Human and mouse essentiality screens as a resource for disease gene discovery.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery

Liberation social psychology: learning from Latin America

Liberation Social Psychology (la psicología social de la liberación, LSP) has developed amongst a body of psychologists in Latin America over the last decade. There has been no survey of the field in English, although some of the ideas are of relevance for those working with oppressed groups elsewhere in the world. This article explores the context in which LSP grew from the work of Ignacio Martín-Baró and was developed by Maritza Montero, amongst others. Within LSP, key concepts emerge, including conscientization, realismo-crítico, de-ideologization, a social orientation, the preferential option for the oppressed majorities and methodological eclecticism. The application of LSP is explored with reference to three domains. First, it is suggested that community social psychology as practised in some parts of Latin America reflects LSP in its emphasis on social transformation and participatory methods. Second, psycho-social work with victims of state oppression, which adopts a highly social and societal orientation embodies LSP. Third, social analyses which explicitly adopt socio-psychological-political analyses of the social realities confronting countries in Latin America embrace, in different ways, principles and concepts of LSP. Some of the challenges facing LSP are discussed and open dialogue is encouraged between LSP and critical, community and applied social psychologists. Copyright © 2004 John Wiley & Sons, Ltd

Depot-specific effects of fatty acids on lipid accumulation in children’s adipocytes

Circulating concentrations of fatty acids are elevated in obesity, although their effect on regional fat deposition is relatively unexplored. With the increasing prevalence of childhood obesity, we aimed to investigate whether saturated and unsaturated fatty acids lead to differential lipid accumulation (LA) in children’s subcutaneous and visceral adipocytes. To examine this, subcutaneous and peri-nephric pre-adipocytes, isolated from fat biopsies from 6 pre-pubertal children, were differentiated in vitro before being exposed to palmitate and/or oleate for 24 h. Lipid accumulation was then quantified by nile red staining. Palmitate significantly increased LA in visceral adipocytes at all doses 188 μM (e.g. Palmitate 750 μM: +30.0%[8.2]; p < 0.01), whilst only a dose of 375 μM led to a significant, but smaller, increase in LA in subcutaneous adipocytes (Palmitate 375 μM: +13.0%[4.3]; p = 0.02). In contrast, oleate significantly increased LA in subcutaneous (Oleate 1000 μM: +36.3%[14.0]; p = 0.01), but not visceral (Oleate 1000 μM: +16.2%[9.6]; p = 0.25) adipocytes. These data suggest that saturated and unsaturated fatty acids may exert depot-specific effects on lipid accumulation