HOP expression is regulated by p53 and RAS and characteristic of a cancer gene signature
- Mattison, Stacey A, Blatch, Gregory L, Edkins, Adrienne L
- Authors: Mattison, Stacey A , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66278 , vital:28928 , https://doi.org/10.1007/s12192-016-0755-8
- Description: publisher version , The Hsp70/Hsp90 organising protein (HOP) is a co-chaperone essential for client protein transfer from Hsp70 to Hsp90 within the Hsp90 chaperone machine. Although HOP is upregulated in various cancers, there is limited information from in vitro studies on how HOP expression is regulated in cancer. The main objective of this study was to identify the HOP promoter and investigate its activity in cancerous cells. Bioinformatic analysis of the -2500 to +16 bp region of the HOP gene identified a large CpG island and a range of putative cis-elements. Many of the cis-elements were potentially bound by transcription factors which are activated by oncogenic pathways. Luciferase reporter assays demonstrated that the upstream region of the HOP gene contains an active promoter in vitro. Truncation of this region suggested that the core HOP promoter region was -855 to +16 bp. HOP promoter activity was highest in Hs578T, HEK293T and SV40- transformed MEF1 cell lines which expressed mutant or inactive p53. In a mutant p53 background, expression of wild-type p53 led to a reduction in promoter activity, while inhibition of wild-type p53 in HeLa cells increased HOP promoter activity. Additionally, in Hs578T and HEK293T cell lines containing inactive p53, expression of HRAS increased HOP promoter activity. However, HRAS activation of the HOP promoter was inhibited by p53 overexpression. These findings suggest for the first time that HOP expression in cancer may be regulated by both RAS activation and p53 inhibition. Taken together, these data suggest that HOP may be part of the cancer gene signature induced by a combination of mutant p53 and mutated RAS that is associated with cellular transformation.
- Full Text: false
- Date Issued: 2018
- Authors: Mattison, Stacey A , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66278 , vital:28928 , https://doi.org/10.1007/s12192-016-0755-8
- Description: publisher version , The Hsp70/Hsp90 organising protein (HOP) is a co-chaperone essential for client protein transfer from Hsp70 to Hsp90 within the Hsp90 chaperone machine. Although HOP is upregulated in various cancers, there is limited information from in vitro studies on how HOP expression is regulated in cancer. The main objective of this study was to identify the HOP promoter and investigate its activity in cancerous cells. Bioinformatic analysis of the -2500 to +16 bp region of the HOP gene identified a large CpG island and a range of putative cis-elements. Many of the cis-elements were potentially bound by transcription factors which are activated by oncogenic pathways. Luciferase reporter assays demonstrated that the upstream region of the HOP gene contains an active promoter in vitro. Truncation of this region suggested that the core HOP promoter region was -855 to +16 bp. HOP promoter activity was highest in Hs578T, HEK293T and SV40- transformed MEF1 cell lines which expressed mutant or inactive p53. In a mutant p53 background, expression of wild-type p53 led to a reduction in promoter activity, while inhibition of wild-type p53 in HeLa cells increased HOP promoter activity. Additionally, in Hs578T and HEK293T cell lines containing inactive p53, expression of HRAS increased HOP promoter activity. However, HRAS activation of the HOP promoter was inhibited by p53 overexpression. These findings suggest for the first time that HOP expression in cancer may be regulated by both RAS activation and p53 inhibition. Taken together, these data suggest that HOP may be part of the cancer gene signature induced by a combination of mutant p53 and mutated RAS that is associated with cellular transformation.
- Full Text: false
- Date Issued: 2018
Capital or critique?: when journalism education seeks to influence the field
- Boshoff, Priscilla A, Garman, Anthea
- Authors: Boshoff, Priscilla A , Garman, Anthea
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/143392 , vital:38242 , DOI: 10.1080/02560046.2016.1262437
- Description: Drawing on Bourdieu’s theories of field and capital, we examine the limitations that a journalism school at a prestigious university faces in making a meaningful contribution to the field within a developing country. In the postapartheid South African media landscape, journalism is under pressure both from global forces and a political imperative to address social justice. Given the heterogeneity of the journalistic field and the fact that what counts as capital in it is contested, the School of Journalism and Media Studies at Rhodes University attempts to redefine the parameters by inculcating a particular approach to and philosophy of journalism practice. While Rhodes wants to educate excellent (professional) journalists, it is guided by an overt political mission to cultivate a journalism that is not necessarily ‘in sync’ with the wider field. Ironically, most undergraduates come from the economic and cultural elite, with specific intentions to accumulate the capital which Rhodes bestows. Students are confronted with their privilege and with alternative ideas about the purpose of journalism, and are asked to make choices and take up positions. We consider whether this critical praxis approach is able to influence the ‘state of play’ – or the distribution of power – within the field.
- Full Text:
- Date Issued: 2017
- Authors: Boshoff, Priscilla A , Garman, Anthea
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/143392 , vital:38242 , DOI: 10.1080/02560046.2016.1262437
- Description: Drawing on Bourdieu’s theories of field and capital, we examine the limitations that a journalism school at a prestigious university faces in making a meaningful contribution to the field within a developing country. In the postapartheid South African media landscape, journalism is under pressure both from global forces and a political imperative to address social justice. Given the heterogeneity of the journalistic field and the fact that what counts as capital in it is contested, the School of Journalism and Media Studies at Rhodes University attempts to redefine the parameters by inculcating a particular approach to and philosophy of journalism practice. While Rhodes wants to educate excellent (professional) journalists, it is guided by an overt political mission to cultivate a journalism that is not necessarily ‘in sync’ with the wider field. Ironically, most undergraduates come from the economic and cultural elite, with specific intentions to accumulate the capital which Rhodes bestows. Students are confronted with their privilege and with alternative ideas about the purpose of journalism, and are asked to make choices and take up positions. We consider whether this critical praxis approach is able to influence the ‘state of play’ – or the distribution of power – within the field.
- Full Text:
- Date Issued: 2017
Counting on demographic equity to transform institutional cultures at historically white South African universities?:
- Booi, Masixole, Vincent, Louise, Liccardo, Sabrina
- Authors: Booi, Masixole , Vincent, Louise , Liccardo, Sabrina
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/141946 , vital:38018 , DOI: 10.1080/07294360.2017.1289155
- Description: The post-apartheid higher education transformation project is faced with the challenge of recruiting and retaining black academics and other senior staff. But when we shift the focus from participation rates to equality–inequality within historically white universities (HWUs), then the discourse changes from demographic equity and redress to institutional culture and diversity. HWUs invoke the need to maintain their position as leading higher education institutions globally, and notions of ‘quality’ and ‘excellence’ have emerged as discursive practices, which serve to perpetuate exclusion. The question then arises as to which forms of capital comprise the Gold Standard at HWUs? Several South African universities have responded to the challenge of recruiting and retaining black academics by initiating programmes for the ‘accelerated development’ of these candidates.
- Full Text:
- Date Issued: 2017
- Authors: Booi, Masixole , Vincent, Louise , Liccardo, Sabrina
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/141946 , vital:38018 , DOI: 10.1080/07294360.2017.1289155
- Description: The post-apartheid higher education transformation project is faced with the challenge of recruiting and retaining black academics and other senior staff. But when we shift the focus from participation rates to equality–inequality within historically white universities (HWUs), then the discourse changes from demographic equity and redress to institutional culture and diversity. HWUs invoke the need to maintain their position as leading higher education institutions globally, and notions of ‘quality’ and ‘excellence’ have emerged as discursive practices, which serve to perpetuate exclusion. The question then arises as to which forms of capital comprise the Gold Standard at HWUs? Several South African universities have responded to the challenge of recruiting and retaining black academics by initiating programmes for the ‘accelerated development’ of these candidates.
- Full Text:
- Date Issued: 2017
Environmental and social recovery asymmetries to large-scale disturbances in small island communities
- Aswani, Shankar, Van Putten, Ingrid, Miñarro, Sara
- Authors: Aswani, Shankar , Van Putten, Ingrid , Miñarro, Sara
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/67325 , vital:29073 , https://doi.org/10.1007/s11069-016-2685-2
- Description: publisher version , People’s livelihoods in tropical small-island developing states are greatly dependent on marine ecosystem services. Yet services such as fisheries and coastal buffering are being degraded at an alarming rate, thus making people increasing vulnerable to protracted and sudden environmental changes. In the context of the occurrences of extreme events such as earthquakes and tsunamis, it is vital to uncover the processes that make people in these island states resilient, or not, to environmental disruptions. This paper compares people’s perceptions of social and environmental impacts after an extreme event in the Western Solomon Islands (11 different villages on 8 different islands) to better understand how knowledge systems influence the coupling of human and natural systems. We examine the factors that contributed to perceptions of respective recovery in the environmental versus the social domains across communities with different traditional governance and modernization characteristics in a tsunami impact gradient. First, we separately assessed, at the community and individual level, the potential determinants of perceived recovery in the environmental and social domains. At the community level, the average values of the perceived environmental and social recovery were calculated for each community (1 year after the tsunami), and at the individual level, normally distributed environmental and social recovery variables (based on the difference in perceptions immediately and 1 year after the tsunami) were used as dependent variables in two General Linear Models. Results suggest that environmental and social resilience are not always coupled correspondingly and, less unexpectedly, that asymmetries during recovery can occur as a result of the underlying social and ecological context and existing adaptive capacity. More generally, the study shows how by evaluating post-disturbance perceptional data in tsunami-affected communities, we can better understand how subjective perceptions of change can affect the (de)-coupling of human and natural systems.
- Full Text: false
- Date Issued: 2017
- Authors: Aswani, Shankar , Van Putten, Ingrid , Miñarro, Sara
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/67325 , vital:29073 , https://doi.org/10.1007/s11069-016-2685-2
- Description: publisher version , People’s livelihoods in tropical small-island developing states are greatly dependent on marine ecosystem services. Yet services such as fisheries and coastal buffering are being degraded at an alarming rate, thus making people increasing vulnerable to protracted and sudden environmental changes. In the context of the occurrences of extreme events such as earthquakes and tsunamis, it is vital to uncover the processes that make people in these island states resilient, or not, to environmental disruptions. This paper compares people’s perceptions of social and environmental impacts after an extreme event in the Western Solomon Islands (11 different villages on 8 different islands) to better understand how knowledge systems influence the coupling of human and natural systems. We examine the factors that contributed to perceptions of respective recovery in the environmental versus the social domains across communities with different traditional governance and modernization characteristics in a tsunami impact gradient. First, we separately assessed, at the community and individual level, the potential determinants of perceived recovery in the environmental and social domains. At the community level, the average values of the perceived environmental and social recovery were calculated for each community (1 year after the tsunami), and at the individual level, normally distributed environmental and social recovery variables (based on the difference in perceptions immediately and 1 year after the tsunami) were used as dependent variables in two General Linear Models. Results suggest that environmental and social resilience are not always coupled correspondingly and, less unexpectedly, that asymmetries during recovery can occur as a result of the underlying social and ecological context and existing adaptive capacity. More generally, the study shows how by evaluating post-disturbance perceptional data in tsunami-affected communities, we can better understand how subjective perceptions of change can affect the (de)-coupling of human and natural systems.
- Full Text: false
- Date Issued: 2017
One size does not fit all: critical insights for effective community-based resource management in Melanesia
- Aswani, Shankar, Albert, Simon, Love, Mark
- Authors: Aswani, Shankar , Albert, Simon , Love, Mark
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/145392 , vital:38434 , DOI: 10.1016/j.marpol.2017.03.041
- Description: In recent years, Fiji's approach of combining traditional systems of community-based coastal management and modern management systems has become a successful blueprint for marine conservation, particularly the Locally Managed Marine Area (LMMA) network model. As a result of this success, conservation practitioners have imported the Fiji LMMA model to the Solomon Islands and in Vanuatu in hope of replicating the purported success attained in Fiji. This paper argues that because tenure systems and associated political systems in Fiji, the Solomon Islands, and Vanuatu are substantially different, one cannot simply extrapolate the more centralized tenurial and political Fiji model to the decentralized tenurial and politically eclectic Solomons and Vanuatu. This paper provides an analysis of some of the various approaches used in these countries to make a case for why socio-political diversity and historical particulars matter to resource management and conservation-in-practice (and for any development interventions).
- Full Text:
- Date Issued: 2017
- Authors: Aswani, Shankar , Albert, Simon , Love, Mark
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/145392 , vital:38434 , DOI: 10.1016/j.marpol.2017.03.041
- Description: In recent years, Fiji's approach of combining traditional systems of community-based coastal management and modern management systems has become a successful blueprint for marine conservation, particularly the Locally Managed Marine Area (LMMA) network model. As a result of this success, conservation practitioners have imported the Fiji LMMA model to the Solomon Islands and in Vanuatu in hope of replicating the purported success attained in Fiji. This paper argues that because tenure systems and associated political systems in Fiji, the Solomon Islands, and Vanuatu are substantially different, one cannot simply extrapolate the more centralized tenurial and political Fiji model to the decentralized tenurial and politically eclectic Solomons and Vanuatu. This paper provides an analysis of some of the various approaches used in these countries to make a case for why socio-political diversity and historical particulars matter to resource management and conservation-in-practice (and for any development interventions).
- Full Text:
- Date Issued: 2017
The influence of dose on the kinetic parameters and dosimetric features of the main thermoluminescence glow peak in α-Al2O3: C, Mg
- Kalita, Jitumani M, Chithambo, Makaiko L
- Authors: Kalita, Jitumani M , Chithambo, Makaiko L
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/119834 , vital:34787 , https://doi.org/10.1016/j.nimb.2016.12.027
- Description: The influence of dose (0.1–100 Gy) on the kinetic parameters and the dosimetric features of the main glow peak of α-Al2O3:C,Mg have been investigated. Thermoluminescence (TL) measured at 1 °C/s shows a very high intensity glow peak at 161 °C and six secondary peaks at 42, 72, 193, 279, 330, 370 °C respectively. Analysis shows that the main peak follows first order kinetics irrespective of the irradiation dose. The activation energy is found to be consistent at 1.37 eV and the frequency factor is of the order of 1014 s−1 for any dose between 0.1 and 100 Gy. Further, the analysis for thermal quenching of the main peak of 0.1 Gy irradiated sample shows that the activation energy for thermal quenching is (0.94 ± 0.04) eV.
- Full Text: false
- Date Issued: 2017
- Authors: Kalita, Jitumani M , Chithambo, Makaiko L
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/119834 , vital:34787 , https://doi.org/10.1016/j.nimb.2016.12.027
- Description: The influence of dose (0.1–100 Gy) on the kinetic parameters and the dosimetric features of the main glow peak of α-Al2O3:C,Mg have been investigated. Thermoluminescence (TL) measured at 1 °C/s shows a very high intensity glow peak at 161 °C and six secondary peaks at 42, 72, 193, 279, 330, 370 °C respectively. Analysis shows that the main peak follows first order kinetics irrespective of the irradiation dose. The activation energy is found to be consistent at 1.37 eV and the frequency factor is of the order of 1014 s−1 for any dose between 0.1 and 100 Gy. Further, the analysis for thermal quenching of the main peak of 0.1 Gy irradiated sample shows that the activation energy for thermal quenching is (0.94 ± 0.04) eV.
- Full Text: false
- Date Issued: 2017
Tracks and Traces: Andrew Tshabangu’s ‘Footprints’
- Authors: Lila, Philiswa
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/147138 , vital:38596 , https://artthrob.co.za/2017/03/08/tracks-and-traces-andrew-tshabangus-footprints/
- Description: Andrew Tshabangu ‘Footprints’ at the Standard Bank Art Gallery is a hand-picked collection of photographs that span the past 20 years of Tshabangu’s career. Curated by Thembinkosi Goniwe, the narrative is uncomplicated and uncluttered, thus allowing the images breathing space for engagement. The display is precise with careful attention to detail, appearing neat, slick and efficient; a characteristic mirrored in Tshabangu’s photography.
- Full Text:
- Date Issued: 2017
- Authors: Lila, Philiswa
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/147138 , vital:38596 , https://artthrob.co.za/2017/03/08/tracks-and-traces-andrew-tshabangus-footprints/
- Description: Andrew Tshabangu ‘Footprints’ at the Standard Bank Art Gallery is a hand-picked collection of photographs that span the past 20 years of Tshabangu’s career. Curated by Thembinkosi Goniwe, the narrative is uncomplicated and uncluttered, thus allowing the images breathing space for engagement. The display is precise with careful attention to detail, appearing neat, slick and efficient; a characteristic mirrored in Tshabangu’s photography.
- Full Text:
- Date Issued: 2017
Unexpected transformations of 3-(bromoacetyl)coumarin provides new evidence for the mechanism of thiol mediated dehalogenation of α-halocarbonyls
- Magwenzi, Faith N, Khanye, Setshaba D, Veale, Clinton G L
- Authors: Magwenzi, Faith N , Khanye, Setshaba D , Veale, Clinton G L
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66200 , vital:28916 , https://doi.org/10.1016/j.tetlet.2017.01.082
- Description: publisher version , The mechanism for the thiol mediated dehalogenation of α-halogenated carbonyls has remained an unresolved problem, despite its ongoing application in synthetic organic chemistry. Nakamura and co-workers first proposed that net dehalogenation occurs via sequential nucleophilic substitutions, while Israel and co-workers concluded that the rate at which dehalogenation occurred suggested that dehalogenation proceeds in a single concerted step. In this study, we investigated the debromination and nucleophilic substitution of 3-(bromoacetyl)coumarin with a variety of thiophenols, whose electron donating or withdrawing natures resulted in large variations in the degree of nucleophilic substitution and dehalogenation products, respectively. Results from these experiments, in addition to an unexpected formation of thioether containing dibenzo[b,d]pyran-6-ones from a Robinson annulation, has provided new evidence for this disputed mechanism.
- Full Text: false
- Date Issued: 2017
- Authors: Magwenzi, Faith N , Khanye, Setshaba D , Veale, Clinton G L
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66200 , vital:28916 , https://doi.org/10.1016/j.tetlet.2017.01.082
- Description: publisher version , The mechanism for the thiol mediated dehalogenation of α-halogenated carbonyls has remained an unresolved problem, despite its ongoing application in synthetic organic chemistry. Nakamura and co-workers first proposed that net dehalogenation occurs via sequential nucleophilic substitutions, while Israel and co-workers concluded that the rate at which dehalogenation occurred suggested that dehalogenation proceeds in a single concerted step. In this study, we investigated the debromination and nucleophilic substitution of 3-(bromoacetyl)coumarin with a variety of thiophenols, whose electron donating or withdrawing natures resulted in large variations in the degree of nucleophilic substitution and dehalogenation products, respectively. Results from these experiments, in addition to an unexpected formation of thioether containing dibenzo[b,d]pyran-6-ones from a Robinson annulation, has provided new evidence for this disputed mechanism.
- Full Text: false
- Date Issued: 2017
Russian wheat aphids: Breakfast, lunch, and supper. Feasting on small grains in South Africa
- Botha, Christiaan E J, Sacranie, S, Gallagher, Sean, Hill, Jaclyn M
- Authors: Botha, Christiaan E J , Sacranie, S , Gallagher, Sean , Hill, Jaclyn M
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/69031 , vital:29374 , https://doi.org/10.1016/j.sajb.2016.12.006
- Description: The Russian Wheat Aphid (Diuraphis noxia, RWA) negatively impacts commercially grown barley and wheat in South Africa. Climate change, the attendant rise in [CO2], and the appearance of new RWA biotypes have the potential to induce severe crop yield loss in agriculturally important wheat and barley cultivars. This study presents data showing changes in relative aphid population numbers, concurrently with assessments of plant damage under controlled environmental conditions, under ambient and elevated (450 ppm) [CO2]. Extensive structural damage to the vascular tissue and disruption to the transport systems were revealed using light, fluorescence and electron microscopy. This, coupled with biotype population studies, demonstrated that RWA has the capacity to inflict severe, potentially permanent damage to vegetative small grain plants. Furthermore, some currently ‘resistant’ cultivars may well lose resistance as a direct result of increasing atmospheric [CO2]. A small (50 ppm) increase in atmospheric [CO2] may result in increased aphid population numbers, potentially serious plant damage and, by implication, a potentially negative impact on yield, as increased aphid density per plant leads to an accelerated disruption of the assimilate and transpiration transport pathways. These outcomes pose a direct threat to the commercial small grain industry of South Africa and by extension, to other small grain production areas elsewhere.
- Full Text: false
- Date Issued: 2016
- Authors: Botha, Christiaan E J , Sacranie, S , Gallagher, Sean , Hill, Jaclyn M
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/69031 , vital:29374 , https://doi.org/10.1016/j.sajb.2016.12.006
- Description: The Russian Wheat Aphid (Diuraphis noxia, RWA) negatively impacts commercially grown barley and wheat in South Africa. Climate change, the attendant rise in [CO2], and the appearance of new RWA biotypes have the potential to induce severe crop yield loss in agriculturally important wheat and barley cultivars. This study presents data showing changes in relative aphid population numbers, concurrently with assessments of plant damage under controlled environmental conditions, under ambient and elevated (450 ppm) [CO2]. Extensive structural damage to the vascular tissue and disruption to the transport systems were revealed using light, fluorescence and electron microscopy. This, coupled with biotype population studies, demonstrated that RWA has the capacity to inflict severe, potentially permanent damage to vegetative small grain plants. Furthermore, some currently ‘resistant’ cultivars may well lose resistance as a direct result of increasing atmospheric [CO2]. A small (50 ppm) increase in atmospheric [CO2] may result in increased aphid population numbers, potentially serious plant damage and, by implication, a potentially negative impact on yield, as increased aphid density per plant leads to an accelerated disruption of the assimilate and transpiration transport pathways. These outcomes pose a direct threat to the commercial small grain industry of South Africa and by extension, to other small grain production areas elsewhere.
- Full Text: false
- Date Issued: 2016
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