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Biology subjects

Drapeau, M.

Publications and source records attributed to Drapeau, M..

2 recordsLinked to original sources

The archaeological potential of the northern Luangwa Valley, Zambia: the Luwumbu basin.

The Luangwa Basin, Zambia, which forms part of the Zambezi drainage, is strategically located between the Central African plateau and the East African Rift system. The Luangwa River and major tributaries, such as the Luwumbu River, are perennial water sources supporting essential resources that sustain human communities and a rich and diverse fauna and flora. The archaeological record of Luangwa is relatively unknown, despite early archaeological exploration hinting at its potential. Recent research in the southern Luangwa valley, however, suggests that it preserves a long record of hominin occupation spanning the Early to Late Stone Age. The research described here details fieldwork carried out in northeastern Luangwa, in the Luwumbu Basin, that confirms that a relatively deep package of Quaternary deposits, containing evidence of the Stone Age occupation of the region persists in the upper piedmont zone.

evolutionary biology↗

Discovery and mechanism of action of small molecule inhibitors of ceramidases

Sphingolipid metabolism is tightly controlled by enzymes to regulate essential processes such as energy utilisation and cell proliferation. The central metabolite is ceramide, a pro-apoptotic lipid catabolized by ceramidase enzymes to ultimately produce pro-proliferative sphingosine-1-phosphate. Human ceramidases can be soluble proteins (acid and neutral ceramidase) or integral membrane proteins (alkaline ceramidases). Increasing ceramide levels to increase apoptosis has shown efficacy as a cancer treatment using small molecules inhibiting a soluble ceramidase. Due to the transmembrane nature of alkaline ceramidases, no specific small molecule inhibitors have been reported. Here, we report novel fluorescent substrates (FRETceramides) of ceramidases that can be used to monitor enzyme activity in real-time. We use FRETceramides to discover the first drug-like inhibitors of alkaline ceramidase 3 (ACER3) which are active in cell-based assays. Biophysical characterization of enzyme:inhibitor interactions reveal a new paradigm for inhibition of lipid metabolising enzymes with non-lipidic small molecules. Table of contents summaryUse of synthetic fluorescent ceramide molecules allows the discovery of the first selective drug-like small molecule inhibitors for alkaline ceramidase 3, an intra-membrane enzyme involved in sphingolipid metabolism in health and disease.

biochemistry↗