title: Time to Diagnosis and Persistence: The Two Major Determinants of Effective Tuberculosis Control

authors: Ruthe, Alaine Tess

subjects: tuberculosis

abstract: The greatest challenge confronting effective tuberculosis (TB) eradication is the time to diagnosis, and duration of treatment of chronically infected individuals which represent a pool of infection. In an attempt to help limit the spread of TB in New Zealand, a fast SNP based diagnostic test was developed, to quickly identify the highly transmissible and virulent endemic Rangipo strain. The role of VapBC toxin-antitoxin systems in M. tuberculosis has been the subject of great interest recently, due to their expanded number in the genome and links with virulence and the regulation of cell growth in response to environmental stress. Their ability to regulate growth under adverse conditions for presumed survival advantages possibly leading to dormancy or persistence, make them ideal candidates for the development of new M. tuberculosis treatments. To establish differential expression of vapC, and therefore identify possible pathways and functions of the VapBC proteins, RT-qPCR was used to assess the expression levels of vapB and vapC in M. smegmatis under conditions of stress. No consistant changes in vapC mRNA levels were observed, resulting in the hypothesis that it is not the transcriptional differences which are important in the regulation of VapC, but post-transcriptional factors. In order to investigate the function(s) of M. tuberculosis VapBCs, these VapBC proteins were expressed and purified in M. smegmatis, and the VapC toxin tested for RNase activity. The purification, expression, RNase testing and bioinformatic analysis of M. tuberculosis VapCs suggested that VapCRv2530c, VapCRv0065 and VapCRv0617 may all target the same recognition sequence, UA*GG. Bioinformatic analysis revealed an abundance of this target sequence in horizontal gene transfer and TA genes, raising the possibility that VapC toxins could be functioning as selfish elements, or initiating transcriptional regulation cascades when a rapid change in the proteomic response and metabolic state of the cell is required. It is intriguing that the three M. tuberculosis VapC proteins tested thus far appear to target the same recognition sequence, possibly suggesting that all 47 VapCs are RNases and are targeting the same sequence. Alternatively; VapCs may belong to sub-groups targeting different sequences, allowing M. tuberculosis to exude both gross and fine metabolic control; or, they may share the same target, but are regulated by different activators triggered in response to different environmental stimuli.

text: Time to Diagnosis and Persistence: The Two Major Determinants of Effective Tuberculosis Control The greatest challenge confronting effective tuberculosis (TB) eradication is the time to diagnosis, and duration of treatment of chronically infected individuals which represent a pool of infection. In an attempt to help limit the spread of TB in New Zealand, a fast SNP based diagnostic test was developed, to quickly identify the highly transmissible and virulent endemic Rangipo strain. The role of VapBC toxin-antitoxin systems in M. tuberculosis has been the subject of great interest recently, due to their expanded number in the genome and links with virulence and the regulation of cell growth in response to environmental stress. Their ability to regulate growth under adverse conditions for presumed survival advantages possibly leading to dormancy or persistence, make them ideal candidates for the development of new M. tuberculosis treatments. To establish differential expression of vapC, and therefore identify possible pathways and functions of the VapBC proteins, RT-qPCR was used to assess the expression levels of vapB and vapC in M. smegmatis under conditions of stress. No consistant changes in vapC mRNA levels were observed, resulting in the hypothesis that it is not the transcriptional differences which are important in the regulation of VapC, but post-transcriptional factors. In order to investigate the function(s) of M. tuberculosis VapBCs, these VapBC proteins were expressed and purified in M. smegmatis, and the VapC toxin tested for RNase activity. The purification, expression, RNase testing and bioinformatic analysis of M. tuberculosis VapCs suggested that VapCRv2530c, VapCRv0065 and VapCRv0617 may all target the same recognition sequence, UA*GG. Bioinformatic analysis revealed an abundance of this target sequence in horizontal gene transfer and TA genes, raising the possibility that VapC toxins could be functioning as selfish elements, or initiating transcriptional regulation cascades when a rapid change in the proteomic response and metabolic state of the cell is required. It is intriguing that the three M. tuberculosis VapC proteins tested thus far appear to target the same recognition sequence, possibly suggesting that all 47 VapCs are RNases and are targeting the same sequence. Alternatively; VapCs may belong to sub-groups targeting different sequences, allowing M. tuberculosis to exude both gross and fine metabolic control; or, they may share the same target, but are regulated by different activators triggered in response to different environmental stimuli.

year: 2015

title: Tuururu: Owl poem

authors: August, Tipene

subjects: toikupu

abstract: Poem composed by Tipene August.

text: Tuururu: Owl poem Poem composed by Tipene August.

year: 2001-02

title: Preparation, microstructure and properties of Ti-6Al-4V rods by powder compact extrusion of powder mixture

authors: Yang, Fei

subjects: Extrusion

abstract: Ti-6Al-4V (wt%) alloy rods were prepared successfully using a low-cost method that combines mixing elemental and master alloy powders and powder compact extrusion. The microstructure and mechanical properties of the rods and the effects of extrusion temperature on them were investigated. The results showed that the microstructure and mechanical properties of the extruded rods were strongly affected by the extrusion temperature. With increasing extrusion temperature from 1200°C to 1300°C and keeping the powder compact holding time unchanged at 2 minutes, the fraction of undissolved V rich particles in the microstructure of the extruded rod decreased substantially to zero, the level of composition homogenization increased dramatically to the highest level, and the UTS and elongation of the extruded rods increased significantly from 886MPa and 1.2% to 1300MPa and 7.1%, respectively. The tensile properties of the Ti-6Al-4V alloy rods produced by powder compact extrusion of the powder mixture are comparable to those of Ti-6Al-4V alloy produced by ingot metallurgy and thermomechanical processing.

text: Preparation, microstructure and properties of Ti-6Al-4V rods by powder compact extrusion of powder mixture Ti-6Al-4V (wt%) alloy rods were prepared successfully using a low-cost method that combines mixing elemental and master alloy powders and powder compact extrusion. The microstructure and mechanical properties of the rods and the effects of extrusion temperature on them were investigated. The results showed that the microstructure and mechanical properties of the extruded rods were strongly affected by the extrusion temperature. With increasing extrusion temperature from 1200°C to 1300°C and keeping the powder compact holding time unchanged at 2 minutes, the fraction of undissolved V rich particles in the microstructure of the extruded rod decreased substantially to zero, the level of composition homogenization increased dramatically to the highest level, and the UTS and elongation of the extruded rods increased significantly from 886MPa and 1.2% to 1300MPa and 7.1%, respectively. The tensile properties of the Ti-6Al-4V alloy rods produced by powder compact extrusion of the powder mixture are comparable to those of Ti-6Al-4V alloy produced by ingot metallurgy and thermomechanical processing.

year: 2012