The Balance of RanBP1 and RCC1 Is Critical for Nuclear Assembly and Nuclear Transport

Ran is a small GTPase that is essential for nuclear transport, mRNA processing, maintenance of structural integrity of nuclei, and cell cycle control. RanBP1 is a highly conserved Ran guanine nucleotide dissociation inhibitor. We sought to use Xenopus egg extracts for the development of an in vitro assay for RanBP1 activity in nuclear assembly, protein import, and DNA replication. Surprisingly, when we used anti-RanBP1 antibodies to immunodeplete RanBP1 from Xenopus egg extracts, we found that the extracts were also depleted of RCC1, Ran’s guanine nucleotide exchange factor, suggesting that these proteins form a stable complex. In contrast to previous observations using extracts that had been depleted of RCC1 only, extracts lacking both RanBP1 and RCC1 (codepleted extracts) did not exhibit defects in assays of nuclear assembly, nuclear transport, or DNA replication. Addition of either recombinant RanBP1 or RCC1 to codepleted extracts to restore only one of the depleted proteins caused abnormal nuclear assembly and inhibited nuclear transport and DNA replication in a manner that could be rescued by further addition of RCC1 or RanBP1, respectively. Exogenous mutant Ran proteins could partially rescue nuclear function in extracts without RanBP1 or without RCC1, in a manner that was correlated with their nucleotide binding state. These results suggest that little RanBP1 or RCC1 is required for nuclear assembly, nuclear import, or DNA replication in the absence of the other protein. The results further suggest that the balance of GTP- and GDP-Ran is critical for proper nuclear assembly and function in vitro.

The impact on general practitioners of the changing balance of care for elderly people living in institutions

Objectives: To describe utilisation of general practitioners by elderly people resident in communal establishments; to examine variations in general practitioner utilisation and estimate the likely impact of the “downsizing” of long stay provision in NHS hospitals.

Genetic Manipulation of Alcohol Dehydrogenase Levels in Ripening Tomato Fruit Affects the Balance of Some Flavor Aldehydes and Alcohols1

Tomato (Lycopersicon esculentum) plants were transformed with gene constructs containing a tomato alcohol dehydrogenase (ADH) cDNA (ADH 2) coupled in a sense orientation with either the constitutive cauliflower mosaic virus 35S promoter or the fruit-specific tomato polygalacturonase promoter. Ripening fruit from plants transformed with the constitutively expressed transgene(s) had a range of ADH activities; some plants had no detectable activity, whereas others had significantly higher ADH activity, up to twice that of controls. Transformed plants with fruit-specific expression of the transgene(s) also displayed a range of enhanced ADH activities in the ripening fruit, but no suppression was observed. Modified ADH levels in the ripening fruit influenced the balance between some of the aldehydes and the corresponding alcohols associated with flavor production. Hexanol and Z-3-hexenol levels were increased in fruit with increased ADH activity and reduced in fruit with low ADH activity. Concentrations of the respective aldehydes were generally unaltered. The phenotypes of modified fruit ADH activity and volatile abundance were transmitted to second-generation plants in accordance with the patterns of inheritance of the transgenes. In a preliminary taste trial, fruit with elevated ADH activity and higher levels of alcohols were identified as having a more intense “ripe fruit” flavor.

Regulation of herbivore growth by the balance of light and nutrients.

Experiments using planktonic organisms revealed that the balance of radiant energy and available nutrients regulated herbivore growth rates through their effects on abundance and chemical composition of primary producers. Both algae and herbivores were energy limited at low light/nutrient ratios, but both were nutrient limited at high light/nutrient ratios. Herbivore growth increased with increasing light intensity at low values of the light/nutrient ratio due to increases in algal biomass, but growth decreased with increasing light at a high light/nutrient ratio due to decreases in algal quality. Herbivore production therefore was maximal at intermediate levels of the light/nutrient ratio. The results contribute to an understanding of mass transfer mechanisms in ecosystems and illustrate the importance of integration of energy-based and material-based currencies in ecology.

British Balance of Competence Reviews, Part I: ‘Competences about right, so far’. EPIN Working Paper No. 35, October 2013

The first in a series for a CEPS-EPIN project entitled “The British Question and the Search for a Fresh European Narrative” this paper is pegged on an ambitious ongoing exercise by the British government to review all the competences of the European Union. The intention is that this should provide a basis for informed debate before the referendum on the UK remaining in the EU or not, which is scheduled for 2017. This paper summarises the first six reviews, each of which runs to around 80 pages, covering foreign policy, development policy, taxation, the single market, food safety, and public health. The present authors then add their own assessments of these materials. While understandably giving due place to British interests, they are of general European relevance. The substantive conclusions of this first set of reviews are that the competences of the EU are judged by respondents to be ‘about right’ on the whole, which came as a surprise to eurosceptic MPs and the tabloid media. Our own view is that the reviews are objective and impressively researched, and these populist complaints are illustrating the huge gap between the views of informed stakeholders and general public opinion, and therefore also the hazard of subjecting the ‘in or out’ choice for decision by referendum. If the referendum is to endorse the UK’s continuing membership there will have to emerge some fresh popular narratives about the EU. The paper therefore concludes with some thoughts along these lines, both for the UK and the EU as a whole.

British Balance of Competence Reviews, Part II: Again, a huge contradiction between the evidence and Eurosceptic populism. EPIN Paper No. 40, June 2014

This paper is the second in a series for a CEPS project entitled “The British Question and the Search for a Fresh European Narrative”. It is pegged on an ambitious exercise by the British government to review all the competences of the European Union on the basis of evidence submitted by independent stakeholders. In all, 32 sectoral policy reviews are being produced over the period 2013-2015, as input into public information and debate leading up to a referendum on whether the UK should remain in, or secede from, the EU, planned for 2017. This second set of reviews covers a broad range of EU policies (for the single market for goods, external trade, transport policy, environment, climate change, research, asylum, non-EU immigration, civil judicial cooperation, tourism, culture and sport). The findings confirm what emerged from the first set of reviews, namely that there is little or no case for repatriation of EU competences at the level they are defined in the treaties. This does not exclude that at a more detailed level there can be individual actions or laws that might be done better or not at all. However, that is the task of all the institutions to work at on a regular basis, and hardly a rationale for secession. For the UK in particular the EU has shown considerable flexibility in agreeing to special arrangements, such as in the case of the policies here reviewed of asylum, non-EU immigration and civil judicial cooperation. In other areas reviewed here, such as the single market for goods, external trade, transport, environment, climate change and research, there is a good fit between the EU’s policies and UK priorities, with the EU perceived by stakeholders as an ‘amplifier’ of British interests.

Ukraine: Can meaningful reform come out of conflict? Bruegel Policy Contribution 2014/08, August 2014

Apart from threats to its national security and territorial integrity, Ukraine faces serious economic challenges. These result from the slow pace of economic and institutional reform in the previous two decades, the populist policies of the Yanukovych era and the consequences of the conflict with Russia. The new Ukrainian authorities have made pro-reform declarations, but these do not seem to be supported sufficiently by concrete policy measures, especially in the critical areas of fiscal, balance-of-payment and structural adjustment. Also, the international financial aid package granted to Ukraine has not been accompanied by sufficiently strong policy conditionality. Ukraine urgently needs a complex programme of far-reaching economic and institutional reform, which will include both short-term fiscal and macroeconomic adjustment measures and medium- to long-term structural and institutional changes. Energy subsidies and the low retirement age are the two critical policy areas that require adjustment to avoid sovereign default and a balance-of-payments crisis.

The Dano case – Or time for the UK to digest realities about the balance of competences between the EU and national levels. CEPS Commentary, 14 November 2014

The European Court of Justice's new judgment on the Dano case should be reverberating around the UK. In Michael Emerson's view, it shows how national competences can be deftly used to control for 'benefit tourism' without challenging EU law, and that the Court is not acting as the agent of 'EU competence creep', as alleged in the Eurosceptic's stereotype.