bioRxiv Science⌕ Search

Biology subjects

Paris, A.

Publications and source records attributed to Paris, A..

4 recordsLinked to original sources

Combining cancer chemotherapeutics with bacterial DNA repair inhibitors to develop novel antimicrobials

Cancer chemotherapeutics kill rapidly dividing cells, which includes cells of the immune system. The resulting neutropenia predisposes patients to infection, which delays treatment and is a major cause of morbidity and mortality. Here we have exploited the cytotoxicity of the anti-cancer compound cisplatin to screen for FDA-approved drugs that impair bacterial nucleotide excision DNA repair (NER), the primary mechanism bacteria use to repair cisplatin lesions. Five compounds have emerged of which three possess ideal antimicrobial properties including cell penetrance, specific activity for NER, and the ability to kill a multi-drug resistant clinically relevant E. coli strain. Targeting NER offers a new therapeutic approach for infections in cancer patients by combining antimicrobial activity with cancer chemotherapy.

biochemistry↗

The maturity in fetal pigs using a multi-fluid metabolomic approach

In mammalian species, the first days after birth are an important period for survival and the rates of mortality before weaning are high. In pigs, the perinatal deaths average 20% of the litter, with important economic and societal consequences. Among the factors influencing piglet survival at birth, the maturity is likely to be one of the most important. Maturity can be defined as the outcome of complex mechanisms of intra-uterine development and maturation occurring during the last month of gestation. Here, we provide new insights on maturity by studying the end of gestation at two different stages (three weeks before term and close to term) in two breeds of pigs that strongly differ in terms of neonatal survival. Since metabolomics is a promising approach for phenotype characterization or biomarker discovery, we provide a complete understanding of the metabolome of the fetuses in late gestation in three fluids (plasma, urine, and amniotic fluid). We found that biological processes related to amino acid and carbohy-drate metabolisms are critical for piglet maturity. We also confirmed some previously described metabolites associated with delayed growth (e.g., proline and myo-inositol). Altogether, our study proposes new routes for a better characterization of piglet maturity at birth.

developmental biology↗

Specific metabolic signatures of fish exposed to cyanobacterial blooms

With the increasing impact of the global warming, occurrences of cyanobacterial blooms in aquatic ecosystems are becoming a main ecological concern around the world. Due to their capacity to produce potential toxic metabolites, interactions between the cyanobacteria/cyanotoxin complex and the other freshwater organisms have been widely studied in the past years. Non-targeted metabolomic analyses have the powerful capacity to study a high number of metabolites at the same time and thus to understand in depth the molecular interactions between various organisms in different environmental scenario and notably during cyanobacterial blooms. In this way during summer 2015, liver metabolomes of two fish species, sampled in peri-urban lakes of the ile-de-France region containing or not high concentrations of cyanobacteria, were studied. The results suggest that similar metabolome changes occur in both fish species exposed to cyanobacterial blooms compared to them not exposed. Metabolites implicated in protein synthesis, protection against ROS, steroid metabolism, cell signaling, energy storage and membrane integrity/stability have shown the most contrasted changes. Furthermore, it seems that metabolomic studies will provide new information and research perspectives in various ecological fields and notably concerning cyanobacteria/fish interactions but also a promising tool for environmental monitoring of water pollutions.

ecology↗

ASICS: an R package for a whole analysis workflow of 1D 1H NMR spectra

In metabolomics, the detection of new biomarkers from NMR spectra is a promising approach. However, this analysis remains difficult due to the lack of a whole workflow that handles spectra pre-processing, automatic identification and quantification of metabolites and statistical analyses.\n\nWe present ASICS, an R package that contains a complete workflow to analyse spectra from NMR experiments. It contains an automatic approach to identify and quantify metabolites in a complex mixture spectrum and uses the results of the quantification in untargeted and targeted statistical analyses. ASICS was shown to improve the precision of quantification in comparison to existing methods on two independant datasets. In addition, ASICS successfully recovered most metabolites that were found important to explain a two level condition describing the samples by a manual and expert analysis based on bucketting. It also found new relevant metabolites involved in metabolic pathways related to risk factors associated with the conditions.\n\nThis workflow is available through the R package ASICS, available on the Bioconductor platform.

systems biology↗