Application of Artificial Intelligence to the Prediction of the Antimicrobial Activity of Essential Oils

Essential oils (EOs) are vastly used as natural antibiotics in Complementary and Alternative Medicine (CAM). Their intrinsic chemical variability and synergisms/antagonisms between its components make difficult to ensure consistent effects through different batches. Our aim is to evaluate the use of artificial neural networks (ANNs) for the prediction of their antimicrobial activity. Methods. The chemical composition and antimicrobial activity of 49 EOs, extracts, and/or fractions was extracted from NCCLS compliant works. The fast artificial neural networks (FANN) software was used and the output data reflected the antimicrobial activity of these EOs against four common pathogens: Staphylococcus aureus, Escherichia coli, Candida albicans, and Clostridium perfringens as measured by standardised disk diffusion assays. Results. ANNs were able to predict >70% of the antimicrobial activities within a 10 mm maximum error range. Similarly, ANNs were able to predict 2 or 3 different bioactivities at the same time. The accuracy of the prediction was only limited by the inherent errors of the popular antimicrobial disk susceptibility test and the nature of the pathogens. Conclusions. ANNs can be reliable, fast, and cheap tools for the prediction of the antimicrobial activity of EOs thus improving their use in CAM

Application of Artificial Intelligence to the Prediction of the Antimicrobial Activity of Essential Oils

Essential oils (EOs) are vastly used as natural antibiotics in Complementary and Alternative Medicine (CAM). Their intrinsic chemical variability and synergisms/antagonisms between its components make difficult to ensure consistent effects through different batches. Our aim is to evaluate the use of artificial neural networks (ANNs) for the prediction of their antimicrobial activity. Methods. The chemical composition and antimicrobial activity of 49 EOs, extracts, and/or fractions was extracted from NCCLS compliant works. The fast artificial neural networks (FANN) software was used and the output data reflected the antimicrobial activity of these EOs against four common pathogens: Staphylococcus aureus, Escherichia coli, Candida albicans, and Clostridium perfringens as measured by standardised disk diffusion assays. Results. ANNs were able to predict >70% of the antimicrobial activities within a 10 mm maximum error range. Similarly, ANNs were able to predict 2 or 3 different bioactivities at the same time. The accuracy of the prediction was only limited by the inherent errors of the popular antimicrobial disk susceptibility test and the nature of the pathogens. Conclusions. ANNs can be reliable, fast, and cheap tools for the prediction of the antimicrobial activity of EOs thus improving their use in CAM

A coordinated DNA damage response promotes adult quiescent neural stem cell activation

Stem and differentiated cells frequently differ in their response to DNA damage, which can determine tissue sensitivity. By exploiting insight into the spatial arrangement of subdomains within the adult neural subventricular zone (SVZ) in vivo, we show distinct responses to ionising radiation (IR) between neural stem and progenitor cells. Further, we reveal different DNA damage responses between neonatal and adult neural stem cells (NSCs). Neural progenitors (transit amplifying cells and neuroblasts) but not NSCs (quiescent and activated) undergo apoptosis after 2 Gy IR. This response is cell type- rather than proliferationdependent and does not appear to be driven by distinctions in DNA damage induction or repair capacity. Moreover, exposure to 2 Gy IR promotes proliferation arrest and differentiation in the adult SVZ. These 3 responses are ataxia telangiectasia mutated (ATM)- dependent and promote quiescent NSC (qNSC) activation, which does not occur in the subdomains that lack progenitors. Neuroblasts arising post-IR derive from activated qNSCs rather than irradiated progenitors, minimising damage compounded by replication or mitosis. We propose that rather than conferring sensitive cell death, apoptosis is a form of rapid cell death that serves to remove damaged progenitors and promote qNSC activation. Significantly, analysis of the neonatal (P5) SVZ reveals that although progenitors remain sensitive to apoptosis, they fail to efficiently arrest proliferation. Consequently, their repopulation occurs rapidly from irradiated progenitors rather than via qNSC activation

The Human Papillomavirus E6 Oncogene Represses a Cell Adhesion Pathway and Disrupts Focal Adhesion through Degradation of TAp63β upon Transformation

Cervical carcinomas result from cellular transformation by the human papillomavirus (HPV) E6 and E7 oncogenes which are constitutively expressed in cancer cells. The E6 oncogene degrades p53 thereby modulating a large set of p53 target genes as shown previously in the cervical carcinoma cell line HeLa. Here we show that the TAp63β isoform of the p63 transcription factor is also a target of E6. The p63 gene plays an essential role in skin homeostasis and is expressed as at least six isoforms. One of these isoforms, ΔNp63α, has been found overexpressed in squamous cell carcinomas and is shown here to be constitutively expressed in Caski cells associated with HPV16. We therefore explored the role of p63 in these cells by performing microarray analyses after repression of endogenous E6/E7 expression. Upon repression of the oncogenes, a large set of p53 target genes was found activated together with many p63 target genes related to cell adhesion. However, through siRNA silencing and ectopic expression of various p63 isoforms we demonstrated that TAp63β is involved in activation of this cell adhesion pathway instead of the constitutively expressed ΔNp63α and β. Furthermore, we showed in cotransfection experiments, combined with E6AP siRNA silencing, that E6 induces an accelerated degradation of TAp63β although not through the E6AP ubiquitin ligase used for degradation of p53. Repression of E6 transcription also induces stabilization of endogenous TAp63β in cervical carcinoma cells that lead to an increased concentration of focal adhesions at the cell surface. Consequently, TAp63β is the only p63 isoform suppressed by E6 in cervical carcinoma as demonstrated previously for p53. Down-modulation of focal adhesions through disruption of TAp63β therefore appears as a novel E6-dependent pathway in transformation. These findings identify a major physiological role for TAp63β in anchorage independent growth that might represent a new critical pathway in human carcinogenesis

LRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells

Adult neural stem cells (NSCs) must tightly regulate quiescence and proliferation. Single-cell analysis has suggested a continuum of cell states as NSCs exit quiescence. Here we capture and characterize in vitro primed quiescent NSCs and identify LRIG1 as an important regulator. We show that BMP-4 signaling induces a dormant non-cycling quiescent state (d-qNSCs), whereas combined BMP-4/FGF-2 signaling induces a distinct primed quiescent state poised for cell cycle re-entry. Primed quiescent NSCs (p-qNSCs) are defined by high levels of LRIG1 and CD9, as well as an interferon response signature, and can efficiently engraft into the adult subventricular zone (SVZ) niche. Genetic disruption of Lrig1 in vivo within the SVZ NSCs leads an enhanced proliferation. Mechanistically, LRIG1 primes quiescent NSCs for cell cycle re-entry and EGFR responsiveness by enabling EGFR protein levels to increase but limiting signaling activation. LRIG1 is therefore an important functional regulator of NSC exit from quiescence

Isolation of Neural Stem and Progenitor Cells from the Adult Brain and Live Imaging of Their Cell Cycle with the FUCCI System.

International audienceNeural stem cells (NSCs) enter quiescence in early embryonic stages to create a reservoir of dormant NSCs able to enter proliferation and produce neuronal precursors in the adult mammalian brain. Various approaches of fluorescent-activated cell sorting (FACS) have emerged to allow the distinction between quiescent NSCs (qNSCs), their activated counterpart (aNSCs), and the resulting progeny. In this article, we review two FACS techniques that can be used alternatively. We also show that their association with transgenic Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) mice allows an unprecedented overlook on the cell cycle dynamics of adult NSCs

Identification of factors involved in neurogenesis recovery following irradiation of the adult mouse subventricular zone, a preliminary study

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The human papillomavirus e6 oncogene represses a cell adhesion pathway and disrupts focal adhesion through degradation of tap63? upon transformation

10.1371/journal.ppat.1002256PLoS Pathogens79e100225

Identification of factors involved in neurogenesis recovery following irradiation of the adult mouse subventricular zone, a preliminary study

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