Maxent as an inevitable force in cell differentiation

The maximum entropy principle applies to any thermodynamic system, including biological systems. It has been widely explored in the framework of ecology, where Shannon entropy is used as a diversity index, and it is maximized in order to find maximum entropy distributions between or within species. There is wide agreement between theoretical deductions of such distributions and real data of ecosystems. Microbial systems are also supposed to satisfy the maximum entropy principle. In particular, cell differentiation can be studied in terms of diversity, and Shannon index may be used to quantify and maximize such diversity. Cell differentiation is here considered in a wide sense, and three different examples where theory, experiments and simulations converge on accomplishing Maxent are shown. First, a simple bacterial batch culture, were biomass distribution between cells (gamma distribution) fits the maximum diversity principle with two constraints related with energetic requirements and diversity in cell division. Then, a more sophisticated system where malaria infected red blood cells in in vitro culture are studied from their infection state; in this case, the maximization of entropy requires only one constraint regarding energetic requirements, which results on an exponential distribution of infection states. Finally, and at an upper scale, a cell differentiation case in terms of spatial distribution and aggregation; this is the case of tuberculosis lesions in lungs, which also fit the exponential distribution. In all cases a transient phase is initially seen, followed by a thermodynamically stationary phase where distributions remain approximately constant and similar to those theoretically deduced with Maxent. The importance of considering diversity and its evolution in dynamic microbial systems is shown. Differentiation of cells according to individual properties or functionalities as well as their spatial organization in upper structures seem to occur according to the maximum diversity principle. In addition, microbial individual-based ecology (µIBE), that combines individual-based modelling and experimentation, is shown as an appropriate strategy to study dynamic emergent behaviours related with diversity.Postprint (published version

Ciència en temps de pandèmia. Models i eines per a l'anàlisi i control de la COVID-19

Conferència realitzada el Dissabte, 27 de Febrer de 2021A finals de 2019, arribaven notícies de la Xina sobre l'aparició i proliferació d'un nou virus, el SARS-CoV-2. D'entrada, ens ho miràvem des de la distància, amb la secreta esperança que l'epidèmia seria controlada i no arribaria a casa nostra. Quan es van detectar els primers casos a Europa, al febrer, no estàvem preparats pel que ens venia a sobre: ens enfrontàvem a una malaltia totalment desconeguda, de la que no en sabíem gairebé res, i que esdevindria una pandèmia per la qual no teníem mecanismes de gestió i control a punt. En aquell moment va començar una autèntica marató: la de científics i científiques que es van posar a treballar a contrarellotge per resoldre tots els interrogants que plantejava la situació d'emergència. Les matemàtiques han estat una de les eines que ens han ajudat a lluitar contra la situació del darrer any, facilitant la comprensió de la dinàmica epidemiològica de la COVID-19 i donant suport a les estratègies de control

Origin of tuberculosis in the Paleolithic predicts unprecedented population growth and female resistance

The project leading to these results has received funding from "la Caixa" Foundation (ID 100010434), under agreement LCF/PR/GN16/10290002Current data estimate the origin of Mycobacterium tuberculosis complex (MtbC) infection around 73,000 years before the common era (BCE), and its evolution to "modern" lineages around 46,000 BCE. Being MtbC a major killer of humanity, the question is how both species could persist. To answer this question, we have developed two new epidemiological models (SEIR type), adapted to sex dimorphism and comparing coinfection and superinfection for different MtbC lineages. We have attributed a higher resistance/tolerance to females to explain the lower incidence noted in this sex, a better health status in the Paleolithic compared to the Neolithic, and a higher dissemination of "modern" lineages compared to "ancient" ones. Our findings show the extraordinary impact caused by "modern" lineages, provoking the extinction of the groups infected. This could only be overcomed by an unprecedented population increase (x20 times in 100 years) and helped with the protection generated by previous infection with "ancient" lineages. Our findings also suggest a key role of female resistance against MtbC. This data obliges us to rethink the growth population parameters in the Paleolithic, which is crucial to understanding the survival of both MtbC and humans, and to decipher the nature of human female resistance against TB

Proposta d’intervenció educativa: les cançons com una eina principal d’aprenentatge al primer curs del Segon Cicle d’Educació Infantil

Treball Final de Grau en Mestre o Mestra d'Educació Infantil. Codi: MI1040. Curs acadèmic: 2019/2020Com molts pedagògics i psicòlegs musicals demostren, l’educació musical és molt important a l’hora d’aprendre, sobretot en edats primerenques. A través d’aquesta se promou la inclusió educativa i la participació activa en l’aula. Aquest treball tracta d’explicar una proposta d’intervenció educativa didàctica dirigida als i les docents d’Educació Infantil per tal de dur a terme les tres àrees curriculars del Real Decret (DOGV 38/2008) a través de la música. Una de tantes ferramentes que hi ha per tal de fer-ho són les cançons. Per tant, s’exposa l’ús de les cançons infantils en relació amb les àrees del currículum. Les cançons són un model positiu en l’àmbit educatiu, ja que és una bona forma d’adquirir coneixements de forma lúdica i didàctica. A més a més, no solament poden ser l’eix per facilitar l’aprenentatge, sinó que poden influenciar a l’hora del desenvolupament cognitiu, psicomotriu i emocional dels xiquets i xiquetes. L’objectiu principal és que els i les mestres d’Educació Infantil tinguen un exemple de recursos innovadors on suportar-se per tal de treballar la música correctament. Un d’aquests és un projecte basat amb l’estiu el qual es divideix en 15 sessions. Dins de cada sessió hi ha activitats per treballar-les al nivell de 3 anys. Aquestes activitats estan basades amb una metodologia qualitativa, activa i globalitzada. Així mateix, fent una avaluació global, continua i formativa, tenint en compte l’atenció a la diversitat. Finalment, cal destacar que aquesta proposta no és fomentar la música a l’aula com un aspecte agradable, juganer i recreatiu, que també ho és. Si no fer que siga una ferramenta més perquè l’alumnat aconsegueixa els objectius curriculars d’una forma diferent: positiva i motivadora.Como muchos pedagógicos y psicólogos musicales demuestran, la educación musical es muy importante a la hora de aprender, sobre todo en edades tempranas. A través de esta se promueve la inclusión y la participación en el aula. Este trabajo trata de explicar una propuesta de intervención educativa didáctica dirigida a los y las docentes de Educación Infantil para llevar a cabo las tres áreas curriculares del Real Decreto (DOGV 38/2008) a través de la música. Una de las herramientas que existe para poder hacerlo son las canciones. Por tanto, se expone el uso de las canciones infantiles en relación con las áreas del currículum. Las canciones son un modelo positivo en el ámbito educativo, ya que es una buena forma de adquirir conocimientos de forma lúdica y didáctica. Además, no solamente pueden ser el eje para facilitar el aprendizaje, sino que pueden influenciar a la hora del desarrollo cognitivo, psicomotriz y emocional de los niños y las niñas. El objetivo principal es que los y las maestres de Educación Infantil tengan un ejemplo de recursos innovadores donde apoyarse para trabajar la música correctamente. Uno de estos es un proyecto basado en el verano el cual se divide en 15 sesiones. Dentro de cada sesión hay actividades parar trabajarlas al nivel de 3 años. Estas actividades están basadas con una metodología cualitativa, activa y globalizadora. Haciendo una evaluación global, continua y formativa, teniendo en cuenta la atención a la diversidad. Finalmente, cabe destacar que esta propuesta no es fomentar la música en el aula como un aspecto agradable y recreativo, que también lo es. Si no hacer que sea una herramienta más para que el alumnado consiga los objetivos curriculares de una forma diferente: positiva y motivadora

The origin and maintenance of tuberculosis is explained by the induction of smear-negative disease in the paleolithic

Is it possible that the origin of Mycobacterium tuberculosis (Mtb) infection was around 70,000 years before the common era? At that time Homo sapiens was just another primate species with discrete growth and a very low-density geographic occupation. Therefore, it is difficult to understand the origin of a highly virulent obligate human pathogen. We have designed a new SEIR model (TBSpectr) that allows the differentiation of smear-positive and -negative tuberculosis. The model reconciles currently accepted growth rates for the Middle Paleolithic (0.003%/year) and Neolithic (0.1%/year). The obtained data link the origin of Mtb infection in the Middle Paleolithic to the induction of smear-negative TB, and reveal that its persistence required interrelations among hunter–gatherer groups, while the risk of human extinction was negligible. It also highlights the number of people infected per case and the fast progression to disease for Mtb infection maintenance, as well as the link between poor health in the Neolithic with the increased incidence of more severe forms of TB (smear-positive). In conclusion, our data support the origin of TB as a well-tolerated, highly persistent disease, even in low-density populations, showing the difficulty of its eradication and highlighting the necessity for providing better health conditions to humans to reduce its severity.Peer ReviewedObjectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

CD5L promotes M2 macrophage polarization through autophagy-mediated upregulation of ID3

CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questioned whether CD5L is able to influence human macrophage plasticity, and drive its polarization toward any specific phenotype. We compared CD5L-induced phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in human monocytes. Phenotypic markers were quantified by RT-qPCR and flow cytometry, and a mathematical algorithm was built for their analysis. Moreover, we compared ROS production, phagocytic capacity, and inflammatory responses to LPS. CD5L drove cells toward a polarization similar to that induced by IL10. Furthermore, IL10- and CD5L-treated macrophages showed increased LC3-II content and colocalization with acidic compartments, thereby pointing to the enhancement of autophagy-dependent processes. Accordingly, siRNA targeting ATG7 in THP1 cells blocked CD5L-induced CD163 and Mer tyrosine kinase mRNA and efferocytosis. In these cells, gene expression profiling and validation indicated the upregulation of the transcription factor ID3 by CD5L through ATG7. In agreement, ID3 silencing reversed polarization by CD5L. Our data point to a significant contribution of CD5L-mediated autophagy to the induction of ID3 and provide the first evidence that CD5L drives macrophage polarization.Peer ReviewedPostprint (published version

Ultrastructural myocardial changes in seven cats with spontaneous hypertrophic cardiomyopathy

AbstractObjectivesHypertrophic cardiomyopathy (HCM) is the most common heart disease in cats and shares clinical and pathological characteristics with human HCM. Little is known about the pathogenic mechanisms underlying development of spontaneous feline HCM.AnimalsThe study population consisted of seven cats diagnosed with HCM and eight age-matched cats with no evidence of cardiac disease.MethodsFresh myocardial biopsies taken from the middle of the left ventricular posterior free wall were obtained and examined with transmission electron microscopy.ResultsElectron microscopic examination showed ultrastructural aberrations of the myocardial cytoarchitecture and of the interstitium in the seven cats with HCM. In the most severely affected cats the myofibrils were disorganized and subsarcolemmal mitochondria were depleted. In control cats, contraction band artifacts were commonly seen.ConclusionsIn this preliminary study we show that ultrastructural changes of the myocardium in seven cats with HCM involve the cytoskeleton and mitochondria. We suggest that our findings are important for future research aiming at elucidating the pathogenic mechanisms underlying the phenotypic expression of feline HCM.The results of this study prompt for a larger scale study, including quantitative measurements of mitochondrial distribution and cytoskeletal derangements in feline HCM

Exploring lag phase and growth initiation of a yeast culture by means of an Individual-based Model

Postprint (published version

The need for detailed COVID-19 data in Spain

The COVID-19 epidemic has impacted the population of Spain far more than most feared or projected. As of Sept 25, 2020, more than 700 000 individuals had tested positive, and more than 31 000 deaths with a positive test had been recorded.1 Earlier in this pandemic, the Spanish Ministry of Health provided data by age and sex for the whole country in its daily COVID-19 situation updates (in Adobe PDF format), as well as daily data on total hospitalisations, intensive care unit admissions, discharges, and deaths by region. However, since May 19, 2020, disaggregated data have not been provided in the daily updates.1 In recent months, data improvements have been made by the National Centre of Epidemiology (CNE), and open data on total counts by region are updated and revised daily.2 However, at the time of writing, age-specific data from the CNE is given only in weekly publications (as Adobe PDF files), without geographic detail or retrospective corrections, and with cumulative counts tabulated only from mid-May onwards. Therefore, properly merging age-specific time series after the first wave is difficult or impossible.Peer reviewe