First evaluation of the cookie-cutter sharks (Isistius sp.) predation pattern on different cetacean species in Martinique

International audienceCookie-cutter sharks (Isistius sp.) are small squaloid sharks that live in tropical and sub-tropical oceans. Their name comes from their unique tactic of feeding, which enables them to parasitize marine mega-fauna, like cetaceans. Due to their morphological and anatomical characteristics, they are responsible of crater-like wounds on the skin of marine mammals. Little is known on Isistius sp. around the globe especially in Martinique, which represents a potential habitat. The main goal of this study was to assess the impact of cookie-cutter sharks on cetaceans by determining (1) seasonal changes in the occurrence of bites, (2) intra- and interspecific differences in frequencies and locations of bites among the different species of cetaceans, and (3) link behavior patterns of both cookie-cutter sharks and cetaceans. Data were collected from a 3-year photo-identification database of Cetaceans in Caribbean coast of Martinique. 431 wounds of various stages on 396 individuals from nine species of marine mammals were recorded. Results did not show any significant variation in the occurrence of wounds between seasons. Intermediate state was more important, most injuries were observed on the SCF (Superior Central Flank) (62.40%) and in a lesser extent on young individuals (3.25%). The predation of cookie-cutter sharks on different cetacean species has been confirmed consistently in Martinique. Further studies are required with both scientists and fishermen to better understand their specific role in this marine ecosystem

Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors

© 2020 The Authors Castration-resistant prostate cancers (CRPCs) lose sensitivity to androgen-deprivation therapies but frequently remain dependent on oncogenic transcription driven by the androgen receptor (AR) and its splice variants. To discover modulators of AR-variant activity, we used a lysate-based small-molecule microarray assay and identified KI-ARv-03 as an AR-variant complex binder that reduces AR-driven transcription and proliferation in prostate cancer cells. We deduced KI-ARv-03 to be a potent, selective inhibitor of CDK9, an important cofactor for AR, MYC, and other oncogenic transcription factors. Further optimization resulted in KB-0742, an orally bioavailable, selective CDK9 inhibitor with potent anti-tumor activity in CRPC models. In 22Rv1 cells, KB-0742 rapidly downregulates nascent transcription, preferentially depleting short half-life transcripts and AR-driven oncogenic programs. In vivo, oral administration of KB-0742 significantly reduced tumor growth in CRPC, supporting CDK9 inhibition as a promising therapeutic strategy to target AR dependence in CRPC. In the pursuit of hormone receptor modulators in prostate cancer, a potent, ultraselective CDK9 inhibitor is discovered. This study describes the most selective inhibitors of CDK9 known to date and provides compelling preclinical in vitro and in vivo support for CDK9 as a therapeutic target