659 research outputs found
‘When I see them I feel like beating them’: Corruption and the South African Police Service
South African survey data on citizen attitudes towards police have, for the past ten years, indicated a lack of trust in law enforcers. Similarly, the SAPS has, since the early nineties, developed a public image as a widely corrupt organisation. In 2010 the SAPS reverted to military ranks and adopted a discourse of 'force' in an attempt to improve discipline, effectiveness and image. This paper presents a summary of findings from 15 focus groups conducted in mid-2010 that sought to explore public experiences and perceptions of police and police corruption
On the record: Interview with Francois Beukman, Executive Director of the Independent Complaints Directorate
The Independent Complaints Directorate (ICD) is South Africa’s primary independent agency responsible for investigating complaints against the police. It was established in 1997 under Chapter 10 of the South African Police Service Act. The Act makes the ICD’s sole compulsory mandate the investigation of deaths in police custody or as a result of police action. However, the ICD has also been open to receipt of complaints of police involvement in criminal activity, and failure to comply with the Domestic Violence Act.A new Bill, the Independent Police Investigations Directorate (IPID) Bill, is likely to be adopted in the third quarter of 2011. The new Act will significantly change the current functions of the ICD and will guide the transformation of the ICD into the Independent Police Investigations Directorate (IPID), providing it with its own legislation (independent of the SAPS Act). Under the new legislation the IPID will be mandated to investigate not only deaths in police custody or as a result of police action, but also complaints relating to the discharge of an official firearm by a police official; rape by a police official, rape of any person in police custody; complaints of torture or assault against a police official in the execution of his or her duties; and systemic corruption. The Bill also puts an onus on SAPS managers to report to the IPID on action taken against members following the submission of post-investigation IPID recommendations.Andrew Faull speaks to ICD Executive Director, Francois Beukman, about the changes taking place
An antibody raised against a pathogenic serpin variant induces mutant-like behaviour in the wild-type protein
A monoclonal antibody (mAb) that binds to a transient intermediate may act as a catalyst for the corresponding reaction; here we show this principle can extend on a macro molecular scale to the induction of mutant-like oligomerization in a wild-type protein. Using the common pathogenic E342K (Z) variant of α1-antitrypsin as antigen-whose native state is susceptible to the formation of a proto-oligomeric intermediate-we have produced a mAb (5E3) that increases the rate of oligomerization of the wild-type (M) variant. Employing ELISA, gel shift, thermal stability and FRET time-course experiments, we show that mAb5E3 does not bind to the native state of α1-antitrypsin, but recognizes a cryptic epitope in the vicinity of the post-helix A loop and strand 4C that is revealed upon transition to the polymerization intermediate, and which persists in the ensuing oligomer. This epitope is not shared by loop-inserted monomeric conformations. We show the increased amenity to polymerization by either the pathogenic E342K mutation or the binding of mAb5E3 occurs without affecting the energetic barrier to polymerization. As mAb5E3 also does not alter the relative stability of the monomer to intermediate, it acts in a manner similar to the E342K mutant, by facilitating the conformational interchange between these two states
The pathogenic exon 1 HTT protein is produced by incomplete splicing in Huntington’s disease patients
We have previously shown that exon 1 of the huntingtin gene does not always splice to exon 2 resulting in the production of a small polyadenylated mRNA (HTTexon1) that encodes the highly pathogenic exon 1 HTT protein. The level of this read-through product is proportional to CAG repeat length and is present in all knock-in mouse models of Huntington’s disease (HD) with CAG lengths of 50 and above and in the YAC128 and BACHD mouse models, both of which express a copy of the human HTT gene. We have now developed specific protocols for the quantitative analysis of the transcript levels of HTTexon1 in human tissue and applied these to a series of fibroblast lines and post-mortem brain samples from individuals with either adult-onset or juvenile-onset HD. We found that the HTTexon1 mRNA is present in fibroblasts from juvenile HD patients and can also be readily detected in the sensory motor cortex, hippocampus and cerebellum of post-mortem brains from HD individuals, particularly in those with early onset disease. This finding will have important implications for strategies to lower mutant HTT levels in patients and the design of future therapeutics
Effect of photoperiod and host distribution on the horizontal transmission of Isaria fumosorosea (Hypocreales: Cordycipitaceae) in greenhouse whitefly assessed using a novel model bioassay
A model bioassay was used to evaluate the epizootic potential and determine the horizontal transmission efficiency of Isaria fumosorosea Trinidadian strains against Trialeurodes vaporariorum pharate adults under optimum conditions (25±0.5°C, ~100% RH) at two different photoperiods. Untreated pharate adults were arranged on laminated graph paper at different distributions to simulate varying infestation levels on a leaf surface. Four potential hosts were located 7, 14 and 21 mm away from a central sporulating cadaver simulating high, medium and low infestation levels, respectively. Percent hosts colonized were recorded 7, 12, 14 and 21 days post-treatment during a 16- and 24-h photophase. After 21 days, mean percent hosts colonized at the highest, middle and lowest infestation levels were 93 and 100%, 22 and 58%, 25 and 39% under a 16- and 24-h photophase, respectively. From the results, it was concluded that the longer the photophase, the greater the percentage of hosts colonized, and as host distance increased from the central sporulating cadaver, colonization decreased. The use of this novel model bioassay technique is the first attempt to evaluate the epizootic potential and determine the horizontal transmission efficiency of I. fumosorosea Trinidadian strains under optimal environmental conditions at different photoperiods. This bioassay can be used to assess horizontal transmission efficiency for the selection of fungi being considered for commercial biopesticide development
An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behavior
Serpins are important regulators of proteolytic pathways with an antiprotease activity that involves a conformational transition from a metastable to a hyperstable state. Certain mutations permit the transition to occur in the absence of a protease; when associated with an intermolecular interaction, this yields linear polymers of hyperstable serpin molecules, which accumulate at the site of synthesis. This is the basis of many pathologies termed the serpinopathies. We have previously identified a monoclonal antibody (mAb4B12) that, in single-chain form, blocks α1-Antitrypsin (α1-AT) polymerisation in cells. Here, we describe the structural basis for this activity. The mAb4B12 epitope was found to encompass residues Glu32, Glu39 and His43 on helix A and Leu306 on helix I. This is not a region typically associated with the serpin mechanism of conformational change, and correspondingly the epitope was present in all tested structural forms of the protein. Antibody binding rendered β-sheet A - on the opposite face of the molecule - more liable to adopt an 'open' state, mediated by changes distal to the breach region and proximal to helix F. The allosteric propagation of induced changes through the molecule was evidenced by an increased rate of peptide incorporation and destabilisation of a preformed serpin-enzyme complex following mAb4B12 binding. These data suggest that prematurely shifting the β-sheet A equilibrium towards the 'open' state out of sequence with other changes suppresses polymer formation. This work identifies a region potentially exploitable for a rational design of ligands that is able to dynamically influence α1-AT polymerisation
Attentional focus and performance anxiety: Effects on simulated race-driving performance and heart rate variability
Previous studies have demonstrated that an external focus can enhance motor learning compared to an internal focus. The benefits of adopting an external focus are attributed to the use of less effortful automatic control processes, while an internal focus relies upon more effort-intensive consciously controlled processes.The aim of this study was to compare the effectiveness of a distal external focus with an internal focus in the acquisition of a simulated driving task and subsequent performance in a competitive condition designed to increase state anxiety.To provide further evidence for the automatic nature of externally controlled movements, the study included heart rate variability (HRV) as an index of mental effort. Sixteen participants completed eight blocks of four laps in either a distal external or internal focus condition, followed by two blocks of four laps in the competitive condition. During acquisition, the performance of both groups improved; however, the distal external focus group outperformed the internal focus group.The poorer performance of the internal focus group was accompanied by a larger reduction in HRV, indicating a greater investment of mental effort. In the competition condition, state anxiety increased, and for both groups, performance improved as a function of the increased anxiety. Increased heart rate and self-reported mental effort accompanied the performance improvement. The distal external focus group also outperformed the internal focus group across both neutral and competitive conditions and this more effective performance was again associated with lower levels of HRV. Overall, the results offer support for the suggestion that an external focus promotes a more automatic mode of functioning. In the competitive condition, both foci enhanced performance and while the improved performance may have been achieved at the expense of greater compensatory mental effort, this was not reflected in HRV scores. © 2012 Mullen, Faull, Jones and Kingston
Integrating Phosphoproteome and Transcriptome Reveals New Determinants of Macrophage Multinucleation
This research was originally published in Molecular and Cellular Proteomics. Rotival M, Ko JH, Srivastava PK, Kerloc'h A, Montoya A, Mauro C, Faull P, Cutillas PR, Petretto E, Behmoaras J. Integrating phosphoproteome and transcriptome reveals new determinants of macrophage multinucleation. Molecular and Cellular Proteomics. 2014. Vol:pp-pp. © the American Society for Biochemistry and Molecular Biology.File embargoed until 22 Dec 2015
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