Redistribution of β-catenin in response to EGF and lithium signalling in human oesophageal squamous carcinoma cell lines

BACKGROUND: The β-catenin link between membrane-bound cadherins and the actin cytoskeleton regulates cell adhesion and consequently metastasis. Abnormal stabilisation of β-catenin enhances its transcriptional activities. Factors affecting β-catenin's functions are important in understanding metastatic diseases such as oesophageal squamous cell carcinoma (SCC). RESULTS: In human oesophageal SCCs β-catenin localises predominantly to the plasma membrane. The presence of free β-catenin in the cytoplasm/nucleus was low. This indicates that β-catenin's activities are skewed towards cell-cell adhesion in these oesophageal SCCs. Exposure to EGF or Li alone, produced a slight increase in membrane concentrations but only Li induced β-catenin stabilisation in the cytoplasm. In combination, EGF and Li decreased membrane-associated β-catenin, concomitantly increasing cytoplasmic concentrations. Convergence of these signalling pathways appears to induce a β-catenin shift from the membrane into the cytoplasm. CONCLUSION: Therefore, although the adhesive role of β-catenin appears to be intact, exogenous signals increase the stability of free β-catenin thereby reducing cell-cell adhesion in these tumours

Modulation of integrin-linked kinase (ILK) expression in human oesophageal squamous cell carcinoma cell lines by the EGF and TGFβ1 growth factors

BACKGROUND: Integrin-linked kinase (ILK) is a ubiquitously expressed protein kinase that has emerged as one of the points of convergence between integrin- and growth factor-signalling pathways. RESULTS: In this study we identify the ILK isoform expressed in five human oesophageal squamous cell carcinoma cell lines of South African origin as ILK1, and demonstrate its cellular distribution. ILK expression, although similar in the majority of the cell lines, did show variation. Furthermore, the ILK expressed was shown to be catalytically functional. The effect of growth factors on ILK expression was examined. An increase in ILK expression, following EGF and TGFβ1 exposure, was a trend across all the five oesophageal carcinoma cell lines tested. CONCLUSION: These results suggest that growth factor modulation of ILK expression relies on the internalisation/recycling of growth factor receptors and stimulation of the PI3K pathway, which may have implications with regards to cell adhesion and tumourigenesis

No safety without emotional safety

This Personal View highlights how emotional safety is required for a person to keep themselves physically safe. We explain how trying to control behaviour to increase physical safety in the short term can carry the unintended consequence of reducing emotional safety, which might in turn result in higher levels of stress and hopelessness. We use examples from institutions with psychiatric inpatients to describe these processes. We argue that emotional and physical safety cannot be separated, and therefore that the absence of emotional safety compromises basic care either in an acute crisis or in the long term. Staff who fear being criticised, and so feel driven to take autonomy and responsibility away from patients, unwittingly undermine patients' experience of being empathically understood and supported, adding to patients' sense of emotional turmoil and lack of safety. We suggest that a change in culture and regulatory reform is required to bring psychiatric care more in line with the psychological needs of patients to achieve both physical and emotional safety

Disparate Vulnerability to Membership Inference Attacks

A membership inference attack (MIA) against a machine-learning model enables an attacker to determine whether a given data record was part of the model's training data or not. In this paper, we provide an in-depth study of the phenomenon of disparate vulnerability against MIAs: unequal success rate of MIAs against different population subgroups. We first establish necessary and sufficient conditions for MIAs to be prevented, both on average and for population subgroups, using a notion of distributional generalization. Second, we derive connections of disparate vulnerability to algorithmic fairness and to differential privacy. We show that fairness can only prevent disparate vulnerability against limited classes of adversaries. Differential privacy bounds disparate vulnerability but can significantly reduce the accuracy of the model. We show that estimating disparate vulnerability to MIAs by naïvely applying existing attacks can lead to overestimation. We then establish which attacks are suitable for estimating disparate vulnerability, and provide a statistical framework for doing so reliably. We conduct experiments on synthetic and real-world data finding statistically significant evidence of disparate vulnerability in realistic settings

The application of mHealth to mental health: opportunities and challenges

Recent advances in smartphones and wearable biosensors enable the gathering of ‘real-time’ psychological, behavioural and physiological data, in increasingly precise and unobtrusive ways. It is therefore now possible to collect moment-to-moment information about an individuals’ moods, cognitions and activities, as well as automated data about their whereabouts, behaviour and physiological states. In this paper, we discuss the potential of these new mobile digital technologies for transforming mental health research and clinical practice. By drawing on a recent research project, we illustrate how traditional boundaries between research and clinical practice are becoming increasingly blurred and how in turn, this is leading to exciting new developments in the assessment and management of common mental disorders. The potential risks and key challenges associated with applying mobile technology to mental health are also discussed

Sigurðar saga fóts (The Saga of Sigurðr Foot): A Translation

This is the first English translation of the short Icelandic romance Sigurðar saga fóts, with an introduction presenting the evidence for its dating and immediate literary context. Like most Icelandic romances, Sigurðar saga is a bridal-quest story; the support of a foster-brother is key to the hero winning the bride; and the foster-brothers start out as opponents before recognising their mutual excellence and swearing foster-brotherhood. Uniquely, however, the men who become foster-brothers begin by competing for the same bride (Signý): the eponymous Sigurðr fótr wins Signý only because Ásmundr gives her to him in exchange for foster-brotherhood. Ásmundr’s decision can be read as demonstrating with unusual starkness the superior importance in much Icelandic romance of homosocial relationships over heterosexual ones, giving the saga a certain paradigmatic status. Translating the saga in an open-access forum and reconstructing its literary context will, we hope, encourage further analyses