Prevalence and determinants of Leishmania major infection in emerging and old foci in Tunisia

International audienceBackground: Zoonotic Cutaneous Leishmaniasis (ZCL) due to Leishmania major (L. major) is still a serious public health problem in Tunisia. This study aimed to compare the prevalence and risk factors associated with L. major infection in old and new foci using leishmanin skin test (LST) in central Tunisia. Methods: A cross sectional household survey was carried out between January and may09 on a sample of 2686 healthy individuals aged between 5 and 65 years. We determined the prevalence of L. major infection using the LST. Risk factors of LST positivity were assessed using a logistic regression model. Results: The overall prevalence of LST positivity was 57% (95% CI: 53-59). The prevalence of L. major infection was significantly higher in the old focus (99%; 95% CI: 98-100) than in the emerging foci (43%; 95% CI: 39-46) (p = <0.001). Multivariate analysis of LST positivity risk factors showed that age, the nature of the foci (old/emerging), personal and family history of ZCL are determinants of positive LST results. Conclusion: The results updated the current epidemiologic profile of ZLC in central Tunisia. Past history of transmission in a population should be considered as a potential confounder in future clinical trials for drugs and vaccines against L. major cutaneous leishmaniasis

A Screen for Morphological Complexity Identifies Regulators of Switch-like Transitions between Discrete Cell Shapes

The way in which cells adopt different morphologies is not fully understood. Cell shape could be a continuous variable or restricted to a set of discrete forms. We developed quantitative methods to describe cell shape and show that Drosophila hemocytes in culture are a heterogeneous mixture of five discrete morphologies. In an RNAi screen of genes affecting the morphological complexity of heterogeneous populations, we found that most genes regulate the transition between discrete shapes rather than generating new morphologies. In particular, we identified a subset of genes, including the tumour suppressor PTEN, that decrease the heterogeneity of the population leading to populations enriched in rounded or elongated forms. We show that these genes have a highly conserved function as regulators of cell shape in both mouse and human metastatic melanoma cells

Non-muscle Myosin II reactivation and cytoskeletal remodelling as a new vulnerability in therapy-resistant melanoma

Trabajo presentado en el 3rd ASEICA Educational Symposium, celebrado en modalidad virtual del 23 al 25 de noviembre de 2021.MAPK-targeted therapies (MAPKi) and immune checkpoint blockers (ICB) improve survival of subsets of melanoma patients. However, therapy resistance is a persistent problem. Cross-resistance to MAPKi and ICB may be driven by common transcriptomic alterations in pathways controlling invasion and metastasis. Using phosphoproteomic and transcriptomic analyses, we find that adaptation to treatment and acquisition of resistance to MAPKi involve cytoskeletal remodelling and changes in levels in the ROCK-non-muscle Myosin II (NMII) pathway, which is essential for cancer invasion and metastasis. NMII activity is decreased shortly after MAPK is blocked. However, persister cells promptly restore NMII activity to increase survival, and this becomes a vulnerability, since survival of MAPKi- and ICB-resistant cells is highly dependent on ROCK-NMII. Efficacy of MAPKi and ICB can be improved by combination with ROCK inhibitors, which have a dual action by impairing melanoma cell survival (through induction of lethal reactive oxygen species and unresolved DNA damage) and reducing myeloid- and lymphoid-driven immunosuppression, ultimately overcoming cross-resistance in vivo. In human tumours, high ROCK-NMII levels identify MAPKi-, ICB-resistant melanomas, and treatment-naïve melanomas with worse prognosis. Therefore, a subset of MAPKi- and ICB-resistant melanomas is more susceptible to ROCK-NMII blockade, suggesting clinical opportunities for combination therapies

Genetic Diversity Analysis of Onion (Allium cepa L.) from the Arid Region of Tunisia Using Phenotypic Traits and SSR Markers

The present study was carried out to evaluate and characterize, for the first time, the genetic potential of a collection of onion (Allium cepa L.) local accessions from the arid region of southern Tunisia. The genetic diversity among 135 onion individuals, belonging to 23 accessions, was evaluated using microsatellite (SSR) markers and phenotypic information. A total of 35 alleles were generated with 11 SSRs. The polymorphic information content (PIC) value ranged from 0.08 to 0.95, with an average PIC of 0.43. The expected heterozygosity averaged 0.37, and the observed heterozygosity averaged 0.42. The analysis of molecular variance (AMOVA) revealed that 79% of genetic variation existed within individuals. Structure and cluster analysis grouped the accessions into two major clusters: landraces and pre-breeding lines. For the phenotypic traits evaluated, field trials were conducted in two different environments. Significant differences among accessions were shown, and for most traits, there was also a significant environmental effect and a significant interaction between environment and accession. Great variability was found for all the traits that could be exploited to create new varieties of onion adapted to local conditions by selecting appropriate parents in hybridization breeding.Esta investigación fue financiada en parte por el laboratorio de investigación LR21AGR03-Producción y Protección para una Horticultura Sostenible, financiado por el Ministerio de Educación Superior e Investigación Científica de Túnez y parcialmente financiado por el proyecto A11-20R financiado por el Gobierno de Aragón y por el programa AGROALNEXT apoyado por MCIN con financiación de la Unión Europea NextGenerationEU (PRTR-C17.I1).diversitylandracesmicrosatellitesbreedingphenotypicG × E interactionPublishe

The Myosin II cytoskeleton as a new vulnerability in therapy-resistant melanoma

Trabajo presentado en VIB Conference: Tumor Heterogeneity, Plasticity and Therapy, celebrado en modalidad virtual del 05 al 06 de mayo de 2021.MAPK-targeted therapies (MAPKi) and immune checkpoint blockers (ICB) improve survival of subsets of melanoma patients. However, therapy resistance is a persistent problem. Cross-resistance to MAPKi and ICB has been suggested to be driven, in part, by common transcriptomic alterations in pathways controlling invasion and metastasis. We find that adaptation to treatment and acquisition of resistance to MAPKi involve cytoskeletal remodelling and changes in expression levels in the ROCK-Myosin II pathway, which plays a key role in cancer invasion and metastasis. Myosin II activity is decreased shortly after MAPK is blocked. However, resistant cells promptly restore Myosin II activity to increase survival, and this becomes a vulnerability, since survival of MAPKi- and ICB-resistant cells is highly dependent on ROCK-Myosin II. Efficacy of MAPKi and ICB can be improved by combination with ROCK inhibitors, which have a dual action by impairing melanoma cell survival (through induction of lethal reactive oxygen species and unresolved DNA damage) and myeloid- and lymphoiddriven immunosuppression, overcoming cross-resistance. In human tumours, high ROCK-Myosin II activity and their associated transcriptome identify MAPKi-, ICBresistant melanomas, and treatment-naïve melanomas with worse prognosis. Therefore, a subset of MAPKi- and ICB-resistant melanomas is intrinsically more susceptible to ROCK-Myosin II inhibition, suggesting clinical opportunities for combination therapies

The Myosin II cytoskeleton as a new vulnerability in therapy-resistant melanoma

Trabajo presentado en el XIX Congreso de la Sociedad Española de Biología Celular, celebrado en Boadilla del Monte (España) del 26 al 29 de octubre de 2021.MAPK-targeted therapies (MAPKi) and immune checkpoint blockers (ICB) improve survival of subsets of melanoma patients. However, therapy resistance is a persistent problem. Cross-resistance to MAPKi and ICB has been suggested to be driven, in part, by common transcriptomic alterations in pathways controlling invasion and metastasis. We find that adaptation to treatment and acquisition of resistance to MAPKi involve cytoskeletal remodelling and changes in expression levels in the ROCK-Myosin II pathway, which plays a key role in cancer invasion and metastasis. Myosin II activity is decreased shortly after MAPK is blocked. However, resistant cells promptly restore Myosin II activity to increase survival, and this becomes a vulnerability, since survival of MAPKi- and ICB-resistant cells is highly dependent on ROCK-Myosin II. Efficacy of MAPKi and ICB can be improved by combination with ROCK inhibitors, which have a dual action by impairing melanoma cell survival (through induction of lethal reactive oxygen species, unresolved DNA damage and cell cycle arrest) and myeloid- and lymphoid-driven immunosuppression, ultimately overcoming cross-resistance. In human tumours, high ROCK-Myosin II activity and their associated transcriptome identify MAPKi-, ICB-resistant melanomas, and treatment-naïve melanomas with worse prognosis. Therefore, a subset of MAPKi- and ICB-resistant melanomas is intrinsically more susceptible to ROCK-Myosin II inhibition, suggesting clinical opportunities for combination therapies

Temporal Dynamics and Impact of Climate Factors on the Incidence of Zoonotic Cutaneous Leishmaniasis in Central Tunisia

Old world cutaneous leishmaniasis is a vector-borne disease occurring in rural areas of developing countries. The main reservoirs are the rodents Psammomys obesus and Meriones shawi. Zoonotic Leishmania transmission cycle is maintained in the burrows of rodents where the sand fly Phlebotomus papatasi finds the ideal environment and source of blood meals. In the present study we showed seasonality of the incidence of disease during the same cycle with an inter-epidemic period ranging from 4 to 7 years. We evaluated the impact of climate variables (rainfall, humidity and temperature) on the incidence of zoonotic cutaneous leishmaniais in central Tunisia. We confirmed that the risk of disease is mainly influenced by the humidity related to the months of July to September during the same season and mean rainfall lagged by 12 to 14 months

Etude du rôle de la NADPH oxydase 1 dans la régulation de la migration des cellules d'adénocarcinome colique

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Solution properties controls global fibril morphology.

<p>Different solution properties are plotted against the total acid-acyl contents (A.A.E.A.) for (a) conductivity, (b) pH, and (c) surface tension. The approximate regimes of fibril morphology are highlighted in each graph. For (b) and (c), a pair of blue lines are drawn to enclose the range of conditions which resulted in the formation of straight fibers. It is to note that for G10-A70, the A.A.∶E.A. ratios of 1, 1.5 and 4 were tested, and this can be seen as the increase in conductivity in (a).</p