Developmental expression of myostatin in cardiomyocytes and its effect on foetal and neonatal rat cardiomyocyte proliferation

Objectives: Myostatin, a member of the transforming growth factor-beta (TGF-beta) family, plays a key role in skeletal muscle myogenesis by limiting hyperplastic and hypertrophic muscle growth. In cardiac muscle, myostatin has been shown to limit agonist-induced cardiac hypertrophic growth. However, its role in cardiac hyperplastic growth remains undetermined. The aim of this study was to characterise the expression of myostatin in developing myocardium, determine its effect on cardiomyocyte proliferation, and explore the signalling mechanisms affected by myostatin in dividing cardiomyocytes. Methods: We used quantitative PCR and Western blotting to study the expression of myostatin in cardiomyocytes isolated from rat myocardium at different developmental ages. We. determined the effect of recombinant myostatin on proliferation and cell viability in dividing cardiomyocytes in culture. We analysed myostatin's effect on cardiomyocyte cell cycle progression by flow cytometry and used Western blotting to explore the signalling mechanisms involved. Results: Myostatin is expressed differentially in cardiomyocytes during cardiac development such that increasing expression correlated with a low cardiomyocyte proliferation index. Proliferating foetal cardiomyocytes, from embryos at 18 days of gestation, expressed low levels of myostatin mRNA and protein, whereas isolated cardiomyocytes from postnatal day 10 hearts, wherein the majority of cardiomyocytes have lost their ability to proliferate, displayed a 6-fold increase in myostatin expression. Our in vitro studies demonstrated that myostatin inhibited proliferation of dividing foetal and neonatal cardiomyocytes. Flow cytometric analysis showed that this inhibition occurs mainly via a block in the G1-S phase transition of the cardiomyocyte cell cycle. Western blot analysis showed that part of the mechanism underpinning the inhibition of cardiomyocyte proliferation by myostatin involves phosphorylation of SMAD2 and altered expressions of the cell cycle proteins p21 and CDK2. Conclusions: We conclude that myostatin is an inhibitor of cardiomyocyte proliferation with the potential to limit cardiomyocyte hyperplastic growth by altering cardiac cell cycle progression. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All fights reserved.

Aspects of isolation underpinning mitotic behaviour in lupin protoplasts

This study reports on the influence of critical isolation factors on the subsequent culture of protoplasts of Lupinus albus L. Protoplasts were isolated from in vitro seedling cotyledons of five early maturing accessions in which protoplast yields and division frequencies appeared to be correlated as a high protoplast yield corresponded with a high division frequency. The overall difference among the accessions for mitosis was non- significant, although the highest yield and division frequency were observed in accession LA132, with Alban giving a significantly lower level. Accession Lucrop produced the lowest number of protoplasts, all of which collapsed during culture. Of the enzyme types used for tissue maceration, Pectolyase Y23, was significantly inferior to Macerase in terms of giving way to mitosis. The extent of division in Macerase- isolated protoplast population was 266% higher than that in the Pectolyase Y23- isolated one. The physiological maturity level of the explant, expressed in terms of developmental age, was optimal when 14 - 18- day- old seedling cotyledons were used for protoplast production and culture, rather than more mature ones, despite higher protoplast yields in the latter. On K8p medium, the protoplast division frequency was 129% greater when 18- day- old seedling cotyledons were used, than that with any other treatment. This work on protoplast culture of the potentially important lupin species, which is a pulse rich in dietary protein, oil and fibre, allows a further understanding of the biology, with an aim to advance lupin biotechnology.

Collaterally cued labelling framework underpinning semantic-level visual content descriptor

In this paper, we introduce a novel high-level visual content descriptor devised for performing semantic-based image classification and retrieval. The work can be treated as an attempt for bridging the so called "semantic gap". The proposed image feature vector model is fundamentally underpinned by an automatic image labelling framework, called Collaterally Cued Labelling (CCL), which incorporates the collateral knowledge extracted from the collateral texts accompanying the images with the state-of-the-art low-level visual feature extraction techniques for automatically assigning textual keywords to image regions. A subset of the Corel image collection was used for evaluating the proposed method. The experimental results indicate that our semantic-level visual content descriptors outperform both conventional visual and textual image feature models.

Model inter-comparison between statistical and dynamic model assessments of the long-term stability of blanket peat in Great Britain (1940-2099)

We compared output from 3 dynamic process-based models (DMs: ECOSSE, MILLENNIA and the Durham Carbon Model) and 9 bioclimatic envelope models (BCEMs; including BBOG ensemble and PEATSTASH) ranging from simple threshold to semi-process-based models. Model simulations were run at 4 British peatland sites using historical climate data and climate projections under a medium (A1B) emissions scenario from the 11-RCM (regional climate model) ensemble underpinning UKCP09. The models showed that blanket peatlands are vulnerable to projected climate change; however, predictions varied between models as well as between sites. All BCEMs predicted a shift from presence to absence of a climate associated with blanket peat, where the sites with the lowest total annual precipitation were closest to the presence/absence threshold. DMs showed a more variable response. ECOSSE predicted a decline in net C sink and shift to net C source by the end of this century. The Durham Carbon Model predicted a smaller decline in the net C sink strength, but no shift to net C source. MILLENNIA predicted a slight overall increase in the net C sink. In contrast to the BCEM projections, the DMs predicted that the sites with coolest temperatures and greatest total annual precipitation showed the largest change in carbon sinks. In this model inter-comparison, the greatest variation in model output in response to climate change projections was not between the BCEMs and DMs but between the DMs themselves, because of different approaches to modelling soil organic matter pools and decomposition amongst other processes. The difference in the sign of the response has major implications for future climate feedbacks, climate policy and peatland management. Enhanced data collection, in particular monitoring peatland response to current change, would significantly improve model development and projections of future change.

The CloudSat mission and the A-train: a new dimension of space-based observations of clouds and precipitation

CloudSat is a satellite experiment designed to measure the vertical structure of clouds from space. The expected launch of CloudSat is planned for 2004, and once launched, CloudSat will orbit in formation as part of a constellation of satellites (the A-Train) that includes NASA's Aqua and Aura satellites, a NASA-CNES lidar satellite (CALIPSO), and a CNES satellite carrying a polarimeter (PARASOL). A unique feature that CloudSat brings to this constellation is the ability to fly a precise orbit enabling the fields of view of the CloudSat radar to be overlapped with the CALIPSO lidar footprint and the other measurements of the constellation. The precision and near simultaneity of this overlap creates a unique multisatellite observing system for studying the atmospheric processes essential to the hydrological cycle.The vertical profiles of cloud properties provided by CloudSat on the global scale fill a critical gap in the investigation of feedback mechanisms linking clouds to climate. Measuring these profiles requires a combination of active and passive instruments, and this will be achieved by combining the radar data of CloudSat with data from other active and passive sensors of the constellation. This paper describes the underpinning science and general overview of the mission, provides some idea of the expected products and anticipated application of these products, and the potential capability of the A-Train for cloud observations. Notably, the CloudSat mission is expected to stimulate new areas of research on clouds. The mission also provides an important opportunity to demonstrate active sensor technology for future scientific and tactical applications. The CloudSat mission is a partnership between NASA's JPL, the Canadian Space Agency, Colorado State University, the U.S. Air Force, and the U.S. Department of Energy.

Flavonoids as modulators of memory and learning: molecular interactions resulting in behavioural effects

There is considerable interest in the potential of a group of dietary-derived phytochemicals known as flavonoids in modulating neuronal function and thereby influencing memory, learning and cognitive function. The present review begins by detailing the molecular events that underlie the acquisition and consolidation of new memories in the brain in order to provide a critical background to understanding the impact of flavonoid-rich diets or pure flavonoids on memory. Data suggests that despite limited brain bioavailability, dietary supplementation with flavonoid-rich foods, such as blueberry, green tea and Ginkgo biloba lead to significant reversals of age-related deficits on spatial memory and learning. Furthermore, animal and cellular studies suggest that the mechanisms underpinning their ability to induce improvements in memory are linked to the potential of absorbed flavonoids and their metabolites to interact with and modulate critical signalling pathways, transcription factors and gene and/or protein expression which control memory and learning processes in the hippocampus; the brain structure where spatial learning occurs. Overall, current evidence suggests that human translation of these animal investigations are warranted, as are further studies, to better understand the precise cause-and-effect relationship between flavonoid intake and cognitive outputs.

Drama, disability and education

This book explores the question, what can society learn about disability through the way it is portrayed in TV, films and plays? The text examines and analyses the way disability is portrayed in drama, and how that portrayal may be interpreted by young audiences. Investigating how disabilities have been represented on stage in the past, this book discusses what may be inferred from plays which feature disabled characters through a variety of critical approaches. The book provides an annotated chronology that traces the history of plays that have featured disabled characters. It analyses how disability is used as a dramatic metaphor and considers the ethics of dramatising a disabled character. Critical accounts of units of work in mainstream school seeking to raise disability awareness through engagement with practical drama and dramatic texts are given along with detailed discussions of the issues underpinning two previously unpublished playscripts written for young audiences and description and evaluation of a drama project in a special school. In tackling questions and issues that have not, hitherto, been well covered, Drama, Disability and Education will be of enormous interest to drama students, teachers, researchers and pedagogues who work with disabled people or are concerned with raising awareness and understanding of disability.

Collaboration of the weather and climate communities to advance subseasonal-to-seasonal prediction

The World Weather Research Programme (WWRP) and the World Climate Research Programme (WCRP) have identified collaborations and scientific priorities to accelerate advances in analysis and prediction at subseasonal-to-seasonal time scales, which include i) advancing knowledge of mesoscale–planetary-scale interactions and their prediction; ii) developing high-resolution global–regional climate simulations, with advanced representation of physical processes, to improve the predictive skill of subseasonal and seasonal variability of high-impact events, such as seasonal droughts and floods, blocking, and tropical and extratropical cyclones; iii) contributing to the improvement of data assimilation methods for monitoring and predicting used in coupled ocean–atmosphere–land and Earth system models; and iv) developing and transferring diagnostic and prognostic information tailored to socioeconomic decision making. The document puts forward specific underpinning research, linkage, and requirements necessary to achieve the goals of the proposed collaboration.

Housing or property? The dynamics of housing policy and property principles in the right to buy

This paper examines the interplay and tension between housing law and policy and property law, in the specific context of the right to buy (RTB). It focuses on funding arrangements between the RTB tenant and another party. It first examines how courts determine the parties' respective entitlements in the home, highlighting the difficulty of categorising, under traditional property law principles, a contribution in the form of the statutory discount conferred on the RTB tenant. Secondly, it considers possible exploitation of the RTB scheme, both at the macro level of exploitation of the policy underpinning the legislation and, at the micro level, of exploitation of the tenant. The measures contained in the Housing Act 2004 intended to curb exploitation of the RTB are analysed to determine what can be considered to be legitimate and illegitimate uses of the scheme. It is argued that, despite the government's implicit approval, certain funding arrangements by non-resident relatives fail to give effect to the spirit of the scheme.

Risk allocation in a public–private partnership: a case study of construction and operation of kindergartens in Kazakhstan

In Kazakhstan, a transitional nation in Central Asia, the development of public–private partnerships (PPPs) is at its early stage and increasingly of strategic importance. This case study investigates risk allocation in an ongoing project: the construction and operation of 11 kindergartens in the city of Karaganda in the concession form for 14 years. Drawing on a conceptual framework of effective risk allocation, the study identifies principal PPP risks, provides a critical assessment of how and in what way each partner bears a certain risk, highlights the reasons underpinning risk allocation decisions and delineates the lessons learned. The findings show that the government has effectively transferred most risks to the private sector partner, whilst both partners share the demand risk of childcare services and the project default risk. The strong elements of risk allocation include clear assignment of parties’ responsibilities, streamlined financing schemes and incentives to complete the main project phases on time. However, risk allocation has missed an opportunity to create incentives for service quality improvements and take advantage of economies of scale. The most controversial element of risk allocation, as the study finds, is a revenue stream that an operator is supposed to receive from the provision of services unrelated to childcare, as neither partner is able to mitigate this revenue risk. The article concludes that in the kindergartens’ PPP, the government has achieved almost complete transfer of risks to the private sector partner. However, the costs of transfer are extensive government financial outlays that seriously compromise the PPP value for money.

Concessionary nature of public-private partnerships in Russia and Kazakhstan: a critical review

This article provides a critical overview of Public-Private Partnerships (PPPs) in Russia and Kazakhstan and examines the rationale underpinning such partnerships. The analysis discusses the reasons why governments in Russia and Kazakhstan focus principally on concessions as a form of PPP and goes on to provide a critical assessment of the key approaches and situational factors relating to concessions in these two countries. The article finds that external globalization impulses pressed Russia and Kazakhstan to align their policies and institutions with western orthodoxy and perceived international best practice. An ever-increasing emphasis on use of PPPs has been a key feature of this alignment. However, the governments of Russia and Kazakhstan have increasingly resorted to concessions as progress with the development and implementation of Western style PPP models has stalled. This article concludes that the governments of Russia and Kazakhstan have demonstrated an overly optimistic approach to PPP and as a result may have substantially understated their overall concessional risks and costs. Features of Russian and Kazakhstani PPP arrangements such as ambiguity in output specification and extensive reliance on government subsidies, combined with lack of expertise of private partners, may significantly decrease concession benefits.

Conceptualising public-private partnerships: a critical appraisal of approaches to meanings and forms

Purpose – The purpose of this article is to survey various meanings attached to a public-private partnership (PPP) and related aspects in Western literature, and identify commonalities and differences between them. Additionally, the article intends to critically assess conflicting and overlapping views on contractual and institutional PPPs, their forms and models, and draw insights for transitional economies. Design/methodology/approach – The article contrasts and compares views on PPP meanings, forms and models within Western PPP literature, and also draws comparisons with understanding of partnership aspects in the Russian language sources. The article examines theories underpinning PPPs, builds connections to PPP advantages and drawbacks, and provides critical assessment of net benefits that PPPs may bring along to the society. Findings – The article concludes that future PPP research in transitional countries such as Kazakhstan and Russia, particularly in the area of organisational and power arrangements in partnerships, may delineate new concepts such as government as a guarantor of a PPP project, social significance of a PPP project, and risk management in a country's contextual environment. Practical implications – In transitional countries, in which PPPs are in their infancy, clarification of theoretical positions, and identification of commonalities and differences between meanings attached to the PPP terminology may enable better decisions by researchers and practitioners in their selection and further development of partnerships and related concepts. Originality/value – Research in the field of PPPs in transitional countries such as Russia and Kazakhstan is in its infancy. The paper intends to contribute to the body of knowledge about PPPs by providing detailed account and categorisation of their principal meanings, forms, models, underpinning theories, and drawing insights for future research in transitional countries.

Motherhood, evolutionary psychology and mirror neurons or: ‘Grammar is politics by other means’

Through a close analysis of socio-biologist Sarah Blaffer Hrdy’s work on motherhood and ‘mirror neurons’ it is argued that Hrdy’s claims exemplify how research that ostensibly bases itself on neuroscience, including in literary studies ‘literary Darwinism’, relies after all not on scientific, but on political assumptions, namely on underlying, unquestioned claims about the autonomous, transparent, liberal agent of consumer capitalism. These underpinning assumptions, it is further argued, involve the suppression or overlooking of an alternative, prior tradition of feminist theory, including feminist science criticism.

Effects of agricultural management practices on earthworm populations and crop yield: validation and application of a mechanistic modelling approach

There is little consensus on how agriculture will meet future food demands sustainably. Soils and their biota play a crucial role by mediating ecosystem services that support agricultural productivity. However, a multitude of site-specific environmental factors and management practices interact to affect the ability of soil biota to perform vital functions, confounding the interpretation of results from experimental approaches. Insights can be gained through models, which integrate the physiological, biological and ecological mechanisms underpinning soil functions. We present a powerful modelling approach for predicting how agricultural management practices (pesticide applications and tillage) affect soil functioning through earthworm populations. By combining energy budgets and individual-based simulation models, and integrating key behavioural and ecological drivers, we accurately predict population responses to pesticide applications in different climatic conditions. We use the model to analyse the ecological consequences of different weed management practices. Our results demonstrate that an important link between agricultural management (herbicide applications and zero, reduced and conventional tillage) and earthworms is the maintenance of soil organic matter (SOM). We show how zero and reduced tillage practices can increase crop yields while preserving natural ecosystem functions. This demonstrates how management practices which aim to sustain agricultural productivity should account for their effects on earthworm populations, as their proliferation stimulates agricultural productivity. Synthesis and applications. Our results indicate that conventional tillage practices have longer term effects on soil biota than pesticide control, if the pesticide has a short dissipation time. The risk of earthworm populations becoming exposed to toxic pesticides will be reduced under dry soil conditions. Similarly, an increase in soil organic matter could increase the recovery rate of earthworm populations. However, effects are not necessarily additive and the impact of different management practices on earthworms depends on their timing and the prevailing environmental conditions. Our model can be used to determine which combinations of crop management practices and climatic conditions pose least overall risk to earthworm populations. Linking our model mechanistically to crop yield models would aid the optimization of crop management systems by exploring the trade-off between different ecosystem services.