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.

Extracellular disulfide exchange and the regulation of cellular function

An emerging concept is that disulfide bonds can act as a dynamic scaffold to present mature proteins in different conformational and functional states on the cell surface. Two examples are the conversion of the receptor, integrin a alpha(IIb)beta(3), from a low affinity to a high affinity state, and the interaction of CD4 receptor with the HIV-1 envelope glycoprotein gp120 to promote virus-cell fusion. In both of these cases there is a remodeling of the protein disulfide bonding pattern. The formation and rearrangement of disulfide bonds is modulated by a family of enzymes known as the thiol isomerases, which include protein disulfide isomerase (PDI), ERp5, ERp57, and ERp72. While these enzymes were reported originally to be restricted in location to the endoplasmic reticulum, in some cells thiol isomerases are found on the cell surface. This may indicate a wider role for these enzymes in cell function. In platelets it has been shown that reagents that react with cell surface sulfhydryl groups are capable of blocking a number of functional responses, including integrin-mediated aggregation, adhesion, and granule secretion. Furthermore, the use of function blocking antibodies to either PDI or ERp5 causes inhibition of these functional responses. This review summarizes current knowledge of the extracellular regulation of disulfide exchange and the implications of this in the regulation of cell function.

Polymer-supported nitroxyl catalysts for selective oxidation of alcohols

Novel non-toxic poly(ethylene glycol)-supported 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) moieties are demonstrated to give an excellent interfacial catalysis for the selective oxidation of alcohols to the corresponding carbonyl species in biphasic media and investigation for the recovery of these new macromolecular catalysts via precipitation with diethyl ether after catalysis has also been briefly studied.

Advances in cycloaddition polymerizations

Cycloaddition reactions have been employed in polymer synthesis since the mid-nineteen sixties. This critical review will highlight recent notable advances in this field. For example, [2 + 2] cycloaddition reactions have been utilized in numerous polymerizations to enable the construction of strained polymer systems such as poly(2-azetidinone)s that can, in turn, afford polyfunctional beta-amino acid derived polymers. Polymers have also been synthesized successfully via (3 + 2) cycloaddition methods utilizing both thermal and high-pressure conditions. 'Click chemistry'-a process involving the reaction of azides with olefins, has also been adopted to generate linear and hyperbranched polymer architectures in a very efficient manner. [4 + 2] Cycloadditions have also been utilized under thermal and high-pressure conditions to produce rigid polymers such as polyimides and polyphenylenes. These cycloaddition polymerization methods afford polymers with potential for use in high performance polymers applications such as high temperature resistant coatings and polymeric organic light emitting diodes.

Intercalation of diiodine molecules in cis-Ru(bpy)(2)Cl-2

Reaction of diiodine with cis-Ru(bpy)(2)Cl-2 in methanol at room temperature yields a thermally stable intercalate cis-Ru(bpy)(2)Cl-2 center dot 1.7I(2) (1) which has been characterised by X-ray crystallography. Iodine is leeched from 1 as it reacts with acetone at room temperature. (C) 2005 Elsevier B.V. All rights reserved.

When school is not enough: new initiatives in intergenerational language transmission in Wales

This paper examines language reproduction in the family in the context of a highly innovative project in Wales, where the Welsh language has been in decline for over a century. Although Welsh-medium schooling has played a pivotal role in slowing and even reversing language shift in recent decades, there is mounting evidence of the dangers of over-reliance on education. The Twf (Growth) Project was established in 2002 with funding from the National Assembly for Wales with the aim of raising awareness of the benefits of bilingualism among parents and prospective parents. Analysis of interviews with the main stakeholders in the project (managers, the Twf project officers, parents, health workers and a range of other partners), publicity materials and observations of project staff at work suggests that the achievements of the project lie in two main areas: the recognition of the need for building strong alliances with professional groups and organisations that work with families with young children; and the development of a marketing strategy appropriate for the target audience. It is argued that the experience of the project will be of interest to those addressing the issue of intergenerational transmission in a range of other minority language settings.

A novel radix-3/9 algorithm for type-III generalized discrete Hartley transform

A novel radix-3/9 algorithm for type-III generalized discrete Hartley transform (GDHT) is proposed, which applies to length-3(P) sequences. This algorithm is especially efficient in the case that multiplication is much more time-consuming than addition. A comparison analysis shows that the proposed algorithm outperforms a known algorithm when one multiplication is more time-consuming than five additions. When combined with any known radix-2 type-III GDHT algorithm, the new algorithm also applies to length-2(q)3(P) sequences.

Decreased frequency of North Atlantic polar lows associated with future climate warming

Every winter, the high-latitude oceans are struck by severe storms that are considerably smaller than the weather-dominating synoptic depressions1. Accompanied by strong winds and heavy precipitation, these often explosively developing mesoscale cyclones—termed polar lows1—constitute a threat to offshore activities such as shipping or oil and gas exploitation. Yet owing to their small scale, polar lows are poorly represented in the observational and global reanalysis data2 often used for climatological investigations of atmospheric features and cannot be assessed in coarse-resolution global simulations of possible future climates. Here we show that in a future anthropogenically warmed climate, the frequency of polar lows is projected to decline. We used a series of regional climate model simulations to downscale a set of global climate change scenarios3 from the Intergovernmental Panel of Climate Change. In this process, we first simulated the formation of polar low systems in the North Atlantic and then counted the individual cases. A previous study4 using NCEP/NCAR re-analysis data5 revealed that polar low frequency from 1948 to 2005 did not systematically change. Now, in projections for the end of the twenty-first century, we found a significantly lower number of polar lows and a northward shift of their mean genesis region in response to elevated atmospheric greenhouse gas concentration. This change can be related to changes in the North Atlantic sea surface temperature and mid-troposphere temperature; the latter is found to rise faster than the former so that the resulting stability is increased, hindering the formation or intensification of polar lows. Our results provide a rare example of a climate change effect in which a type of extreme weather is likely to decrease, rather than increase.

Neural networks for identification of nonlinear systems under random piecewise polynomial disturbances

The problem of identification of a nonlinear dynamic system is considered. A two-layer neural network is used for the solution of the problem. Systems disturbed with unmeasurable noise are considered, although it is known that the disturbance is a random piecewise polynomial process. Absorption polynomials and nonquadratic loss functions are used to reduce the effect of this disturbance on the estimates of the optimal memory of the neural-network model.

Correcting for local oscillator phase offset in a DVB-T compliant receiver under multipath conditions

In 1997, the UK implemented the worlds first commercial digital terrestrial television system. Under the ETS 300 744 standard, the chosen modulation method, COFDM, is assumed to be multipath resilient. Previous work has shown that this is not necessarily the case. It has been shown that the local oscillator required for demodulation from intermediate-frequency to baseband must be very accurate. This paper shows that under multipath conditions, standard methods for obtaining local oscillator phase lock may not be adequate. This paper demonstrates a set of algorithms designed for use with a simple local oscillator circuit which will allow correction for local oscillator phase offset to maintain a low bit error rate with multipath present.