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El objetivo principal es el desarrollo de materiales educativos y pedagógicos contra el estigma, que abordan la problemática de la salud mental y el malestar emocional, a través del análisis y el trabajo sobre obras artísticas (fotografías, esculturas, partituras, textos escritos, etc) elaboradas por estudiantes universitarios que han sufrido o sufren experiencias y procesos de depresión, ansiedad y/o malestar emocional. El material desarrollado servirá para un aprendizaje profundo y significativo de distintas formas de abordar los problemas de salud mental, desde una perspectiva no estigmatizante, por parte del alumnado que pueda beneficiarse del proyecto presentado. Se han desarrollado los siguientes materiales: 1. Módulo “¿Qué es la salud mental?”; 2. Módulo “Salud, bienestar e Inclusión social a través del Arte y la Cultura”; 3. Módulo “Análisis sociológico del discurso”; 4. Módulo “Ejercicios prácticos: Mitos y realidades en salud mental”; 5. Guion de trabajo durante las sesiones; 6. Guía “Análisis para el trabajo con las obras seleccionadas”. Este material se ha incluido como contenido interactivo en la herramienta online Genially y puede ser consultado en el siguiente enlace: https://view.genially.com/661cff2010ced40014bdbc09 more...

The innate immune system represents the first defense barrier against pathogens and cellular perturbations in higher eukaryotes. Its response relies on SMOCs (supramolecular organizing centers):complexes composed of a receptor, adaptor, and effector protein that are recruited sequentially under the proper stimulus to coordinate the cellular response. This unique system helps to amplify the signal,although their functioning and regulation are still under study. The NLRP3 [NLR [NOD (nucleotideoligomerization domain)-like receptor] family pyrin domain-containing 3] inflammasome and theFas/CD95 (cluster of differentiation 95) DISC (death-inducing signaling complex), which regulate pyroptosis and extrinsic apoptosis, respectively, constitute two great examples of human SMOCs. Besides, when cellular damage exceeds a threshold, the innate immune system promotes the induction of regulated-cell death programs to protect the organism, among which pyroptosis and necroptosis play a prominent role. Their effectors, GSDMD (Gasdermin D) and MLKL (mixed lineagekinase domain like pseudokinase), respectively, are pore-forming proteins that trigger the disruptionof the plasma membrane and, thus, cell death. They differ in their mechanism of activation, byproteolysis and phosphorylation, respectively. However, they also target intracellular compartmentsby a mechanism not fully understood. Saccharomyces cerevisiae has long been used as a eukaryotic model to characterize proteins associated with human diseases, including those involved in the innate immune response, due to the numerous advantages provided by this microorganism and the high degree of conservation between human and yeast cellular structures and signaling pathways..., El sistema inmune innato representa la primera barrera de defensa contra patógenos y daños celulares en eucariotas superiores. Su respuesta se apoya en los SMOCs(centros organizadores supramoleculares): complejos formados por un receptor, un adaptador y un efector que son reclutados secuencialmente en presencia del estímulo adecuado para coordinar la respuesta celular. Este sistema único ayuda a amplificar la señal, aunque su funcionamiento y regulación todavía están siendo estudiados. El inflamasoma de NLRP3 [NLR [NOD (nucleotide oligomerization domain)-likereceptor] family pyrin domain-containing 3] y el DISC (death-inducing signaling complex) de Fas/CD95(cluster of differentiation 95), que regulan la piroptosis y la apoptosis extrínseca, respectivamente, constituyen dos ejemplos de SMOCs en células humanas. Además, cuando el daño celular supera un determinado límite, el sistema inmune innato promueve la inducción de los programas de muerte celular regulada para proteger al organismo, entre los que sobresalen la piroptosis y la necroptosis. Sus efectores, la GSDMD (Gasdermina D) y MLKL (mixed lineage kinase domain like pseudokinase), respectivamente, son proteínas formadoras de poros que desencadenan la ruptura de la membrana plasmática y, como consecuencia, la muerte celular. Esas proteínas difieren en su mecanismo de activación, por proteolisis y fosforilación, respectivamente. Sin embargo, también afectan a compartimentos intracelulares mediante un mecanismo que todavía no se comprende completamente. Saccharomyces cerevisiae se ha utilizado desde hace mucho tiempo como modelo eucariótico para el estudio de proteínas asociadas a enfermedades humanas, incluyendo aquellas relacionadas con la respuesta inmune innata, gracias a las numerosas ventajas que proporciona este microorganismo y al alto grado de conservación entre las estructuras celulares y las rutas de señalización humanas y fúngicas... more...

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR/Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across patient derived models of DIPG, highlighting the therapeutic potential of the blood-brain barrier–penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human-equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors. To exploit genetic dependence and overcome resistance while maintaining compliance and therapeutic benefit, we combined paxalisib with the antihyperglycemic drug metformin. Metformin restored glucose homeostasis and decreased phosphorylation of the insulin receptor in vivo, a common mechanism of PI3K-inhibitor resistance, extending survival of orthotopic models. DIPG models treated with paxalisib increased calcium-activated PKC signaling. The brain penetrant PKC inhibitor enzastaurin, in combination with paxalisib, synergistically extended the survival of multiple orthotopic patient-derived and immunocompetent syngeneic allograft models; benefits potentiated in combination with metformin and standard-of-care radiotherapy. Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-Seq, identifying changes in myelination and tumor immune microenvironment crosstalk. Collectively, this study has identified what we believe to be a clinically relevant DIPG therapeutic combinational strategy. more...

The demand for digital skills for life and work is growing every day. There is currently a Digital Education Action Plan (2021-2027), an initiative of the European Union (EU) to support the effective adaptation of education and training of all EU members in the digital age. The aim of this study is therefore to determine the level of digital competence of students at the Faculty of Business, Finance and Tourism of the University of Extremadura (Spain) and to identify whether or not there is a gender digital divide. To this end, a sample of 332 students from the aforementioned faculty was selected and, by applying the Digital Competences in Higher Education Questionnaire (CDES), the data collected were analysed using the SPSS software. The results of the study reflect a high level of digital competences (64.8%), 65.9% being male and 68.6% female, concluding, therefore, that there is no gender digital divide in our study universe., La demanda de competencias digitales para la vida y el trabajo es cada día mayor. Existiendo en la actualidad el Plan de Acción de Educación Digital (2021-2027), una iniciativa de la Unión Europea (UE) para apoyar una adaptación eficaz de la educación y formación de todos los miembros de la UE en la era digital. Se pretende por tanto con este estudio, determinar el nivel de competencia digital del alumnado de la Facultad de Empresa, Finanzas y Turismo de la Universidad de Extremadura (España) e identificar si existe o no, una brecha digital de género. Para ello, se ha seleccionado una muestra de 332 alumnos de la citada facultad y, mediante la aplicación del Cuestionario de Competencias Digitales en Educación Superior (CDES), se han analizado los datos recogidos con el programa informático SPSS. Los resultados del trabajo reflejan un alto nivel de competencias digitales (67,19%), siendo el 65,9% hombres y el 68,6% las mujeres concluyendo, por tanto, que no existe brecha digital de género en nuestro universo de estudio. more...

Single-cell transcriptomics has emerged as the preferred tool to define cell identity through the analysis of gene expression signatures. However, there are limited studies that have comprehensively compared the performance of different scRNAseq systems in complex tissues. Here, we present a systematic comparison of two well-established high throughput 3'-scRNAseq platforms: 10× Chromium and BD Rhapsody, using tumours that present high cell diversity. Our experimental design includes both fresh and artificially damaged samples from the same tumours, which also provides a comparable dataset to examine their performance under challenging conditions. The performance metrics used in this study consist of gene sensitivity, mitochondrial content, reproducibility, clustering capabilities, cell type representation and ambient RNA contamination. These analyses showed that BD Rhapsody and 10× Chromium have similar gene sensitivity, while BD Rhapsody has the highest mitochondrial content. Interestingly, we found cell type detection biases between platforms, including a lower proportion of endothelial and myofibroblast cells in BD Rhapsody and lower gene sensitivity in granulocytes for 10× Chromium. Moreover, the source of the ambient noise was different between plate-based and droplet-based platforms. In conclusion, our reported platform differential performance should be considered for the selection of the scRNAseq method during the study experimental designs. more...

El presente Trabajo de Fin de Grado (TFG) tiene como objetivo desarrollar un sistema de evaluación en educación física que minimice las desventajas causadas por el efecto de la edad relativa (RAE). El efecto de la edad relativa, se refiere a las diferencias en rendimiento y oportunidades derivadas de las variaciones de edad dentro del mismo grupo académico. Para abordar esta problemática, se propone un sistema de evaluación, formativa y continua, para ello se realiza una prueba inicial a través del Test Motor SportComp, una herramienta muy eficaz para evaluar la coordinación motriz global de los estudiantes al inicio del curso, proporcionando así una referencia inicial para plantear un sistema de evaluación personalizado que minimice las desventajas del RAE los cuales no solo se limitan a un rendimiento académico inmediato sino que también pueden tener implicaciones a largo plazo sobre la salud física, la autoestima, y las actitudes hacia la actividad deportiva. Numerosos estudios muestran que estos sistemas de evaluación pueden mitigar el impacto negativo del RAE, promoviendo un ambiente de aprendizaje inclusivo y equitativo. Este TFG concluye que la adaptación de los métodos de evaluación y la utilización de herramientas específicas son esenciales para asegurar una valoración justa del progreso y las competencias motrices de los estudiantes. more...

The Covid-19 pandemic has caused a significant effect on our mental health. In this research, we aim to analyse gender-related differences in the psychological impact of the Covid-19 lockdown in Spain. A cross-sectional study was conducted through an online survey (n = 1041) with two measurements: at two and five weeks after the declaration of the state of emergency and stay-at-home order in Spain. The presence of depressive symptoms, anxiety and post-traumatic stress disorder (PTSD), perceived loneliness and spiritual well-being were evaluated. Linear mixed models with random slopes were calculated for each variable in the study in order to analyse the effect of longitudinal measures and interaction with gender. Women showed more symptoms of depression, anxiety and PTSD, more feelings of loneliness and less spiritual well-being compared to men. The psychological impact caused by the pandemic is maintained over time and increases for depression. Covid-19 appears to be having a greater psychological impact on women than men. More attention needs to be paid to this issue to establish the causes and reduce these differences., Depto. de Personalidad, Evaluación y Psicología Clínica, Fac. de Psicología, TRUE, pub more...

This work was supported by grant PIE13/00041 from Instituto de Salud Carlos III and co-funded by Fondo Europeo de Desarrollo Regional (FEDER) to MM, IG-A, FS-M and MY-M, and BFU2014-55478-R from Ministerio de Economía y Competitividad to MY-M., Extracellular vesicles (EVs) are emerging as potent non-invasive biomarkers. However, current methodologies are time consuming and difficult to translate to clinical practice. To analyse EV-encapsulated circulating miRNA, we searched for a quick, easy and economic method to enrich frozen human serum samples for EV. We compared the efficiency of several protocols and commercial kits to isolate EVs. Different methods based on precipitation, columns or filter systems were tested and compared with ultracentrifugation, which is the most classical protocol to isolate EVs. EV samples were assessed for purity and quantity by nanoparticle tracking analysis and western blot or cytometry against major EV protein markers. For biomarker validation, levels of a set of miRNAs were determined in EV fractions and compared with their levels in total serum. EVs isolated with precipitation-based methods were enriched for a subgroup of miRNAs that corresponded to miRNAs described to be encapsulated into EVs (miR-126, miR-30c and miR-143), while the detection of miR-21, miR-16-5p and miR-19a was very low compared with total serum. Our results point to precipitation using polyethylene glycol (PEG) as a suitable method for an easy and cheap enrichment of serum EVs for miRNA analyses. The overall performance of PEG was very similar, or better than other commercial precipitating reagents, in both protein and miRNA yield, but in comparison to them PEG is much cheaper. Other methods presented poorer results, mostly when assessing miRNA by qPCR analyses. Using PEG precipitation in a longitudinal study with human samples, we demonstrated that miRNA could be assessed in frozen samples up to 8 years of storage. We report a method based on a cut-off value of mean of fold EV detection versus serum that provides an estimate of the degree of encapsulation of a given miRNA., Depto. de Biología Celular, Fac. de Ciencias Biológicas, TRUE, pub more...

Mental health stigma is a relevant phenomenon with implications for the people who suffer from it. Despite its importance, no studies have been carried out in Spain at national level with a representative sample of the population. Aims: The aim of this research is to analyze the stigma associated with MHPs in a representative sample of the Spanish population for the first time. Method: A cross-sectional quantitative descriptive study was carried out with a representative sample of the population (N = 2746). Descriptive analyses and regressions are carried out on the different dimensions of stigma such as attitude, attribution and intention of social distance. Results: Medium levels of stigma are obtained in stigmatizing attitudes and attributions, and medium-low levels in the intention of social distance. The best predictors of stigma in its different dimensions are attitudes, attributions and intention of social distance themselves. Progressive political ideology is related to less stigma in all dimensions. Knowing someone with mental health problems and talking openly about it together with higher education are also relevant protectors. Mixed results are obtained regarding age, gender and help-seeking. Conclusion: National programs and campaigns focused on attitudes, attributions and behavioral intentions are necessary to reduce the stigma still present in Spanish society., Depto. de Personalidad, Evaluación y Psicología Clínica, Fac. de Psicología, TRUE, pub more...

Background: Mental health stigma is a relevant phenomenon with implications for the people who suffer from it. Despite its importance, no studies have been carried out in Spain at national level with a representative sample of the population. Aims: The aim of this research is to analyze the stigma associated with MHPs in a representative sample of the Spanish population for the first time. Method: A cross-sectional quantitative descriptive study was carried out with a representative sample of the population (N = 2746). Descriptive analyses and regressions are carried out on the different dimensions of stigma such as attitude, attribution and intention of social distance. Results: Medium levels of stigma are obtained in stigmatizing attitudes and attributions, and medium-low levels in the intention of social distance. The best predictors of stigma in its different dimensions are attitudes, attributions and intention of social distance themselves. Progressive political ideology is related to less stigma in all dimensions. Knowing someone with mental health problems and talking openly about it together with higher education are also relevant protectors. Mixed results are obtained regarding age, gender and help-seeking. Conclusion: National programs and campaigns focused on attitudes, attributions and behavioral intentions are necessary to reduce the stigma still present in Spanish society., Depto. de Personalidad, Evaluación y Psicología Clínica, Depto. de Psicobiología y Metodología en Ciencias del Comportamiento, Fac. de Psicología, TRUE, pub more...

Background: This study aims to longitudinally assess the psychological impact of the COVID-19 pandemic in the general Spanish population. It uses four assessment points: two weeks after the start of confinement, one month after, two months after, and one year after the first evaluation. Methods: Evaluations were conducted through an online survey, with a sample of 3,480 people at the first data collection and 1,041, 569, and 550 people at successive evaluation points. Depressive symptoms (PHQ-2), anxiety (GAD-2), post-traumatic stress (PCL-C-2), social support (EMAS), loneliness (UCLA-3), and discrimination (InDI-d) were evaluated. Results: Significant changes were found in the variables depression and anxiety with a greater presence of this kind of symptomatology after one year (p < .01). There were also significant changes in the variable social support, which showed a substantial reduction after one year (p < .001). Similarly, there were significant variations in the variable intersectional discrimination (p < .001), with greater levels of discrimination. The temporal models show no significant differences in terms of post-traumatic symptomatology (p = .12) or loneliness (p = .19). Conclusions: The pandemic had a negative impact on mental health and these effects were further exacerbated one year later., Antecedentes: el objetivo es evaluar el impacto psicológico de la pandemia generada por la COVID-19 en la población general española longitudinalmente en cuatro momentos: tras dos semanas del inicio del confinamiento, al mes, a los dos meses y al año. Método: las evaluaciones se realizaron mediante una encuesta online, se siguió a una muestra de 3.480 personas en la primera recogida de datos y de 1.041, 569 y 550 personas en los sucesivos momentos de evaluación. Se evaluó la presencia de síntomas depresivos (PHQ-2), de ansiedad (GAD-2), de estrés postraumático (PCL-C-2), el apoyo social (EMAS), la soledad (UCLA-3) y la discriminación (InDI-D). Resultados: se han producido cambios significativos en las variables de depresión y ansiedad con una presencia mayor de dicha sintomatología al año (p < .01), así como en la variable de apoyo social, que muestra una reducción significativa un año después (p < .001), y en la discriminación interseccional, con una mayor discriminación (p < .001). Los modelos temporales no muestran diferencias significativas en cuanto a sintomatología postraumática (p = .12) ni soledad (p = .19). Conclusiones: la pandemia ha tenido un impacto negativo en la salud mental y estos efectos son todavía peores un año después., Depto. de Personalidad, Evaluación y Psicología Clínica, Fac. de Psicología, TRUE, pub more...

Hay pocos datos sobre la necesidad de cuidados intensivos o la duración adecuada de la estancia hospitalaria de los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST). Con el fin de optimizar los recursos, se intentó determinar la necesidad de ingreso en la unidad de cuidados coronarios (UCC) de los pacientes con IAMCEST que permanecían en clase Killip I tras una tras una intervención coronaria percutánea primaria (ICPP) satisfactoria. Desde agosto de 2006 hasta junio de 2008, analizamos los datos de todos los pacientes ingresados en nuestra UCC que cumplían estos criterios, un total de 278. Se registraron prospectivamente todos los acontecimientos adversos intrahospitalarios y la supervivencia libre de acontecimientos a los 30 y 90 días (muerte por cualquier causa, ictus, nuevo síndrome coronario agudo, rehospitalización por cardiopatía isquémica o por insuficiencia cardiaca). El tratamiento médico se optimizó de acuerdo con las recomendaciones de las guías vigentes. Resultados: Se implantó un stent coronario en el 96% de los pacientes. Ninguno de los pacientes presentó un acontecimiento adverso que no pudiera resolverse en una unidad de cuidados intermedios. La supervivencia a 30 y 90 días fue del 99,6% y el 98,3% respectivamente. La supervivencia sin eventos fue del 97,3% a los 30 días y 94,3% a los 90 días. La mediana de estancia fue de tres días en la UCC y de cinco días en el hospital. Conclusiones: Los pacientes con IAMCEST tratados con ICPP que permanecen en clase I de Killip tras el procedimiento y reciben un tratamiento farmacológico óptimo tienen un pronóstico excelente. Es probable que todos ellos puedan ser ingresados de forma segura en una unidad de cuidados intermedios., Depto. de Medicina, Fac. de Medicina, TRUE, pub more...

Psychopathology networks consist of aspects (e.g., symptoms) of mental disorders (nodes) and the connections between those aspects (edges). This article aims to analyze the research literature on network analysis in psychopathology and mental health for the last ten years. Statistical descriptive analysis was complemented with two bibliometric techniques: performance analysis and co-word analysis. There is an increase in publications that has passed from 1 article published in 2010 to 172 papers published in 2020. The 398 articles in the sample have 1,910 authors in total, being most of them occasional contributors. The Journal of Affective Disorders is the one with the highest number of publications on network analysis in psychopathology and mental health, followed by the Journal of Abnormal Psychology and Psychological Medicine stand out. The present study shows that this perspective in psychopathology and mental health is a recent field of study, but with solid advances in recent years from a wide variety of researchers, mainly from USA and Europe, who have extensively studied symptom networks in depression, anxiety, and post-traumatic stress disorders. However, gaps are identified in other psychological behaviors such as suicide, populations such as the elderly, and gender studies., Depto. de Personalidad, Evaluación y Psicología Clínica, Fac. de Psicología, TRUE, pub more...

Background: Stigma and discrimination have been associated with different diseases and pandemics, with negative consequences for the people who suffered them and for their communities. Currently, COVID-19 has become a new source of stigmatization. Aims: The aim of the present study is to analyze longitudinally the evolution of intersectional perceived discrimination and internalized stigma among the general population of Spain, at three points in time throughout the confinement. Method: Participants completed an online survey. Results: Results show an increase in both variables from the first to the second evaluation, and a slight decrease from the second to the third evaluation. Moreover, these changes are explained by depression, anxiety and family support. Conclusions: These findings indicate the factors that need to be considered to reduce the perception of discrimination and the internalization of stigma, and their detrimental consequences, during an especially stressful event such as the current pandemic outbreak., Depto. de Personalidad, Evaluación y Psicología Clínica, Fac. de Psicología, TRUE, pub more...

Depto. de Personalidad, Evaluación y Psicología Clínica, Fac. de Psicología, TRUE, pub

Introduction: Women have been shown to be a vulnerable group in relation to mental health problems over time. Despite this, gender-focused studies are uncommon. The aim of this research is to study mental health in a sample of people with mental health problems and to analyze the differences and predictors focusing on gender. Methods: A cross-sectional study is conducted in a heterogeneous clinical sample in terms of mental health problems (N = 160). Interviews with hetero-reported standardized questionnaires to collect the data are conducted. Descriptive analyses, mean difference and a regression analysis on mental health are carried out taking into account different sociodemographic, clinical and psychosocial variables. Results: Women in the study present worse levels of mental health and subjective severity of the disorder. The main predictors of mental health are being female, followed by severity, shorter time with the diagnosis and internalized stigma. Conclusion: Being female is the most robust predictor of worse mental health and symptomatology. Recommendations according to the results found proposing a gender perspective are suggested., Real Colegio Complutense, Banco Santander, Depto. de Personalidad, Evaluación y Psicología Clínica, Fac. de Psicología, TRUE, pub more...

The halophile H. elongata and its salt tolerance was characterized regarding its metabolism, growth behavior and natural ability to synthesize compatible solutes - ectoine or the precursor g-NADA. Using Metabolic Engineering, different strategies for optimizing a producer strain were applied. In a secretion strain ectoine synthesis was enhanced using supply and demand driven approaches. Further, a novel platform strain able to assimilate nitrogen with a reduced energy cost was created., Die Salztoleranz des halophilen Bakteriums H. elongata wurde im Hinblick auf den Metabolismus, das Wachstum und die natürliche Produktion Kompatibler Solute - Ectoine oder dessen Vorläufer g-NADA - näher charakterisiert. Auf dieser Basis wurden verschiedene Metabolic Engineering Strategien zur Erzeugung eines optimierten Produktionsstammes angewandt. In einem Sekretionsstamm wurde die Ectoine Synthese durch sich ergänzende Konzepte orientiert zum einen an Angebot und zum anderen an Bedarf verbessert. Zudem wurde ein neuer Plattformstamm erzeugt, der Stickstoff mit weniger Energiekosten aufnehmen kann. more...

The conserved process of cell division in bacteria has been a long-standing target for antimicrobials, although there are few examples of potent broad-spectrum compounds that inhibit this process. Most currently available compounds acting on division are directed towards the FtsZ protein, a self-assembling GTPase that is a central element of the division machinery in most bacteria. Benzodioxane-benzamides are promising candidates, but poorly explored in Gram-negatives. We have tested a number of these compounds on E. coli FtsZ and found that many of them significantly stabilized the polymers against disassembly and reduced the GTPase activity. Reconstitution in crowded cell-like conditions showed that FtsZ bundles were also susceptible to these compounds, including some compounds that were inactive on protofilaments in dilute conditions. They efficiently killed E. coli cells defective in the AcrAB efflux pump. The activity of the compounds on cell growth and division generally showed a good correlation with their effect in vitro, and our experiments are consistent with FtsZ being the target in vivo. Our results uncover the detrimental effects of benzodioxane-benzamides on permeable E. coli cells via its central division protein, implying that lead compounds may be found within this class for the development of antibiotics against Gram-negative bacteria. more...

Cytokinesis is a fundamental process for bacterial survival and proliferation, involving the formation of a ring by filaments of the GTPase FtsZ, spatio-temporally regulated through the coordinated action of several factors. The mechanisms of this regulation remain largely unsolved, but the inhibition of FtsZ polymerization by the nucleoid occlusion factor SlmA and filament stabilization by the widely conserved cross-linking protein ZapA are known to play key roles. It was recently described that FtsZ, SlmA and its target DNA sequences (SlmA-binding sequence (SBS)) form phase-separated biomolecular condensates, a type of structure associated with cellular compartmentalization and resistance to stress. Using biochemical reconstitution and orthogonal biophysical approaches, we show that FtsZ-SlmA-SBS condensates captured ZapA in crowding conditions and when encapsulated inside cell-like microfluidics microdroplets. We found that, through non-competitive binding, the nucleotide-dependent FtsZ condensate/polymer interconversion was regulated by the ZapA/SlmA ratio. This suggests a highly concentration-responsive tuning of the interconversion that favours FtsZ polymer stabilization by ZapA under conditions mimicking intracellular crowding. These results highlight the importance of biomolecular condensates as concentration hubs for bacterial division factors, which can provide clues to their role in cell function and bacterial survival of stress conditions, such as those generated by antibiotic treatment. more...

In most bacteria, division depends on a cytoskeletal structure, the FtsZ ring, that functions as a scaffold to recruit additional proteins, with which it forms the machinery responsible for division, the divisome. The detailed architecture of the ring, in particular the mechanisms of assembly, stabilization, and disassembly, are still largely unknown. Here, we highlight the role of FtsZ-associated proteins (Zaps) that stabilize the FtsZ ring by crosslinking the filaments. Among Zap proteins, ZapD binds the C-terminal domain of FtsZ, which serves as a hub for its regulation. We demonstrate that ZapD crosslinks FtsZ filaments into ring-like structures formed by a discontinuous arrangement of short filaments. Using cryo-electron tomography combined with biochemical analysis, we reveal the three-dimensional organization of the ring-like structures and shed light on the mechanism of FtsZ filament crosslinking by ZapD. Together, our data provide a model of how FtsZ-associated proteins can stabilize FtsZ filaments into discontinuous ring-like structures reminiscent of that existing in the bacterial cell. more...

Bacterial division is driven by a contractile ring consisting of a multiprotein complex, which accurately assembles at midcell. For its formation, the polymerization of the GTPase protein FtsZ is required as scaffold for the rest of the proteins involved. The control mechanisms underlying division ring positioning remain largely unknown. However, the nucleoid occlusion protein SlmA and the cross-linking protein ZapA are known to be relevant. FtsZ, SlmA and its DNA sequence have shown to form biomolecular condensates, structures emerging as a mechanism to organize intracellular space, linked to stress tolerance., We have found that FtsZ-SlmA-SBS condensates are able to recruit ZapA in crowding conditions in bulk and also when encapsulated inside cell-like microfluidics microdroplets. Our combined biophysical and reconstitution approach showed that the ZapA/SlmA ratio controls FtsZ condensate/polymer interconversion through non-competitive binding and that FtsZ polymer stabilization by ZapA is favored under crowding conditions. These findings underline the significance of condensates as concentrated hubs of proteins, which can shed light on cell survival under stress conditions, such as those induced by antibiotic treatment. more...