Trauma as counter-revolutionary colonisation: narratives from (post)revolutionary Egypt

We argue that multiple levels of trauma were present in Egypt before, during and after the 2011 revolution. Individual, social and political trauma constitute a triangle of traumatisation which was strategically employed by the Egyptian counter-revolutionary forces – primarily the army and the leadership of the Muslim Brotherhood – to maintain their political and economic power over and above the social, economic and political interests of others. Through the destruction of physical bodies, the fragmentation and polarisation of social relations and the violent closure of the newly emerged political public sphere, these actors actively repressed the potential for creative and revolutionary transformation. To better understand this multi-layered notion of trauma, we turn to Habermas’ ‘colonisation of the lifeworld’ thesis which offers a critical lens through which to examine the wider political and economic structures and context in which trauma occurred as well as its effects on the personal, social and political realms. In doing so, we develop a novel conception of trauma that acknowledges individual, social and political dimensions. We apply this conceptual framing to empirical narratives of trauma in Egypt’s pre- and post-revolutionary phases, thus both developing a non-Western application of Habermas’ framework and revealing ethnographic accounts of the revolution by activists in Cairo

Psychopolitics: Peter Sedgwick’s legacy for mental health movements

This paper re-considers the relevance of Peter Sedgwick's Psychopolitics (1982) for a politics of mental health. Psychopolitics offered an indictment of ‘anti-psychiatry’ the failure of which, Sedgwick argued, lay in its deconstruction of the category of ‘mental illness’, a gesture that resulted in a politics of nihilism. ‘The radical who is only a radical nihilist’, Sedgwick observed, ‘is for all practical purposes the most adamant of conservatives’. Sedgwick argued, rather, that the concept of ‘mental illness’ could be a truly critical concept if it was deployed ‘to make demands upon the health service facilities of the society in which we live’. The paper contextualizes Psychopolitics within the ‘crisis tendencies’ of its time, surveying the shifting welfare landscape of the subsequent 25 years alongside Sedgwick's continuing relevance. It considers the dilemma that the discourse of ‘mental illness’ – Sedgwick's critical concept – has fallen out of favour with radical mental health movements yet remains paradigmatic within psychiatry itself. Finally, the paper endorses a contemporary perspective that, while necessarily updating Psychopolitics, remains nonetheless ‘Sedgwickian’

Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns

Introduction: Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles. Methods: We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay. Results: Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation. Conclusions: We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers

EZH2 Depletion Blocks the Proliferation of Colon Cancer Cells

The Enhancer of Zeste 2 (EZH2) protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi)-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer

Large Scale Gene Expression Profiles of Regenerating Inner Ear Sensory Epithelia

Loss of inner ear sensory hair cells (HC) is a leading cause of human hearing loss and balance disorders. Unlike mammals, many lower vertebrates can regenerate these cells. We used cross-species microarrays to examine this process in the avian inner ear. Specifically, changes in expression of over 1700 transcription factor (TF) genes were investigated in hair cells of auditory and vestibular organs following treatment with two different damaging agents and regeneration in vitro. Multiple components of seven distinct known signaling pathways were clearly identifiable: TGFβ, PAX, NOTCH, WNT, NFKappaB, INSULIN/IGF1 and AP1. Numerous components of apoptotic and cell cycle control pathways were differentially expressed, including p27KIP and TFs that regulate its expression. A comparison of expression trends across tissues and treatments revealed identical patterns of expression that occurred at identical times during regenerative proliferation. Network analysis of the patterns of gene expression in this large dataset also revealed the additional presence of many components (and possible network interactions) of estrogen receptor signaling, circadian rhythm genes and parts of the polycomb complex (among others). Equal numbers of differentially expressed genes were identified that have not yet been placed into any known pathway. Specific time points and tissues also exhibited interesting differences: For example, 45 zinc finger genes were specifically up-regulated at later stages of cochlear regeneration. These results are the first of their kind and should provide the starting point for more detailed investigations of the role of these many pathways in HC recovery, and for a description of their possible interactions

Epigenetic Signatures Associated with Different Levels of Differentiation Potential in Human Stem Cells

BACKGROUND: The therapeutic use of multipotent stem cells depends on their differentiation potential, which has been shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic profiles. METHODOLOGY/PRINCIPAL FINDINGS: to address this issue, we have investigated the levels of epigenetic regulation in well characterized populations of pluripotent embryonic stem cells (ESC) and multipotent adult stem cells (ASC) at the trancriptome, methylome, histone modification and microRNA levels. Differences in gene expression profiles allowed classification of stem cells into three separate populations including ESC, multipotent adult progenitor cells (MAPC) and mesenchymal stromal cells (MSC). The analysis of the PcG repressive marks, histone modifications and gene promoter methylation of differentiation and pluripotency genes demonstrated that stem cell populations with a wider differentiation potential (ESC and MAPC) showed stronger representation of epigenetic repressive marks in differentiation genes and that this epigenetic signature was progressively lost with restriction of stem cell potential. Our analysis of microRNA established specific microRNA signatures suggesting specific microRNAs involved in regulation of pluripotent and differentiation genes. CONCLUSIONS/SIGNIFICANCE: Our study leads us to propose a model where the level of epigenetic regulation, as a combination of DNA methylation and histone modification marks, at differentiation genes defines degrees of differentiation potential from progenitor and multipotent stem cells to pluripotent stem cells

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality in the world, with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) comprising the two major cell types. Although these cell types can be distinguished readily at the histological level, knowledge of their underlying molecular differences is very limited. In this study, we compared 14 SCLC cell lines against 27 NSCLC cell lines using an integrated array comparative genomic hybridisation and gene expression profiling approach to identify subtype-specific disruptions. Using stringent criteria, we have identified 159 of the genes that are responsible for the different biology of these cell types. Sorting of these genes by their biological functions revealed the differential disruption of key components involved in cell cycle pathways. Our novel comparative combined genome and transcriptome analysis not only identified differentially altered genes, but also revealed that certain shared pathways are preferentially disrupted at different steps in these cell types. Small cell lung cancer exhibited increased expression of MRP5, activation of Wnt pathway inhibitors, and upregulation of p38 MAPK activating genes, while NSCLC showed downregulation of CDKN2A, and upregulation of MAPK9 and EGFR. This information suggests that cell cycle upregulation in SCLC and NSCLC occurs through drastically different mechanisms, highlighting the need for differential molecular target selection in the treatment of these cancers

What is psychiatry? Co-producing complexity in mental health

What is psychiatry? Such a question is increasingly important to engage with in light of the development of new diagnostic frameworks that have wide-ranging and international clinical and societal implications. I suggest in this reflective essay that ‘psychiatry' is not a singular entity that enjoins consistent forms of critique along familiar axes; rather, it is a heterogeneous assemblage of interacting material and symbolic elements (some of which endure, and some of which are subject to innovation). In underscoring the diversity of psychiatry, I seek to move towards further sociological purchase on what remains a contested and influential set of discourses and practices. This approach foregrounds the relationships between scientific knowledge, biomedical institutions, social action and subjective experience; these articulations co-produce both psychiatry and each other. One corollary of this emphasis on multiplicity and incoherence within psychiatric theory, research and practice, is that critiques which elide this complexity are rendered problematic. Engagements with psychiatry are, I argue, best furthered by recognising its multifaceted nature