Regulation of gene and protein expression in cardiac myocyte hypertrophy and apoptosis

Considerable efforts have been expended in elucidating the inter-cellular and intra-cellular signaling pathways which elicit cardiac myocyte hypertrophy or apoptosis, and in identifying the changes which are associated with the end-stage of the response. The challenge now is to link the two. Although some of the signaling effects will be the acute modulation of existing protein function, long-term effects which bring about and maintain the hypertrophic state or which culminate in cell death are mediated at the level of gene and protein expression. With the advances in micro-array technology and genome sequencing, it is now possible to obtain a picture of the global gene expression profile in myocytes or in whole heart which dictates the proteins which could be made. This is not the final picture since additional regulation at the level of translation modulates the relative proportions of each protein that can be made from the transcriptome. Even here, further regulation of protein stability and turnover means that ultimately it is still necessary to examine the proteome to determine what may cause the functional changes in a cell. Thus, in order to gain a full picture of events which regulate the response and gain some insight into possible points of intervention for therapy, it is necessary to examine gene expression, mRNA translation and protein expression in concert.

Numerical simulation of the 12 May 1997 CME Event: The role of magnetic reconnection

We perform a numerical study of the evolution of a Coronal Mass Ejection (CME) and its interaction with the coronal magnetic field based on the 12 May 1997, CME event using a global MagnetoHydroDynamic (MHD) model for the solar corona. The ambient solar wind steady-state solution is driven by photospheric magnetic field data, while the solar eruption is obtained by superimposing an unstable flux rope onto the steady-state solution. During the initial stage of CME expansion, the core flux rope reconnects with the neighboring field, which facilitates lateral expansion of the CME footprint in the low corona. The flux rope field also reconnects with the oppositely orientated overlying magnetic field in the manner of the breakout model. During this stage of the eruption, the simulated CME rotates counter-clockwise to achieve an orientation that is in agreement with the interplanetary flux rope observed at 1 AU. A significant component of the CME that expands into interplanetary space comprises one of the side lobes created mainly as a result of reconnection with the overlying field. Within 3 hours, reconnection effectively modifies the CME connectivity from the initial condition where both footpoints are rooted in the active region to a situation where one footpoint is displaced into the quiet Sun, at a significant distance (≈1R ) from the original source region. The expansion and rotation due to interaction with the overlying magnetic field stops when the CME reaches the outer edge of the helmet streamer belt, where the field is organized on a global scale. The simulation thus offers a new view of the role reconnection plays in rotating a CME flux rope and transporting its footpoints while preserving its core structure.

Exploring options for managing strategies for pea-barley intercropping using a modeling approach

A modeling Study was carried out into pea-barley intercropping in northern Europe. The two objectives were (a) to compare pea-barley intercropping to sole cropping in terms of grain and nitrogen yield amounts and stability, and (b) to explore options for managing pea-barley intercropping systems in order to maximize the biomass produced and the grain and nitrogen yields according to the available resources, such as light, water and nitrogen. The study consisted of simulations taking into account soil and weather variability among three sites located in northern European Countries (Denmark, United Kingdom and France), and using 10 years of weather records. A preliminary stage evaluated the STICS intercrop model's ability to predict grain and nitrogen yields of the two species, using a 2-year dataset from trials conducted at the three sites. The work was carried out in two phases, (a) the model was run to investigate the potentialities of intercrops as compared to sole crops, and (b) the model was run to explore options for managing pea-barley intercropping, asking the following three questions: (i) in order to increase light capture, Would it be worth delaying the sowing dates of one species? (ii) How to manage sowing density and seed proportion of each species in the intercrop to improve total grain yield and N use efficiency? (iii) How to optimize the use of nitrogen resources by choosing the most suitable preceding crop and/or the most appropriate soil? It was found that (1) intercropping made better use of environmental resources as regards yield amount and stability than sole cropping, with a noticeable site effect, (2) pea growth in intercrops was strongly linked to soil moisture, and barley yield was determined by nitrogen uptake and light interception due to its height relative to pea, (3) sowing barley before pea led to a relative grain yield reduction averaged over all three sites, but sowing strategy must be adapted to the location, being dependent on temperature and thus latitude, (4) density and species proportions had a small effect on total grain yield, underlining the interspecific offset in the use of environmental growth resources which led to similar total grain yields whatever the pea-barley design, and (5) long-term strategies including mineralization management through organic residue supply and rotation management were very valuable, always favoring intercrop total grain yield and N accumulation. (C) 2009 Elsevier B.V. All rights reserved.

The poliovirus 2C cis-acting replication element-mediated uridylylation of VPg is not required for synthesis of negative-sense genomes

Nucleotides in the terminal loop of the poliovirus 2C cis-acting replication element (2C(CRE)), a 61 nt structured RNA, function as the template for the addition of two uridylate (U) residues to the viral protein VPg. This uridylylation reaction leads to the formation of VPgpUpU, which is used by the viral RNA polymerase as a nucleotide-peptide primer for genome replication. Although VPg primes both positive- and negative-strand replication, the specific requirement for 2C(CRE)-mediated uridylylation for one or both events has not been demonstrated. We have used a cell-free in vitro translation and replication reaction to demonstrate that 2C(CRE) is not required for the initiation of the negative-sense strand, which is synthesized in the absence of 2C(CRE)-mediated VPgpUpU formation. We propose that the 3' poly(A) tail could serve as the template for the formation of a VPg-poly(U) primer that functions in the initiation of negative-sense strands.

Assessing the process of knowledge transfer – An empirical study

This paper investigates and evaluates the process of knowledge transfer in construction projects. Due to the highly competitive nature of business environments, knowledge transfer between organisations has become increasingly popular in recent years. However, although organisations can realise remarkable benefits by transferring knowledge from one unit to another, successful knowledge transfer can be difficult to achieve. The discussions presented in the paper are mainly based on findings of two case studies. The two cases were selected from Private Finance Initiative (PFI) projects in the UK. According to the case study findings, different stages of a knowledge transfer process can be overlapped, omitted, repeated as well as intermitted and then restarted. One of the significant findings of the case studies was the role of the "knowledge mediator". In selected case studies, there were external consultants and expert staff in the form of knowledge mediators. The importance of their roles was frequently highlighted by the interview participants. They were not only facilitating the close liaison between the knowledge source and the receiver, but also their role was strongly associated with practices of translation and interpretation. This combined role of mediator/translator, therefore, appears to be particularly significant for inter-organisational knowledge transfer in PFI projects.

A linear model for the structure of turbulence beneath surface water waves

The structure of turbulence in the ocean surface layer is investigated using a simplified semi-analytical model based on rapid-distortion theory. In this model, which is linear with respect to the turbulence, the flow comprises a mean Eulerian shear current, the Stokes drift of an irrotational surface wave, which accounts for the irreversible effect of the waves on the turbulence, and the turbulence itself, whose time evolution is calculated. By analysing the equations of motion used in the model, which are linearised versions of the Craik–Leibovich equations containing a ‘vortex force’, it is found that a flow including mean shear and a Stokes drift is formally equivalent to a flow including mean shear and rotation. In particular, Craik and Leibovich’s condition for the linear instability of the first kind of flow is equivalent to Bradshaw’s condition for the linear instability of the second. However, the present study goes beyond linear stability analyses by considering flow disturbances of finite amplitude, which allows calculating turbulence statistics and addressing cases where the linear stability is neutral. Results from the model show that the turbulence displays a structure with a continuous variation of the anisotropy and elongation, ranging from streaky structures, for distortion by shear only, to streamwise vortices resembling Langmuir circulations, for distortion by Stokes drift only. The TKE grows faster for distortion by a shear and a Stokes drift gradient with the same sign (a situation relevant to wind waves), but the turbulence is more isotropic in that case (which is linearly unstable to Langmuir circulations).

Asymptotic gravity wave drag expressions for non-hydrostatic rotating flow over a ridge

Asymptotic expressions are derived for the mountain wave drag in flow with constant wind and static stability over a ridge when both rotation and non-hydrostatic effects are important. These expressions, which are much more manageable than the corresponding exact drag expressions (when these do exist) are found to provide accurate approximations to the drag, even when non-hydrostatic and rotation effects are strong, despite having been developed for cases where these effects are weak. The derived expressions are compared with approximations to the drag found previously, and their asymptotic behaviour in various limits is studied.

Adaptation-induced collective dynamics of a single-cell protozoan

We investigate the behavior of a single-cell protozoan in a narrow tubular ring. This environment forces them to swim under a one-dimensional periodic boundary condition. Above a critical density, single-cell protozoa aggregate spontaneously without external stimulation. The high-density zone of swimming cells exhibits a characteristic collective dynamics including translation and boundary fluctuation. We analyzed the velocity distribution and turn rate of swimming cells and found that the regulation of the turing rate leads to a stable aggregation and that acceleration of velocity triggers instability of aggregation. These two opposing effects may help to explain the spontaneous dynamics of collective behavior. We also propose a stochastic model for the mechanism underlying the collective behavior of swimming cells.

Rigid body trajectories in different 6D spaces

The objective of this paper is to show that the group SE(3) with an imposed Lie-Poisson structure can be used to determine the trajectory in a spatial frame of a rigid body in Euclidean space. Identical results for the trajectory are obtained in spherical and hyperbolic space by scaling the linear displacements appropriately since the influence of the moments of inertia on the trajectories tends to zero as the scaling factor increases. The semidirect product of the linear and rotational motions gives the trajectory from a body frame perspective. It is shown that this cannot be used to determine the trajectory in the spatial frame. The body frame trajectory is thus independent of the velocity coupling. In addition, it is shown that the analysis can be greatly simplified by aligning the axes of the spatial frame with the axis of symmetry which is unchanging for a natural system with no forces and rotation about an axis of symmetry.

A continuum anisotropic model of sea-ice dynamics

We develop the essential ingredients of a new, continuum and anisotropic model of sea-ice dynamics designed for eventual use in climate simulation. These ingredients are a constitutive law for sea-ice stress, relating stress to the material properties of sea ice and to internal variables describing the sea-ice state, and equations describing the evolution of these variables. The sea-ice cover is treated as a densely flawed two-dimensional continuum consisting of a uniform field of thick ice that is uniformly permeated with narrow linear regions of thinner ice called leads. Lead orientation, thickness and width distributions are described by second-rank tensor internal variables: the structure, thickness and width tensors, whose dynamics are governed by corresponding evolution equations accounting for processes such as new lead generation and rotation as the ice cover deforms. These evolution equations contain contractions of higher-order tensor expressions that require closures. We develop a sea-ice stress constitutive law that relates sea-ice stress to the structure tensor, thickness tensor and strain rate. For the special case of empty leads (containing no ice), linear closures are adopted and we present calculations for simple shear, convergence and divergence.

Undying voices: the poetry of Roman Britain

An anthology (comprising introduction, text, translation, and notes) of Britain's most ancient (surviving) poetry (Latin/Greek, with an English translation).

Institutional multilingualism in NGOs: Amnesty International’s strategic understanding of multilingualism

Institutional multilingualism is most often associated with large intergovernmental institutions such as the European Union and the United Nations. Multilingualism in non-governmental organisations (NGOs), however, has remained invisible to a large extent. Yet these organisations have been identified as very powerful in world politics in the globalised 21st century. Like international governmental organisations (IGOs), they operate across linguistic and language borders. This raises the questions if NGOs actually use language and translation in the same way as IGOs. This article examines Amnesty International as a case study and explores what official multilingualism means for this organisation, how it is reflected in its language policy, and how it is put into practice. By gaining insight into the particular case of Amnesty International, this article aims to make a contribution to institutional translation studies.

Cellular mechanisms of cardiac hypertrophy.

Hypertrophy of myocytes in the heart ventricles is an important adaptation that in vivo occurs in response to a requirement for increased contractile power. It involves changes at the level of gene transcription, stimulation of the rate of protein synthesis (translation), and increased assembly of myofibrils. There is mounting evidence of the involvement of reversible protein phosphorylation and dephosphorylation in most of these processes. Protein kinase C, mitogen-activated protein kinases, and transcription factors have been implicated in the modulation of the transcriptional changes. Activation of translation may also be mediated through protein phosphorylation/dephosphorylation, although this has not been clearly established in the heart. Here we provide a critical overview of the signalling pathways involved in the hypertrophic response and provide a scheme to account for many of its features.

From insect to man: Photorhabdus sheds light on the emergence of human pathogenicity

Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway.