A Decade of Antifungal Leads from Natural Products:2010-2019

In this review, we discuss novel natural products discovered within the last decade that are reported to have antifungal activity against pathogenic species. Nearly a hundred natural products were identified that originate from bacteria, algae, fungi, sponges, and plants. Fungi were the most prolific source of antifungal compounds discovered during the period of review. The structural diversity of these antifungal leads encompasses all the major classes of natural products including polyketides, shikimate metabolites, terpenoids, alkaloids, and peptides

Relationships Linking Amplification Level to Gene Over-Expression in Gliomas

Background: Gene amplification is thought to promote over-expression of genes favouring tumour development. Because amplified regions are usually megabase-long, amplification often concerns numerous syntenic or non-syntenic genes, among which only a subset is over-expressed. The rationale for these differences remains poorly understood. Methodology/Principal Finding: To address this question, we used quantitative RT-PCR to determine the expression level of a series of co-amplified genes in five xenografted and one fresh human gliomas. These gliomas were chosen because we have previously characterised in detail the genetic content of their amplicons. In all the cases, the amplified sequences lie on extra-chromosomal DNA molecules, as commonly observed in gliomas. We show here that genes transcribed in nonamplified gliomas are over-expressed when amplified, roughly in proportion to their copy number, while non-expressed genes remain inactive. When specific antibodies were available, we also compared protein expression in amplified and nonamplified tumours. We found that protein accumulation barely correlates with the level of mRNA expression in some of these tumours. Conclusions/Significance: Here we show that the tissue-specific pattern of gene expression is maintained upon amplification in gliomas. Our study relies on a single type of tumour and a limited number of cases. However, it strongly suggests that, even when amplified, genes that are normally silent in a given cell type play no role in tumour progression

Platination de l'ADN télomérique (des structures quadruplexes au double brin)

Les télomères sont des complexes nucléoprotéiques composés de séquences riches en guanines, double brin et simple brin. Ce dernier peut adopter des structures particulières, les structures quadruplexes qui sont des cibles pharmacologiques intéressantes car leur stabilisation entraîne l'inhibition de la télomérase, enzyme impliquée dans la prolifération des cellules cancéreuses. Les protéines TRF1 et TRF2 sont essentielles aux fonctions principales des télomères : la protection et le maintien de l'intégrité des chromosomes. Le c/s-platine est un agent anticancéreux utilisé en clinique depuis 1979 qui se fixe spécifiquement sur les N7 des guanines. Les télomères semblent donc être des cibles privilégiées du c/s-platine. In vitro, les complexes de platine permettent de stabiliser les structures quadruplexes et empêchent la fixation des protéines TRF1 et TRF2. In vivo, la fixation des complexes de platine devrait donc induire la déstabilisation et donc le dysfonctionnement des télomères.Telomeric DMA consists of highly repetitive short sequences of guanines residues followed by single-stranded DNA at the 3' end. In the presence of monovalent cations, the single strand is able to adopt stable quadruplex structures that were shown to inhibit telomerase, an enzyme involved in the immortalisation of cancerous cells. Proteins TRF1 and TRF2 are essential for the main function of telomeres: the protection of telomeres and the preservation of their integrity. Cis-platin is an antitumour drug used since 1979 in cancer therapy; it binds preferentially to guanines. Telomeric DNA appears as a potential target of this complex. In vitro, platinum complexes stabilise quadruplex structure and impede TRF1 and TRF2 binding. In vivo, the platination of telomeric DNA should interfere with the telomere integrity either by blocking the quadruplex structure or by impeding the binding of TRF1 and TRF2 and should provoke telomere destabilisation and dysfunction.PARIS-BIUP (751062107) / SudocSudocFranceF

Telomere Strand-Specific Length Analysis by Fluorescent In Situ Hybridization (Q-CO-FISH)

International audienc

Telomere Length Analysis by Quantitative Fluorescent in Situ Hybridization (Q-FISH)

International audienc

Telomere Strand-Specific Length Analysis by Fluorescent In Situ Hybridization (Q-CO-FISH)

International audienc