Collective and single cell behavior in epithelial contact inhibition

Control of cell proliferation is a fundamental aspect of tissue physiology central to morphogenesis, wound healing and cancer. Although many of the molecular genetic factors are now known, the system level regulation of growth is still poorly understood. A simple form of inhibition of cell proliferation is encountered in vitro in normally differentiating epithelial cell cultures and is known as "contact inhibition". The study presented here provides a quantitative characterization of contact inhibition dynamics on tissue-wide and single cell levels. Using long-term tracking of cultured MDCK cells we demonstrate that inhibition of cell division in a confluent monolayer follows inhibition of cell motility and sets in when mechanical constraint on local expansion causes divisions to reduce cell area. We quantify cell motility and cell cycle statistics in the low density confluent regime and their change across the transition to epithelial morphology which occurs with increasing cell density. We then study the dynamics of cell area distribution arising through reductive division, determine the average mitotic rate as a function of cell size and demonstrate that complete arrest of mitosis occurs when cell area falls below a critical value. We also present a simple computational model of growth mechanics which captures all aspects of the observed behavior. Our measurements and analysis show that contact inhibition is a consequence of mechanical interaction and constraint rather than interfacial contact alone, and define quantitative phenotypes that can guide future studies of molecular mechanisms underlying contact inhibition

Rhythm in the speech of a person with right hemisphere damage: Applying the pairwise variability index

Although several aspects of prosody have been studied in speakers with right hemisphere damage (RHD), rhythm remains largely uninvestigated. This study compares the rhythm of an Australian English speaker with right hemisphere damage (due to a stroke, but with no concomitant dysarthria) to that of a neurologically unimpaired individual. The speakers' rhythm is compared using the pairwise variability index (PVI) which allows for an acoustic characterization of rhythm by comparing the duration of successive vocalic and intervocalic intervals. A sample of speech from a structured interview between a speech and language therapist and each participant was analysed. Previous research has shown that speakers with RHD may have difficulties with intonation production, and therefore it was hypothesized that there may also be rhythmic disturbance. Results show that the neurologically normal control uses a similar rhythm to that reported for British English (there are no previous studies available for Australian English), whilst the speaker with RHD produces speech with a less strongly stress-timed rhythm. This finding was statistically significant for the intervocalic intervals measured (t(8) = 4.7, p < .01), and suggests that some aspects of prosody may be right lateralized for this speaker. The findings are discussed in relation to previous findings of dysprosody in RHD populations, and in relation to syllable-timed speech of people with other neurological conditions

Pleasure and pedagogy: the consumption of DVD add-ons among Irish teenagers

This article addresses the issue of young people and media use in the digital age, more specifically the interconnection between new media pleasures and pedagogy as they relate to the consumption of DVD add-ons. Arguing against the view of new media as having predominantly detrimental effects on young people, the authors claim that new media can enable young people to develop media literacy skills and are of the view that media literacy strategies must be based on an understanding and legitimating of young people's use patterns and pleasures. The discussion is based on a pilot research project on the use patterns and pleasures of use with a sample of Irish teenagers. They found that DVDs were used predominantly in the home context, and that, while there was variability in use between the groups, overall they developed critical literacy skills and competences which were interwoven into their social life and projects of identity construction. The authors suggest that these findings could be used to develop DVDs and their add-on features as a learning resource in the more formal educational setting and they go on to outline the potential teaching benefits of their use across a range of pedagogical areas

Rhythm and Vowel Quality in Accents of English

In a sample of 27 speakers of Scottish Standard English two notoriously variable consonantal features are investigated: the contrast of /m/ and /w/ and non-prevocalic /r/, the latter both in terms of its presence or absence and the phonetic form it takes, if present. The pattern of realisation of non-prevocalic /r/ largely confirms previously reported findings. But there are a number of surprising results regarding the merger of /m/ and /w/ and the loss of non-prevocalic /r/: While the former is more likely to happen in younger speakers and females, the latter seems more likely in older speakers and males. This is suggestive of change in progress leading to a loss of the /m/ - /w/ contrast, while the variation found in non-prevocalic /r/ follows an almost inverse sociolinguistic pattern that does not suggest any such change and is additionally largely explicable in language-internal terms. One phenomenon requiring further investigation is the curious effect direct contact with Southern English accents seems to have on non-prevocalic /r/: innovation on the structural level (i.e. loss) and conservatism on the realisational level (i.e. increased incidence of [r] and [r]) appear to be conditioned by the same sociolinguistic factors

Managing for change: October 11, 1989

Bi-weekly newsletter of University Hospital's Change Project, provided to managers at the hospital

Orbital inflammatory complications of Crohn’s disease: a rare case series

Orbital inflammatory disease is a rare ophthalmic manifestation of Crohn’s disease. Inflammation is characteristically non-specific, involving one or multiple structures of the orbit. Mechanisms of disease and optimal methods of treatment are poorly understood. The aim of this report is to present three cases of orbital involvement in Crohn’s disease. A retrospective case note review of patients with orbital inflammatory disease and Crohn’s disease was performed at our academic centre to determine the clinical, imaging and histopathological features of this condition and its relationship to intestinal Crohn’s disease. Three patients were identified with orbital inflammatory manifestations complicating Crohn’s disease. All patients described were female with active intestinal disease and had a history of treatment with immunosuppressive therapies. Similarities were observed in clinical presentations with variance noted in radiological and histopathological findings. In all cases, symptoms improved with oral corticosteroids or non-steroidal drugs in combination with anti-tumour necrosis factor (anti-TNF) agents. Inflammatory bowel disease-related orbital complications are rare but potentially vision-threatening. It is important to consider mimics of orbital inflammatory disease such as systemic inflammatory disease, malignancy, congenital malformations, infection and trauma when formulating a comprehensive differential diagnosis. Therapeutic intervention is directed towards preservation of vision and orbital function and reducing the acute inflammatory process. Corticosteroids are typically the initial treatment of choice for moderate-to-severe disease, although several classes of immunomodulatory agents have been variably useful in treating this condition. Heightened awareness and close cooperation between gastroenterologists and ophthalmologists is mandatory

Looking for big 'fry': the motives and methods of middle-class international property investors

Anxieties about the effects of international property investment in world cities like London have mainly focused on super-rich investors and corporate vehicles that have generated price inflation of assets and accelerated exclusion from an already expensive market. In fact, many international investors in the city’s housing market are middle-class individuals, and focusing on Hong Kong as an emblematic example of such processes, we examine their motives and the products offered to them by important investment intermediaries. We find that an important rationale for these investments lies in local class-based uncertainties and existential anxieties concerning the future of Hong Kong itself. We focus on the cultural roots of these investor rationalities but also consider the role of investment intermediaries who have helped bolster confidence while shielding investors from the consequences of their aggregated market power - concerns in London over household displacement from foreign investment. We suggest that what may seem to be the predatory search to ‘fry’ property (炒樓), a Hongkonger colloquialism referring to the search for high performing investments, should also be understood as actions anchored in and generated by the habitus of the Hong Kong middle-class whose lives have been moulded by historical geopolitical uncertainty and worries about its longer-term social positioning and security

The architectures of media power: editing, the newsroom, and urban public space

This paper considers the relation of the newsroom and the city as a lens into the more general relation of production spaces and mediated publics. Leading theoretically from Lee and LiPuma’s (2002) notion of ‘cultures of circulation’, and drawing on an ethnography of the Toronto Star, the paper focuses on how media forms circulate and are enacted through particular practices and material settings. With its attention to the urban milieus and orientations of media organizations, this paper exhibits both affinities with but also differences to current interests in the urban architectures of media, which describe and theorize how media get ‘built into’ the urban experience more generally. In looking at editing practices situated in the newsroom, an emphasis is placed on the phenomenological appearance of media forms both as objects for material assembly as well as more abstracted subjects of reflexivity, anticipation and purposiveness. Although this is explored with detailed attention to the settings of the newsroom and the city, the paper seeks to also provide insight into the more general question of how publicness is material shaped and sited

Speech rhythm: a metaphor?

Is speech rhythmic? In the absence of evidence for a traditional view that languages strive to coordinate either syllables or stress-feet with regular time intervals, we consider the alternative that languages exhibit contrastive rhythm subsisting merely in the alternation of stronger and weaker elements. This is initially plausible, particularly for languages with a steep ‘prominence gradient’, i.e. a large disparity between stronger and weaker elements; but we point out that alternation is poorly achieved even by a ‘stress-timed’ language such as English, and, historically, languages have conspicuously failed to adopt simple phonological remedies that would ensure alternation. Languages seem more concerned to allow ‘syntagmatic contrast’ between successive units and to use durational effects to support linguistic functions than to facilitate rhythm. Furthermore, some languages (e.g. Tamil, Korean) lack the lexical prominence which would most straightforwardly underpin prominence alternation. We conclude that speech is not incontestibly rhythmic, and may even be antirhythmic. However, its linguistic structure and patterning allow the metaphorical extension of rhythm in varying degrees and in different ways depending on the language, and that it is this analogical process which allows speech to be matched to external rhythms

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient