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A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase

Immunomodulatory drugs bind to cereblon (CRBN) to confer differentiated substrate specificity on the CRL4CRBN E3 ubiquitin ligase. Here we report the identification of a new cereblon modulator, CC-885, with potent anti-tumour activity. The anti-tumour activity of CC-885 is mediated through the cereblon-dependent ubiquitination and degradation of the translation termination factor GSPT1. Patient-derived acute myeloid leukaemia tumour...

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Species-specific wiring for direction selectivity in the mammalian retina

Directionally tuned signalling in starburst amacrine cell (SAC) dendrites lies at the heart of the circuit that detects the direction of moving stimuli in the mammalian retina. The relative contributions of intrinsic cellular properties and network connectivity to SAC direction selectivity remain unclear. Here we present a detailed connectomic reconstruction of SAC circuitry in mouse retina and describe two previously unknown features of synapse...

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A combinatorial strategy for treating KRAS-mutant lung cancer

Therapeutic targeting of KRAS-mutant lung adenocarcinoma represents a major goal of clinical oncology. KRAS itself has proved difficult to inhibit, and the effectiveness of agents that target key KRAS effectors has been thwarted by activation of compensatory or parallel pathways that limit their efficacy as single agents. Here we take a systematic approach towards identifying combination targets for trametinib, a MEK inhibitor approved by...

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From expert pitchfork user to competent Mac user

(credit: Kris Connor/ Getty Images)

I grew up in a low-tech household. My dad only replaced something if it caught fire. We owned about 15 cars (mostly Humber 80s), and 13 of them were used to keep the other two running. Same story for tractors and any other farm equipment you care to name. Dad’s basic...

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