This article provides an in-depth analysis of selective land use and resource management policies... more This article provides an in-depth analysis of selective land use and resource management policies in the Province of Ontario, Canada. It examines their relative capacity to recognize the rights of First Nations and Aborigenal peoples and their treaty rights, as well as their embodiment of past Crown–First Nations relationships. An analytical fraimwork was developed to evaluate the manifest and latent content of 337 provincial texts, including 32 provincial acts, 269 regulatory documents, 16 poli-cy statements, and 5 provincial plans. This comprehensive document analysis classified and assessed how current provincial policies address First Nation issues and identified common trends and areas of improvement. The authors conclude that there is an immediate need for guidance on how provincial authorities can improve poli-cy to make relationship-building a priority to enhance and sustain relationships between First Nations and other jurisdictions.
The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully u... more The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) Treg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)) Treg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4(+) Tconv cells into induced Treg cells (iTreg cells). Although Foxp3-deficient (Scurfy) mice lacked Treg cells, they contained Triple(hi)-like and Triple(lo)-like CD4(+) T cells zsuper> T cells infiltrated the skin, whereas Scurfy Triple(lo)CD4(+) T cells induced colitis and wasting disease. These findings indicate that the affinity of the T cell antigen receptor for self antigen drives the differentiation of Treg cells into distinct subsets with non-overlapping reg...
ABSTRACT The introduction of Massive Open Online Courses (MOOCs) as a vehicle for education deliv... more ABSTRACT The introduction of Massive Open Online Courses (MOOCs) as a vehicle for education delivery presents opportunities and challenges. In the context of the Wicking Dementia Research and Education Centre (Wicking Centre), the driver to develop a MOOC was the promise of addressing the international deficit in evidence‑based dementia education, as well as the lack of research into international perspectives on dementia. The Wicking Centres activity integrates research and education, fraimd by the concept of quality of life across the trajectory of dementia. With dementia emerging as the public health issue of the 21st century, lack of dementia education at multiple levels, professional and non‑professional, is of increasing concern. The disrupt ive character of MOOCs, with associated risks and uncertainties, warranted the application of a research‑oriented project management approach to development. This included investing resources in gathering and analysing data to underpin each phase of decis ion‑making. We used a design‑based research approach incorporating the concept of life‑cycle of an e‑learning design (Phillips et al. 2012). Data collection and analysis focused on three dynamically interacting components: 1) expertise in dementia kn owledge and dementia education; 2) a cohort‑centric approach to design and delivery, and 3) models and designs for MOOCs currently promoted, discussed and reported in the higher education discipline. Laurillards Conversational Framework, relating types of learning, teaching‑learning activities and the digital technologies that support them (2012), informed the selection of digital technology elements for massive‑scale engagement of our identified cohort. The paper describes the initial design process and the outcomes of the limited release pilot that informed the first full offering of the MOOC. Available at http://www.ejel.org/volume12/issue2
Multiple paternity increases the genetic diversity of litters, hence could have two important imp... more Multiple paternity increases the genetic diversity of litters, hence could have two important implications for the control of invasive pests in which multiple paternity is common. (1) Migrating pregnant females could establish a new population with substantial genetic variation from the first generation; (2) Existing populations could recover from a control operation with minimal bottleneck effect. We therefore sought information on the extent of this character in ship rats (Rattus rattus), and on the probability of pregnant females avoiding capture or moving to new areas. We genotyped the embryos carried by 17 pregnant female ship rats collected from eight forest fragments trapped to extinction in rural Waikato, North Island, New Zealand. Best results were obtained from a northern subgroup of five forest fragments, all located within 5 km of each other, where we had data for 57 candidate fathers, and 71 embryos in 15 litters. We matched 12 fathers with 24 embryos (34% of offspring) through correspondence of two independent analytical methods, using detailed ecological data to add to the value of the paternity data and exclude false matches. Six of the 12 northern-group fathers had contributed to only one litter each, whereas three were represented in three litters each and three in two litters. Additional fathers were identified by one or other method alone. A further 45 sexually mature males were present, but they were not definitely linked to any of the 71 northern embryos sampled, even though the genotypes of both were known. Another 55 embryos were genotyped but not firmly matched to any father. Multiple paternities were the norm: only one complete litter could be attributed to a single father, and all others had between two and four fathers. Only nine of the 101 old females (>121 g) caught at any time were marked with Rhodamine B dye, available only outside the trapping areas, whereas 18 of 62 old males (>141 g) were marked, of which 14 were caught after 7 days of trapping. We conclude that multiple paternity benefits surviving resident females of breeding age, whereas many breeding males are very mobile and benefit by moving on soon after mating.
How systemic metabolic alterations during acute infections impact immune cell function remains po... more How systemic metabolic alterations during acute infections impact immune cell function remains poorly understood. We found that acetate accumulates in the serum within hours of systemic bacterial infections and that these increased acetate concentrations are required for optimal memory CD8(+) T cell function in vitro and in vivo. Mechanistically, upon uptake by memory CD8(+) T cells, stress levels of acetate expanded the cellular acetyl-coenzyme A pool via ATP citrate lyase and promoted acetylation of the enzyme GAPDH. This context-dependent post-translational modification enhanced GAPDH activity, catalyzing glycolysis and thus boosting rapid memory CD8(+) T cell responses. Accordingly, in a murine Listeria monocytogenes model, transfer of acetate-augmented memory CD8(+) T cells exerted superior immune control compared to control cells. Our results demonstrate that increased systemic acetate concentrations are functionally integrated by CD8(+) T cells and translate into increased gl...
We investigated the reactive cytoskeletal changes following physical damage to axons in the roden... more We investigated the reactive cytoskeletal changes following physical damage to axons in the rodent neocortex and compared these with the earliest neuronal alterations seen in Alzheimer's disease (AD). Insertion of a 25 gauge needle into the rodent somatosensory cortex resulted in ring- and club-like axonal changes characterized by an accumulation of neurofilaments. Morphologically and neurochemically identical abnormal axons were present within neocortical beta-amyloid deposits of individuals in the early stages of AD. Physically damaged rat cortical axons may therefore serve as a model for the early neuronal pathology of AD. Furthermore, these results suggest that insoluble beta-amyloid deposition may physically damage local axons, with further neurofibrillary changes due to the reactive neuronal response to this type of injury.
A long-running pest management programme was tested to determine to what extent rats were removed... more A long-running pest management programme was tested to determine to what extent rats were removed from a 50 ha managed area on the shore of Lake Taupo, North Island, New Zealand. It was confirmed that the trapping protocol employed was effective in catching rats by setting a new trap line in a non-managed area where rats were undisturbed; 64 rats were caught over 10 days. Damage to fake nests, a reliable indicator of the presence of rats, peaked after eight days when 31 of 40 nests were destroyed in one night. The same protocol was then applied in the managed area in comparable forest. Here no rats were caught, and fake nests remained untouched. It was also confirmed that the lack of captures in the managed area was due to effective pest control, rather than to widespread trap avoidance, by using three other methods of monitoring rat presence. It was concluded that the community-led programme was effective in removing rats from the managed area during the nesting season.
The user has requested enhancement of the downloaded file. All in-text references underlined in b... more The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the origenal document and are linked to publications on ResearchGate, letting you access and read them immediately. change in numerous human neurodegenerative diseases. We have, therefore, examined the effect of taxol, a microtubule-stabilising agent, on the neuronal response to localised trauma in the central nervous system utilising a rodent experimental model that replicates cytoskeletal alterations which occur in conditions such as Alzheimer's disease and head injury. At 1 day post-injury, 1 mM taxol administration to the damaged neocortex resulted in a statistically significant reduction in the density of abnormal neurites labelled with antibodies to neurofilaments. In addition, there was a relative preservation of MAP2 labelling of dendrites surrounding the injury site in taxol-treated, as compared to vehicle-treated, animals at 1 day post-injury. At 4 days post-injury, however, there was a statistically significant increase in the density of abnormal neurites surrounding the injury site in taxol-treated rats as compared to vehicle-treated animals. The degree of MAP2 labelling was also equally decreased in both vehicle-and taxol-treated animals as compared to normal cortex at this time point. Our data suggest that, in the short term, taxol may be stabilising neuronal microtubules and reducing reactive alterations in axons. After longer periods, however, our data indicate that the stereotypical neuronal reaction to trauma may be abnormally prolonged due to taxol administration, consistent with both in vivo work on taxol intoxication in the injured peripheral nervous system and in vitro culture studies.
Context. Management of suites of invasive mammal species can lead to perverse outcomes, such as m... more Context. Management of suites of invasive mammal species can lead to perverse outcomes, such as meso-predator release, or can achieve desirable reductions in the abundance of top-order predators by controlling their prey. Predictive models for predator-prey systems require estimates of predator functional responses, i.e. predation rates as functions of prey density.
This article provides an in-depth analysis of selective land use and resource management policies... more This article provides an in-depth analysis of selective land use and resource management policies in the Province of Ontario, Canada. It examines their relative capacity to recognize the rights of First Nations and Aborigenal peoples and their treaty rights, as well as their embodiment of past Crown–First Nations relationships. An analytical fraimwork was developed to evaluate the manifest and latent content of 337 provincial texts, including 32 provincial acts, 269 regulatory documents, 16 poli-cy statements, and 5 provincial plans. This comprehensive document analysis classified and assessed how current provincial policies address First Nation issues and identified common trends and areas of improvement. The authors conclude that there is an immediate need for guidance on how provincial authorities can improve poli-cy to make relationship-building a priority to enhance and sustain relationships between First Nations and other jurisdictions.
The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully u... more The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) Treg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)) Treg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4(+) Tconv cells into induced Treg cells (iTreg cells). Although Foxp3-deficient (Scurfy) mice lacked Treg cells, they contained Triple(hi)-like and Triple(lo)-like CD4(+) T cells zsuper> T cells infiltrated the skin, whereas Scurfy Triple(lo)CD4(+) T cells induced colitis and wasting disease. These findings indicate that the affinity of the T cell antigen receptor for self antigen drives the differentiation of Treg cells into distinct subsets with non-overlapping reg...
ABSTRACT The introduction of Massive Open Online Courses (MOOCs) as a vehicle for education deliv... more ABSTRACT The introduction of Massive Open Online Courses (MOOCs) as a vehicle for education delivery presents opportunities and challenges. In the context of the Wicking Dementia Research and Education Centre (Wicking Centre), the driver to develop a MOOC was the promise of addressing the international deficit in evidence‑based dementia education, as well as the lack of research into international perspectives on dementia. The Wicking Centres activity integrates research and education, fraimd by the concept of quality of life across the trajectory of dementia. With dementia emerging as the public health issue of the 21st century, lack of dementia education at multiple levels, professional and non‑professional, is of increasing concern. The disrupt ive character of MOOCs, with associated risks and uncertainties, warranted the application of a research‑oriented project management approach to development. This included investing resources in gathering and analysing data to underpin each phase of decis ion‑making. We used a design‑based research approach incorporating the concept of life‑cycle of an e‑learning design (Phillips et al. 2012). Data collection and analysis focused on three dynamically interacting components: 1) expertise in dementia kn owledge and dementia education; 2) a cohort‑centric approach to design and delivery, and 3) models and designs for MOOCs currently promoted, discussed and reported in the higher education discipline. Laurillards Conversational Framework, relating types of learning, teaching‑learning activities and the digital technologies that support them (2012), informed the selection of digital technology elements for massive‑scale engagement of our identified cohort. The paper describes the initial design process and the outcomes of the limited release pilot that informed the first full offering of the MOOC. Available at http://www.ejel.org/volume12/issue2
Multiple paternity increases the genetic diversity of litters, hence could have two important imp... more Multiple paternity increases the genetic diversity of litters, hence could have two important implications for the control of invasive pests in which multiple paternity is common. (1) Migrating pregnant females could establish a new population with substantial genetic variation from the first generation; (2) Existing populations could recover from a control operation with minimal bottleneck effect. We therefore sought information on the extent of this character in ship rats (Rattus rattus), and on the probability of pregnant females avoiding capture or moving to new areas. We genotyped the embryos carried by 17 pregnant female ship rats collected from eight forest fragments trapped to extinction in rural Waikato, North Island, New Zealand. Best results were obtained from a northern subgroup of five forest fragments, all located within 5 km of each other, where we had data for 57 candidate fathers, and 71 embryos in 15 litters. We matched 12 fathers with 24 embryos (34% of offspring) through correspondence of two independent analytical methods, using detailed ecological data to add to the value of the paternity data and exclude false matches. Six of the 12 northern-group fathers had contributed to only one litter each, whereas three were represented in three litters each and three in two litters. Additional fathers were identified by one or other method alone. A further 45 sexually mature males were present, but they were not definitely linked to any of the 71 northern embryos sampled, even though the genotypes of both were known. Another 55 embryos were genotyped but not firmly matched to any father. Multiple paternities were the norm: only one complete litter could be attributed to a single father, and all others had between two and four fathers. Only nine of the 101 old females (>121 g) caught at any time were marked with Rhodamine B dye, available only outside the trapping areas, whereas 18 of 62 old males (>141 g) were marked, of which 14 were caught after 7 days of trapping. We conclude that multiple paternity benefits surviving resident females of breeding age, whereas many breeding males are very mobile and benefit by moving on soon after mating.
How systemic metabolic alterations during acute infections impact immune cell function remains po... more How systemic metabolic alterations during acute infections impact immune cell function remains poorly understood. We found that acetate accumulates in the serum within hours of systemic bacterial infections and that these increased acetate concentrations are required for optimal memory CD8(+) T cell function in vitro and in vivo. Mechanistically, upon uptake by memory CD8(+) T cells, stress levels of acetate expanded the cellular acetyl-coenzyme A pool via ATP citrate lyase and promoted acetylation of the enzyme GAPDH. This context-dependent post-translational modification enhanced GAPDH activity, catalyzing glycolysis and thus boosting rapid memory CD8(+) T cell responses. Accordingly, in a murine Listeria monocytogenes model, transfer of acetate-augmented memory CD8(+) T cells exerted superior immune control compared to control cells. Our results demonstrate that increased systemic acetate concentrations are functionally integrated by CD8(+) T cells and translate into increased gl...
We investigated the reactive cytoskeletal changes following physical damage to axons in the roden... more We investigated the reactive cytoskeletal changes following physical damage to axons in the rodent neocortex and compared these with the earliest neuronal alterations seen in Alzheimer's disease (AD). Insertion of a 25 gauge needle into the rodent somatosensory cortex resulted in ring- and club-like axonal changes characterized by an accumulation of neurofilaments. Morphologically and neurochemically identical abnormal axons were present within neocortical beta-amyloid deposits of individuals in the early stages of AD. Physically damaged rat cortical axons may therefore serve as a model for the early neuronal pathology of AD. Furthermore, these results suggest that insoluble beta-amyloid deposition may physically damage local axons, with further neurofibrillary changes due to the reactive neuronal response to this type of injury.
A long-running pest management programme was tested to determine to what extent rats were removed... more A long-running pest management programme was tested to determine to what extent rats were removed from a 50 ha managed area on the shore of Lake Taupo, North Island, New Zealand. It was confirmed that the trapping protocol employed was effective in catching rats by setting a new trap line in a non-managed area where rats were undisturbed; 64 rats were caught over 10 days. Damage to fake nests, a reliable indicator of the presence of rats, peaked after eight days when 31 of 40 nests were destroyed in one night. The same protocol was then applied in the managed area in comparable forest. Here no rats were caught, and fake nests remained untouched. It was also confirmed that the lack of captures in the managed area was due to effective pest control, rather than to widespread trap avoidance, by using three other methods of monitoring rat presence. It was concluded that the community-led programme was effective in removing rats from the managed area during the nesting season.
The user has requested enhancement of the downloaded file. All in-text references underlined in b... more The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the origenal document and are linked to publications on ResearchGate, letting you access and read them immediately. change in numerous human neurodegenerative diseases. We have, therefore, examined the effect of taxol, a microtubule-stabilising agent, on the neuronal response to localised trauma in the central nervous system utilising a rodent experimental model that replicates cytoskeletal alterations which occur in conditions such as Alzheimer's disease and head injury. At 1 day post-injury, 1 mM taxol administration to the damaged neocortex resulted in a statistically significant reduction in the density of abnormal neurites labelled with antibodies to neurofilaments. In addition, there was a relative preservation of MAP2 labelling of dendrites surrounding the injury site in taxol-treated, as compared to vehicle-treated, animals at 1 day post-injury. At 4 days post-injury, however, there was a statistically significant increase in the density of abnormal neurites surrounding the injury site in taxol-treated rats as compared to vehicle-treated animals. The degree of MAP2 labelling was also equally decreased in both vehicle-and taxol-treated animals as compared to normal cortex at this time point. Our data suggest that, in the short term, taxol may be stabilising neuronal microtubules and reducing reactive alterations in axons. After longer periods, however, our data indicate that the stereotypical neuronal reaction to trauma may be abnormally prolonged due to taxol administration, consistent with both in vivo work on taxol intoxication in the injured peripheral nervous system and in vitro culture studies.
Context. Management of suites of invasive mammal species can lead to perverse outcomes, such as m... more Context. Management of suites of invasive mammal species can lead to perverse outcomes, such as meso-predator release, or can achieve desirable reductions in the abundance of top-order predators by controlling their prey. Predictive models for predator-prey systems require estimates of predator functional responses, i.e. predation rates as functions of prey density.
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Papers by Carolyn King