Over expression of Plk1 does not induce cell division in rat cardiac myocytes in vitro

BACKGROUND: Mammalian cardiac myocytes withdraw from the cell cycle during post-natal development, resulting in a non-proliferating, fully differentiated adult phenotype that is unable to repair damage to the myocardium, such as occurs following a myocardial infarction. We and others previously have shown that forced expression of certain cell cycle molecules in adult cardiac myocytes can promote cell cycle progression and division in these cells. The mitotic serine/threonine kinase, Polo-like kinase-1 (Plk1), is known to phosphorylate and activate a number of mitotic targets, including Cdc2/Cyclin B1, and to promote cell division. PRINCIPAL FINDINGS: The mammalian Plk family are all differentially regulated during the development of rat cardiac myocytes, with Plk1 showing the most dramatic decrease in both mRNA, protein and activity in the adult. We determined the potential of Plk1 to induce cell cycle progression and division in cultured rat cardiac myocytes. A persistent and progressive loss of Plk1 expression was observed during myocyte development that correlated with the withdrawal of adult rat cardiac myocytes from the cell cycle. Interestingly, when Plk1 was over-expressed in cardiac myocytes by adenovirus infection, it was not able to promote cell cycle progression, as determined by cell number and percent binucleation. CONCLUSIONS: We conclude that, in contrast to Cdc2/Cyclin B1 over-expression, the forced expression of Plk1 in adult cardiac myocytes is not sufficient to induce cell division and myocardial repair.

Vesicular systems for delivering conventional small organic molecules and larger macromolecules to and through human skin

The history of using vesicular systems for drug delivery to and through skin started nearly three decades ago with a study utilizing phospholipid liposomes to improve skin deposition and reduce systemic effects of triamcinolone acetonide. Subsequently, many researchers evaluated liposomes with respect to skin delivery, with the majority of them recording localized effects and relatively few studies showing transdermal delivery effects. Shortly after this, Transfersomes were developed with claims about their ability to deliver their payload into and through the skin with efficiencies similar to subcutaneous administration. Since these vesicles are ultradeformable, they were thought to penetrate intact skin deep enough to reach the systemic circulation. Their mechanisms of action remain controversial with diverse processes being reported. Parallel to this development, other classes of vesicles were produced with ethanol being included into the vesicles to provide flexibility (as in ethosomes) and vesicles were constructed from surfactants and cholesterol (as in niosomes). Thee ultradeformable vesicles showed variable efficiency in delivering low molecular weight and macromolecular drugs. This article will critically evaluate vesicular systems for dermal and transdermal delivery of drugs considering both their efficacy and potential mechanisms of action.

Beyond Belief: Harry Potter in text and film

Despite the fact that the Harry Potter books have won a place in the cultural consciousness and have had enjoyed immense commercial success, they were not accepted within many faith groups at the outset. Using the term ‘religion’ to refers to any system of belief that may be recognised by symbols , I look extracts from three of the novels, alongside their subsequent cinematic adaptations, in order to consider the construction of representations of religion in the films and the contribution made by the films to this debate.

Organic farming in isolated landscapes does not benefit flower-visiting insects and pollination

Organic farming has often been found to provide benefits for biodiversity, but the benefits can depend on the species considered and characteristics of the surrounding landscape. In an intensively farmed area of Northeast Italy we investigated whether isolated organic farms, in a conventionally farmed landscape, provided local benefits for insect pollinators and pollination services. We quantified the relative effects of local management (i.e. the farm system), landscape management (proportion of surrounding uncultivated land) and interactions between them. We compared six organic and six conventional vine fields. The proportion of surrounding uncultivated land was calculated for each site at radii of 200, 500, 1000 and 2000 m. The organic fields did not differ from the conventional in their floral resources or proportion of surrounding uncultivated land. Data were collected on pollinator abundance and species richness, visitation rates to, and pollination of experimental potted plants. None of these factors were significantly affected by the farming system. The abundance of visits to the potted plants in the conventional fields tended to be negatively affected by the proportion of surrounding uncultivated land. The proportion fruit set, weight of seeds per plant and seed weight in conventional and organic fields were all negatively affected by the proportion of surrounding uncultivated land. In vine fields the impact of the surrounding landscape was stronger than the local management. Enhancement of biodiversity through organic farming should not be assumed to be ubiquitous, as potential benefits may be offset by the crop type, organicmanagement practices and the specific habitat requirements in the surrounding landscape.

Variability of the North Atlantic eddy-driven jet stream

Much of the atmospheric variability in the North Atlantic sector is associated with variations in the eddy-driven component of the zonal flow. Here we present a simple method to specifically diagnose this component of the flow using the low-level wind field (925–700 hpa ). We focus on the North Atlantic winter season in the ERA-40 reanalysis. Diagnostics of the latitude and speed of the eddy-driven jet stream are compared with conventional diagnostics of the North Atlantic Oscillation (NAO) and the East Atlantic (EA) pattern. This shows that the NAO and the EA both describe combined changes in the latitude and speed of the jet stream. It is therefore necessary, but not always sufficient, to consider both the NAO and the EA in identifying changes in the jet stream. The jet stream analysis suggests that there are three preferred latitudinal positions of the North Atlantic eddy-driven jet stream in winter. This result is in very good agreement with the application of a statistical mixture model to the two-dimensional state space defined by the NAO and the EA. These results are consistent with several other studies which identify four European/Atlantic regimes, comprising three jet stream patterns plus European blocking events.

Understanding construction consortia: Theory, practice and opinions

Firms form consortia in order to win contracts. Once a project has been awarded to a consortium each member then concentrates on his or her own contract with the client. Therefore, consortia are marketing devices, which present the impression of teamworking, but the production process is just as fragmented as under conventional procurement methods. In this way, the consortium forms a barrier between the client and the actual construction production process. Firms form consortia, not as a simple development of normal ways of working, but because the circumstances for specific projects make it a necessary vehicle. These circumstances include projects that are too large or too complex to undertake alone or projects that require on-going services which cannot be provided by the individual firms inhouse. It is not a preferred way of working, because participants carry extra risk in the form of liability for the actions of their partners in the consortium. The behaviour of members of consortia is determined by their relative power, based on several factors, including financial commitment and ease of replacement. The level of supply chain visibility to the public sector client and to the industry is reduced by the existence of a consortium because the consortium forms an additional obstacle between the client and the firms undertaking the actual construction work. Supply chain visibility matters to the client who otherwise loses control over the process of construction or service provision, while remaining accountable for cost overruns. To overcome this separation there is a convincing argument in favour of adopting the approach put forward in the Project Partnering Contract 2000 (PPC2000) Agreement. Members of consortia do not necessarily go on to work in the same consortia again because members need to respond flexibly to opportunities as and when they arise. Decision-making processes within consortia tend to be on an ad hoc basis. Construction risk is taken by the contractor and the construction supply chain but the reputational risk is carried by all the firms associated with a consortium. There is a wide variation in the manner that consortia are formed, determined by the individual circumstances of each project; its requirements, size and complexity, and the attitude of individual project leaders. However, there are a number of close working relationships based on generic models of consortia-like arrangements for the purpose of building production, such as the Housing Corporation Guidance Notes and the PPC2000.

Interactions between herbal and conventional medicines

Herb-drug interactions are subject to much interest at present, but for various reasons reports may be unreliable or unsubstantiated. Herbal medicines are variable in composition and quality, which may affect their interaction profile as well as the reliability of reports concerning them. In this review, clinical and experimental reports have been collated, evaluated and summarised, and the theoretical and clinical evidence presented. There is an explanation of the particular issues involved with herbal medicines as compared with conventional drugs, and reasons why comparisons may or may not be valid, which is intended for those without specialist experience in herbal products. It has become apparent that only a few herbal drugs have so far been cited in interaction reports, for example St John's Wort, Ginkgo biloba, Dan Shen, liquorice, Ma huang and garlic, and that the main drugs involved are those which are already susceptible to interactions with many other conventional drugs, such as warfarin, protease inhibitors and anti-cancer drugs. An attempt has been made to put the matter into perspective and recommendations have been given for health professionals to advise or develop strategies to safeguard patients, without resorting to speculation or scaremongering.

Differences in perceived risks and benefits of herbal, over-the-counter conventional, and prescribed conventional, medicines, and the implications of this for the safe and effective use of herbal products

Objectives: To investigate people's views about the efficacy and specific risks of herbal, over-the-counter (OTC) conventional, and prescribed conventional medicines, and their likelihood of taking a second (herbal or OTC conventional) product in addition to a prescribed medicine. Methods: Experiment 1 (1 factor within-participant design); Experiment 2 (1 factor between-participant design). Convenience samples of general population were given a hypothetical scenario and required to make a number of judgements. Results: People believed herbal remedies to be less effective, but less risky than OTC and prescribed conventional medicines. Herbal medicines were not seen as being safer simply because of their easier availability. Participants indicated that they would be more likely to take a herbal medicine than a conventional OTC medicine in addition to a prescribed medicine, and less likely to consult their doctor in advance. Conclusion: People believe that herbal medicines are natural and relatively safe and can be used with less caution. People need to be given clear information about the risks and benefits of herbal medicines if they are to use such products safety and effectively. (c) 2006 Elsevier Ltd. All rights reserved.

Optimal 3D surface reconstruction from a small number of conventional 2D X-ray images

This paper describes a method for reconstructing 3D frontier points, contour generators and surfaces of anatomical objects or smooth surfaces from a small number, e. g. 10, of conventional 2D X-ray images. The X-ray images are taken at different viewing directions with full prior knowledge of the X-ray source and sensor configurations. Unlike previous works, we empirically demonstrate that if the viewing directions are uniformly distributed around the object's viewing sphere, then the reconstructed 3D points automatically cluster closely on a highly curved part of the surface and are widely spread on smooth or flat parts. The advantage of this property is that the reconstructed points along a surface or a contour generator are not under-sampled or under-represented because surfaces or contours should be sampled or represented with more densely points where their curvatures are high. The more complex the contour's shape, the greater is the number of points required, but the greater the number of points is automatically generated by the proposed method. Given that the number of viewing directions is fixed and the viewing directions are uniformly distributed, the number and distribution of the reconstructed points depend on the shape or the curvature of the surface regardless of the size of the surface or the size of the object. The technique may be used not only in medicine but also in industrial applications.

Effects of reduced height (Rht) and photoperiod insensitivity (Ppd) alleles on yield of wheat in contrasting production systems

Near isogenic lines (NILs) varying for reduced height (Rht) and photoperiod insensitivity (Ppd-D1) alleles in a cv. Mercia background (rht (tall), Rht-B1b, Rht-D1b, Rht-B1c, Rht8c+Ppd-D1a, Rht-D1c, Rht12) were compared for interception of photosynthetically active radiation (PAR), radiation use efficiency (RUE), above-ground biomass (AGB), harvest index (HI), height, weed prevalence, lodging and grain yield, at one field site but within contrasting (‘organic’ v ‘conventional’) rotational and agronomic contexts, in each of three years. In the final year, further NILs (rht (tall), Rht-B1b, Rht-D1b, Rht-B1c, Rht-B1b+Rht-D1b, Rht-D1b+Rht-B1c) in Maris Huntsman and Maris Widgeon backgrounds were added together with 64 lines of a doubled haploid (DH) population [Savannah (Rht-D1b) × Renesansa (Rht-8c+Ppd-D1a)]. There were highly significant genotype × system interactions for grain yield, mostly because differences were greater in the conventional system than in the organic system. Quadratic fits of NIL grain yield against height were appropriate for both systems when all NILs and years were included. Extreme dwarfing was associated with reduced PAR, RUE, AGB, HI, and increased weed prevalence. Intermediate dwarfing was often associated with improved HI in the conventional system, but not in the organic system. Heights in excess of the optimum for yield were associated particularly with reduced HI and, in the conventional system, lodging. There was no statistical evidence that optimum height for grain yield varied with system although fits peaked at 85cm and 96cm in the conventional and organic systems, respectively. Amongst the DH lines, the marker for Ppd-D1a was associated with earlier flowering, and just in the conventional system also with reduced PAR, AGB and grain yield. The marker for Rht-D1b was associated with reduced height, and again just in the conventional system, with increased HI and grain yield. The marker for Rht8c reduced height, and in the conventional system only, increased HI. When using the System × DH line means as observations grain yield was associated with height and early vegetative growth in the organic system, but not in the conventional system. In the conventional system, PAR interception after anthesis correlated with yield. Savannah was the highest yielding line in the conventional system, producing significantly more grain than several lines that out yielded it in the organic system.