Pharmacophore-guided discovery of CDC25 inhibitors causing cell cycle arrest and tumor regression.

CDC25 phosphatases play a key role in cell cycle transitions and are important targets for cancer therapy. Here, we set out to discover novel CDC25 inhibitors. Using a combination of computational methods, we defined a minimal common pharmacophore in established CDC25 inhibitors and performed virtual screening of a proprietary library.

Cell engineering with microfluidic squeezing preserves functionality of primary immune cells in vivo.

The translational potential of cell-based therapies is often limited by complications related to effectively engineering and manufacturing functional cells. While the use of electroporation is widespread, the impact of electroporation on cell state and function has yet to be fully characterized. Here, we use a genome-wide approach to study optimized electroporation treatment and identify striking disruptions in the expression profiles of key functional transcripts of human T cells.

The transcription factor Ets21C drives tumor growth by cooperating with AP-1.

Tumorigenesis is driven by genetic alterations that perturb the signaling networks regulating proliferation or cell death. In order to block tumor growth, one has to precisely know how these signaling pathways function and interplay. Here, we identified the transcription factor Ets21C as a pivotal regulator of tumor growth and propose a new model of how Ets21C could affect this process.

The Drosophila TNF receptor Grindelwald couples loss of cell polarity and neoplastic growth.

Disruption of epithelial polarity is a key event in the acquisition of neoplastic growth. JNK signalling is known to play an important part in driving the malignant progression of many epithelial tumours, although the link between loss of polarity and JNK signalling remains elusive. In a Drosophila genome-wide genetic screen designed to identify molecules implicated in neoplastic growth, we identified grindelwald (grnd), a gene encoding a transmembrane protein with homology to members of the tumour necrosis factor receptor (TNFR) superfamily.

Impact of Antarctic Circumpolar Current development on late Paleogene ocean structure.

Global cooling and the development of continental-scale Antarctic glaciation occurred in the late middle Eocene to early Oligocene (~38 to 28 million years ago), accompanied by deep-ocean reorganization attributed to gradual Antarctic Circumpolar Current (ACC) development. Our benthic foraminiferal stable isotope comparisons show that a large δ(13)C offset developed between mid-depth (~600 meters) and deep (>1000 meters) western North Atlantic waters in the early Oligocene, indicating the development of intermediate-depth δ(13)C and O(2) minima closely linked in the modern ocean to northward incursion of Antarctic Intermediate Water. At the same time, the ocean's coldest waters became restricted to south of the ACC, probably forming a bottom-ocean layer, as in the modern ocean.