel; Padullés, Bernat; Durán González, María Angeles; Carrasco Jordan, Josep Lluís; Ribal, María José; Franco de Castro, Agustín; Izquierdo Reyes, Laura; Alcaraz Asensio, Antonio; Mengual Brichs, Lourdes
Objective: To evaluate the performance of Bladder Epicheck® (BE; Nucleix Ltd., Rehovot, Israel) in predicting tumour recurrence and bacillus Calmette-Guérin (BCG) failure during the first year after induction treatment. Patients and methods: Prospective study including 65 patients with non-muscle-invasive bladder cancer treated with BCG between 2018 and 2021. Urine samples analysed with BE were collected before and after BCG induction. Logistic binary regression was used to assess the association between clinical and pathological variables and BE results with tumour recurrence and BCG failure during the first year after induction treatment. Results: During follow-up, 16 (24.6%) patients experienced a bladder cancer event, 11 (68.8%) of which were BCG failure (high-grade recurrence) and five (31.2%) were low-grade recurrences. The median (range) time to overall recurrence was 7.3 (3.8-17.4) months. A significant association was found between the risk of tumour recurrence/BCG failure and post-BCG cystoscopy (odds ratio [OR] 10.0; P < 0.001 and OR 13.1; P < 0.001, respectively), post-BCG BE result (OR 16.9; P < 0.001 and OR 33.1; P < 0.001, respectively) and pre/post-BCG EpiScore value variation (OR 14.4; P = 0.001 and OR 7.1; P = 0.018, respectively). A nomogram including these three variables outperformed the Club Urológico Español de Tratamiento Oncológico (CUETO) risk tables to predict any bladder cancer event after BCG induction (area under the curve 95.1% vs 67.1%). Result validation in a larger and independent series is needed. Conclusions: The BE post-BCG status and variations in EpiScore values can help us identify patients at higher risk of any bladder cancer event and BCG failure promptly. These data can have an impact on disease management.
Prospective validation of the EASL management algorithm for acute kidney injury in cirrhosis
(Elsevier, 2024-09) Ma, Ann T.; Solé, Cristina; Juanola Mayos, Adrià ; Escudé, Laia; Napoleone, Laura; Avitabile, Emma; Pérez-Guasch, Martina; Carol, Marta; Pompili, Enrico; Gratacós Ginès, Jordi; Soria, Anna; Rubio, Ana Belén; Cervera Carbonell, Marta; Moreta, Maria José; Morales Ruiz, Manuel; Solà, Elsa; Poch, Esteban; Fabrellas i Padrès, Núria; Graupera, Isabel; Pose Méndez, Elisa; Ginès i Gibert, Pere
Background & Aims The management of acute kidney injury (AKI) in cirrhosis is challenging. The EASL guidelines proposed an algorithm for the management of AKI, but this has never been validated. We aimed to prospectively evaluate this algorithm in clinical practice. Methods We performed a prospective cohort study in consecutive hospitalized patients with cirrhosis and AKI. The EASL management algorithm includes identification/treatment of precipitating factors, 2-day albumin infusion in patients with AKI ≥stage 1B, and treatment with terlipressin in patients with hepatorenal syndrome (HRS-AKI). The primary outcome was treatment response, which included both full and partial response. Secondary outcomes were survival and adverse events associated with terlipressin therapy. Results A total of 202 AKI episodes in 139 patients were included. Overall treatment response was 80%, while renal replacement therapy was required in only 8%. Response to albumin infusion was achieved in one-third of episodes. Of patients not responding to albumin, most (74%) did not meet the diagnostic criteria of HRS-AKI, with acute tubular necrosis (ATN) being the most common phenotype. The response rate in patients not meeting the criteria for HRS-AKI was 70%. Only 30 patients met the diagnostic criteria for HRS-AKI, and their response rate to terlipressin was 61%. Median time from AKI diagnosis to terlipressin initiation was only 2.5 days. While uNGAL (urinary neutrophil gelatinase-associated lipocalin) could differentiate ATN from other phenotypes (AUROC 0.78), it did not predict response to therapy in HRS-AKI. Ninety-day transplant-free survival was negatively associated with MELD-Na, ATN and HRS-AKI as well as uNGAL. Three patients treated with terlipressin developed pulmonary edema. Conclusions The application of the EASL AKI algorithm is associated with very good response rates and does not significantly delay initiation of terlipressin therapy. Impact and implications The occurrence of acute kidney injury (AKI) in patients with cirrhosis is associated with poor short-term mortality. Improving its rapid identification and prompt management was the focus of the recently proposed EASL AKI algorithm. This is the first prospective study demonstrating that high AKI response rates are achieved with the use of this algorithm, which includes identification of AKI, treatment of precipitating factors, a 2-day albumin challenge in patients with AKI ≥1B, and supportive therapy in patients with persistent AKI not meeting HRS-AKI criteria or terlipressin with albumin in those with HRS-AKI. These findings support the use of this algorithm in clinical practice.
Adhesion G protein-coupled receptors
(Elsevier, 2026-05-01) Langenhan, Tobias; Anderson, Garret R.; Araç, Demet; Aust, Gabriela; Avila Zozaya, Monserrat; Bagger, Sofie Morsing; Barth, Patrick; Berndt, Sandra; Blacklow, Stephen C.; Blanco Redondo, Beatriz; Boucard, Antony A.; Bridges, James; Brodmerkel, Lara Sophie; Caron, Kathleen M.; Yin, Kwan Chung; Dates, Andrew N.; Araujo Farias, Virginea de; Toro Ruiz, Daniel del; Duman, Joseph G.; Engel, Felix B.; Favara, David M.; Formstone, Caroline J.; Fu, Chaoyu; Garcia De Las Bayonas, Alain; Georgiadi, Anastasia; Gloriam, David E.; Hall, Randy A.; Hamann, Jörg; Hildebrand, Peter W.; Hsiao, Cheng-Chih; Huang, Bill X.; Javitch, Jonathan A.; Kim, Hee-Yong; Kittel, Robert J.; Kleinau, Gunnar; Leduc, Richard; Liebscher, Ines; Lin, Hsi-Hsien; Linnert, Joshua; Ludwig, Marie Gabrielle; Martinelli, David C.; Mathiasen, Signe; Matúš, Daniel; Melkumyan, Mariam; Moreno Salinas, Ana L.; Mulder, Jan; Nash, Michael; Pal, Kasturi; Pederick, Daniel T.; Perry Hauser, Nicole A.; Piao, Xianhua; Ping, Yu-Qi; Placantonakis, Dimitris G.; Pohl, Fabian; Prömel, Simone; Rosenkilde, Mette M.; Sabbagh, Laurent; Sando, Richard C.; Scheerer, Patrick; Schöneberg, Torsten; Seiradake, Elena; Selcho, Mareike; Seufert, Florian; Singh, Abhishek Kumar; Skiniotis, Georgios; Spiess, Katja; Sträter, Norbert; Strutt, David; Südhof, Thomas C.; Sun, Jinpeng; Tall, Gregory G.; Thor, Doreen; Tilley, Douglas G.; Tolias, Kimberley F.; Vallon, Mario; Meir, Erwin G. Van; Vanhollebeke, Benoit; Wiggin, Giselle R.; Wolfrum, Uwe; Yan, Jie; Zaidman, Nathan A.; Zou, Yimin; Scholz, Nicole
Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and to establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly evident. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in the field and provides a comprehensive assessment of the current understanding of aGPCR biology here. This includes a focus on human and mammalian aGPCRs, their evolutionary origins, methodological approaches and model systems for their investigation, as well as emerging approaches for their therapeutic targeting
Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones
(Elsevier, 2026-03-27) Thampi, Namitha; Calvo, Cristina; Rodríguez Cortez, Virginia Carolina; Martínez-Moreno, Alba; Roca-Ho, Heleia; Vinyoles, Meritxell; Bueno, Clara; Espinosa-Aroca, Lady; Pablo-Fontecha, Verónica; Camps, Jordi; Fuente-González, A. de la; Puente, Xose S; Solé, Francesc; Foijer, Floris; Menéndez Buján, Pablo; Molina, Òscar
Aneuploidy is a hallmark of cancer but often reduces cellular fitness. In childhood B cell acute lymphoblastic leukemia (cB-ALL), hyperdiploidy is the most common cytogenetic abnormality and arises in utero from early hematopoietic stem/progenitor cells (HSPCs), yet its impact on early hematopoiesis remains unclear. We model two proposed routes to hyperdiploidy, chromosome mis-segregation and cytokinesis failure, by transiently exposing human fetal liver-derived HSPCs to reversine or cytochalasin D. Induced hyperdiploidy impaired fitness and delayed differentiation in vitro, causing hyperdiploid cells to be rapidly outcompeted by euploid counterparts. Nonetheless, hyperdiploid cells engrafted immunodeficient mice, where rare clones persisted long term and acquired non-random chromosomal gains frequently observed in cB-ALL. Despite this persistence, they did not initiate leukemia. These findings support a two-step model in which hyperdiploid fetal clones require additional perinatal/postnatal events for malignant transformation. Our work establishes a valuable human model for studying early aneuploidy-driven events in childhood leukemia.
Decoding the Conformation of Polylactic Acid in Block Copolymer Micelles
(American Chemical Society, 2026-01-28) Muñoz López, José María; Tuveri, Gian Marco; Barbieri, Valentino; Basile, Marco; Cosenza, V.; Lorenz, Christian D.; Ruiz-Perez, Lorena; Battaglia, Giuseppe
Understanding how molecular features dictate the self-assembly of amphiphilic block copolymers into well-defined nanostructures is essential for the rational design of advanced soft materials. However, the large number of interdependent parameters involved, such as particle size, aggregation number, interfacial curvature, and molecular weight, makes it challenging to establish general design principles. Here we establish a scaling-based framework for PEG-b-PLA micelles with a fixed hydrophilic–hydrophobic ratio. Systematic variation of molecular weights enables precise control of micelle size and aggregation number, quantified by DLS, cryo-TEM, and MALS.
Biocompatible 3D printed yttria-stabilized zirconia parts using direct ink writing
(SAGE Publications, 2024) Buj Corral, Irene; Sanz Fraile, Héctor; Tejo-Otero, Aitor; Vidal, Daniel; Padilla Sanchez, Jose Antonio; Xuriguera Martín, María Elena; Otero Diaz, Jorge
Metals such as titanium or Cr-Co alloys have been the most widely used materials in biomedical applications that requirehigh mechanical properties, like implants. However, these materials present the disadvantage of releasing ion metals intothe body. As an alternative, prostheses made of ceramic materials have been developed, as they produce less debris andhave better durability. The aim of the present work is to test the biocompatibility of 3D-printed yttria-stabilized zirconia
parts by culturing human bone-marrow-derived mesenchymal stem cells. Two different scaffols were 3D printed having a
liner infill pattern, with 80 % and 95 % infill rate respectively. Results on surface roughness and biocompatibility tests
confirmed that 3 mol % yttria-stabilized zirconia is a highly promising material as it presented high biocompatibility. In adition,
similar results were obtained with or without the use of a type I collagen coating., which suggest that coating couldbe avoided when on zirconia substraes.
Low-dose cannabidiol treatment prevents chronic stress-induced phenotypes and is associated with multiple synaptic changes across various brain regions
(Elsevier Ltd., 2025-05-21) Borràs Pernas, Sara; Sancho Balsells, Anna; Patterer, Lisa; Wang, Maoyu; Toro Ruiz, Daniel del; Alberch i Vié, Jordi, 1959-; Schibano, Daniele; Espel, Joan; Heybeck, Maya; Scheidel, Bernhard; Giralt Torroella, Albert
Major Depressive Disorder (MDD) is a heterogeneous and debilitating mood disorder often associated with stress. Although current treatments are available, they remain ineffective for approximately 30 % of affected individuals and are frequently accompanied by undesirable side effects. Cannabidiol (CBD) has emerged as a potential and safe therapeutic option for alleviating depressive symptoms; however, the underlying molecular mechanisms through which this compound exerts its beneficial effects are not yet fully understood. In this study, we demonstrate that a very low dose of CBD (1 mg/kg) can partially reverse some sequelae induced by chronic stress, a well-established mouse model used to simulate depressive-like symptoms. Using mass spectrometry to analyze different brain regions, we observed several improvements following CBD treatment, particularly in the medial prefrontal cortex (mPFC), across multiple neurotransmission systems (including glutamatergic and serotonergic pathways). Microstructural experiments, utilizing double-labeling of F-Actin and VGlut1-positive clusters, revealed a complete restoration of mature synapses in the mPFC of mice treated with CBD. In conclusion, our findings indicate that a very low dose of CBD is effective in counteracting the adverse effects of chronic stress, possibly through the synaptic remodeling of excitatory synapses in the mPFC.
Cortex folding by combined progenitor expansion and adhesion-controlled neuronal migration
(Nature Publishing Group, 2025-08-28) Chun, Seung Hee; Yoon, Da Eun; Diaz Almeida, Daniel Santiago; Todorov, Mihail Ivilinov; Straub, Tobias; Ruff, Tobias; Shao, Wei; Yang, Jianjun; Seyit Bremer, Gönül; Shen, Yi-Ru; Ertürk, Ali; Toro Ruiz, Daniel del; Shi, Songhai; Klein, Rüdiger
Folding of the mammalian cerebral cortex into sulcal fissures and gyral peaks is the result of complex processes that are incompletely understood. Previously we showed that genetic deletion of Flrt1/3 adhesion molecules causes folding of the smooth mouse cortex into sulci resulting from increased lateral dispersion and faster neuron migration, without progenitor expansion. Here, we show in mice that combining the Flrt1/3 double knockout with an additional genetic deletion that causes progenitor expansion, greatly enhances cortex folding. Expansion of intermediate progenitors by deletion of Cep83 leads to a relative increase in Flrt-mutant neurons resulting in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 leads to a relative reduction in Flrt-mutant neurons resulting in enhanced formation of gyri. These results together with computational modeling identify key developmental mechanisms, such as adhesive properties, cell densities and migration of cortical neurons, that cooperate to promote cortical gyrification.
Identification of a crosstalk between ClC-1 C-terminal CBS domains and the transmembrane region
(The Physiological Society, 2025-02-07) Gaitán-Peñas, Héctor; Pérez González, Anna Priscil·la; González Subías, Marc; Zdebik, Anselm A.; Gasull Casanova, Xavier; Buey, Ruben M.; Errasti-Murugarren, Ekaitz; Estévez Povedano, Raúl
CLC channels and transporters have large C-terminal regions which contain two cystathionine β-synthetase (CBS) domains. It has been hypothesized that conformational changes in these domains upon nucleotide binding modulate the gating of the CLC dimer. It is not clear how rearrangements that occur in the CBS domains are transmitted to the ion pathway, as CBS domains interact with the rest of the channel at multiple locations and some of these sites are not visible in recent solved cryogenic electron microscopy structures or are difficult to model using the AlphaFold server. Using ClC-1 as a model, we started working with a described ClC-1 mutation (H835R) located in the first alpha helix of the CBS2 domain which changes the voltage dependence of gating. We then identified several residues located in the disorganized loop after helix R (R-linker) that revert the phenotype of this mutation. We additionally proved that R-linker's function is connected to the CBS2 domain as current intensity, plasma membrane levels and gating defects of several R-linker variants were corrected by adding the mutation H835R. Furthermore, cross-linking studies using newly developed split-cysless ClC-1 channels containing specific cysteine mutants in the R-linker and the CBS2 domain indicate that these two regions are in close contact. Considering these new results, we propose that conformational changes occurring in the CBS domains could be transmitted to the CLC intracellular chloride binding site by means of its interaction with the R-linker.
Protocol for tailored in vitro neuronal networks on high-density microelectrode arrays with polydimethylsiloxane microstructures
(Elsevier B.V., 2026-03-20) Haeb, Anna-Christina; Yamamoto, Hideaki; Roach, Paul; Merryweather, Daniel; Sato, Y.; Tornero, Daniel; Soriano i Fradera, Jordi
Complementary metal-oxide-semiconductor (CMOS)-based high-density microelectrode arrays (HD-MEAs) enable neuronal recordings with high spatiotemporal resolution. However, integrating polydimethylsiloxane (PDMS) microstructures onto HD-MEA surfaces to control network architecture is currently challenging and platform specific. Here, we present a protocol for PDMS fabrication, HD-MEA chip preparation, PDMS-HD-MEA microstructure alignment, and cell culture, including alternatives. Our results show reproducible formation of modular networks with characteristic activity patterns across different systems. This protocol supports engineering of defined neuronal architectures while maintaining compatibility with various HD-MEA systems.
Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation
(Springer Verlag, 2024-03-27) García Lunar, Inés; Jorge, Inmaculada; Sáiz, Jorge; Solanes, Núria; Dantas, Ana Paula; Rodríguez Arias, Juan José; Ascaso, María; Galán Arriola, Carlos; Jimenez Trinidad, Francisco Rafael; Sandoval, Elena; Nuche, Jorge; Moran Garrido, Maria; Camafeita, Emilio; Rigol Muxart, Montserrat; Sánchez González, Javier; Fuster, Valentín; Vázquez, Jesus; Barbas, Coral; Ibáñez Cabeza, Borja; Pereda, Daniel; García Álvarez, Ana
Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine–histidine–purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH.
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.
Mapping mechanical stress in curved epithelia of designed size and shape
(Nature Publishing Group, 2023-07-07) Marín Llauradó, Ariadna; Kale, Sohan; Ouzeri, Adam; Golde, Tom; Sunyer Borrell, Raimon; Torres Sánchez, Alejandro; Latorre Ibars, Ernest; Gómez González, Manuel; Roca-Cusachs Soulere, Pere; Arroyo, Marino; Trepat Guixer, Xavier
The function of organs such as lungs, kidneys and mammary glands relies on the three-dimensional geometry of their epithelium. To adopt shapes such as spheres, tubes and ellipsoids, epithelia generate mechanical stresses that are generally unknown. Here we engineer curved epithelial monolayers of controlled size and shape and map their state of stress. We design pressurized epithelia with circular, rectangular and ellipsoidal footprints. We develop a computational method, called curved monolayer stress microscopy, to map the stress tensor in these epithelia. This method establishes a correspondence between epithelial shape and mechanical stress without assumptions of material properties. In epithelia with spherical geometry we show that stress weakly increases with areal strain in a size-independent manner. In epithelia with rectangular and ellipsoidal cross-section we find pronounced stress anisotropies that impact cell alignment. Our approach enables a systematic study of how geometry and stress influence epithelial fate and function in three-dimensions.
Mutation in KARS: A novel mechanism for severe anaphylaxis
(Mosby, 2020-12-29) Ribó, Pau; Guo, Yanru; Aranda Moratalla, Juan; Ainsua Enrich, Erola; Navinés Ferrer, Arnau; Guerrero, Mario; Pascal i Capdevila, Mariona; Cruz, Cinthia de la; Orozco López, Modesto; Muñoz-Cano, Rosa; Martín Andorrà, Margarita
Background: Anaphylaxis is a severe allergic reaction that can be lethal if not treated adequately. The underlying molecular mechanisms responsible for the severity are mostly unknown. Objective: This study is based on a clinical case of a patient with extremely severe anaphylaxis to paper wasp venom. This patient has a mutation in the KARS gene, which encodes lysyl-tRNA synthetase (LysRS), a moonlight protein with a canonical function in protein synthesis and a noncanonical function in antigen dependent-FcεRI activation in mast cells. In this study, the objective was to characterize the mutation at the molecular level. Methods: Analysis of the KARS mutation was carried out using biochemical and functional approaches, cell transfection, Western blot, confocal microscopy, cell degranulation, prostaglandin D2 secretion, and proteases gene transcription. Structural analysis using molecular dynamics simulations and well-tempered metadynamics was also performed. Results: The mutation found, P542R (proline was replaced by arginine at aminoacid 542), affects the location of the protein as we show in biochemical and structural analyses. The mutation resembles active LysRS and causes a constitutive activation of the microphthalmia transcription factor, which is involved in critical mast cell functions such as synthesis of mediators and granule biogenesis. Moreover, the structural analysis provides insights into how LysRS works in mast cell activation. Conclusions: A link between the aberrant LysRS-P542R function and mast cell-exacerbated activation with increase in proinflammatory mediator release after antigen-IgE-dependent response could be established.
Clinical and Lung Microbiome Impact of Chronic Versus Intermittent Pseudomonas aeruginosa Infection in Bronchiectasis
(Elsevier, 2025-03-18) Vila Estapé, Jordi; Martínez Hernández, Daniel; Otero Diaz, Jorge; Farré Ventura, Ramon; Høiby, Niels; Torres Martí, Antoni; Fernández Barat, Laia; López Aladid, Rubén; Alcaraz Serrano, Victoria; Vázquez Burgos, Nil; Bueno Freire, Leticia; Pastor Ibáñez, Roque; Lingren, Lena; Sanz Fraile, Héctor; Oscanoa Huamán, Patricia; Motos Galera, Ana; Cabrera Ortega, Roberto
Background: In patients with non-cystic fibrosis bronchiectasis (BE) Pseudomonas aeruginosa (PA) has been recently associated with low rather than high number of exacerbations without distinguishing chronic versus intermittent infection. The aim of our study was to determine whether the intermittent or chronic stage of P. aeruginosa (PA) infection is associated with the rate of exacerbations, quality of life and respiratory microbiome biodiversity after a one-year follow-up. Methods: We conducted a longitudinal study, with 1-year follow-up, in patients with BE intermittently or chronically infected by PA involving sequential (3-monthly) measurements of microbiological (cultures, PA load, phenotype and biofilms presence) immunological (Serum IgGs against P. aeruginosa were measured by ELISA immunoassay) and clinical variables (Quality-of-Life and the number exacerbations). Additionaly, 16S sequencing was performed on a MiSeq Platform and compared between chronically infected patients with the mucoid PA versus intermittently infected patients with the non-mucoid PA. Results: We collected 235 sputa and 262 serum samples from 80 BE patients, 61 with chronic and 19 with intermittent PA infection. Chronically compared to intermittently. Presented reduced quality of life but less hospitalized exacerbations after 1-year follow-up. Chronically infected patients presented reduced sputum biodiversity and higher systemic IgGs against P. aeruginosa levels that were associated to decreased number of hospitalized exacerbations. Conclusions: The assessment of Chronic versus intermittent P. aeruginosa infection has clinical implications such as quality of life, rate of hospitalized exacerbations and lung microbiome biodiversity. The distinction of these two phenotypes is easy to perform in clinical practice.
Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina
(Elsevier, 2022-10-10) Barbacena, Pedro; Dominguez Cejudo, Maria; Fonseca, Catarina G.; Gómez González, Manuel; Faure, Laura M.; Zarkada, Georgia; Pena, Andreia; Pezzarossa, Anna; Ramalho, Daniela; Giarratano, Ylenia; Ouarné, Marie; Barata, David; Fortunato, Isabela Corina Santos; Henao Misikova, Lenka; Mauldin, Ian; Carvalho, Yulia; Trepat Guixer, Xavier; Roca-Cusachs Soulere, Pere; Eichmann, Anne; Bernabeu, Miguel O.; Franco, Claudio A.
Blood-vessel formation generates unique vascular patterns in each individual. The principles governing the apparent stochasticity of this process remain to be elucidated. Using mathematical methods, we find that the transition between two fundamental vascular morphogenetic programs—sprouting angiogenesis and vascular remodeling—is established by a shift of collective front-to-rear polarity of endothelial cells in the mouse retina. We demonstrate that the competition between biochemical (VEGFA) and mechanical (blood-flow-induced shear stress) cues controls this collective polarity shift. Shear stress increases tension at focal adhesions overriding VEGFA-driven collective polarization, which relies on tension at adherens junctions. We propose that vascular morphogenetic cues compete to regulate individual cell polarity and migration through tension shifts that translates into tissue-level emergent behaviors, ultimately leading to uniquely organized vascular patterns.
Cerebrospinal fluid cytokines in multiple system atrophy: A cross-sectional Catalan MSA registry study
(Elsevier B.V., 2019-08-01) Compta, Yaroslau; Dias, Sara P.; Giraldo, Darly M.; Pérez Soriano, Alexandra; Muñoz, Esteban; Saura Martí, Josep; Fernández, Manel; Bravo, Paloma; Cámara, Ana; Pulido Salgado, Marta; Painous Martí, Cèlia; Rios, Jose; Martí Domènech, Ma. Josep; CMSAR consortium
Introduction Neuroinflammation is a potential player in neurodegenerative conditions, particularly the aggressive ones, such as multiple system atrophy (MSA). Previous reports on cytokine levels in MSA using serum or cerebrospinal fluid (CSF) have been inconsistent, including small samples and a limited number of cytokines, often without comparison to Parkinson's disease (PD), a main MSA differential diagnosis. Methods Cross-sectional study of CSF levels of 38 cytokines using a multiplex assay in 73 participants: 39 MSA patients (19 with parkinsonian type [MSAp], 20 with cerebellar type [MSAc]; 31 probable, 8 possible), 19 PD patients and 15 neurologically unimpaired controls. None of the participants was under non-steroidal anti-inflammatory drugs at the time of the lumbar puncture. Results There were not significant differences in sex and age among participants. In global non-parametric comparisons FDR-corrected for multiple comparisons, CSF levels of 5 cytokines (FGF-2, IL-10, MCP-3, IL-12p40, MDC) differed among the three groups. In pair-wise FDR-corrected non-parametric comparisons 12 cytokines (FGF-2, eotaxin, fractalkine, IFN-α2, IL-10, MCP-3, IL-12p40, MDC, IL-17, IL-7, MIP-1β, TNF-α) were significantly higher in MSA vs. non-MSA cases (PD + controls pooled together). Of these, MCP-3 and MDC were the most significant ones, also differed in MSA vs. PD, and were significant MSA-predictors in binary logistic regression models and ROC curves adjusted for age. CSF levels of fractalkine and MIP-1α showed a strong and significant positive correlation with UMSARS-2 scores. Conclusion Increased CSF levels of cytokines such as MCP-3, MDC, fractalkine and MIP-1α deserve consideration as potential diagnostic or severity biomarkers of MSA.
3D Micropatterned Traction Force Microscopy: A Technique to Control 3D Cell Shape While Measuring Cell-Substrate Force Transmissio
(Wiley-VCH Verlag, 2024-10-23) Faure, Laura M.; Gómez González, Manuel; Baguer, Ona; Comelles Pujadas, Jordi; Martínez, Elena; Arroyo, Marino; Trepat Guixer, Xavier; Roca-Cusachs Soulere, Pere
Cell shape and function are intimately linked, in a way that is mediated by the forces exerted between cells and their environment. The relationship between cell shape and forces has been extensively studied for cells seeded on flat 2D substrates, but not for cells in more physiological 3D settings. Here, a technique called 3D micropatterned traction force microscopy (3D-µTFM) to confine cells in 3D wells of defined shape, while simultaneously measuring the forces transmitted between cells and their microenvironment is demonstrated. This technique is based on the 3D micropatterning of polyacrylamide wells and on the calculation of 3D traction force from their deformation. With 3D-µTFM, it is shown that MCF10A breast epithelial cells exert defined, reproducible patterns of forces on their microenvironment, which can be both contractile and extensile. Cells switch from a global contractile to extensile behavior as their volume is reduced are further shown. The technique enables the quantitative study of cell mechanobiology with full access to 3D cellular forces while having accurate control over cell morphology and the mechanical conditions of the microenvironment.
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.

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