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

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

Partnership for Whom?

Summary The article examines in what sense various donors understand and interpret the term ‘partnership’ and whether relations between local NGOs and their donors actually fulfill the meaning of this term in Cambodia. The article contrasts supporting schemes to NGOs by Japanese government aid, by Oxfam Great Britain and Coopération Internationale pour 1e Développement et la Solidarité (CIDSE). The question posed is: which scheme and conditions appear to promote partnership better, especially in terms of accountability to the ultimate target beneficiaries? The post?genocidal civil war in Cambodia seriously damaged any notion of community. Consequently, evidence indicates that donors that assist the capacity?building of Cambodian NGOs and those particularly concerned with community organising are more likely to establish a relationship and assistance that is more accountable to the beneficiaries. They do so by basing ‘partnership’ on an organisational rather than project?focused relationship with Cambodian NGOs and communities. On the other hand, it appears that donors that do not support the capacity?building of Cambodian NGOs, but only support project implementation, lack interest in ensuring accountability of their projects to the poor. Such an approach to partnership is more prone to making both international and local NGOs accountable to donors as project implementors, rather than to their partners and their beneficiaries

Deletion of TSPO causes dysregulation of cholesterol metabolism in mouse retina

Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the inner membrane. TSPO is highly expressed in retinal pigment epithelial (RPE) cells, and TSPO ligands have shown therapeutic potential for the treatment of AMD. Here, we characterized retinal pathology of Tspo knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that Tspo KO mice had normal retinal morphology (by light microscopy) but showed elevated levels of cholesterol, triglycerides and phospholipids with perturbed cholesterol efflux in the RPE cells of Tspo KO mice. Expression of cholesterol-associated genes (Nr1h3, Abca1, Abcg1, Cyp27a1 and Cyp46a1) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in Tspo KO retinas. Furthermore, microglial activation was also observed in Tspo KO mouse retinas. These findings provide new insights into the function of TSPO in the retina and may aid in the design of new therapeutic strategies for the treatment of AMD

Veterinary student competence in equine lameness recognition and assessment: a mixed methods study

The development of perceptual skills is an important aspect of veterinary education. The authors investigated veterinary student competency in lameness evaluation at two stages, before (third year) and during (fourth/fifth year) clinical rotations. Students evaluated horses in videos, where horses were presented during trot on a straight line and in circles. Eye-tracking data were recorded during assessment on the straight line to follow student gaze. On completing the task, students filled in a structured questionnaire. Results showed that the experienced students outperformed inexperienced students, although even experienced students may classify one in four horses incorrectly. Mistakes largely arose from classifying an incorrect limb as lame. The correct detection of sound horses was at chance level. While the experienced student cohort primarily looked at upper body movement (head and sacrum) during lameness assessment, the inexperienced cohort focused on limb movement. Student self-assessment of performance was realistic, and task difficulty was most commonly rated between 3 and 4 out of 5. The inexperienced students named a considerably greater number of visual lameness features than the experienced students. Future dedicated training based on the findings presented here may help students to develop more reliable lameness assessment skills

European mobility of United Kingdom educated graduates. Who stays, who goes?

Official figures from the Home Office show an increase in mobility of the highly-skilled from the United Kingdom (UK) to other European countries. This paper analyses the social composition of intra-European mobile graduates from the UK in the context of recent political developments (Bologna-Process, European Higher Education Area). Using quantitative and qualitative data from a longitudinal study of students and its follow-up study, the paper compares the social composition and current activity of intra-European mobile graduates with those remaining in the UK. Personal and higher education-related variables together with the current type of employment were significant for the distinction between intra-European mobile graduates and ‘UK stayers’. UK-educated mobile graduates were identified as ‘Eurostars’, who come from high social classes or studied at high tariff higher education institutions. Mobility was identified as one way for UK-educated graduates to avoid employment in non-graduate jobs and add further value to their undergraduate degrees