Molecular evolution of proadrenomedullin N-terminal 20 peptide (PAMP):evidence for gene co-option

Posttranslational processing of proadrenomedullin generates two biologically active peptides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP). Sequence comparison of homologous proadrenomedullin genes in vertebrate evolution shows a high degree of stability in the reading frame for AM, whereas PAMP sequence changes rapidly. Here we investigate the functional significance of PAMP phylogenetic variation studying two of PAMP's better characterized physiological activities, angiogenic potential and antimicrobial capability, with synthetic peptides carrying the predicted sequence for human, mouse, chicken, and fish PAMP. All tested peptides induced angiogenesis when compared with untreated controls, but chicken and fish PAMP, which lack terminal amidation, were apparently less angiogenic than their human and mouse homologs. Confirming the role of amidation in angiogenesis, Gly-extended and free acid variants of human PAMP produced responses similar to the natural nonamidated peptides. In contrast, antimicrobial activity was restricted to human PAMP, indicating that this function may have been acquired at a late time during the evolution of PAMP. Interestingly, free acid human PAMP retained antimicrobial activity whereas the Gly-extended form did not. This fact may reflect the need for maintaining a tightly defined structural conformation in the pore-forming mechanism proposed for these antimicrobial agents. The evolution of PAMP provides an example of an angiogenic peptide that developed antimicrobial capabilities without losing its original function.

Foveal relocation surgery:Is it a reasonable option for patients with age-related macular degeneration?

Foveal relocation (or translocation) has been reintroduced recently as a possible treatment for patients with subfoveal choroidal neovascular membranes secondary to age-related macular degeneration and degenerative myopia. Different surgical techniques have been proposed and the results, although encouraging, are not completely satisfactory yet. Most surgical procedures described are technically difficult and require special vitreo-retinal expertise. Furthermore, although marked improvements in visual acuity have been observed in some patients, others do not experience visual improvement, even after a successful surgery. Additionally, devastating complications, such as proliferative vitreo-retinopathy (PVR) can occur, impairing the final visual outcome. Although foveal relocation surgery may be a promising direction in research and development, as yet, there is no randomised controlled trial to show that it is more effective than any other forms of treatment for macular degeneration. The validity of this surgical approach needs to be evaluated by the results of longer-term follow-up. This article reviews the current surgical techniques for foveal relocation, their outcomes and complications, and discusses the surgical problems that vitreo-retinal surgeons face when performing foveal relocation surgery.

Financial Taxes and the Sand in the Wheels of Financialization:Legal Challenges for the EU Directive Implementing Enhanced Cooperation in the Area of Financial Transaction Tax

One of the many results of the Global Financial Crisis was the insight that the financial sector is under-taxed compared to other industries. In light of the huge bailouts and continued subsidies for financial institutions that are characterized as too-big-to-fail demands came on the agenda to make finance pay for the mega-crisis it caused. The most prominent examples of such taxes are a Financial Transaction Tax (FTT) and a Financial Activities Tax (FAT). Possible effects of such taxes on the economic constitution and increasingly in particular on the European Single Market have been discussed controversially over the last decades already. Especially with the decision of eleven EU member states to adapt an FTT using the enhanced cooperation procedure a number of additional legal challenges for implementing such a tax have emerged. This paper analyzes how tax measures of indirectly regulating the financial industry differ, what legal challenges they pose, and what their overall contribution would be in making the financial system more stable and resilient. It also analyzes the legal arguments against enhanced cooperation in this area and the legal issues related to the British lawsuit against the Commission’s Directive proposal in the European Court of Justice on grounds of the extra-territoriality application of tax. The paper concludes that the feasibility of an FTT is legally sound and given the FTT’s advantages over a FAT the EU Directive should be implemented as a first step for a European-wide FTT. However, significant uncertainties about its implementation remain at this stage.

Use of Inhaled Tobramycin in Cystic Fibrosis

Chronic infection with Pseudomonas aeruginosa is associated with poor outcomes in patients with cystic fibrosis (CF). It leads to a reduced quality of life, acceleration of the decline in lung function, and increased frequency and severity of pulmonary exacerbations. Tobramycin, administered by inhalation as a long-term therapy, decreases bacterial density in airways, reduces exacerbation frequency, and improves quality of life and lung function in patients with chronic P. aeruginosa infection. In the last decade, tobramycin inhalation has become an important contributor to CF treatment as a means to control chronic infection and as a first-line treatment for the eradication of early acquisition of P. aeruginosa. Recently, a dry powder inhalation (DPI) form of tobramycin has become available, which is more convenient for administration and has comparable efficacy to the tobramycin solution. This DPI, the Podhaler™ (Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA), requires less time for treatment delivery and is more portable than a nebulizer, and so is a welcome additional therapeutic option for many patients.

National institutions and employers’ age management practices in Britain and Germany:‘Path dependence’and option exploration

We pursue a comparative analysis of employers’ age management practices in Britain and Germany, asking how valid ‘convergence’ and ‘Varieties of Capitalism’ theories are. After rejecting the convergence verdict, we proceed to ask how far ‘path dependence’ helps explain inter-country differences. Through 19 interviews with British and German experts, we find that firms have reacted in different ways to promptings from the EU and the two states. Change has been modest and a rhetoric-reality gap exists in firms as they seek to hedge. We point to continuities in German institutional methods of developing new initiatives, and the emerging role of British NGOs in helping firms and the state develop new options. We argue that ‘path dependence’ offers insight into the national comparison, but also advance the idea of national modes of firm optionexploration as an important way of conceptualizing the processes involved.

A Conventional Internal Combustion Engine Versus a Range Extended Electric Vehicle Under the Current Regulatory Regime in the United Kingdom

Transport accounts for 22% of greenhouse gas emissions in the United Kingdom and cars are expected tomore than double by 2050. Car manufacturers are continually aiming for a substantially reduced carbonfootprint through improved fuel efficiency and better powertrain performance due to the strict EuropeanUnion emissions standards. However, road tax, not just fuel efficiency, is a key consideration of consumerswhen purchasing a car. While measures have been taken to reduce emissions through stricter standards, infuture, alternative technologies will be used. Electric vehicles, hybrid vehicles and range extended electricvehicles have been identified as some of these future technologies. In this research a virtual test bed of aconventional internal combustion engine and a range extended electric vehicle family saloon car were builtin AVL’s vehicle and powertrain system level simulation tool, CRUISE, to simulate the New EuropeanDrive Cycle and the results were then soft-linked to a techno-economic model to compare the effectivenessof current support mechanisms over the full life cycle of both cars. The key finding indicates that althoughcarbon emissions are substantially reduced, switching is still not financially the best option for either theconsumer or the government in the long run.