Regulation of the cardiomyocyte transcriptome vs translatome by endothelin-1 and insulin: translational regulation of 5' terminal oligopyrimidine tract (TOP) mRNAs by insulin

Background: Changes in cellular phenotype result from underlying changes in mRNA transcription and translation. Endothelin-1 stimulates cardiomyocyte hypertrophy with associated changes in mRNA/protein expression and an increase in the rate of protein synthesis. Insulin also increases the rate of translation but does not promote overt cardiomyocyte hypertrophy. One mechanism of translational regulation is through 5' terminal oligopyrimidine tracts (TOPs) that, in response to growth stimuli, promote mRNA recruitment to polysomes for increased translation. TOP mRNAs include those encoding ribosomal proteins, but the full panoply remains to be established. Here, we used microarrays to compare the effects of endothelin-1 and insulin on the global transcriptome of neonatal rat cardiomyocytes, and on mRNA recruitment to polysomes (i.e. the translatome). Results: Globally, endothelin-1 and insulin (1 h) promoted >1.5-fold significant (false discovery rate < 0.05) changes in expression of 341 and 38 RNAs, respectively. For these transcripts with this level of change there was little evidence of translational regulation. However, 1336 and 712 RNAs had >1.25-fold significant changes in expression in total and/or polysomal RNA induced by endothelin-1 or insulin, respectively, of which ~35% of endothelin-1-responsive and ~56% of insulin-responsive transcripts were translationally regulated. Of mRNAs for established proteins recruited to polysomes in response to insulin, 49 were known TOP mRNAs with a further 15 probable/possible TOP mRNAs, but 49 had no identifiable TOP sequences or other consistent features in the 5' untranslated region. Conclusions: Endothelin-1, rather than insulin, substantially affects global transcript expression to promote cardiomyocyte hypertrophy. Effects on RNA recruitment to polysomes are subtle, with differential effects of endothelin-1 and insulin on specific transcripts. Furthermore, although insulin promotes recruitment of TOP mRNAs to cardiomyocyte polysomes, not all recruited mRNAs are TOP mRNAs.

Proof of concept of automated mapping of weeds in arable fields

The project investigated whether it would be possible to remove the main technical hindrance to precision application of herbicides to arable crops in the UK, namely creating geo-referenced weed maps for each field. The ultimate goal is an information system so that agronomists and farmers can plan precision weed control and create spraying maps. The project focussed on black-grass in wheat, but research was also carried out on barley and beans and on wild-oats, barren brome, rye-grass, cleavers and thistles which form stable patches in arable fields. Farmers may also make special efforts to control them. Using cameras mounted on farm machinery, the project explored the feasibility of automating the process of mapping black-grass in fields. Geo-referenced images were captured from June to December 2009, using sprayers, a tractor, combine harvesters and on foot. Cameras were mounted on the sprayer boom, on windows or on top of tractor and combine cabs and images were captured with a range of vibration levels and at speeds up to 20 km h-1. For acceptability to farmers, it was important that every image containing black-grass was classified as containing black-grass; false negatives are highly undesirable. The software algorithms recorded no false negatives in sample images analysed to date, although some black-grass heads were unclassified and there were also false positives. The density of black-grass heads per unit area estimated by machine vision increased as a linear function of the actual density with a mean detection rate of 47% of black-grass heads in sample images at T3 within a density range of 13 to 1230 heads m-2. A final part of the project was to create geo-referenced weed maps using software written in previous HGCA-funded projects and two examples show that geo-location by machine vision compares well with manually-mapped weed patches. The consortium therefore demonstrated for the first time the feasibility of using a GPS-linked computer-controlled camera system mounted on farm machinery (tractor, sprayer or combine) to geo-reference black-grass in winter wheat between black-grass head emergence and seed shedding.

Preliminary observations on the presence of sustained tendon strain and eccentric contractions of the wrist extensors during a common manual task: implications for lateral epicondylitis

Lateral epicondylitis (LE) is hypothesized to occur as a result of repetitive, strenuous and abnormal postural activities of the elbow and wrist. There is still a lack of understanding of how wrist and forearm positions contribute to this condition during common manual tasks. In this study the wrist kinematics and the wrist extensors’ musculotendon patterns were investigated during a manual task believed to elicit LE symptoms in susceptible subjects. A 42-year-old right-handed male, with no history of LE, performed a repetitive movement involving pushing and turning a spring-loaded mechanism. Motion capture data were acquired for the upper limb and an inverse kinematic and dynamic analysis was subsequently carried out. Results illustrated the presence of eccentric contractions sustained by the extensor carpi radialis longus (ECRL), together with an almost constant level of tendon strain of both extensor carpi radialis brevis (ECRB) and extensor digitorum communis lateral (EDCL) branch. It is believed that these factors may partly contribute to the onset of LE as they are both responsible for the creation of microtears at the tendons’ origins. The methodology of this study can be used to explore muscle actions during movements that might cause or exacerbate LE.

An improved lesion detection approach based on similarity measurement between fuzzy intensity segmentation and spatial probability maps

The application of automatic segmentation methods in lesion detection is desirable. However, such methods are restricted by intensity similarities between lesioned and healthy brain tissue. Using multi-spectral magnetic resonance imaging (MRI) modalities may overcome this problem but it is not always practicable. In this article, a lesion detection approach requiring a single MRI modality is presented, which is an improved method based on a recent publication. This new method assumes that a low similarity should be found in the regions of lesions when the likeness between an intensity based fuzzy segmentation and a location based tissue probabilities is measured. The usage of a normalized similarity measurement enables the current method to fine-tune the threshold for lesion detection, thus maximizing the possibility of reaching high detection accuracy. Importantly, an extra cleaning step is included in the current approach which removes enlarged ventricles from detected lesions. The performance investigation using simulated lesions demonstrated that not only the majority of lesions were well detected but also normal tissues were identified effectively. Tests on images acquired in stroke patients further confirmed the strength of the method in lesion detection. When compared with the previous version, the current approach showed a higher sensitivity in detecting small lesions and had less false positives around the ventricle and the edge of the brain

Last charge of the knights? Iraq, Afghanistan and the special relationship

At the heart of the ‘special relationship’ ideology, there is supposed to be a grand bargain. In exchange for paying the ‘blood price’ as America's ally, Britain will be rewarded with exceptional influence over American foreign policy and its strategic behaviour. Soldiers and statesman continue to articulate this idea. Since 9/11, the notion of Britain playing ‘Greece’ to America's ‘Rome’ gained new life thanks to Anglophiles on both sides of the Atlantic. One potent version of this ideology was that the more seasoned British would teach Americans how to fight ‘small wars’ in Iraq and Afghanistan, thereby bolstering their role as tutor to the superpower. Britain does derive benefits from the Anglo-American alliance and has made momentous contributions to the wars in Afghanistan and Iraq. Yet British solidarity and sacrifices have not purchased special influence in Washington. This is partly due to Atlanticist ideology, which sets Britain unrealistic standards by which it is judged, and partly because the notion of ‘special influence’ is misleading as it loses sight of the complexities of American policy-making. The overall result of expeditionary wars has been to strain British credibility in American eyes and to display its lack of consistent influence both over high policy and the design and execution of US military campaigns. While there may be good arguments in favour of the UK continuing its efforts in Afghanistan, the notion that the war fortifies Britain's vicarious world status is a dangerous illusion that leads to repeated overstretch and disappointment. Now that Britain is in the foothills of a strategic defence review, it is important that the British abandon this false consciousness.

Near real-time flood detection in urban and rural areas using high resolution Synthetic Aperture Radar images

A near real-time flood detection algorithm giving a synoptic overview of the extent of flooding in both urban and rural areas, and capable of working during night-time and day-time even if cloud was present, could be a useful tool for operational flood relief management. The paper describes an automatic algorithm using high resolution Synthetic Aperture Radar (SAR) satellite data that builds on existing approaches, including the use of image segmentation techniques prior to object classification to cope with the very large number of pixels in these scenes. Flood detection in urban areas is guided by the flood extent derived in adjacent rural areas. The algorithm assumes that high resolution topographic height data are available for at least the urban areas of the scene, in order that a SAR simulator may be used to estimate areas of radar shadow and layover. The algorithm proved capable of detecting flooding in rural areas using TerraSAR-X with good accuracy, classifying 89% of flooded pixels correctly, with an associated false positive rate of 6%. Of the urban water pixels visible to TerraSAR-X, 75% were correctly detected, with a false positive rate of 24%. If all urban water pixels were considered, including those in shadow and layover regions, these figures fell to 57% and 18% respectively.

Modern lovers

Modern Lovers was a survey show of contemporary art practices in dialogue with modernism, bringing together established and emerging artists based in London and international artists from Berlin, Jerusalem and Zagreb. The show features video, film, installation, sculpture, music and performance work that addresses the legacy of the avant garde and the survival of its aesthetics within contemporary culture. In 1976, as punk rock was busy smashing the cultural rubble left behind by the second world war and rejecting the consumer society that had emerged from the ruins, one band bravely announced that it wanted no part in this destruction. Jonathan Richman's Modern Lovers sang about how they still loved the old world. Neither parents nor girlfriends could understand, but the decaying inner city with its false promises of progress still held a fascination for Richman, who claimed he wanted to keep his place in this arcane landscape. Punk's assault on culture was the logical conclusion of modernism's linear narrative of art as a force of innovation that must reject preceding artistic movements to establish new ones. Echoing the negations of Dada, it set out to put an end to this narrative, an end to culture. It is partly because of this inherently destructive and totalising side of Modernism that it has come under harsh critique in the post modern era. Nevertheless, we are still caught up in the same dialectic of progress, revolution and destruction. Post modernism has failed to unseat our desire for the revolutionary moment, even as it has been co-opted to the degree of meaninglessness by the discourses of marketing and Capitalism. But, like Jonathan Richman, the artists in the exhibition "Modern Lovers" keep returning to modernism for something else. Instead of taking it at its word when it proffers revolution, they turn to it in search of reform. Still loving the old world and desiring a dialogue with the past, perhaps as an antidote to the eternal present of Capitalism, they are willing to engage with its aesthetics and ideas on equal ground. Leaving behind the ironic deconstructions of post modernism, they find perspectives worth salvaging and juxtapose them with contemporary visual productions. Trading in the grand narratives of modernity for a more personal approach, they don't seek the purity of form that drove the avant garde movements that inspire them but rather revel in adulteration, dilution and contamination of the past by the present". A live performance by sala-manca was sponsored by the British Council and took place May 26th, 19:00. MODERN LOVERS was accompanied by a catalogue (14.80 cm x 14.80 cm) including essays by Avi Pitchon, the sala-manca group and the curators. A discussion panel about the exhibition themes, as well as the catalogue launch,took place at Goldsmiths College's cinema on the 27th of May at 14:00, chaired by Dr. Suhail Malik (Senior Lecturer & Course Leader Postgraduate Fine Art Critical Studies at Goldsmiths College) and with the participation of Tom Morton (curator, Cubitt Gallery, and regular contributor to Frieze magazine), sala-manca (artist group), Dr. Amanda Beech (artist, curator and senior lecturer at the Wimbledon School of Art), Matthew Poole (course director of MA Gallery Studies, dept. of Art History and Theory at the University of Essex).

Dear living person

‘Dear Living Person,’ Chapter included in edited collection incl. texts by Claire Fontaine, Gareth James, Paul Chan and Sam Lewitt. The chapter is written from the perspective of a recently deceased corpse. It examines the claims art makes to moving beyond boundaries and testing limits (of medium, discipline, and category) as a cliché of transcendence. This is described in relation to the operation of the false ‘master’ limit between the living and the dead, with reference to Reza Negarestani’s vivid reenactment of Etruscan torture, and contemporary performances of institutional critique: Fraser, Krebber and Carpenter.

Dear living person

This chapter is written from the perspective of a recently deceased corpse. It examines the claims art makes to moving beyond boundaries and testing limits (of medium, discipline, and category) as a cliché of transcendence. This is described in relation to the operation of the false ‘master’ limit between the living and the dead, with reference to Reza Negarestani’s vivid reenactment of Etruscan torture, and contemporary performances of institutional critique: Fraser, Krebber and Carpenter.

Improvement of the GenTHREADER method for genomic fold recognition

Motivation: In order to enhance genome annotation, the fully automatic fold recognition method GenTHREADER has been improved and benchmarked. The previous version of GenTHREADER consisted of a simple neural network which was trained to combine sequence alignment score, length information and energy potentials derived from threading into a single score representing the relationship between two proteins, as designated by CATH. The improved version incorporates PSI-BLAST searches, which have been jumpstarted with structural alignment profiles from FSSP, and now also makes use of PSIPRED predicted secondary structure and bi-directional scoring in order to calculate the final alignment score. Pairwise potentials and solvation potentials are calculated from the given sequence alignment which are then used as inputs to a multi-layer, feed-forward neural network, along with the alignment score, alignment length and sequence length. The neural network has also been expanded to accommodate the secondary structure element alignment (SSEA) score as an extra input and it is now trained to learn the FSSP Z-score as a measurement of similarity between two proteins. Results: The improvements made to GenTHREADER increase the number of remote homologues that can be detected with a low error rate, implying higher reliability of score, whilst also increasing the quality of the models produced. We find that up to five times as many true positives can be detected with low error rate per query. Total MaxSub score is doubled at low false positive rates using the improved method.

Are patterns of growth adaptive?

Models which define fitness in terms of per capita rate of increase of phenotypes are used to analyse patterns of individual growth. It is shown that sigmoid growth curves are an optimal strategy (i.e. maximize fitness) if (Assumption 1a) mortality decreases with body size; (2a) mortality is a convex function of specific growth rate, viewed from above; (3) there is a constraint on growth rate, which is attained in the first phase of growth. If the constraint is not attained then size should increase at a progressively reducing rate. These predictions are biologically plausible. Catch-up growth, for retarded individuals, is generally not an optimal strategy though in special cases (e.g. seasonal breeding) it might be. Growth may be advantageous after first breeding if birth rate is a convex function of G (the fraction of production devoted to growth) viewed from above (Assumption 5a), or if mortality rate is a convex function of G, viewed from above (Assumption 6c). If assumptions 5a and 6c are both false, growth should cease at the age of first reproduction. These predictions could be used to evaluate the incidence of indeterminate versus determinate growth in the animal kingdom though the data currently available do not allow quantitative tests. In animals with invariant adult size a method is given which allows one to calculate whether an increase in body size is favoured given that fecundity and developmental time are thereby increased.

Vertical toleration as a liberal ideal

This paper argues that the direct, vertical toleration of certain types of citizen by the Rawlsian liberal state is appropriate and required in circumstances in which these types of citizen pose a threat to the stability of the state. By countering the claim that vertical toleration is redundant given a commitment to the Rawlsian version of the liberal democratic ideal, and by articulating a version of that ideal that shows this claim to be false, the paper reaffirms the centrality of vertical toleration in the Rawlsian liberal account of state-citizen relations.

Prefrontal control of familiarity and recollection in working memory

Left inferior frontal gyrus (IFG) is a critical neural substrate for the resolution of proactive interference (PI) in working memory. We hypothesized that left IFG achieves this by controlling the influence of familiarity- versus recollection-based information about memory probes. Consistent with this idea, we observed evidence for an early (200 msec)-peaking signal corresponding to memory probe familiarity and a late (500 msec)-resolving signal corresponding to full accrual of trial-related contextual ("recollection-based") information. Next, we applied brief trains of repetitive transcranial magnetic stimulation (rTMS) time locked to these mnemonic signals, to left IFG and to a control region. Only early rTMS of left IFG produced a modulation of the false alarm rate for high-PI probes. Additionally, the magnitude of this effect was predicted by individual differences in susceptibility to PI. These results suggest that left IFG-based control may bias the influence of familiarity- and recollection-based signals on recognition decisions.

Food health claims – What consumers understand

Issues pertaining to consumer understanding of food health claims are complex and difficult to disentangle because there is a surprising lack of multidisciplinary research aimed at evaluating how consumers are influenced by factors impacting on the evaluation process. In the EU, current legislation is designed to protect consumers from misleading and false claims but there is much debate about the concept of the ‘average consumer’ referred to in the legislation. This review provides an overview of the current legislative framework, discusses the concept of the ‘average consumer’ and brings together findings on consumer understanding from an international perspective. It examines factors related to the personal characteristics of individuals such as socio-demographic status, knowledge, and attitudes, and factors pertaining to food and food supplement products such as the wording of claims and the communication of the strength and consistency of the scientific evidence. As well as providing insights for future research, the conclusions highlight the importance of enhancing the communication of scientific evidence to improve consumer understanding of food health claims.

Detection of Salmonella enteritidis in eggs by the polymerase chain reaction

A polymerase chain reaction (PCR) for the specific detection of the gene sequence, sefA, encoded by all isolates of Salmonella enteritidis, was developed. The PCR could detect as few as four S enteritidis washed bacterial cells but egg contents inhibited the PCR. Eggs spiked with 50 S enteritidis bacterial cells were homogenised, inoculated into buffered peptone water and grown at 37 degrees C for 16 hours, when the PCR was successful. A positive internal control was developed to differentiate between true and false negative PCR results for the detection of S enteritidis. In a limited trial of the egg handling procedures and the PCR, one of 250 chickens' eggs from retail outlets was found to be contaminated with S enteritidis.