Cellular senescence in naevi and immortalisation in melanoma: a role for p16?

Cellular senescence, the irreversible proliferative arrest seen in somatic cells after a limited number of divisions, is considered a crucial barrier to cancer, but direct evidence for this in vivo was lacking until recently. The best-known form of human cell senescence is attributed to telomere shortening and a DNA-damage response through p53 and p21. There is also a more rapid form of senescence, dependent on the p16-retinoblastoma pathway. p16 (CDKN2A) is a known melanoma susceptibility gene. Here, we use retrovirally mediated gene transfer to confirm that the normal form of senescence in cultured human melanocytes involves p16, since disruption of the p16/retinoblastoma pathway is required as well as telomerase activation for immortalisation. Expression (immunostaining) patterns of senescence mediators and markers in melanocytic lesions provide strong evidence that cell senescence occurs in benign melanocytic naevi (moles) in vivo and does not involve p53 or p21 upregulation, although p16 is widely expressed. In comparison, dysplastic naevi and early (radial growth-phase, RGP) melanomas show less p16 and some p53 and p21 immunostaining. All RGP melanomas expressed p21, suggesting areas of p53-mediated senescence, while most areas of advanced (vertical growth-phase) melanomas lacked both p16 and p21, implying escape from both forms of senescence (immortalisation). Moreover, nuclear p16 but not p21 expression can be induced in human melanocytes by oncogenic BRAF, as found in around 80% of naevi. We conclude that cell senescence can form a barrier to melanoma development. This also provides a potential explanation of why p16 is a melanoma suppressor gene

Teachers' resilience: conceived, perceived or lived-in

[Extract] Schools in Western countries are places where work related conditions lead to teacher disaffection and attrition. To mitigate this employers and scholars advocate fostering teacher resilience. This chapter presents a critical examination of teacher resilience. Originally conceived as a personal trait, later research showed human resilience is an attribute that can be developed. Resilience is one’s ability to manage stressors and maintain adaptive functioning across all domains of life. Latterly, scholars investigated resilience in teachers, mainly through qualitative or quantitative self-report studies. This research constitutes perceived teacher resilience, because as formulated, teacher resilience is conceptually flawed, limited in scope, based on teachers’ functioning within their professional lives. We do not know what constitutes long serving teachers’ actual, lived-in resilience: what enables teachers to maintain their wellbeing and effectiveness in the classroom, reflecting human resilience as originally conceived. For an accurate profile of teacher resilience we must study those still teaching, and teachers who have exited the profession to determine why they left. Perhaps exiting the profession signals a resilient person who does accept working conditions that do not support wellbeing or teaching effectiveness. Perhaps ‘teacher resilience’ is inaccurately used in the context of teacher attrition and disaffection

Passively Q-switched 0.1mJ fiber laser system at 1.53µm

We demonstrate a passively Q-switched fiber laser system generating pulses with as much as 0.1 mJ pulse energy at 1.53µm and > 1kHz repetition rate. This was achieved with a simple MOPA (master oscillator, power amplifier) scheme with a single pump source, realized with large mode area fiber and multiple reflections on a semiconductor saturable absorber mirror (SESAM)

0.1mJ pulses from a passively Q-switched fiber source

We demonstrate a passively Q-switched fiber MOPA generating pulses of 0.1mJ at 1.53µm and >1kHz repetition rate. We used a single pump source, large mode area fiber and multiple reflections on a SESAM

The open architecture of European human rights law

The evolution of the European human rights regime is often described in constitutionalist terms: as the move towards an integrated order with the European Convention of Human Rights as its “constitutional instrument” at the top. In this article, I seek to show that this description is misguided and that the regime is better regarded as pluralist – as characterised by a heterarchical relationship between its constituent parts that is ultimately defined politically and not legally. The emergence and workings of this pluralist order are traced through the interaction of the European Court of Human Rights with domestic courts in Spain, France, the European Union and the United Kingdom. All these cases not only show conflicts over questions of ultimate supremacy but also significant convergence and harmony in day-to-day practice. I begin to identify factors that have led to this convergence and conclude that central characteristics of pluralism – incrementalism and the openness of ultimate authority – seem to have contributed to the generally smooth evolution of the European human rights regime in a significant way. This finding suggests a broader appeal of pluralist models as alternatives to constitutionalism in the construction of postnational authority and law