Globular Cluster Scale Sizes in Giant Galaxies: Orbital Anisotropy and Tidally Under-filling Clusters in M87, NGC 1399, and NGC 5128

We investigate the shallow increase in globular cluster half-light radii with projected galactocentric distance $R_{gc}$ observed in the giant galaxies M87, NGC 1399, and NGC 5128. To model the trend in each galaxy, we explore the effects of orbital anisotropy and tidally under-filling clusters. While a strong degeneracy exists between the two parameters, we use kinematic studies to help constrain the distance $R_\beta$ beyond which cluster orbits become anisotropic, as well as the distance $R_{f\alpha}$ beyond which clusters are tidally under-filling. For M87 we find $R_\beta > 27$ kpc and $20 < R_{f\alpha} 13$ kpc and $10 < R_{f\alpha} < 30$ kpc. The connection of $R_{f\alpha}$ with each galaxy's mass profile indicates the relationship between size and $R_{gc}$ may be imposed at formation, with only inner clusters being tidally affected. The best fitted models suggest the dynamical histories of brightest cluster galaxies yield similar present-day distributions of cluster properties. For NGC 5128, the central giant in a small galaxy group, we find $R_\beta > 5$ kpc and $R_{f\alpha} > 30$ kpc. While we cannot rule out a dependence on $R_{gc}$, NGC 5128 is well fitted by a tidally filling cluster population with an isotropic distribution of orbits, suggesting it may have formed via an initial fast accretion phase. Perturbations from the surrounding environment may also affect a galaxy's orbital anisotropy profile, as outer clusters in M87 and NGC 1399 have primarily radial orbits while outer NGC 5128 clusters remain isotropic.Comment: 16 pages, 7 figures, 4 tables, Accepted for publication in MNRA

Understanding the role of eIF4A in gene regulation in health and disease

Eukaryotic initiation factor 4A (eIF4A) is an ATP-dependent RNA helicase responsible for unwinding the secondary structure of mRNAs. In humans, eIF4A exists as three separate paralogs: eIF4AI and eIF4AII possess a high degree of homology while eIF4AIII is distinct. Knockdown of eIF4AII had no effect on the expression of a reporter construct containing a structured RNA hairpin. Knockdown of eIF4AI and treatment with hippuristanol (an eIF4A inhibitor) caused a dramatic reduction in the hairpin-mediated gene. This reporter system was developed as part of this project to act as a screen for eIF4A activity along with an in vitro screening approach. The activity of eIF4A is suppressed in vivo by the tumour suppressor PDCD4. The fact that loss of PDCD4 function increases the severity of DNA damage is probably attributable its eIF4A-suppressive activity. Based on previous microarray data, it was supposed that eIF4A inhibition may be therapeutically beneficial in the treatment of Alzheimer's disease. As part of this project, it was demonstrated that eIF4A suppression significantly reduced the expression of reporter genes preceded by the 5’ UTRs of genes predicted to play harmful roles in Alzheimer’s disease. The expression of reporter genes preceded by the 5’ UTR sequences of genes predicted to be beneficial in Alzheimer's were not affected by this suppression. Reporter plasmids containing the 5’ UTR sequences of the oncogenes ODC1, EGFR and VEGFA have high requirements for eIF4A as estimated using hippuristanol. eIF4A inhibition did not significantly affect the reporters containing the 5’ UTRs of non-pathogenic genes. The EGFR 5’ UTR was found to contain an IRES which explains why EGFR is upregulated in response to hypoxia

Frontiers of marine science

On 9–13 October 2010 early career scientists from the UK and Australia across marine research fields were given the opportunity to come together in Perth, Australia to discuss the frontiers of marine research and exchange ideas

Understanding the role of eIF4A in gene regulation in health and disease

Eukaryotic initiation factor 4A (eIF4A) is an ATP-dependent RNA helicase responsible for unwinding the secondary structure of mRNAs. In humans, eIF4A exists as three separate paralogs: eIF4AI and eIF4AII possess a high degree of homology while eIF4AIII is distinct. Knockdown of eIF4AII had no effect on the expression of a reporter construct containing a structured RNA hairpin. Knockdown of eIF4AI and treatment with hippuristanol (an eIF4A inhibitor) caused a dramatic reduction in the hairpin-mediated gene. This reporter system was developed as part of this project to act as a screen for eIF4A activity along with an in vitro screening approach. The activity of eIF4A is suppressed in vivo by the tumour suppressor PDCD4. The fact that loss of PDCD4 function increases the severity of DNA damage is probably attributable its eIF4A-suppressive activity. Based on previous microarray data, it was supposed that eIF4A inhibition may be therapeutically beneficial in the treatment of Alzheimer's disease. As part of this project, it was demonstrated that eIF4A suppression significantly reduced the expression of reporter genes preceded by the 5’ UTRs of genes predicted to play harmful roles in Alzheimer’s disease. The expression of reporter genes preceded by the 5’ UTR sequences of genes predicted to be beneficial in Alzheimer's were not affected by this suppression. Reporter plasmids containing the 5’ UTR sequences of the oncogenes ODC1, EGFR and VEGFA have high requirements for eIF4A as estimated using hippuristanol. eIF4A inhibition did not significantly affect the reporters containing the 5’ UTRs of non-pathogenic genes. The EGFR 5’ UTR was found to contain an IRES which explains why EGFR is upregulated in response to hypoxia

eIF4A Inhibition Allows Translational Regulation of mRNAs Encoding Proteins Involved in Alzheimer's Disease

Alzheimer's disease (AD) is the main cause of dementia in our increasingly aging population. The debilitating cognitive and behavioral symptoms characteristic of AD make it an extremely distressing illness for patients and carers. Although drugs have been developed to treat AD symptoms and to slow disease progression, there is currently no cure. The incidence of AD is predicted to increase to over one hundred million by 2050, placing a heavy burden on communities and economies, and making the development of effective therapies an urgent priority. Two proteins are thought to have major contributory roles in AD: the microtubule associated protein tau, also known as MAPT; and the amyloid-beta peptide (A-beta), a cleavage product of amyloid precursor protein (APP). Oxidative stress is also implicated in AD pathology from an early stage. By targeting eIF4A, an RNA helicase involved in translation initiation, the synthesis of APP and tau, but not neuroprotective proteins, can be simultaneously and specifically reduced, representing a novel avenue for AD intervention. We also show that protection from oxidative stress is increased upon eIF4A inhibition. We demonstrate that the reduction of these proteins is not due to changes in mRNA levels or increased protein degradation, but is a consequence of translational repression conferred by inhibition of the helicase activity of eIF4A. Inhibition of eIF4A selectively and simultaneously modulates the synthesis of proteins involved in Alzheimer's disease: reducing A-beta and tau synthesis, while increasing proteins predicted to be neuroprotective

Intra-party decision-making in contemporary Europe: improving representation or ruling with empty shells?

Political observers agree that parties in European parliamentary democracies are more likely than previously to give party members opportunities to vote in decisions about party policies or personnel. Observers are less agreed about the implications of these apparent procedural trends. Some, including Peter Mair, saw them as evidence of the hollowing-out of party democracies; others have seen them as enhancing citizens’ opportunities for meaningful political participation. Because this is ultimately an empirical question as well as a normative one, these radically conflicting interpretations make it crucial to examine which interpretation is best supported by usage to date This is the task we undertake in this article. We use data from the Political Party Database Project (PPDB) to investigate the extent to which parties in 26 European countries have adopted and employed intra-party ballots. We also ask whether there is evidence that such procedures are changing intra-party relationships. We find that balloting of party members is indeed widely used, but it is by no means universal. We find much less support for the implication that such ballots are associated with less competitive contests, or that the new devices are generally used in ways that devalue party-member bonds

Monomeric PcrA helicase processively unwinds plasmid lengths of DNA in the presence of the initiator protein RepD

The helicase PcrA unwinds DNA during asymmetric replication of plasmids, acting with an initiator protein, in our case RepD. Detailed kinetics of PcrA activity were measured using bulk solution and a single-molecule imaging technique to investigate the oligomeric state of the active helicase complex, its processivity and the mechanism of unwinding. By tethering either DNA or PcrA to a microscope coverslip surface, unwinding of both linear and natural circular plasmid DNA by PcrA/RepD was followed in real-time using total internal reflection fluorescence microscopy. Visualization was achieved using a fluorescent single-stranded DNA-binding protein. The single-molecule data show that PcrA, in combination with RepD, can unwind plasmid lengths of DNA in a single run, and that PcrA is active as a monomer. Although the average rate of unwinding was similar in single-molecule and bulk solution assays, the single-molecule experiments revealed a wide distribution of unwinding speeds by different molecules. The average rate of unwinding was several-fold slower than the PcrA translocation rate on single-stranded DNA, suggesting that DNA unwinding may proceed via a partially passive mechanism. However, the fastest dsDNA unwinding rates measured in the single-molecule unwinding assays approached the PcrA translocation speed measured on ssDNA