New electoral registration rules mean students are likely to be under-represented in the 2015 election

In this post, Jack Blumenau, Simon Hix, and Tony Travers argue that recent changes to the electoral registration process are likely to have significant consequences for the representation of students in the election in May

Chambord – Château, parterres nord et est

Créés à partir de 1730, les jardins des parterres nord et est du château de Chambord ont connu plusieurs états à partir de leur abandon progressif dès le du début du xixe s. Leur emprise de 6,5 ha a fait l’objet d’un projet de restauration destiné à recréer les dispositions du dernier état du xviiie s. Ce projet a été fondé sur une documentation historique et iconographique fournie, complétée par des études documentaires (Ponsot 2003 ; Potillion 2013 ; Villeneuve, Jourd’heuil 2015), un diagno..

Building Large Phylogenetic Trees on Coarse-Grained Parallel Machines

Abstract Phylogenetic analysis is an area of computational biology concerned with the reconstruction of evolutionary relationships between organisms, genes, and gene families. Maximum likelihood evaluation has proven to be one of the most reliable methods for constructing phylogenetic trees. The huge computational requirements associated with maximum likelihood analysis means that it is not feasible to produce large phylogenetic trees using a single processor. We have completed a fully cross platform coarse-grained distributed application, DPRml, which overcomes many of the limitations imposed by the current set of parallel phylogenetic programs. We have completed a set of efficiency tests that show how to maximise efficiency while using the program to build large phylogenetic trees. The software is publicly available under the terms of the GNU general public licence from the system webpage at http://www.cs.nuim.ie/distributed

RAMICS: Trainable, high-speed and biologically relevant alignment of high-throughput sequencing reads to coding DNA

The challenge presented by high-throughput sequencing necessitates the development of novel tools for accurate alignment of reads to reference sequences. Current approaches focus on using heuristics to map reads quickly to large genomes, rather than generating highly accurate alignments in coding regions. Such approaches are, thus, unsuited for applications such as amplicon-based analysis and the realignment phase of exome sequencing and RNA-seq, where accurate and biologically relevant alignment of coding regions is critical. To facilitate such analyses, we have developed a novel tool, RAMICS, that is tailored to mapping large numbers of sequence reads to short lengths (<10 000 bp) of coding DNA

Structural insights into the mechanism of negative regulation of single-box high mobility group proteins by the acidic tail domain.

The Drosophila and plant (maize) functional counterparts of the abundant vertebrate chromosomal protein HMGB1 (HMG-D and ZmHMGB1, respectively) differ from HMGB1 in having a single HMG box, as well as basic and acidic flanking regions that vary greatly in length and charge. We show that despite these variations, HMG-D and ZmHMGB1 exist in dynamic assemblies in which the basic HMG boxes and linkers associate with their intrinsically disordered, predominantly acidic, tails in a manner analogous to that observed previously for HMGB1. The DNA-binding surfaces of the boxes and linkers are occluded in "auto-inhibited" forms of the protein, which are in equilibrium with transient, more open structures that are "binding-competent." This strongly suggests that the mechanism of auto-inhibition may be a general one. HMG-D and ZmHMGB1 differ from HMGB1 in having phosphorylation sites in their tail and linker regions. In both cases, in vitro phosphorylation of serine residues within the acidic tail stabilizes the assembled form, suggesting another level of regulation for interaction with DNA, chromatin, and other proteins that is not possible for the uniformly acidic (hence unphosphorylatable) tail of HMGB1.This work was supported by the Biotechnology and Biological Sciences Research Council through the award of Grant BB/D002257/1 (to J. O. T.) and a grant from the Deutsche Forschungsgemeinschaft (DFG) (to K. D. G.).This is the final published version. It first appeared at http://www.jbc.org/content/289/43/29817.long

Reverse transcriptase drug resistance mutations in HIV-1 subtype C infected patients on ART in Karonga District, Malawi

<p>Abstract</p> <p>Background</p> <p>Drug resistance testing before initiation of, or during, antiretroviral therapy (ART) is not routinely performed in resource-limited settings. High levels of viral resistance circulating within the population will have impact on treatment programs by increasing the chances of transmission of resistant strains and treatment failure. Here, we investigate Drug Resistance Mutations (DRMs) from blood samples obtained at regular intervals from patients on ART (Baseline-22 months) in Karonga District, Malawi. One hundred and forty nine reverse transcriptase (RT) consensus sequences were obtained via nested PCR and automated sequencing from blood samples collected at three-month intervals from 75 HIV-1 subtype C infected individuals in the ART programme.</p> <p>Results</p> <p>Fifteen individuals showed DRMs, and in ten individuals DRMs were seen from baseline samples (reported to be ART naïve). Three individuals in whom no DRMs were observed at baseline showed the emergence of DRMs during ART exposure. Four individuals who did show DRMs at baseline showed additional DRMs at subsequent time points, while two individuals showed evidence of DRMs at baseline and either no DRMs, or different DRMs, at later timepoints. Three individuals had immune failure but none appeared to be failing clinically.</p> <p>Conclusion</p> <p>Despite the presence of DRMs to drugs included in the current regimen in some individuals, and immune failure in three, no signs of clinical failure were seen during this study. This cohort will continue to be monitored as part of the Karonga Prevention Study so that the long-term impact of these mutations can be assessed. Documenting proviral population is also important in monitoring the emergence of drug resistance as selective pressure provided by ART compromises the current plasma population, archived viruses can re-emerge</p

The Influence of N-Linked Glycans on the MolecularDynamics of the HIV-1 gp120 V3 Loop

N-linked glycans attached to specific amino acids of the gp120 envelope trimer of a HIV virion can modulate the binding affinity of gp120 to CD4, influence coreceptor tropism, and play an important role in neutralising antibody responses. Because of the challenges associated with crystallising fully glycosylated proteins, most structural investigations have focused on describing the features of a non-glycosylated HIV-1 gp120 protein. Here, we use a computational approach to determine the influence of N-linked glycans on the dynamics of the HIV-1 gp120 protein and, in particular, the V3 loop. We compare the conformational dynamics of a non-glycosylated gp120 structure to that of two glycosylated gp120 structures, one with a single, and a second with five, covalently linked high-mannose glycans. Our findings provide a clear illustration of the significant effect that N-linked glycosylation has on the temporal and spatial properties of the underlying protein structure. We find that glycans surrounding the V3 loop modulate its dynamics, conferring to the loop a marked propensity towards a more narrow conformation relative to its non-glycosylated counterpart. The conformational effect on the V3 loop provides further support for the suggestion that N-linked glycosylation plays a role in determining HIV-1 coreceptor tropism.Scopu

Trends in genotypic HIV-1 antiretroviral resistance between 2006 and 2012 in South African patients receiving first- and second-line antiretroviral treatment regimens

The original publication is available at http://www.plosone.org/Publication of this article was funded by the Stellenbosch University Open Access Fund.BibliographyObjectives: South Africa’s national antiretroviral (ARV) treatment program expanded in 2010 to include the nucleoside reverse transcriptase (RT) inhibitors (NRTI) tenofovir (TDF) for adults and abacavir (ABC) for children. We investigated the associated changes in genotypic drug resistance patterns in patients with first-line ARV treatment failure since the introduction of these drugs, and protease inhibitor (PI) resistance patterns in patients who received ritonavir-boosted lopinavir (LPV/r)-containing therapy. Methods: We analysed ARV treatment histories and HIV-1 RT and protease mutations in plasma samples submitted to the Tygerberg Academic Hospital National Health Service Laboratory. Results: Between 2006 and 2012, 1,667 plasma samples from 1,416 ARV-treated patients, including 588 children and infants, were submitted for genotypic resistance testing. Compared with 720 recipients of a d4T or AZT-containing first-line regimen, the 153 recipients of a TDF-containing first-line regimen were more likely to have the RT mutations K65R (46% vs 4.0%; p<0.001), Y115F (10% vs. 0.6%; p<0.001), L74VI (8.5% vs. 1.8%; p<0.001), and K70EGQ (7.8% vs. 0.4%) and recipients of an ABC-containing first-line regimen were more likely to have K65R (17% vs 4.0%; p<0.001), Y115F (30% vs 0.6%; p<0.001), and L74VI (56% vs 1.8%; p<0.001). Among the 490 LPV/r recipients, 55 (11%) had ≥1 LPV-resistance mutations including 45 (9.6%) with intermediate or high-level LPV resistance. Low (20 patients) and intermediate (3 patients) darunavir (DRV) cross resistance was present in 23 (4.6%) patients. Conclusions: Among patients experiencing virological failure on a first-line regimen containing two NRTI plus one NNRTI, the use of TDF in adults and ABC in children was associated with an increase in four major non- thymidine analogue mutations. In a minority of patients, LPV/r-use was associated with intermediate or high-level LPV resistance with predominantly low-level DRV cross-resistance.Stellenbosch University Open Access FundPublishers' Versio