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While many articles have analyzed the effectiveness of the policies that aimed to limit the spread of COVID-19, very little research work has examined the determinants that drove these policies. Therefore, we proposed to study the determinants that led government authorities to implement more or less restrictive policies to limit the spread of the pandemic. Using the COVID-19 stringency index, we highlighted a positive effect of the incidence rate on the stringency level. Patient capacity in intensive care units was also a key variable. This is indicative of the capacity of countries to have a sufficient and appropriate health system to absorb such pandemic crises. On the other hand, we show that epidemiological data regarding the risk of excess mortality (diabetes, cancer, and cardiovascular pathologies) had a negative effect. We conclude by recalling the importance of policy coordination between countries when it comes to lowering the stringency levels of measures, in order to avoid a resurgence of the epidemic.

International audience; Meriones shawi (M.shawi) is the main reservoir host for zoonotic cutaneous leishmaniasis (ZCL) in Central Tunisia. The incorporation of environmental and climatic effects on the spread of ZCL in M. shawi remains difficult. This study presents an agent-based model (ABM) to overcome these difficulties and examine the impact of environment (i.e. vegetation cover) and climate (i.e. temperature) on M. shawi movement and prevalence. The model simulation considers two agent types: rodent agent and field unit agent. We tested the model according to two types of rodent movement: random and thoughtful. We integrated time dependent normalized difference vegetation index (NDVI) in order to test the land cover effects on rodent movement and ZCL transmission. The results confirmed that the spread of the disease depends on rodent movement. We observed that prevalence and distribution are the closest to field data when the vegetation cover is highest and that rodents go for thoughtful movement. In addition, we found that the nature of movement (random or thoughtful) and prevalence depends strongly on minimum food detection.

Background The epidemiological pattern of hepatitis A infection has shown dynamic changes in many parts of the world due to improved socio-economic conditions and the accumulation of seronegative subjects, which leads to possible outbreaks and increased morbidity rate. In Tunisia, the epidemiological status of hepatits A virus is currently unknown. However, over the past years higher numbers of symptomatic hepatitis A virus infection in school attendants and several outbreaks were reported to the Ministry of Health, especially from regions with the lowest socio-economic levels in the country. The aim of this study was to investigate the current seroprevalence of hepatitis A virus antibodies in central-west Tunisia and assess the impact of hepatitis A virus vaccination on hepatitis A epidemiology. Methods Serum samples from 1379 individuals, aged 5–75 years, were screened for hepatitis A virus antibodies. Adjusted seroprevalence, incidence and force of infection parameters were estimated by a linear age structured SEIR (Susceptible-Exposed-Infectious-Recovered) compartmental model. A vaccine model was then constructed to assess the impact on hepatitis A virus epidemiology of 3 scenarios of vaccination strategies: one dose at 12-months of age, one dose at 6-years and one dose at 12-months and another at 6-years of age during 6 years. Results A rapid increase in anti-hepatitis A virus seroprevalence was noted during infancy and adolescence: 47% of subjects under 10-years-old are infected; the prevalence increases to 77% at 15-years and reaches 97% in subjects aged 30-years. The force of infection is highest between 10 and 30-years of age and the incidence declines with increasing age. The vaccine model showed that the 3-scenarios lead to a significant reduction of the fraction of susceptibles. The two doses scenario gives the best results. Single-dose vaccination at 6-years of age provides more rapid decrease of disease burden in school-aged children, as compared to single-dose vaccination at 12-months, but keeps with a non-negligible fraction of susceptibles among children Conclusions Our study confirms the epidemiological switch from high to intermediate endemicity of hepatitis A virus in Tunisia and provides models that may help undertake best decisions in terms of vaccinations strategies.

International audience; Networks used in biological applications at different scales (molecule, cell and population) are of different types: neuronal, genetic, and social, but they share the same dynamical concepts, in their continuous differential versions (e.g., non-linear Wilson-Cowan system) as well as in their discrete Boolean versions (e.g., non-linear Hopfield system); in both cases, the notion of interaction graph G(J) associated to its Jacobian matrix J, and also the concepts of frustrated nodes, positive or negative circuits of G(J), kinetic energy, entropy, attractors, structural stability, etc., are relevant and useful for studying the dynamics and the robustness of these systems. We will give some general results available for both continuous and discrete biological networks, and then study some specific applications of three new notions of entropy: (i) attractor entropy, (ii) isochronal entropy and (iii) entropy centrality; in three domains: a neural network involved in the memory evocation, a genetic network responsible of the iron control and a social network accounting for the obesity spread in high school environment.

International audience; (1) Background: The aim of this paper is to show that e-health tools like smart homes allow the personalization of the surveillance and preventive education of chronic patients, such as obese persons, in order to maintain a comfortable and preventive lifestyle at home. (2) Technologies and methods: Several types of sensors allow coaching the patient at home, e.g., the sensors recording the activity and monitoring the physiology of the person. All of this information serves to personalize serious games dedicated to preventive education, for example in nutrition and vision. (3) Results: We built a system of personalized preventive education at home based on serious games, derived from the feedback information they provide through a monitoring system. Therefore, it is possible to define (after clustering and personalized calibration) from the at home surveillance of chronic patients different comfort zones where their behavior can be estimated as normal or abnormal and, then, to adapt both alarm levels for surveillance and education programs for prevention, the chosen example of application being obesity.

Mohamed Alibi's presentation at the ISCB Student Council Symposium-Africa 2015, Dar es Salaam, Tanzania

Background Leishmania (L.) are intracellular protozoan parasites able to survive and replicate in the hostile phagolysosomal environment of infected macrophages. They cause leishmaniasis, a heterogeneous group of worldwide-distributed affections, representing a paradigm of neglected diseases that are mainly embedded in impoverished populations. To establish successful infection and ensure their own survival, Leishmania have developed sophisticated strategies to subvert the host macrophage responses. Despite a wealth of gained crucial information, these strategies still remain poorly understood. MicroRNAs (miRNAs), an evolutionarily conserved class of endogenous 22-nucleotide non-coding RNAs, are described to participate in the regulation of almost every cellular process investigated so far. They regulate the expression of target genes both at the levels of mRNA stability and translation; changes in their expression have a profound effect on their target transcripts. Methodology/Principal Findings We report in this study a comprehensive analysis of miRNA expression profiles in L. major-infected human primary macrophages of three healthy donors assessed at different time-points post-infection (three to 24 h). We show that expression of 64 out of 365 analyzed miRNAs was consistently deregulated upon infection with the same trends in all donors. Among these, several are known to be induced by TLR-dependent responses. GO enrichment analysis of experimentally validated miRNA-targeted genes revealed that several pathways and molecular functions were disturbed upon parasite infection. Finally, following parasite infection, miR-210 abundance was enhanced in HIF-1α-dependent manner, though it did not contribute to inhibiting anti-apoptotic pathways through pro-apoptotic caspase-3 regulation. Conclusions/Significance Our data suggest that alteration in miRNA levels likely plays an important role in regulating macrophage functions following L. major infection. These results could contribute to better understanding of the dynamics of gene expression in host cells during leishmaniasis., Author Summary Leishmania parasites belong to different species, each one characterized by specific vectors and reservoirs, and causes cutaneous or visceral disease(s) of variable clinical presentation and severity. In its mammalian host, the parasite is an obligate intracellular pathogen infecting the monocyte/macrophage lineage. Leishmania have developed ambiguous relationships with macrophages. Indeed, these cells are the shelter of invading parasites, where they will grow and eventually will reside in a silent state for life. But macrophages are also the cells that participate, through the induction of several pro-inflammatory mediators and antigen presentation, to shape the host immune response and ultimately kill the invader. To subvert these anti-parasite responses, Leishmania manipulate the host machinery for their own differentiation and survival. We aimed to evaluate the impact of L. major (the causative agent of zoonotic cutaneous leishmaniasis) infection on deregulation of non-coding miRNAs, a class of important regulators of gene expression. Our results revealed the implication of several miRNAs on macrophage fate upon parasite infection through regulation of different pathways, including cell death. Our findings provided a new insight for understanding mechanisms governing this miRNA deregulation by parasite infection and will help to provide clues for the development of control strategies for this disease.

We analyzed the transcriptional signatures of mouse bone marrow-derived macrophages at different times after infection with promastigotes of the protozoan parasite Leishmania major. Ingenuity Pathway Analysis revealed that the macrophage metabolic pathways including carbohydrate and lipid metabolisms were among the most altered pathways at later time points of infection. Indeed, L. major promastiogtes induced increased mRNA levels of the glucose transporter and almost all of the genes associated with glycolysis and lactate dehydrogenase, suggesting a shift to anaerobic glycolysis. On the other hand, L. major promastigotes enhanced the expression of scavenger receptors involved in the uptake of Low-Density Lipoprotein (LDL), inhibited the expression of genes coding for proteins regulating cholesterol efflux, and induced the synthesis of triacylglycerides. These data suggested that Leishmania infection disturbs cholesterol and triglycerides homeostasis and may lead to cholesterol accumulation and foam cell formation. Using Filipin and Bodipy staining, we showed cholesterol and triglycerides accumulation in infected macrophages. Moreover, Bodipy-positive lipid droplets accumulated in close proximity to parasitophorous vacuoles, suggesting that intracellular L. major may take advantage of these organelles as high-energy substrate sources. While the effect of infection on cholesterol accumulation and lipid droplet formation was independent on parasite development, our data indicate that anaerobic glycolysis is actively induced by L. major during the establishment of infection., Author Summary Leishmania are obligated intracellular pathogens that develop almost exclusively in macrophages. Experimental leishmaniasis in mice is one of the most extensively studied models of intracellular infections both at the level of the parasite and host immune responses. We took advantage of Balb/c mice model to investigate gene expression profile through Affymetrix oligonucleotide arrays. In order to have a general and dynamic picture of the complex biological events that are acting in the context of Leishmania intracellular parasitism, we investigated the mouse macrophage response to initial invasion of L. major over a time course that extended from one to 24 hours post-infection. Our results reveal the alteration of several biological processes and metabolic changes. Indeed, similarly to different other pathogens, Leishmania induces cholesterol accumulation and foam cell formation that have been confirmed by confocal microscopy experiments. Whether Leishmania parasites take advantage of this high-energy source is now under investigation. Our findings provided further understandings in host responses to Leishmania infection.

The aim of our work is to model the dynamics of a grouper population in a fishing zone, by holding account at the same time : the natural growth, the predation and the migrations, and to study the impact of the poaching on this population, L'objectif est de modéliser la dynamique d'une population de mérous dans un territoire de pêche d'une côte marine, en tenant compte à la fois de la croissance naturelle, de la pêche et des migrations, et d'étudier l'effet du braconnage sur cette population

The definition of theoretical biology may be controversial. Indeed, the basic definition of theoretical biology classifies it as biomathematics. It assumes that theoretical biology is divided into, at least, four subfields: Biological mathematical modeling, Relational biology/Complex systems biology, Bioinformatics and Biomodeling Computation. In epistemology, theoretical biology is defined as the action of ‘‘theorizing’’ life sciences. It aims to introduce laws; it highlights some biological phenomena and makes possible the identification of new biological principles. The latter definition does not imply a direct relationship with mathematics. In both cases, theoretical biology is a strongly multidisciplinary science, for the tools imported from other science and for the shared ideas. This controversy was one of the main concerns of the French-speaking Society for Theoretical Biology (SFBT). In 1985, it succeeded the Association for the development of Theoretical Methods for Biology (AMTB). The initial purpose of AMTB was to organize Schools; rapidly it took a more general objective: ‘‘the development of methods and theoretical formalisms useful for fundamental biological research and its practical applications’’. The origin of SFBT Conferences comes from 1975, when Jean-Henri Maresquelle, used to invite colleagues with different scientific backgrounds to round tables, twice a year. These meetings lead to scientifically fruitful multidisciplinary

Background Leishmania are obligated intracellular pathogens that replicate almost exclusively in macrophages. The outcome of infection depends largely on parasite pathogenicity and virulence but also on the activation status and genetic background of macrophages. Animal models are essential for a better understanding of pathogenesis of different microbes including Leishmania. Results Here we compared the transcriptional signatures of resistant (C57BL/6) and susceptible (BALB/c) mouse bone marrow-derived macrophages in response to Leishmania major (L. major) promastigotes infection. Microarray results were first analyzed for significant pathways using the Kyoto Encylopedia of Genes and Genomes (KEGG) database. The analysis revealed that a large set of the shared genes is involved in the immune response and that difference in the expression level of some chemokines and chemokine receptors could partially explain differences in resistance. We next focused on up-regulated genes unique to either BALB/c or C57BL/6 derived macrophages and identified, using KEGG database, signal transduction pathways among the most relevant pathways unique to both susceptible and resistant derived macrophages. Indeed, genes unique to C57BL/6 BMdMs were associated with target of rapamycin (mTOR) signaling pathway while a range of genes unique to BALB/c BMdMs, belong to p53 signaling pathway. We next investigated whether, in a given mice strain derived macrophages, the different up-regulated unique genes could be coordinately regulated. Using GeneMapp Cytoscape, we showed that the induced genes unique to BALB/c or C57BL/6 BMdMs are interconnected. Finally, we examined whether the induced pathways unique to BALB/c derived macrophages interfere with the ones unique to C57BL/6 derived macrophages. Protein-protein interaction analysis using String database highlights the existence of a cross-talk between p53 and mTOR signaling pathways respectively specific to susceptible and resistant BMdMs. Conclusions Taken together our results suggest that strains specific pathogenesis may be due to a difference in the magnitude of the same pathways and/or to differentially expressed pathways in the two mouse strains derived macrophages. We identify signal transduction pathways among the most relevant pathways modulated by L. major infection, unique to BALB/c and C57BL/6 BMdM and postulate that the interplay between these potentially interconnected pathways could direct the macrophage response toward a given phenotype.

Background: On March 11, 2020, the WHO announced that the COVID-19 outbreak had become pandemic, indicating that it was au- tonomous on several continents. Tunisia’s targeted containment and screen- ing strategy aligns with the WHO’s initial guidelines. This method is now showing its limitations. Mass screening in some countries shows that asymptomatic patients play an important role in spreading the virus through the population.Objective: Our goals are first to assess Tunisia’s COVID-19 control policies, and then understand the effect of various detection, quarantine and confinement strategies and the rule of asymptomatic patients on the spread of the virus in the Tunisian population. Methods: We develop and analyze a mathematical and epidemiologi- cal models for COVID- 19 in Tunisia. The data come from the Tunisian Health Commission dataset. Results: We calibrate different parameters of the model based on the Tunisian data, we calculate the expression of the basic reproduction num- ber R0 as a function of the model parameters and, finally, we carry out simulations of interventions and compare different strategies for suppress- ing and controlling the epidemic. Conclusions: We show that Tunisia’s control policies are effective in screening infected and asymptomatic persons.

International audience; BACKGROUND: Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages. RESULTS: We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection. CONCLUSION: Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level.