Characterization of Altered immunity in Anaplastic Thyroid Cancer

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Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle

International audienceBackground: Knowledge of age-related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans.Methods: We conducted a large-scale epigenome-wide association study meta-analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18-89 years old). We explored the genomic context of age-related DNA methylation changes in chromatin states, CpG islands, and transcription factor binding sites and performed gene set enrichment analysis. We then integrated the DNA methylation data with known transcriptomic and proteomic age-related changes in skeletal muscle. Finally, we updated our recently developed muscle epigenetic clock (https://bioconductor.org/packages/release/bioc/html/MEAT.html).Results: We identified 6710 differentially methylated regions at a stringent false discovery rate <0.005, spanning 6367 unique genes, many of which related to skeletal muscle structure and development. We found a strong increase in DNA methylation at Polycomb target genes and bivalent chromatin domains and a concomitant decrease in DNA methylation at enhancers. Most differentially methylated genes were not altered at the mRNA or protein level, but they were nonetheless strongly enriched for genes showing age-related differential mRNA and protein expression. After adding a substantial number of samples from five datasets (+371), the updated version of the muscle clock (MEAT 2.0, total n = 1053 samples) performed similarly to the original version of the muscle clock (median of 4.4 vs. 4.6 years in age prediction error), suggesting that the original version of the muscle clock was very accurate.Conclusions: We provide here the most comprehensive picture of DNA methylation ageing in human skeletal muscle and reveal widespread alterations of genes involved in skeletal muscle structure, development, and differentiation. We have made our results available as an open-access, user-friendly, web-based tool called MetaMeth (https://sarah-voisin.shinyapps.io/MetaMeth/)

Study of Leishmania pathogenesis in mice : experimental considerations

Although leishmaniases are endemic in 98 countries, they are still considered neglected tropical diseases. Leishmaniases are characterized by the emergence of new virulent and asymptomatic strains of Leishmania spp. and, as a consequence, by a very diverse clinical spectrum. To fight more efficiently these parasites, the mechanisms of host defense and of parasite virulence need to be thoroughly investigated. To this aim, animal models are widely used. However, the results obtained with these models are influenced by several experimental parameters, such as the mouse genetic background, parasite genotype, inoculation route/infection site, parasite dose and phlebotome saliva. In this review, we propose an update on their influence in the two main clinical forms of the disease: cutaneous and visceral leishmaniases

In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

International audiencePSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in severalLeishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice.We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in aL. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L.braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals weresubdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantuminfection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high orlow levels of IFN-c in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detectedin sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-c, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-a in more. No significant cytokine response wasobserved in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increasein CD4+ T cells producing IFN-c after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between thepercentage of IFN-c-producing CD4+ T cells and the released IFN-c. We showed that the LaPSA-38S protein was able toinduce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infectionindicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacityof Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infectio

A survey of search-based refactoring for software maintenance

This survey reviews published materials relating to the specific area of Search Based Software Engineering concerning software maintenance. 99 papers are selected from online databases to analyze and review the area of Search Based Software Maintenance. The literature addresses different methods to automate the software maintenance process. There are studies that analyze different software metrics, studies that experiment with multi-objective techniques and papers that propose refactoring tools for use. This survey also suggests papers from related areas of research, and introduces some of the concepts and techniques used in the area. The current state of the research is analyzed in order to assess opportunities for future research. This survey is beneficial as an introduction for any researchers aiming to work in the area of Search Based Software Maintenance and will allow them to gain an understanding of the current landscape of the research and the insights gathered. The papers reviewed as well as the refactoring tools introduced are tabulated in order to aid researchers in quickly referencing studies

Application of an electronic tongue for Tunisian olive oils' classification according to olive cultivar or physicochemical parameters

Olive oil commercialization has a great impact on the economy of several countries, namely Tunisia, being prone to frauds. Therefore, it is important to establish analytical techniques to ensure labeling correctness concerning olive oil quality and olive cultivar. Traditional analytical techniques are quite expensive, time consuming and hardly applied in situ, considering the harsh environments of the olive industry. In this work, the feasibility of applying a potentiometric electronic tongue with cross-sensitivity lipid membranes to discriminate Tunisian olive oils according to their quality level (i.e., extra virgin, virgin or lampante olive oils) or autochthonous olive cultivar (i.e., cv Chétoui and cv Shali) was evaluated for the first time. Linear discrimination analysis coupled with the simulated annealing variable selection algorithm showed that the signal profiles of olive oils hydroethanolic extracts allowed olive oils discrimination according to physicochemical quality level (classification model based on 25 signals enabling 84 ± 9% correct classifications for repeated K-fold cross-validation), and olive cultivar (classification model based on 20 signals with an average sensitivity of 94 ± 6% for repeated K-fold cross-validation), regardless of the geographical origin and olive variety or the olive quality, respectively. The results confirmed, for the first time, the potential discrimination of the electronic tongue, attributed to the observed quantitative response (sensitivities ranging from 66.6 to +57.7 mV/decade) of the E-tongue multi-sensors towards standard solutions of polar compounds (aldehydes, esters and alcohols) usually found in olive oils and that are related to their sensory positive attributes like green and fruity.This work was financially supported by Project POCI-01–0145-FEDER-006984–Associate Laboratory LSRE-LCM and by Project UID/QUI/00616/2013–CQ-VR both funded by FEDER—Fundo Europeu de Desenvolvimento Regional through COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI)—and by national funds through FCTFundação para a Ciência e a Tecnologia, Portugal. Strategic funding of UID/BIO/04469/2013 unit is also acknowledged. Nuno Rodrigues thanks FCT, POPH-QREN and FSE for the Ph.D. Grant (SFRH/ BD/104038/2014).info:eu-repo/semantics/publishedVersio