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: Contextualizing Indigenous people and the state of exception: New Zealand's Waikeria Prison protest

authors: Martin, Jessica

abstract: On Tuesday, December 29, 2020, 16 protesters at Waikeria Prison, one of New Zealand's largest male prisons, engaged in a six-day standoff with prison guards to protest inhumane prison conditions. The Department of Corrections framed the event as an aimless riot, delegitimizing the intentional demonstration of resistance against state violence. Imprisoned intellectuals, specifically Imprisoned Black Radical tradition, have long examined and centered the prison as the harshest instrument of the state linked to the struggles of the collective. However, voices from imprisoned intellectuals are rarely considered in academic scholarship despite acute analysis of the state and liberation. This article employs the state of exception to contextualize the Waikeria protest. Particular attention is devoted to the ‘state of continuity,’ which allows for a broader understanding of a permanent state of racialized oppression and marginalization faced by Indigenous and Black communities in racialized-settler-colonial contexts. Populations designated as the exception are thus framed as a threat targeted for militaristic police intervention. This article concludes by extending the discussion of the state of continuity to include how expressions of rage and dissent by Indigenous and Black people are viewed as a direct threat to the sovereign order but are necessary for revolutionary change.

text: Contextualizing Indigenous people and the state of exception: New Zealand's Waikeria Prison protest On Tuesday, December 29, 2020, 16 protesters at Waikeria Prison, one of New Zealand's largest male prisons, engaged in a six-day standoff with prison guards to protest inhumane prison conditions. The Department of Corrections framed the event as an aimless riot, delegitimizing the intentional demonstration of resistance against state violence. Imprisoned intellectuals, specifically Imprisoned Black Radical tradition, have long examined and centered the prison as the harshest instrument of the state linked to the struggles of the collective. However, voices from imprisoned intellectuals are rarely considered in academic scholarship despite acute analysis of the state and liberation. This article employs the state of exception to contextualize the Waikeria protest. Particular attention is devoted to the ‘state of continuity,’ which allows for a broader understanding of a permanent state of racialized oppression and marginalization faced by Indigenous and Black communities in racialized-settler-colonial contexts. Populations designated as the exception are thus framed as a threat targeted for militaristic police intervention. This article concludes by extending the discussion of the state of continuity to include how expressions of rage and dissent by Indigenous and Black people are viewed as a direct threat to the sovereign order but are necessary for revolutionary change.

year: 2024-05-16

title: An expression for land surface water storage monitoring using a two-formation geological weighing lysimeter

authors: Bardsley, W. Earl

subjects: weighing lysimeter

abstract: Field studies have demonstrated that ground surface rainfall accumulation can be detected at depth by synchronous increases in static confined groundwater pore pressures. This opens the way for “geological weighing lysimeters” providing disturbance-free water storage monitoring of the surface environment, in effect by weighing a significant land area in real time. Such systems require specific hydrogeological conditions, which are not easily verified by field observations and replicated observations from multiple geological formations are a prerequisite for quality control. Given replication over two monitored formations, we introduce an expression which utilises the respective formation piezometric water levels to give an improved combined estimate of the ground surface water budget. The expression utilises raw piezometric levels and has the advantage of direct correction for Earth tide noise, which may sometimes be influenced by local effects in addition to the pure solar/lunar tidal potential. The expression is particularly simple, if the two formations have similar (but possibly unknown) undrained Poisson ratios and porosities. Surface water budgets can then be estimated using only the respective formation barometric coefficients and piezometric levels. An example application to two vertically separated confined aquifers at a New Zealand site indicate an improved accuracy over single-formation observations. The two-formation expression for surface storage could find use as an accurate water budget tool with particular application to monitoring diffuse hydrological systems such as wetlands, arid regions, and heavily forested localities.

text: An expression for land surface water storage monitoring using a two-formation geological weighing lysimeter Field studies have demonstrated that ground surface rainfall accumulation can be detected at depth by synchronous increases in static confined groundwater pore pressures. This opens the way for “geological weighing lysimeters” providing disturbance-free water storage monitoring of the surface environment, in effect by weighing a significant land area in real time. Such systems require specific hydrogeological conditions, which are not easily verified by field observations and replicated observations from multiple geological formations are a prerequisite for quality control. Given replication over two monitored formations, we introduce an expression which utilises the respective formation piezometric water levels to give an improved combined estimate of the ground surface water budget. The expression utilises raw piezometric levels and has the advantage of direct correction for Earth tide noise, which may sometimes be influenced by local effects in addition to the pure solar/lunar tidal potential. The expression is particularly simple, if the two formations have similar (but possibly unknown) undrained Poisson ratios and porosities. Surface water budgets can then be estimated using only the respective formation barometric coefficients and piezometric levels. An example application to two vertically separated confined aquifers at a New Zealand site indicate an improved accuracy over single-formation observations. The two-formation expression for surface storage could find use as an accurate water budget tool with particular application to monitoring diffuse hydrological systems such as wetlands, arid regions, and heavily forested localities.

year: 2007