DNA mismatch repair and the DNA damage response to ionizing radiation:making sense of apparently conflicting data

The DNA mismatch repair (MMR) pathway detects and repairs DNA replication errors. While DNA MMR-proficiency is known to play a key role in the sensitivity to a number of DNA damaging agents, its role in the cytotoxicity of ionizing radiation (IR) is less well characterized. Available literature to date is conflicting regarding the influence of MMR status on radiosensitivity, and this has arisen as a subject of controversy in the field. The aim of this paper is to provide the first comprehensive overview of the experimental data linking MMR proteins and the DNA damage response to IR. A PubMed search was conducted using the key words "DNA mismatch repair" and "ionizing radiation". Relevant articles and their references were reviewed for their association between DNA MMR and IR. Recent data suggest that radiation dose and the type of DNA damage induced may dictate the involvement of the MMR system in the cellular response to IR. In particular, the literature supports a role for the MMR system in DNA damage recognition, cell cycle arrest, DNA repair and apoptosis. In this review we discuss our current understanding of the impact of MMR status on the cellular response to radiation in mammalian cells gained from past and present studies and attempt to provide an explanation for how MMR may determine the response to radiation.

Mining Money: the generative capacities of scientific and legal knowledge practices in the making of resource economies

In 1997 a scandal associated with Bre-X, a junior mining firm, and its prospecting activities in Indonesia, exposed to public scrutiny the ways in which mineral exploration firms acquire, assess and report on scientific claims about the natural environment. At stake here was not just how investors understood the provisional nature of scientific knowledge, but also evidence of fraud. Contemporaneous mining scandals not only included the salting of cores, but also unreliable proprietary sample preparation and assay methods, mis-representations of visual field estimates as drilling results and ‘overly optimistic’ geological reports. This paper reports on initiatives taken in the wake of these scandals and prompted by the Mining Standards Task Force (TSE/OSC 1999). For regulators, mandated to increase investor confidence in Canada’s leading role within the global mining industry, efforts focused first and foremost upon identifying and removing sources of error and wilfulness within the production and circulation of scientific knowledge claims. A common goal cross-cutting these initiatives was ‘a faithful representation of nature’ (Daston and Galison 2010), however, as the paper argues, this was manifest in an assemblage of practices governed by distinct and rival regulative visions of science and the making of markets in claims about ‘nature’. These ‘practices of fidelity’, it is argued, can be consequential in shaping the spatial and temporal dynamics of the marketization of nature.

Standardizing the assessment of clinical competence: an overview of intensive care course design.

Rationale for the development of the Certificate in Health Studies: Intensive Care and High Dependency for Adults course developed at Queens University Belfast, Northern Ireland. Structure and content of clinical module reviewed. Clinical assessment strategy discussed. Focus on the utilization of a standardized portfolio, individualized learning contract and objective structured clinical examination (OSCE) to evaluate clinical competence. Evaluation of OSCE as an assessment tool and of the course provision.

Is the Schwabe organ a retained larval eye? Anatomical and behavioural studies of a novel sense organ in adult leptochiton asellus (Mollusca, Polyplacophora) indicate links to larval photoreceptors

The discovery of a sensory organ, the Schwabe organ, was recently reported as a unifying feature of chitons in the order Lepidopleurida. It is a patch of pigmented tissue located on the roof of the pallial cavity, beneath the velum on either side of the mouth. The epithelium is densely innervated and contains two types of potential sensory cells. As the function of the Schwabe organ remains unknown, we have taken a cross-disciplinary approach, using anatomical, histological and behavioural techniques to understand it. In general, the pigmentation that characterises this sensory structure gradually fades after death; however, one particular concentrated pigment dot persists. This dot is positionally homologous to the larval eye in chiton trochophores, found in the same neuroanatomical location, and furthermore the metamorphic migration of the larval eye is ventral in species known to possess Schwabe organs. Here we report the presence of a discrete subsurface epithelial structure in the region of the Schwabe organ in Leptochiton asellus that histologically resembles the chiton larval eye. Behavioural experiments demonstrate that Leptochiton asellus with intact Schwabe organs actively avoid an upwelling light source, while Leptochiton asellus with surgically ablated Schwabe organs and a control species lacking the organ (members of the other extant order, Chitonida) do not (Kruskal-Wallis, H = 24.82, df = 3, p < 0.0001). We propose that the Schwabe organ represents the adult expression of the chiton larval eye, being retained and elaborated in adult lepidopleurans.

Computational Thinking across a Life Course

Symposium of papers on Computational Thinking

The time course of conflict on the Cognitive Reflection Test

Reasoning that is deliberative and reflective often requires the inhibition of intuitive responses. The Cognitive Reflection Test (CRT) is designed to assess people’s ability to suppress incorrect heuristic responses in favour of deliberation. Correct responding on the CRT predicts performance on a range of tasks in which intuitive processes lead to incorrect responses, suggesting indirectly that CRT performance is related to cognitive control. Yet little is known about the cognitive processes underlying performance on the CRT. In the current research, we employed a novel mouse tracking mjavascript:void(0);ethodology to capture the time-course of reasoning on the CRT. Analysis of mouse cursor trajectories revealed that participants were initially drawn towards the incorrect (i.e., intuitive) option even when the correct (deliberative) option was ultimately chosen. Conversely, participants were not attracted to the correct option when they ultimately chose the incorrect intuitive one. We conclude that intuitive processes are activated automatically on the CRT and must be inhibited in order to respond correctly. When participants responded intuitively, there was no evidence that deliberative reasoning had become engaged.

Gramsci, austerity common sense and the attacks on the welfare state: The need to understand and resist the imposition of the global neoliberal agenda and the role of the social work profession.

During the last 30 years governments almost everywhere in the world are furthering a global neoliberal agenda by withdrawing the state from the delivery of services, decreasing social spending and lowering corporate taxation etc. This restructuring has led to a massive transfer of wealth from the welfare state and working class people into capital. In order to legitimize this restructuring conservative governments engage in collective blaming towards their denizens. This presentation will examine some of the well circulated phrases that have been used by the dominant elite in some countries during the last year to legitimize the imposition of austerity measures. Phrases such as, ‘We all partied’ used by the Irish finance minister, Brian Lenihan, to explain the Irish crisis and collectively blame all Irish people, ‘We must all share the pain’, deployed by another Irish Minister Gilmore and the UK coalition administration’s sound bite ‘We are all in this together’, legitimize the imposition of austerity measures. Utilizing the Gramscian concept of common sense (Gramsci, 1971), I call these phrases ‘austerity common sense’. They are austerity common sense because they both reflect and legitimate the austerity agenda. By deploying these phrases, the ruling economic and political elite seek to influence the perception of the people and pre-empt any intention of resistance. The dominant theme of these phrases is that there is no alternative and that austerity measures are somehow self-inflicted and, as such, should not be challenged because we are all to blame. The purpose of this presentation is to explore the “austerity common sense” theme from a Gramscian approach, focus on its implications for the social work profession and discuss the ways to resist the imposition of the global neoliberal agenda.

The Use of Audio Podcasts to Enhance the Delivery of a Computer Networks Course

Experience obtained in the support of mobile learning using podcast audio is reported. The paper outlines design, storage and distribution via a web site. An initial evaluation of the uptake of the approach in a final year computing module was undertaken. Audio objects were tailored to meet different pedagogical needs resulting in a repository of persistent glossary terms and disposable audio lectures distributed by podcasting. An aim of our approach is to document the interest from the students, and evaluate the potential of mobile learning for supplementing revision