Fingering instability in spreading epithelial monolayers: roles of cell polarisation, substrate friction and contractile stresses

Collective cell migration plays a crucial role in many developmental processes that underlie morphogenesis, wound healing, or cancer progression. In such coordinated behaviours, cells are organised in coherent structures and actively migrate to serve different biological purposes. In some contexts, namely during epithelial wound healing, it is well known that a migrating free-edge monolayer develops finger-like instabilities, yet the onset is still under debate. Here, by means of theory and numerical simulations, we shed light on the main mechanisms driving the instability process, analysing the linear and nonlinear dynamics of a continuum compressible polar fluid. In particular, we assess the role of cell polarisation, substrate friction, and contractile stresses. Linear theory shows that it is crucial to analyse the perturbation transient dynamics, since we unravel a plethora of crossovers between different exponential growth rates during the linear regime. Numerical simulations suggest that cell-substrate friction could be the mechanism responsible for the formation of complex finger-like structures at the edge, since it triggers secondary fingering instabilities and tip-splitting phenomena. Finally, we obtain a critical contractile stress that depends on cell-substrate friction and the initial-to-nematic length ratio, characterising an active wetting-dewetting transition. In the dewetting scenario, the monolayer retracts and becomes stable without developing finger-like structures.Comment: 15 pages, 9 figures, 1 table, submitted to Soft Matte

A novel double-hit animal model of schizophrenia: behavioural assessment in male and female mice

Background: A growing body of evidence support that maternal prenatal infections represent a risk factor for schizophrenia in offspring. Moreover, stressful events during critical neurodevelopmental periods, such as adolescence, may trigger the onset of the disease in predisposed individuals. Thus, a prenatal priming event (i.e. maternal infection during pregnancy) that would induce vulnerability, followed by a second stressful hit in peripuberty may lead to the onset of schizophreniaDisclosure statement: Supported by the Basque Government (IT1211-19), the European Union's Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant agreement No 747487) and SAF 2017-88126-R. NC is recipient of a FPI fellowship (PRE2018-084002) from MICINN

Efecto del desprendimiento de las biopelículas formadas en una red de acueducto sobre la calidad del agua

El objetivo de esta investigación fue determinar el efecto del desprendimiento de las biopelículas formadas en una red de distribución de agua potable sobre la calidad del agua que llega a los hogares, ya que ésta puede afectar la calidad de vida y la salud de las personas. Se realizaron análisis de pH, turbiedad, concentración de metales y microbiológicos en una red de acueducto para evaluar el efecto de las biopelículas sobre la calidad del agua, encontrando altos niveles de aluminio y de microorganismos esporulados que dificultan su control y representan un potencial problema de salud para la población

Behavioural Evaluation of a Translational Animal Model of Schizophrenia

Presented at 1st Meeting in Translational Pharmacology 38th SEF national meeting/9th SEFF meeting 19–20 June 2018, SpainSchizophrenia (SZ) is a chronic and disabling psychiatric disorder affecting about 1% of the population worldwide. Schizophrenia comprises positive and negative symptoms as well as cognitive deficits. Epidemiological and experimental studies indicate that infections during the gestational period represent a risk factor to develop SZ along lifetime, which in combination with stressful events in adolescence may lead to the SZ onset. The aim of the present study was to create a translational “double-hit” animal model of SZ in male and female mice, based in maternal immune activation (MIA, hit-1)—injection of poly(I:C) to pregnant dams, 7.5 mg/kg i.p.—and social isolation (SI, hit-2) in the peri-pubertal period (3–11 weeks). In the four experimental groups (hit-1, hit-2, double-hit and control) locomotion and anxiety were assessed using the Open Field Test (OFT), and the cognitive status (declarative/episodic memory) was evaluated by means of the Novel Object Recognition Test (NORT). No differences were observed in the spontaneous locomotor activity between any of the groups, neither in females nor in males. However, an increase in the percentage of time spent in the centre of the OFT was significantly associated to the hit-1 (MIA) only in female mice (F[1,53] = 4.252; P = 0.044, n = 57). Moreover, a significant decrease in the discrimination index in the NORT was also associated to the hit-1 (MIA) in the subgroup of female mice (F[1,55] = 7.266; P = 0.0093, n = 59). These preliminary results indicate that MIA produces a greater impact in female mice inducing an anxiolytic-like phenotype and cognitive impairments.Basque Government (IT616/13) MSCA-2016-IF 747487 to C.Muguruza

Intergroup conflict and rational decision making

The literature has been relatively silent about post-conflict processes. However, understanding the way humans deal with post-conflict situations is a challenge in our societies. With this in mind, we focus the present study on the rationality of cooperative decision making after an intergroup conflict, i.e., the extent to which groups take advantage of post-conflict situations to obtain benefits from collaborating with the other group involved in the conflict. Based on dual-process theories of thinking and affect heuristic, we propose that intergroup conflict hinders the rationality of cooperative decision making. We also hypothesize that this rationality improves when groups are involved in an in-group deliberative discussion. Results of a laboratory experiment support the idea that intergroup conflict ¿associated with indicators of the activation of negative feelings (negative affect state and heart rate)¿ has a negative effect on the aforementioned rationality over time and on both group and individual decision making. Although intergroup conflict leads to sub-optimal decision making, rationality improves when groups and individuals subjected to intergroup conflict make decisions after an in-group deliberative discussion. Additionally, the increased rationality of the group decision making after the deliberative discussion is transferred to subsequent individual decision making

Ductus venosus as a marker of fetal growth in first trimester in a population of Colombian pregnant women

Abstract Objectives: to evaluate the relationship between the ductus venosus (DV) and the variables of fetal growth in the first trimester in a Colombian pregnant population. Methods: a descriptive cross-sectional study was carried out with secondary data obtained from a multicenter study.526 patients were included between weeks 11 and 14 for gestational ultrasound follow-up attended in three health care institutions in Bogotá, Colombia, between May 2014 and October 2018. A bivariate descriptive analysis was carried out where the relationship between the characteristics of the DV in the first trimester and ultrasound findings. Results: the flow wave of the DV in the first trimester was normal in the entire sample, with a pulsatility index of the ductus venosus (DVPI) of 0.96±0.18. In addition, a negative correlation was found between the crown-rump length (CRL) and the DVPI (p<0.05). Conclusion: there is a relationship between the DVPI regarding the CRL, indicating an interest in this early marker in relation to fetal growth alterations; however, more studies are required to determine the usefulness of this variable with respect to fetal growth

Generalidades de la farmacovigilancia

A través de los últimos años, el uso de medicamentos se volvió algo cotidiano, por lo mismo se crearon diferentes programas, actividades y procesos, para mitigar aquellos sucesos que atentaban contra la calidad de vida de las personas. Entender la importancia de realizar la una serie de mecanismos que lograran comprobar la efectividad y seguridad de los medicamentos, dio origen a la farmacovigilancia, la cual se encarga de detección, prevención y evaluación de los efectos adversos que se pueden presentar a lo largo del tratamiento farmacológico.Over the last few years, the use of medicines has become a daily occurrence, and different programs, activities and processes have been created to mitigate those events that threaten the quality of life of people. Understanding the importance of carrying out a series of mechanisms to verify the effectiveness and safety of medicines, gave rise to pharmacovigilance, which is responsible for detection, prevention and evaluation of adverse effects that may occur during pharmacological treatment

Global hyperactivation of enhancers stabilizes human and mouse naïve pluripotency through inhibition of CDK8/19 Mediator kinases

Pluripotent stem cells (PSCs) transition between cell states in vitro and reflect developmental changes in the early embryo. PSCs can be stabilized in the naïve state by blocking extracellular differentiation stimuli, particularly FGF-MEK signaling. Here, we report that multiple features of the naïve state in human and mouse PSCs can be recapitulated without affecting FGF-MEK-signaling or global DNA methylation. Mechanistically, chemical inhibition of CDK8 and CDK19 kinases removes their ability to repress the Mediator complex at enhancers. Thus CDK8/19 inhibition increases Mediator-driven recruitment of RNA Pol II to promoters and enhancers. This efficiently stabilizes the naïve transcriptional program and confers resistance to enhancer perturbation by BRD4 inhibition. Moreover, naïve pluripotency during embryonic development coincides with a reduction in CDK8/19. We conclude that global hyperactivation of enhancers drives naïve pluripotency, and this can be achieved in vitro by inhibiting CDK8/19 kinase activity. These principles may apply to other contexts of cellular plasticity

Philosophy, science, and cinema: Feminist perspectives

A lo largo del curso académico 2021-2022, el proyecto “Filosofía, Ciencia y Cine: perspectivas feministas” ha logrado coordinar el trabajo de un elevado número de personal docente y estudiantado que ha participado activamente en la organización de eventos académicos, algunos de ellos previstos en la propuesta original y otros muchos ideados a lo largo del curso. En total, se han llevado a cabo 11 actividades, incluyendo la grabación de dos podcasts, la realización de 8 cinefórums y la celebración de un simposio. Las actividades han obtenido un gran éxito de asistencia y participación y se han difundido ampliamente tanto en la Facultad de Filosofía como en las redes sociales de la Facultad y del proyecto.Depto. de Lógica y Filosofía TeóricaFac. de FilosofíaFALSEsubmitte

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group