3,655 research outputs found

    A simple method to identify kinases that regulate embryonic stem cell pluripotency by high-throughput inhibitor screening

    Get PDF
    Embryonic stem cells (ESCs) can self-renew or differentiate into all cell types, a phenomenon known as pluripotency. Distinct pluripotent states have been described, termed "naïve" and "primed" pluripotency. The mechanisms that control naïve-primed transition are poorly understood. In particular, we remain poorly informed about protein kinases that specify naïve and primed pluripotent states, despite increasing availability of high-quality tool compounds to probe kinase function. Here, we describe a scalable platform to perform targeted small molecule screens for kinase regulators of the naïve-primed pluripotent transition in mouse ESCs. This approach utilizes simple cell culture conditions and standard reagents, materials and equipment to uncover and validate kinase inhibitors with hitherto unappreciated effects on pluripotency. We discuss potential applications for this technology, including screening of other small molecule collections such as increasingly sophisticated kinase inhibitors and emerging libraries of epigenetic tool compounds

    A simple method for estimating larval supply in reef fishes and a preliminary test of population limitation by larval delivery in the kelp bass \u3cem\u3eParalabrax clathratus\u3c/em\u3e

    Get PDF
    This paper describes a method for estimating larval supply of a temperate reef fish, the kelp bass Paralabrax clathratus, that is simple, inexpensive, requires relatively low effort, and integrates larval supply over time. Using this method, we sampled larval supply concurrently at 4 sites spread over about 35 km for nearly an entire settlement season. With these data and visual estimates of recruitment (the density of young-of-the-year after the end of the settlement season), we tested the hypothesis that spatial patterns in recruitment were set by larval supply. This hypothesis was rejected: kelp bass recruitment to the 4 sites was not related to patterns of larval supply. Furthermore, in contrast to the findings of an earlier study, recruitment was not related to the density of the macroalga Macrocystis pyrifera. Recruitment was, however, strongly correlated with the density of 1 yr old kelp bass, suggesting that spatial patterns of recruitment were consistent between the 2 cohorts. Recruitment, however, was not correlated with the density of bass 2+ yr old. We also measured larval supply in a second year and found that spatial patterns of supply were strongly correlated between years at a relatively small scale of 10s to 100s m, but not at a larger scale of several km. This finding suggests that some deterministic process (or set of processes) sets spatial patterns of larval supply at small, but not large scales. At large scales, consistent patterns of recruitment between 2 cohorts in the face of variable larval supply suggest that deterministic, postsettlement processes may generate predictable patterns of recruitment even when the supply of larvae is variable. In addition to demonstrating that spatial patterns in the abundance of demersal fish are not always well predicted by larval supply, this study introduces a technique that may facilitate more thorough exploration of the role of larval supply in determining the dynamics of populations of reef fishes

    Shine 2014 Final Report: Social Prescribing: integrating GP and Community Assets for Health

    Get PDF
    Commissioned by City and Hackney Clinical Commissioning Group, in partnership with the University of East London and Queen Mary University of London
    corecore