title: Estimation of the motor threshold for near-rectangular stimuli using the hodgkin-huxley model

authors: Sorkhabi, Majid Memarian

subjects: Science & Technology

abstract: The motor threshold measurement is a standard in preintervention probing in TMS experiments. We aim to predict the motor threshold for near-rectangular stimuli to efficiently determine the motor threshold size before any experiments take place. Estimating the behavior of large-scale networks requires dynamically accurate and efficient modeling. We utilized a Hodgkin–Huxley (HH) type model to evaluate motor threshold values and computationally validated its function with known true threshold data from 50 participants trials from state-of-the-art published datasets. For monophasic, bidirectional, and unidirectional rectangular stimuli in posterior-anterior or anterior-posterior directions as generated by the cTMS device, computational modeling of the HH model captured the experimentally measured population-averaged motor threshold values at high precision (maximum error ≤ 8%). )e convergence of our biophysically based modeling study with experimental data in humans reveals that the effect of the stimulus shape is strongly correlated with the activation kinetics of the voltage-gated ion channels. The proposed method can reliably predict motor threshold size using the conductance-based neuronal models and could therefore be embedded in new generation neurostimulators. Advancements in neural modeling will make it possible to enhance treatment procedures by reducing the number of delivered magnetic stimuli to participants.

text: Estimation of the motor threshold for near-rectangular stimuli using the hodgkin-huxley model The motor threshold measurement is a standard in preintervention probing in TMS experiments. We aim to predict the motor threshold for near-rectangular stimuli to efficiently determine the motor threshold size before any experiments take place. Estimating the behavior of large-scale networks requires dynamically accurate and efficient modeling. We utilized a Hodgkin–Huxley (HH) type model to evaluate motor threshold values and computationally validated its function with known true threshold data from 50 participants trials from state-of-the-art published datasets. For monophasic, bidirectional, and unidirectional rectangular stimuli in posterior-anterior or anterior-posterior directions as generated by the cTMS device, computational modeling of the HH model captured the experimentally measured population-averaged motor threshold values at high precision (maximum error ≤ 8%). )e convergence of our biophysically based modeling study with experimental data in humans reveals that the effect of the stimulus shape is strongly correlated with the activation kinetics of the voltage-gated ion channels. The proposed method can reliably predict motor threshold size using the conductance-based neuronal models and could therefore be embedded in new generation neurostimulators. Advancements in neural modeling will make it possible to enhance treatment procedures by reducing the number of delivered magnetic stimuli to participants.

year: 2021

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: Adult education within a circular migration scheme. A case study from New Zealand

authors: Morrison, Sandra L.

subjects: adult education

abstract: This article examines the adult education and learning that occurs between a Māori business and the workers they employ from the Pacific nation of Tonga through the Recognised Seasonal Employer (RSE) scheme, a seasonal labour strategy allowing for the temporary entry of migrant workers in the horticulture and viticultural industries, with a preference for workers from the Pacific nations.. Māori are indigenous to NZ but their historical ties extend back to Polynesia in the Pacific and therefore common historical narratives exist between Māori and those from Tonga. A case study approach is used to highlight how adult education is embedded. Central to the success of this case study is the validation and implementation of indigenous knowledges and rituals.

text: Adult education within a circular migration scheme. A case study from New Zealand This article examines the adult education and learning that occurs between a Māori business and the workers they employ from the Pacific nation of Tonga through the Recognised Seasonal Employer (RSE) scheme, a seasonal labour strategy allowing for the temporary entry of migrant workers in the horticulture and viticultural industries, with a preference for workers from the Pacific nations.. Māori are indigenous to NZ but their historical ties extend back to Polynesia in the Pacific and therefore common historical narratives exist between Māori and those from Tonga. A case study approach is used to highlight how adult education is embedded. Central to the success of this case study is the validation and implementation of indigenous knowledges and rituals.

year: 2015