CYLD regulates keratinocyte differentiation and skin cancer progression in humans

CYLD is a gene mutated in familial cylindromatosis and related diseases, leading to the development of skin appendages tumors. Although the deubiquitinase CYLD is a skin tumor suppressor, its role in skin physiology is unknown. Using skin organotypic cultures as experimental model to mimic human skin, we have found that CYLD acts as a regulator of epidermal differentiation in humans through the JNK signaling pathway. We have determined the requirement of CYLD for the maintenance of epidermal polarity, keratinocyte differentiation and apoptosis. We show that CYLD overexpression increases keratinocyte differentiation while CYLD loss of function impairs epidermal differentiation. In addition, we describe the important role of CYLD in the control of human non-melanoma skin cancer progression. Our results show the reversion of the malignancy of human squamous cell carcinomas that express increased levels of CYLD, while its functional inhibition enhances the aggressiveness of these tumors which progress toward spindle cell carcinomas. We have found that the mechanisms through which CYLD regulates skin cancer progression include the control of tumor differentiation, angiogenesis and cell survival. These findings of the role of CYLD in human skin cancer prognosis make our results relevant from a therapeutic point of view, and open new avenues for exploring novel cancer therapies

Measurement of Electron Backscattering in the Energy Range of Neutron β\beta-Decay

We report on the first detailed measurements of electron backscattering from low Z targets at energies up to 124 keV. Both energy and angular distributions of the backscattered electrons are measured and compared with electron transport simulations based on the Geant4 and Penelope Monte Carlo simulation codes. Comparisons are also made with previous, less extensive, measurements and with measurements at lower energies.Comment: 9 pages, 8 figures, accepted for publication in Phys. Rev.

Disenchanting secularism (or the cultivation of soul) as pedagogy in resistance to populist racism and colonial structures in the academy

This paper explores pedagogic strategies for resisting the racism of contemporary populism and age-old coloniality through challenging secularism in the academy, especially in social theory. Secularism sustains racism and imperialism in the contemporary academy and is inscribed, in part, through the norms of social theory. Post-secular social theory has been positioned by some as the decolonial answer, but often replicates the most problematic aspects of secularism. Whereas post-secularism affirms the previously denigrated side of the secular vs religious dualism, I am more interested in unworking those classificatory schemas, setting the critical thought of religious teachers in relation with ‘secular’ social and political theorists such that boundaries erode. The ambition in this is to resist the hierarchical orderings of knowledge that pit Islamic, indigenous, and feminised subjectivity as backwards, dangerous or intrinsically inferior to secular, Christian, rational knowledge. It is also to disenchant the secular Gods (progress, money, growth, health) and hold open space for critical play in relation to the transcendental - to create a permissive, legitimising, space for students’ spiritual dimension, conocimiento, or the cultivation of soul. The paper draws theoretical inspiration from Gloria Anzaldúa, Gayatri Chakravorty Spivak, and Sylvia Wynter. It also draws on a practical experiment in disenchanting secularism through teaching an undergraduate module in social theory called Capitalism and Religion

Optineurin Is Required for CYLD-Dependent Inhibition of TNFα-Induced NF-κB Activation

The nuclear factor kappa B (NF-κB) regulates genes that function in diverse cellular processes like inflammation, immunity and cell survival. The activation of NF-κB is tightly controlled and the deubiquitinase CYLD has emerged as a key negative regulator of NF-κB signalling. Optineurin, mutated in certain glaucomas and amyotrophic lateral sclerosis, is also a negative regulator of NF-κB activation. It competes with NEMO (NF-κB essential modulator) for binding to ubiquitinated RIP (receptor interacting protein) to prevent NF-κB activation. Recently we identified CYLD as optineurin-interacting protein. Here we have analysed the functional significance of interaction of optineurin with CYLD. Our results show that a glaucoma-associated mutant of optineurin, H486R, is altered in its interaction with CYLD. Unlike wild-type optineurin, the H486R mutant did not inhibit tumour necrosis factor α (TNFα)-induced NF-κB activation. CYLD mediated inhibition of TNFα-induced NF-κB activation was abrogated by expression of the H486R mutant. Upon knockdown of optineurin, CYLD was unable to inhibit TNFα-induced NF-κB activation and showed drastically reduced interaction with ubiquitinated RIP. The level of ubiquitinated RIP was increased in optineurin knockdown cells. Deubiquitination of RIP by over-expressed CYLD was abrogated in optineurin knockdown cells. These results suggest that optineurin regulates NF-κB activation by mediating interaction of CYLD with ubiquitinated RIP thus facilitating deubiquitination of RIP

The Gap between the Conditional Wage Distributions of Incumbents and the Newly Hired Employees: Decomposition and Uniform Ordering

We examine the cardinal gap between wage distributions of the incumbents and newly hired workers based on entropic distances that are well-defined welfare theoretic measures. Decomposition of several effects is achieved by identifying several counterfactual distributions of different groups. These go beyond the usual Oaxaca-Blinder decompositions at the (linear) conditional means. Much like quantiles, these entropic distances are well defined inferential objects and functions whose statistical properties have recently been developed. Going beyond these strong rankings and distances, we consider weak uniform ranking of these wage outcomes based on statistical tests for stochastic dominance. We focus the empirical analysis on employees with at least 35 hours of work in the 1996 - 2012 monthly Current Population Survey. Among other findings, we find incumbent workers enjoy a better distribution of wages, but the attribution of the gap to wage inequality and human capital characteristics varies between quantiles. For instance, highly paid new workers are mainly due to human capital components and, in some years, even better wage structure

Ethnic diversity in the UK: new opportunities and changing constraints

The study of ethnicity and migration is a fast evolving field. Much remains to be understood about economic, social, demographic and health outcomes across ethnic groups and generations, and the extent of integration and exclusion of different immigrant-origin groups in countries of destination. While cross-national studies are increasingly shedding light on issues of differential migrant selection and institutional influences, detailed single-country studies, based on high quality nationally representative data have much to offer in enhancing our understanding of diversity within and between groups. The introduction to this special issue on ‘ethnic diversity in the UK: new opportunities and changing constraints’ provides a background to the contributions in the issue by outlining key research agendas relating to immigrant and ethnic minority groups in Western Europe. It then elaborates why the UK represents a good case for exploring ethnic diversity and change; and outlines the contributions made by the papers in the issue. We highlight the distinctive features of the data source used in the papers, Understanding Society, the UK Household Longitudinal Study. We also consider limitations in the data and in the applications in the issue. We conclude by briefly outlining the policy-relevant contributions of the papers in the issue