Allosteric Modulation of Human Hsp90α Conformational Dynamics:
- Penkler, David L, Atilgan, Canan, Tastan Bishop, Özlem
- Authors: Penkler, David L , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162936 , vital:40998 , https://doi.org/10.1021/acs.jcim.7b00630
- Description: Central to Hsp90’s biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90’s regulatory mechanisms, including its modulation by cochaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. In this study, we utilized homology modeling techniques to calculate full-length structures of human Hsp90α in closed and partially open conformations and used these structures as a basis for several molecular dynamics based analyses aimed at elucidating allosteric mechanisms and modulation sites in human Hsp90α.
- Full Text:
- Date Issued: 2018
- Authors: Penkler, David L , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162936 , vital:40998 , https://doi.org/10.1021/acs.jcim.7b00630
- Description: Central to Hsp90’s biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90’s regulatory mechanisms, including its modulation by cochaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. In this study, we utilized homology modeling techniques to calculate full-length structures of human Hsp90α in closed and partially open conformations and used these structures as a basis for several molecular dynamics based analyses aimed at elucidating allosteric mechanisms and modulation sites in human Hsp90α.
- Full Text:
- Date Issued: 2018
Confronting the Colonial Library: teaching Political Studies amidst calls for a decolonised curriculum
- Authors: Matthews, Sally
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/142191 , vital:38057 , DOI: 10.1080/02589346.2018.1418204
- Description: This paper engages with Mudimbe's concept of the ‘colonial library’ with the aim of using this engagement to contribute to current debates about decolonising South African university curricula. The term ‘colonial library’ refers to the body of texts and epistemological order which construct Africa as a symbol of otherness and inferiority. Mudimbe shows that even the most determined attempts to resist the colonial library draw on this same epistemological order. This presents a profound challenge for attempts to decolonise university curricula as it suggests that the colonial library's reach extends into attempts to dismantle it. In response to this challenge, I discuss ways in which we can oppose epistemological ethnocentrism and argue that we need to be open to the possibility of the emancipatory reappropriation of aspects of the colonial library. The paper concludes by relating the foregoing discussion to the South African political studies classroom.
- Full Text:
- Date Issued: 2018
- Authors: Matthews, Sally
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/142191 , vital:38057 , DOI: 10.1080/02589346.2018.1418204
- Description: This paper engages with Mudimbe's concept of the ‘colonial library’ with the aim of using this engagement to contribute to current debates about decolonising South African university curricula. The term ‘colonial library’ refers to the body of texts and epistemological order which construct Africa as a symbol of otherness and inferiority. Mudimbe shows that even the most determined attempts to resist the colonial library draw on this same epistemological order. This presents a profound challenge for attempts to decolonise university curricula as it suggests that the colonial library's reach extends into attempts to dismantle it. In response to this challenge, I discuss ways in which we can oppose epistemological ethnocentrism and argue that we need to be open to the possibility of the emancipatory reappropriation of aspects of the colonial library. The paper concludes by relating the foregoing discussion to the South African political studies classroom.
- Full Text:
- Date Issued: 2018
Mapping the field of Higher Education Research using PhD examination reports
- McKenna, Sioux, Quinn, Lynn, Vorster, Jo-Anne E
- Authors: McKenna, Sioux , Quinn, Lynn , Vorster, Jo-Anne E
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66669 , vital:28979 , ISSN 1469-8366 , https://doi.org/10.1080/07294360.2018.1428178
- Description: Pre-print , The PhD is the highest formal qualification and signifies a scholar’s rite of passage as a legitimate contributor of new knowledge in a field. Examiner reports make claims about what is legitimate in a thesis and what is not and thus articulate the organising principles through which participation in a field is measured. The authors analysed 39 examiners’ reports on 13 PhDs produced over a five-year period by scholars from the Higher Education Research doctoral studies programme at Rhodes University in South Africa. Drawing on aspects of Karl Maton’s Legitimation Code Theory (LCT), this study uses the dimensions of LCT:Specialisation and LCT:Semantics to explore what kinds of knowledge, skills and procedures and what kinds of knowers are validated in the field of Higher Education Research through the examination process. The study found that despite concerns in the literature about the a-theoretical nature of the Higher Education Studies field, examiners valued high-level theoretical and meta-theoretical engagement as well as methodological rigour. In addition, examiners prized the ability to demonstrate a strong ideological position, to use a clear doctoral voice, and to recognise the axiological drive of the field. The analysis showed that examiners were interested in strong contextualisation of the problem-spaces in higher education in South Africa but also commented positively on candidates’ ability to move from troubling an issue within its context to being able to abstract findings so as to contribute to the field as a whole.
- Full Text:
- Date Issued: 2018
- Authors: McKenna, Sioux , Quinn, Lynn , Vorster, Jo-Anne E
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66669 , vital:28979 , ISSN 1469-8366 , https://doi.org/10.1080/07294360.2018.1428178
- Description: Pre-print , The PhD is the highest formal qualification and signifies a scholar’s rite of passage as a legitimate contributor of new knowledge in a field. Examiner reports make claims about what is legitimate in a thesis and what is not and thus articulate the organising principles through which participation in a field is measured. The authors analysed 39 examiners’ reports on 13 PhDs produced over a five-year period by scholars from the Higher Education Research doctoral studies programme at Rhodes University in South Africa. Drawing on aspects of Karl Maton’s Legitimation Code Theory (LCT), this study uses the dimensions of LCT:Specialisation and LCT:Semantics to explore what kinds of knowledge, skills and procedures and what kinds of knowers are validated in the field of Higher Education Research through the examination process. The study found that despite concerns in the literature about the a-theoretical nature of the Higher Education Studies field, examiners valued high-level theoretical and meta-theoretical engagement as well as methodological rigour. In addition, examiners prized the ability to demonstrate a strong ideological position, to use a clear doctoral voice, and to recognise the axiological drive of the field. The analysis showed that examiners were interested in strong contextualisation of the problem-spaces in higher education in South Africa but also commented positively on candidates’ ability to move from troubling an issue within its context to being able to abstract findings so as to contribute to the field as a whole.
- Full Text:
- Date Issued: 2018
The generation and characterisation of neutralising antibodies against the Theiler’s murine encephalomyelitis virus (TMEV) GDVII capsid reveals the potential binding site of the host cell co-receptor, heparan sulfate:
- Upfold, Nicole, Ross, Caroline J, Tastan Bishop, Özlem, Luke, Garry A, Knox, Caroline M
- Authors: Upfold, Nicole , Ross, Caroline J , Tastan Bishop, Özlem , Luke, Garry A , Knox, Caroline M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148181 , vital:38717 , DOI: 10.1016/j.virusres.2017.11.017
- Description: The early stages of picornavirus capsid assembly and the host factors involved are poorly understood. Since the localisation of viral proteins in infected cells can provide information on their function, antibodies against purified Theiler's murine encephalomyelitis virus (TMEV) GDVII capsids were generated by immunisation of rabbits. The resultant anti-TMEV capsid antibodies recognised a C-terminal region of VP1 but not VP2 or VP3 by Western analysis. Examination of the sites of TMEV capsid assembly by indirect immunofluorescence and confocal microscopy showed that at 5 h post infection, capsid signal was diffusely cytoplasmic with strong perinuclear staining and moved into large punctate structures from 6 to 8 h post infection.
- Full Text:
- Date Issued: 2018
- Authors: Upfold, Nicole , Ross, Caroline J , Tastan Bishop, Özlem , Luke, Garry A , Knox, Caroline M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148181 , vital:38717 , DOI: 10.1016/j.virusres.2017.11.017
- Description: The early stages of picornavirus capsid assembly and the host factors involved are poorly understood. Since the localisation of viral proteins in infected cells can provide information on their function, antibodies against purified Theiler's murine encephalomyelitis virus (TMEV) GDVII capsids were generated by immunisation of rabbits. The resultant anti-TMEV capsid antibodies recognised a C-terminal region of VP1 but not VP2 or VP3 by Western analysis. Examination of the sites of TMEV capsid assembly by indirect immunofluorescence and confocal microscopy showed that at 5 h post infection, capsid signal was diffusely cytoplasmic with strong perinuclear staining and moved into large punctate structures from 6 to 8 h post infection.
- Full Text:
- Date Issued: 2018
The National Wellbeing Index in the isiXhosa translation: focus group discussions on how South Africans view the quality of their society
- Moller, Valerie, Roberts, Benjamin J, Zani, Dalindyebo
- Authors: Moller, Valerie , Roberts, Benjamin J , Zani, Dalindyebo
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/67135 , vital:29035 , https://doi.org/10.1007/s11205-016-1481-4
- Description: publisher version , The International Wellbeing Index covers two complementary measures, the Personal Wellbeing Index (PWI) and the National Wellbeing Index (NWI). The focus group study reported here tested the understanding of the NWI when translated into isiXhosa, a language spoken by 6 million South Africans, or 16% of the country’s population. A challenge for the NWI in measuring national well-being is the tendency for meaning to get ‘lost in translation’ in the wording of the instrument, owing to the disparities that exist between levels of living in developed and developing nations. The focussed discussions with native isiXhosa speakers conveyed the different shades of meaning associated with the six domains that make up the NWI. The isiXhosa keywords for the domains of social conditions, the natural environment, national security, and management of the country’s affairs (government) were readily understood, but discussants asked for further clarification of keywords for the domains relating to the economy and business. Conversations showed up the close link between personal and national well-being: discussants drew upon their personal and parochial life experiences along with their knowledge of current affairs to evaluate the nation’s quality of life. They described the social contract between citizens and their government to create a ‘caring society’ that promotes well-being across key domains of national life. Many of the reference standards used to evaluate national well-being were ones postulated to influence personal well-being (Michalos A.C, Social Indicators Research 16(4): 347–413 1985 ). The study also pointed to a potential problem for longitudinal studies if the bipolar satisfaction scale, formerly used to measure the International Wellbeing Index’s PWI and NWI, is changed to a unipolar one. Findings from this pilot study confirm the potential of the NWI as a tool for measuring national well-being cross-culturally.
- Full Text: false
- Date Issued: 2018
- Authors: Moller, Valerie , Roberts, Benjamin J , Zani, Dalindyebo
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/67135 , vital:29035 , https://doi.org/10.1007/s11205-016-1481-4
- Description: publisher version , The International Wellbeing Index covers two complementary measures, the Personal Wellbeing Index (PWI) and the National Wellbeing Index (NWI). The focus group study reported here tested the understanding of the NWI when translated into isiXhosa, a language spoken by 6 million South Africans, or 16% of the country’s population. A challenge for the NWI in measuring national well-being is the tendency for meaning to get ‘lost in translation’ in the wording of the instrument, owing to the disparities that exist between levels of living in developed and developing nations. The focussed discussions with native isiXhosa speakers conveyed the different shades of meaning associated with the six domains that make up the NWI. The isiXhosa keywords for the domains of social conditions, the natural environment, national security, and management of the country’s affairs (government) were readily understood, but discussants asked for further clarification of keywords for the domains relating to the economy and business. Conversations showed up the close link between personal and national well-being: discussants drew upon their personal and parochial life experiences along with their knowledge of current affairs to evaluate the nation’s quality of life. They described the social contract between citizens and their government to create a ‘caring society’ that promotes well-being across key domains of national life. Many of the reference standards used to evaluate national well-being were ones postulated to influence personal well-being (Michalos A.C, Social Indicators Research 16(4): 347–413 1985 ). The study also pointed to a potential problem for longitudinal studies if the bipolar satisfaction scale, formerly used to measure the International Wellbeing Index’s PWI and NWI, is changed to a unipolar one. Findings from this pilot study confirm the potential of the NWI as a tool for measuring national well-being cross-culturally.
- Full Text: false
- Date Issued: 2018
A moderate elevation in [CO 2] results in potential hypervirulence on SABBIErica
- Gallagher, Sean, Hill, Jaclyn M, Murugan, N, Botha, Christiaan E J
- Authors: Gallagher, Sean , Hill, Jaclyn M , Murugan, N , Botha, Christiaan E J
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/68835 , vital:29329 , https://doi.org/10.1016/j.sajb.2017.10.010
- Description: The Russian Wheat Aphid (Diuraphis noxia Kurdjumov, 1913) (RWA) is a serious pest of grain crops and is of considerable concern in South Africa, particularly in terms of barley grown specifically for the brewing industry. This paper highlights the effect of a small (50 ppm) increase in [CO2] on the growth rate of the four South African RWA biotypes on the SABBIErica barley cultivar. Controlled environment experiments revealed that the colony growth rate for RWASA4 was significantly lower than SA1 under ambient conditions as well as significantly lower than SA1, SA2 or SA3 under elevated CO2 conditions. The unexpected difference suggested an atypical, non-preferential feeding habit on SABBIErica, for RWASA4. The small RWASA4 colonies inflicted similar morphological damage to the significantly larger RWASA1 – RWASA3 biotype populations — indicative of potential hypervirulence under elevated CO2. The continuous feeding of RWASA biotypes causes damage to the transport system as well as substantial, catastrophic damage to mesophyll chloroplasts as well as mitochondria within the host plant's leaves. The TEM study revealed evidence of sequential/systematic degeneration of chloroplasts and mitochondria with continued aphid feeding, which we suggest is an indication of potential emergent hypervirulence under elevated CO2 conditions.
- Full Text: false
- Date Issued: 2017
- Authors: Gallagher, Sean , Hill, Jaclyn M , Murugan, N , Botha, Christiaan E J
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/68835 , vital:29329 , https://doi.org/10.1016/j.sajb.2017.10.010
- Description: The Russian Wheat Aphid (Diuraphis noxia Kurdjumov, 1913) (RWA) is a serious pest of grain crops and is of considerable concern in South Africa, particularly in terms of barley grown specifically for the brewing industry. This paper highlights the effect of a small (50 ppm) increase in [CO2] on the growth rate of the four South African RWA biotypes on the SABBIErica barley cultivar. Controlled environment experiments revealed that the colony growth rate for RWASA4 was significantly lower than SA1 under ambient conditions as well as significantly lower than SA1, SA2 or SA3 under elevated CO2 conditions. The unexpected difference suggested an atypical, non-preferential feeding habit on SABBIErica, for RWASA4. The small RWASA4 colonies inflicted similar morphological damage to the significantly larger RWASA1 – RWASA3 biotype populations — indicative of potential hypervirulence under elevated CO2. The continuous feeding of RWASA biotypes causes damage to the transport system as well as substantial, catastrophic damage to mesophyll chloroplasts as well as mitochondria within the host plant's leaves. The TEM study revealed evidence of sequential/systematic degeneration of chloroplasts and mitochondria with continued aphid feeding, which we suggest is an indication of potential emergent hypervirulence under elevated CO2 conditions.
- Full Text: false
- Date Issued: 2017
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