title: An examination of novel archaeal stress response genes

authors: Dinger, Marcel Eduard

abstract: The regulation of gene expression is the fundamental system employed by cells and organisms to respond to changes in their surroundings. To further understand the origins and nature of the processes underlying gene regulatory systems, the stress response in the thermophilic archaeon, Thermococcus zilligii, was examined. Microorganisms respond to stress by triggering physiological and morphological changes, which are largely brought about by adaptive changes in gene expression. The use of a thermophilic archaeon in this research is significant, since this group of organisms is widely regarded to resemble ancient life more closely than other extant life on Earth. Moreover, since the informational processing systems in archaea are thought to be closely related to those of the eukaryal nucleus, the study of the archaeal stress-response may further the understanding of the evolutionary relationship between the Archaea and the Eucarya. The stress response of T. zilligii was examined by analysing the total cytoplasmic protein complements from cultures ranging from mid-log to late stationary phase. Using N-terminal sequencing and BLASTP searches, homologues of four low molecular weight proteins that varied in level were identified in the genome sequences of members of the closely related genus, Pyrococcus. The genes originated from four distinct families, which were named srb, src, srd and sre. 
The srb family represents an essentially undescribed group of genes (COGI433), that occurs primarily amongst members of the Euryarchaeota. Due to the sporadic distribution of srb genes amongst extant life, the srb genes are suggested to have undergone horizontal transfer across large phylogenetic distances on several occasions. A sequence homologous to srb family members was identified as part of a hypothetical ORF in Clostridium perfringens, which encodes a protein that consists of a fusion of a transcriptional regulator belonging to the ArsR family and an SRB homologue. Several srb genes were found to occur as part of putative operons, the majority of which included genes homologous to the MinD family of P-loop ATPases. 
The src family encodes the highly conserved SaclOb family of DNA-binding proteins (COG1581). src genes occur exclusively amongst archaeal genomes, but were absent in Halobacterium sp. NRC-1, Methanopyrus kandleri, Methanosarcina mazei and M. acetivorans. The consensus secondary structure of the SRC proteins consists of a relatively long α-helix flanked by two small β-strands, followed by a second α-helix, and then three further β-strands. 
The srd family encodes proteins that are homologous to the C-terminal half of members of the Lrp/AsnC family of transcriptional regulators (COG1522). It is suggested here that the SRD family forms a logical subgroup that is structurally, and presumably functionally, distinct to the other members of the Lrp/AsnC family. srd genes occur in all nonmethanogenic archaea and in some bacteria. It is suggested that the srd family originated in the archaeal lineage and was later transferred to members of the Bacteria. The srd genes often appear as part of operon-like arrangements, which seem to be unrelated to one another, and consequently it is suggested that the SRD proteins are involved in a relatively generic function, such as transcriptional regulation. 
The sre family represents an undescribed group of highly conserved genes (COG1698) that occur exclusively amongst archaeal genomes. One sre gene was found in every archaeal genome sequenced to date, except for Pyrobaculum aerophilum and Halobacterium sp. NRC-1. Comparison of the SRE and 16S rRNA distance trees suggests that the sre genes were not prone to horizontal transfer. The secondary structure predicted from the SRE sequences consists of four large helical regions separated by short coiled regions. 
Recombinant proteins encoded by the srbPab1, srbPab2, srdPab2 and srePab genes cloned from Pyrococcus abyssi were produced in Escherichia coli and purified. An examination of the predicted quaternary associations of the recombinant proteins revealed that each of the proteins, with the exception rSRBPab2, formed multimeric structures. rSRBPabl formed dimer-sized multimers that occurred at 80°C, but not at room temperature. rSRDPab2 formed dimer-sized molecules that occurred preferentially at 80°C and in the presence of DNA. rSREPab formed structures that were consistent in size with those predicted for dimers and tetramers. Neither rSRBPabl, rSRDPab2 or rSREPab bound to DNA in the conditions examined.

text: An examination of novel archaeal stress response genes The regulation of gene expression is the fundamental system employed by cells and organisms to respond to changes in their surroundings. To further understand the origins and nature of the processes underlying gene regulatory systems, the stress response in the thermophilic archaeon, Thermococcus zilligii, was examined. Microorganisms respond to stress by triggering physiological and morphological changes, which are largely brought about by adaptive changes in gene expression. The use of a thermophilic archaeon in this research is significant, since this group of organisms is widely regarded to resemble ancient life more closely than other extant life on Earth. Moreover, since the informational processing systems in archaea are thought to be closely related to those of the eukaryal nucleus, the study of the archaeal stress-response may further the understanding of the evolutionary relationship between the Archaea and the Eucarya. The stress response of T. zilligii was examined by analysing the total cytoplasmic protein complements from cultures ranging from mid-log to late stationary phase. Using N-terminal sequencing and BLASTP searches, homologues of four low molecular weight proteins that varied in level were identified in the genome sequences of members of the closely related genus, Pyrococcus. The genes originated from four distinct families, which were named srb, src, srd and sre. 
The srb family represents an essentially undescribed group of genes (COGI433), that occurs primarily amongst members of the Euryarchaeota. Due to the sporadic distribution of srb genes amongst extant life, the srb genes are suggested to have undergone horizontal transfer across large phylogenetic distances on several occasions. A sequence homologous to srb family members was identified as part of a hypothetical ORF in Clostridium perfringens, which encodes a protein that consists of a fusion of a transcriptional regulator belonging to the ArsR family and an SRB homologue. Several srb genes were found to occur as part of putative operons, the majority of which included genes homologous to the MinD family of P-loop ATPases. 
The src family encodes the highly conserved SaclOb family of DNA-binding proteins (COG1581). src genes occur exclusively amongst archaeal genomes, but were absent in Halobacterium sp. NRC-1, Methanopyrus kandleri, Methanosarcina mazei and M. acetivorans. The consensus secondary structure of the SRC proteins consists of a relatively long α-helix flanked by two small β-strands, followed by a second α-helix, and then three further β-strands. 
The srd family encodes proteins that are homologous to the C-terminal half of members of the Lrp/AsnC family of transcriptional regulators (COG1522). It is suggested here that the SRD family forms a logical subgroup that is structurally, and presumably functionally, distinct to the other members of the Lrp/AsnC family. srd genes occur in all nonmethanogenic archaea and in some bacteria. It is suggested that the srd family originated in the archaeal lineage and was later transferred to members of the Bacteria. The srd genes often appear as part of operon-like arrangements, which seem to be unrelated to one another, and consequently it is suggested that the SRD proteins are involved in a relatively generic function, such as transcriptional regulation. 
The sre family represents an undescribed group of highly conserved genes (COG1698) that occur exclusively amongst archaeal genomes. One sre gene was found in every archaeal genome sequenced to date, except for Pyrobaculum aerophilum and Halobacterium sp. NRC-1. Comparison of the SRE and 16S rRNA distance trees suggests that the sre genes were not prone to horizontal transfer. The secondary structure predicted from the SRE sequences consists of four large helical regions separated by short coiled regions. 
Recombinant proteins encoded by the srbPab1, srbPab2, srdPab2 and srePab genes cloned from Pyrococcus abyssi were produced in Escherichia coli and purified. An examination of the predicted quaternary associations of the recombinant proteins revealed that each of the proteins, with the exception rSRBPab2, formed multimeric structures. rSRBPabl formed dimer-sized multimers that occurred at 80°C, but not at room temperature. rSRDPab2 formed dimer-sized molecules that occurred preferentially at 80°C and in the presence of DNA. rSREPab formed structures that were consistent in size with those predicted for dimers and tetramers. Neither rSRBPabl, rSRDPab2 or rSREPab bound to DNA in the conditions examined.

year: 2003

title: Epidemiology of giant cell arteritis in Waikato, Aotearoa New Zealand

authors: van Dantzig, Philippa

subjects: data analytics

abstract: Giant cell arteritis (GCA) is the most common primary vasculitis in adults over 50 years of age. Our primary objective was to assess the incidence and prevalence of GCA in Waikato in a bid to deepen our understanding of the epidemiology of GCA in Aotearoa New Zealand. methods: From January 2014 to December 2022, cases of GCA were identified prospectively and retrospectively through temporal artery ultrasound request lists and temporal artery biopsy histology reports. Using electronic health records, data were collected retrospectively on patient demographics and clinical features. These were used to calculate the incidence, prevalence and standardised mortality ratio (SMR) of GCA in Waikato. results: There were 214 patients diagnosed with GCA over the 9-year period. The majority of patients were European (93.9%, 201/214) with Māori patients being significantly younger than European patients. The mean annual incidence of clinical GCA was 14.7 per 100,000 people over 50 years (95% confidence interval [CI] 12.7–16.6). The SMR was 1.18 (95% CI 0.83–1.52). conclusion: This is the largest study to date on the epidemiology of GCA in Aotearoa New Zealand. The incidence of GCA is comparable to other studies performed in Aotearoa New Zealand and appears to be stable over time. GCA is uncommon in Māori, Pacific Islander and Asian ethnic groups.

text: Epidemiology of giant cell arteritis in Waikato, Aotearoa New Zealand Giant cell arteritis (GCA) is the most common primary vasculitis in adults over 50 years of age. Our primary objective was to assess the incidence and prevalence of GCA in Waikato in a bid to deepen our understanding of the epidemiology of GCA in Aotearoa New Zealand. methods: From January 2014 to December 2022, cases of GCA were identified prospectively and retrospectively through temporal artery ultrasound request lists and temporal artery biopsy histology reports. Using electronic health records, data were collected retrospectively on patient demographics and clinical features. These were used to calculate the incidence, prevalence and standardised mortality ratio (SMR) of GCA in Waikato. results: There were 214 patients diagnosed with GCA over the 9-year period. The majority of patients were European (93.9%, 201/214) with Māori patients being significantly younger than European patients. The mean annual incidence of clinical GCA was 14.7 per 100,000 people over 50 years (95% confidence interval [CI] 12.7–16.6). The SMR was 1.18 (95% CI 0.83–1.52). conclusion: This is the largest study to date on the epidemiology of GCA in Aotearoa New Zealand. The incidence of GCA is comparable to other studies performed in Aotearoa New Zealand and appears to be stable over time. GCA is uncommon in Māori, Pacific Islander and Asian ethnic groups.

year: 2024-03-22

title: "Takahi ngā takahanga o ngā tūpuna" - Tramp the pathways of our ancestors

authors: Williams, Taniwha

subjects: Māori health and wellbeing

abstract: The rise of reconnecting to holistic approaches to health to improve wellbeing outcomes for Māori has become increasingly prominent in recent years. Such developments have highlighted the need to introduce traditional Māori concepts, values and practices within whānau, hapū and iwi as vehicles for promoting and improving Māori health. This research had two objectives. Firstly, it aimed to explore the process of reclaiming mātauranga Māori (Māori knowledge systems) with my whānau who had limited access to te ao Māori (the Māori world). The second objective sought to explore the experiences of my whānau reconnecting with te reo me ōna tikanga (Māori language and culture). Using the Whiti Te Rā as a guide informed the design and structure of the wānanga (workshops). The Whiti Te Rā is a therapeutic model designed to improve health and wellbeing outcomes for Māori by developing and enhancing a cultural identity. Central to this model are six Māori customary practices and values that provide pathways to wellbeing and flourishing mauri. These dimensions also have synergies with other models of health – Te Whare Tapa Whā, Te Wheke. Four tāne (men) from my whānau took part in this research. We used the Pūrākau Method to record, explore, and analyse the narratives that emerged following each wānanga. The key findings from this research included connection to history, whakapapa and wairua; connection to pepeha and cultural practices; connection to self as a Māori; connection through whanaungatanga; and connection to taiao (the environment). This study showed that Māori models of health and wellbeing are consistent in demonstrating their effectiveness in connecting Māori to their language and culture. Despite the impact of colonisation, reconnection to customary practices and values was meaningful and valuable to my whānau. Future research is needed to revitalise, regenerate and reclaim a thriving Māori identity.

text: "Takahi ngā takahanga o ngā tūpuna" - Tramp the pathways of our ancestors The rise of reconnecting to holistic approaches to health to improve wellbeing outcomes for Māori has become increasingly prominent in recent years. Such developments have highlighted the need to introduce traditional Māori concepts, values and practices within whānau, hapū and iwi as vehicles for promoting and improving Māori health. This research had two objectives. Firstly, it aimed to explore the process of reclaiming mātauranga Māori (Māori knowledge systems) with my whānau who had limited access to te ao Māori (the Māori world). The second objective sought to explore the experiences of my whānau reconnecting with te reo me ōna tikanga (Māori language and culture). Using the Whiti Te Rā as a guide informed the design and structure of the wānanga (workshops). The Whiti Te Rā is a therapeutic model designed to improve health and wellbeing outcomes for Māori by developing and enhancing a cultural identity. Central to this model are six Māori customary practices and values that provide pathways to wellbeing and flourishing mauri. These dimensions also have synergies with other models of health – Te Whare Tapa Whā, Te Wheke. Four tāne (men) from my whānau took part in this research. We used the Pūrākau Method to record, explore, and analyse the narratives that emerged following each wānanga. The key findings from this research included connection to history, whakapapa and wairua; connection to pepeha and cultural practices; connection to self as a Māori; connection through whanaungatanga; and connection to taiao (the environment). This study showed that Māori models of health and wellbeing are consistent in demonstrating their effectiveness in connecting Māori to their language and culture. Despite the impact of colonisation, reconnection to customary practices and values was meaningful and valuable to my whānau. Future research is needed to revitalise, regenerate and reclaim a thriving Māori identity.

year: 2024