title: Toxin-antitoxin systems of mycobacterium smegmatis are essential for cell survival

authors: Frampton, Rebekah A.

subjects: Bacterial Metabolism

abstract: The role of chromosomal toxin-antitoxin (TA) modules in bacterial physiology remains enigmatic despite their abundance in the genomes of many bacteria. Mycobacterium smegmatis contains three putative TA systems, VapBC, MazEF, and Phd/Doc, and previous work from our group has shown VapBC to be a bona fide TA system. In this study, we show that MazEF and Phd/Doc are also TA systems that are constitutively expressed, transcribed as leaderless transcripts, and subject to autoregulation, and expression of the toxin component leads to growth inhibition that can be rescued by the cognate antitoxin. No phenotype was identified for deletions of the individual TA systems, but a triple deletion strain (ΔvapBC, mazEF, phd/doc), designated ΔTAtriple, exhibited a survival defect in complex growth medium demonstrating an essential role for these TA modules in mycobacterial survival. Transcriptomic analysis revealed no significant differences in gene expression between wild type and the ΔTAtriple mutant under these conditions suggesting that the growth defect was not at a transcriptional level. Metabolomic analysis demonstrated that in response to starvation in complex medium, both the wild type and ΔTAtriple mutant consumed a wide range of amino acids from the external milieu. Analysis of intracellular metabolites revealed a significant difference in the levels of branched-chain amino acids between the wild type and ΔTAtriple mutant, which are proposed to play essential roles in monitoring the nutritional supply and physiological state of the cell and linking catabolic with anabolic reactions. Disruption of this balance in the ΔTAtriple mutant may explain the survival defect in complex growth medium.

text: Toxin-antitoxin systems of mycobacterium smegmatis are essential for cell survival The role of chromosomal toxin-antitoxin (TA) modules in bacterial physiology remains enigmatic despite their abundance in the genomes of many bacteria. Mycobacterium smegmatis contains three putative TA systems, VapBC, MazEF, and Phd/Doc, and previous work from our group has shown VapBC to be a bona fide TA system. In this study, we show that MazEF and Phd/Doc are also TA systems that are constitutively expressed, transcribed as leaderless transcripts, and subject to autoregulation, and expression of the toxin component leads to growth inhibition that can be rescued by the cognate antitoxin. No phenotype was identified for deletions of the individual TA systems, but a triple deletion strain (ΔvapBC, mazEF, phd/doc), designated ΔTAtriple, exhibited a survival defect in complex growth medium demonstrating an essential role for these TA modules in mycobacterial survival. Transcriptomic analysis revealed no significant differences in gene expression between wild type and the ΔTAtriple mutant under these conditions suggesting that the growth defect was not at a transcriptional level. Metabolomic analysis demonstrated that in response to starvation in complex medium, both the wild type and ΔTAtriple mutant consumed a wide range of amino acids from the external milieu. Analysis of intracellular metabolites revealed a significant difference in the levels of branched-chain amino acids between the wild type and ΔTAtriple mutant, which are proposed to play essential roles in monitoring the nutritional supply and physiological state of the cell and linking catabolic with anabolic reactions. Disruption of this balance in the ΔTAtriple mutant may explain the survival defect in complex growth medium.

year: 2011

title: Infrastructure new findings for New Zealand

authors: Grimes, Arthur

subjects: economics

abstract: Infrastructure is a crucial input into economic production, and provision of infrastructure is a key avenue through which government may materially raise economic productivity. Recognising the importance of infrastructure investment, the Foundation for Research, Science and Technology granted Motu and its research partners a four-year research grant to examine the impacts that infrastructure investments have on New Zealand’s economic development. The programme has resulted in a range of empirical research studies that examine the impacts of specific and general infrastructure investments in this country. It has also resulted in contributions addressing theoretical and funding aspects related to infrastructure investment.

text: Infrastructure new findings for New Zealand Infrastructure is a crucial input into economic production, and provision of infrastructure is a key avenue through which government may materially raise economic productivity. Recognising the importance of infrastructure investment, the Foundation for Research, Science and Technology granted Motu and its research partners a four-year research grant to examine the impacts that infrastructure investments have on New Zealand’s economic development. The programme has resulted in a range of empirical research studies that examine the impacts of specific and general infrastructure investments in this country. It has also resulted in contributions addressing theoretical and funding aspects related to infrastructure investment.

year: 2010

title: Maori Te Aroha before the opening of the goldfield (mostly through Pakeha eyes)

authors: Hart, Philip

abstract: The various names of the peaks of the mountain and the legends concerning it reflected a violent past. As proof, several pa have been located, both at Te Aroha and at Waiorongomai, and the names of some of the streams indicate the nature and consequences of the battles fought in this contested area.
Ngati Rahiri was subdivided into three hapu: Ngati Tumutumu, Hgati Hue, and Ngati Kopirimau, descendents of these ancestors. In the nineteenth century, when the population was small, Hou was the senior rangatira, with Tutuki being the subordinate rangatira of the plains. A pa (later known as Tui pa) was constructed at Omahu, to the north of the hot springs, which were prized by Maori and increasingly enjoyed by Pakeha. Some of the land was cultivated, though visiting Pakeha considered that settlers could do much more to develop the agricultural potential. Most Ngati Rahiri were regarded as being ‘friendly’, welcoming (and benefiting from) visitors. Elaborate welcoming ceremonies were held for officials and rangatira, and a hotel operated by a rangatira’s son provided basic accommodation. Under Maori auspices the first race day was held in January 1878. 
Also in 1878, negotiators obtained an agreement to make a road to Paeroa, using Maori workers, and as the benefits of such improvements became apparent there was increased willingness to permit the construction of more roads, a bridge, and the snagging of the river, over the objections of a minority. Pakeha disapproved of how money raised through land sales in particular were wasted on extravagant displays of mana, which were not possible after the end of the 1870s because of lack of money, necessitating seeking paid employment. Friendly contact increased steadily, apart from occasional worries prompted by such events as the shooting of Daldy McWilliams, and a football match in May 1880 reportedly revealed ‘the utmost friendly feeling’ existing between Maori and Pakeha.

text: Maori Te Aroha before the opening of the goldfield (mostly through Pakeha eyes) The various names of the peaks of the mountain and the legends concerning it reflected a violent past. As proof, several pa have been located, both at Te Aroha and at Waiorongomai, and the names of some of the streams indicate the nature and consequences of the battles fought in this contested area.
Ngati Rahiri was subdivided into three hapu: Ngati Tumutumu, Hgati Hue, and Ngati Kopirimau, descendents of these ancestors. In the nineteenth century, when the population was small, Hou was the senior rangatira, with Tutuki being the subordinate rangatira of the plains. A pa (later known as Tui pa) was constructed at Omahu, to the north of the hot springs, which were prized by Maori and increasingly enjoyed by Pakeha. Some of the land was cultivated, though visiting Pakeha considered that settlers could do much more to develop the agricultural potential. Most Ngati Rahiri were regarded as being ‘friendly’, welcoming (and benefiting from) visitors. Elaborate welcoming ceremonies were held for officials and rangatira, and a hotel operated by a rangatira’s son provided basic accommodation. Under Maori auspices the first race day was held in January 1878. 
Also in 1878, negotiators obtained an agreement to make a road to Paeroa, using Maori workers, and as the benefits of such improvements became apparent there was increased willingness to permit the construction of more roads, a bridge, and the snagging of the river, over the objections of a minority. Pakeha disapproved of how money raised through land sales in particular were wasted on extravagant displays of mana, which were not possible after the end of the 1870s because of lack of money, necessitating seeking paid employment. Friendly contact increased steadily, apart from occasional worries prompted by such events as the shooting of Daldy McWilliams, and a football match in May 1880 reportedly revealed ‘the utmost friendly feeling’ existing between Maori and Pakeha.

year: 2016