Integrated computational approaches and tools for allosteric drug discovery:
- Amamuddy, Olivier S, Veldman, Wade, Manyumwa, Colleen, Khairallah, Afrah, Agajanian, Steve, Oluyemi, Odeyemi, Verkhivker, Gennady M, Tastan Bishop, Özlem
- Authors: Amamuddy, Olivier S , Veldman, Wade , Manyumwa, Colleen , Khairallah, Afrah , Agajanian, Steve , Oluyemi, Odeyemi , Verkhivker, Gennady M , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163012 , vital:41004 , https://doi.org/10.3390/ijms21030847
- Description: Understanding molecular mechanisms underlying the complexity of allosteric regulation in proteins has attracted considerable attention in drug discovery due to the benefits and versatility of allosteric modulators in providing desirable selectivity against protein targets while minimizing toxicity and other side effects. The proliferation of novel computational approaches for predicting ligand–protein interactions and binding using dynamic and network-centric perspectives has led to new insights into allosteric mechanisms and facilitated computer-based discovery of allosteric drugs. Although no absolute method of experimental and in silico allosteric drug/site discovery exists, current methods are still being improved. As such, the critical analysis and integration of established approaches into robust, reproducible, and customizable computational pipelines with experimental feedback could make allosteric drug discovery more efficient and reliable. In this article, we review computational approaches for allosteric drug discovery and discuss how these tools can be utilized to develop consensus workflows for in silico identification of allosteric sites and modulators with some applications to pathogen resistance and precision medicine. The emerging realization that allosteric modulators can exploit distinct regulatory mechanisms and can provide access to targeted modulation of protein activities could open opportunities for probing biological processes and in silico design of drug combinations with improved therapeutic indices and a broad range of activities.
- Full Text:
- Date Issued: 2020
- Authors: Amamuddy, Olivier S , Veldman, Wade , Manyumwa, Colleen , Khairallah, Afrah , Agajanian, Steve , Oluyemi, Odeyemi , Verkhivker, Gennady M , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163012 , vital:41004 , https://doi.org/10.3390/ijms21030847
- Description: Understanding molecular mechanisms underlying the complexity of allosteric regulation in proteins has attracted considerable attention in drug discovery due to the benefits and versatility of allosteric modulators in providing desirable selectivity against protein targets while minimizing toxicity and other side effects. The proliferation of novel computational approaches for predicting ligand–protein interactions and binding using dynamic and network-centric perspectives has led to new insights into allosteric mechanisms and facilitated computer-based discovery of allosteric drugs. Although no absolute method of experimental and in silico allosteric drug/site discovery exists, current methods are still being improved. As such, the critical analysis and integration of established approaches into robust, reproducible, and customizable computational pipelines with experimental feedback could make allosteric drug discovery more efficient and reliable. In this article, we review computational approaches for allosteric drug discovery and discuss how these tools can be utilized to develop consensus workflows for in silico identification of allosteric sites and modulators with some applications to pathogen resistance and precision medicine. The emerging realization that allosteric modulators can exploit distinct regulatory mechanisms and can provide access to targeted modulation of protein activities could open opportunities for probing biological processes and in silico design of drug combinations with improved therapeutic indices and a broad range of activities.
- Full Text:
- Date Issued: 2020
Impact of emerging mutations on the dynamic properties the SARS-CoV-2 main protease: an in silico investigation
- Amamuddy, Olivier S, Verkhivker, Gennady M, Tastan Bishop, Özlem
- Authors: Amamuddy, Olivier S , Verkhivker, Gennady M , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163035 , vital:41006 , doi: 10.1021/acs.jcim.0c00634
- Description: The new coronavirus (SARS-CoV-2) is a global threat to world health and its economy. Its main protease (Mpro), which functions as a dimer, cleaves viral precursor proteins in the process of viral maturation. It is a good candidate for drug development owing to its conservation and the absence of a human homolog. An improved understanding of the protein behaviour can accelerate the discovery of effective therapies in order to reduce mortality. 100 ns all-atom molecular dynamics simulations of 50 homology modelled mutant Mpro dimers were performed at pH 7 from filtered sequences obtained from the GISAID database. Protease dynamics were analysed using RMSD, RMSF, Rg, the averaged betweenness centrality and geometry calculations. Domains from each Mpro protomer were found to generally have independent motions, while the dimer-stabilising N-finger region was found to be flexible in most mutants.
- Full Text:
- Date Issued: 2020
- Authors: Amamuddy, Olivier S , Verkhivker, Gennady M , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163035 , vital:41006 , doi: 10.1021/acs.jcim.0c00634
- Description: The new coronavirus (SARS-CoV-2) is a global threat to world health and its economy. Its main protease (Mpro), which functions as a dimer, cleaves viral precursor proteins in the process of viral maturation. It is a good candidate for drug development owing to its conservation and the absence of a human homolog. An improved understanding of the protein behaviour can accelerate the discovery of effective therapies in order to reduce mortality. 100 ns all-atom molecular dynamics simulations of 50 homology modelled mutant Mpro dimers were performed at pH 7 from filtered sequences obtained from the GISAID database. Protease dynamics were analysed using RMSD, RMSF, Rg, the averaged betweenness centrality and geometry calculations. Domains from each Mpro protomer were found to generally have independent motions, while the dimer-stabilising N-finger region was found to be flexible in most mutants.
- Full Text:
- Date Issued: 2020
Impact of early pandemic stage mutations on molecular dynamics of SARS-CoV-2 Mpro:
- Amamuddy, Olivier S, Verkhivker, Gennady M, Tastan Bishop, Özlem
- Authors: Amamuddy, Olivier S , Verkhivker, Gennady M , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162330 , vital:40835 , https://0-doi.org.wam.seals.ac.za/10.1021/acs.jcim.0c00634
- Description: A new coronavirus (SARS-CoV-2) is a global threat to world health and economy. Its dimeric main protease (Mpro), which is required for the proteolytic cleavage of viral precursor proteins, is a good candidate for drug development owing to its conservation and the absence of a human homolog. Improving our understanding of Mpro behavior can accelerate the discovery of effective therapies to reduce mortality. All-atom molecular dynamics (MD) simulations (100 ns) of 50 mutant Mpro dimers obtained from filtered sequences from the GISAID database were analyzed using root-mean-square deviation, root-mean-square fluctuation, Rg, averaged betweenness centrality, and geometry calculations.
- Full Text:
- Date Issued: 2020
- Authors: Amamuddy, Olivier S , Verkhivker, Gennady M , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162330 , vital:40835 , https://0-doi.org.wam.seals.ac.za/10.1021/acs.jcim.0c00634
- Description: A new coronavirus (SARS-CoV-2) is a global threat to world health and economy. Its dimeric main protease (Mpro), which is required for the proteolytic cleavage of viral precursor proteins, is a good candidate for drug development owing to its conservation and the absence of a human homolog. Improving our understanding of Mpro behavior can accelerate the discovery of effective therapies to reduce mortality. All-atom molecular dynamics (MD) simulations (100 ns) of 50 mutant Mpro dimers obtained from filtered sequences from the GISAID database were analyzed using root-mean-square deviation, root-mean-square fluctuation, Rg, averaged betweenness centrality, and geometry calculations.
- Full Text:
- Date Issued: 2020
Determining the unbinding events and conserved motions associated with the pyrazinamide release due to resistance mutations of Mycobacterium tuberculosis pyrazinamidase:
- Amamuddy, Olivier S, Musyoka, Thommas M, Boateng, Rita A, Zabo, Sophakama, Tastan Bishop, Özlem
- Authors: Amamuddy, Olivier S , Musyoka, Thommas M , Boateng, Rita A , Zabo, Sophakama , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148869 , vital:38781 , https://doi.org/10.1016/j.csbj.2020.05.0099
- Description: Pyrazinamide (PZA) is the only first-line antitubercular drug active against latent Mycobacterium tuberculosis (Mtb). It is activated to pyrazinoic acid by the pncA-encoded pyrazinamidase enzyme (PZase). Despite the emergence of PZA drug resistance, the underlying mechanisms of resistance remain unclear. This study investigated part of these mechanisms by modelling a PZA-bound wild type and 82 mutant PZase structures before applying molecular dynamics (MD) with an accurate Fe2+ cofactor coordination geometry.
- Full Text:
- Date Issued: 2020
- Authors: Amamuddy, Olivier S , Musyoka, Thommas M , Boateng, Rita A , Zabo, Sophakama , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148869 , vital:38781 , https://doi.org/10.1016/j.csbj.2020.05.0099
- Description: Pyrazinamide (PZA) is the only first-line antitubercular drug active against latent Mycobacterium tuberculosis (Mtb). It is activated to pyrazinoic acid by the pncA-encoded pyrazinamidase enzyme (PZase). Despite the emergence of PZA drug resistance, the underlying mechanisms of resistance remain unclear. This study investigated part of these mechanisms by modelling a PZA-bound wild type and 82 mutant PZase structures before applying molecular dynamics (MD) with an accurate Fe2+ cofactor coordination geometry.
- Full Text:
- Date Issued: 2020
The African coelacanth genome provides insights into tetrapod evolution:
- Amemiya, Chris T, Alföldi, Jessica, Lee, Alison P, Fan, Shaohua, Philippe, Herve´, MacCallum, Iain, Braasch, Ingo, Manousaki, Tereza, Schneider, Igor, Rohner, Nicolas, Organ, Chris, Chalopin, Domitille, Smith, Jeramiah J, Robinson, Mark, Dorrington, Rosemary A, Gerdol, Marco, Aken, Bronwen, Biscotti, Maria Assunta, Barucca, Marco, Baurain, Denis, Berlin, Aaron, Blatch, Gregory L, Buonocore, Francesco, Burmester, Thorsten, Campbell, Michael S, Canapa, Adriana, Cannon, John P, Christoffels, Alan, De Moro, Gianluca, Edkins, Adrienne L, Fan, Lin, Fausto, Anna Maria, Feiner, Nathalie, Forconi, Mariko, Gamieldien, Junaid, Gnerre, Sante, Gnirke, Andreas, Goldstone, Jared V, Haerty, Wilfried, Hahn, Mark E, Hesse, Uljana, Hoffmann, Steve, Johnson, Jeremy, Karchner, Sibel I, Kuraku, Shigehiro, Lara, Marcia, Levin, Joshua Z, Litman, Gary W, Mauceli, Evan, Miyake, Tsutomu, Mueller, M Gail, Nelson, David R, Nitsche, Anne, Olmo, Ettore, Ota, Tatsuya, Pallavicini, Alberto, Panji, Sumir, Picone, Barbara, Ponting, Chris P, Prohaska, Sonja J, Przybylski, Dariusz, Ratan Saha, Nil, Ravi, Vydianathan, Ribeiro, Filipe J, Sauka-Spengler, Tatjana, Scapigliati, Giuseppe, Searle, Stephen M J, Sharpe, Ted, Simakov, Oleg, Stadler, Peter F, Stegeman, John J, Sumiyama, Kenta, Tabbaa, Diana, Tafer, Hakim, Turner-Maier, Jason, van Heusden, Peter, White, Simon, Williams, Louise, Yandell, Mark, Brinkmann, Henner, Volff, Jean-Nicolas, Tabin, Clifford J, Shubin, Neil, Schartl, Manfred, Jaffe, David B, Postlethwait, John H, Venkatesh, Byrappa, Di Palma, Frederica, Lander, Eric S, Meyer, Axel, Lindblad-Toh, Kerstin
- Authors: Amemiya, Chris T , Alföldi, Jessica , Lee, Alison P , Fan, Shaohua , Philippe, Herve´ , MacCallum, Iain , Braasch, Ingo , Manousaki, Tereza , Schneider, Igor , Rohner, Nicolas , Organ, Chris , Chalopin, Domitille , Smith, Jeramiah J , Robinson, Mark , Dorrington, Rosemary A , Gerdol, Marco , Aken, Bronwen , Biscotti, Maria Assunta , Barucca, Marco , Baurain, Denis , Berlin, Aaron , Blatch, Gregory L , Buonocore, Francesco , Burmester, Thorsten , Campbell, Michael S , Canapa, Adriana , Cannon, John P , Christoffels, Alan , De Moro, Gianluca , Edkins, Adrienne L , Fan, Lin , Fausto, Anna Maria , Feiner, Nathalie , Forconi, Mariko , Gamieldien, Junaid , Gnerre, Sante , Gnirke, Andreas , Goldstone, Jared V , Haerty, Wilfried , Hahn, Mark E , Hesse, Uljana , Hoffmann, Steve , Johnson, Jeremy , Karchner, Sibel I , Kuraku, Shigehiro , Lara, Marcia , Levin, Joshua Z , Litman, Gary W , Mauceli, Evan , Miyake, Tsutomu , Mueller, M Gail , Nelson, David R , Nitsche, Anne , Olmo, Ettore , Ota, Tatsuya , Pallavicini, Alberto , Panji, Sumir , Picone, Barbara , Ponting, Chris P , Prohaska, Sonja J , Przybylski, Dariusz , Ratan Saha, Nil , Ravi, Vydianathan , Ribeiro, Filipe J , Sauka-Spengler, Tatjana , Scapigliati, Giuseppe , Searle, Stephen M J , Sharpe, Ted , Simakov, Oleg , Stadler, Peter F , Stegeman, John J , Sumiyama, Kenta , Tabbaa, Diana , Tafer, Hakim , Turner-Maier, Jason , van Heusden, Peter , White, Simon , Williams, Louise , Yandell, Mark , Brinkmann, Henner , Volff, Jean-Nicolas , Tabin, Clifford J , Shubin, Neil , Schartl, Manfred , Jaffe, David B , Postlethwait, John H , Venkatesh, Byrappa , Di Palma, Frederica , Lander, Eric S , Meyer, Axel , Lindblad-Toh, Kerstin
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165030 , vital:41202 , DOI: 10.1038/nature12027
- Description: The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
- Full Text:
- Date Issued: 2013
- Authors: Amemiya, Chris T , Alföldi, Jessica , Lee, Alison P , Fan, Shaohua , Philippe, Herve´ , MacCallum, Iain , Braasch, Ingo , Manousaki, Tereza , Schneider, Igor , Rohner, Nicolas , Organ, Chris , Chalopin, Domitille , Smith, Jeramiah J , Robinson, Mark , Dorrington, Rosemary A , Gerdol, Marco , Aken, Bronwen , Biscotti, Maria Assunta , Barucca, Marco , Baurain, Denis , Berlin, Aaron , Blatch, Gregory L , Buonocore, Francesco , Burmester, Thorsten , Campbell, Michael S , Canapa, Adriana , Cannon, John P , Christoffels, Alan , De Moro, Gianluca , Edkins, Adrienne L , Fan, Lin , Fausto, Anna Maria , Feiner, Nathalie , Forconi, Mariko , Gamieldien, Junaid , Gnerre, Sante , Gnirke, Andreas , Goldstone, Jared V , Haerty, Wilfried , Hahn, Mark E , Hesse, Uljana , Hoffmann, Steve , Johnson, Jeremy , Karchner, Sibel I , Kuraku, Shigehiro , Lara, Marcia , Levin, Joshua Z , Litman, Gary W , Mauceli, Evan , Miyake, Tsutomu , Mueller, M Gail , Nelson, David R , Nitsche, Anne , Olmo, Ettore , Ota, Tatsuya , Pallavicini, Alberto , Panji, Sumir , Picone, Barbara , Ponting, Chris P , Prohaska, Sonja J , Przybylski, Dariusz , Ratan Saha, Nil , Ravi, Vydianathan , Ribeiro, Filipe J , Sauka-Spengler, Tatjana , Scapigliati, Giuseppe , Searle, Stephen M J , Sharpe, Ted , Simakov, Oleg , Stadler, Peter F , Stegeman, John J , Sumiyama, Kenta , Tabbaa, Diana , Tafer, Hakim , Turner-Maier, Jason , van Heusden, Peter , White, Simon , Williams, Louise , Yandell, Mark , Brinkmann, Henner , Volff, Jean-Nicolas , Tabin, Clifford J , Shubin, Neil , Schartl, Manfred , Jaffe, David B , Postlethwait, John H , Venkatesh, Byrappa , Di Palma, Frederica , Lander, Eric S , Meyer, Axel , Lindblad-Toh, Kerstin
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165030 , vital:41202 , DOI: 10.1038/nature12027
- Description: The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
- Full Text:
- Date Issued: 2013
A civic engagement:
- Authors: Amner, Roderick J
- Date: 2009
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/159366 , vital:40291 , https://hdl.handle.net/10520/EJC139908
- Description: Rod Amner looks at how a small South African newspaper is managing to punch well above its weight.
- Full Text:
- Date Issued: 2009
- Authors: Amner, Roderick J
- Date: 2009
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/159366 , vital:40291 , https://hdl.handle.net/10520/EJC139908
- Description: Rod Amner looks at how a small South African newspaper is managing to punch well above its weight.
- Full Text:
- Date Issued: 2009
Film Review: Hollywood on Safari
- Authors: Amner, Roderick J
- Date: 2009
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/142680 , vital:38101 , https://doi.org/10.1386/jams.1.2.335_4
- Description: Film Review: Hollywood on Safari.
- Full Text:
- Date Issued: 2009
- Authors: Amner, Roderick J
- Date: 2009
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/142680 , vital:38101 , https://doi.org/10.1386/jams.1.2.335_4
- Description: Film Review: Hollywood on Safari.
- Full Text:
- Date Issued: 2009
The writing is on the wall: ways that work
- Authors: Amner, Roderick J
- Date: 2003
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/159102 , vital:40267 , https://hdl.handle.net/10520/EJC146296
- Description: When I proposed to 26 third-year journalism students that our writing class take inspiration from an idea pioneered in places as unfashionable and inhospitable as the former Soviet Union and Nepal, I should have expected the icy stares. But happily, within five weeks, this winter of classroom discontent, had begun to thaw into a tentative spring of journalistic and pedagogical innovation.
- Full Text:
- Date Issued: 2003
- Authors: Amner, Roderick J
- Date: 2003
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/159102 , vital:40267 , https://hdl.handle.net/10520/EJC146296
- Description: When I proposed to 26 third-year journalism students that our writing class take inspiration from an idea pioneered in places as unfashionable and inhospitable as the former Soviet Union and Nepal, I should have expected the icy stares. But happily, within five weeks, this winter of classroom discontent, had begun to thaw into a tentative spring of journalistic and pedagogical innovation.
- Full Text:
- Date Issued: 2003
A tale of 2 investigations:
- Authors: Amner, Roderick J
- Date: 2010
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/159438 , vital:40297 , https://hdl.handle.net/10520/EJC139354
- Description: This is a tale of two in-depth stories, both produced by one Daily Dispatch journalist, Gcina Nstaluba, in 2009. One was wildly successful - it helped change the face of the government's housing policy and won Ntsaluba SA Story of the Year at the 2010 Mondi Shanduka Newspaper Awards. The other was deemed a dismal failure by Ntsaluba himself. Why? And what can these stories teach us and our students about doing journalism in South Africa?
- Full Text:
- Date Issued: 2010
- Authors: Amner, Roderick J
- Date: 2010
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/159438 , vital:40297 , https://hdl.handle.net/10520/EJC139354
- Description: This is a tale of two in-depth stories, both produced by one Daily Dispatch journalist, Gcina Nstaluba, in 2009. One was wildly successful - it helped change the face of the government's housing policy and won Ntsaluba SA Story of the Year at the 2010 Mondi Shanduka Newspaper Awards. The other was deemed a dismal failure by Ntsaluba himself. Why? And what can these stories teach us and our students about doing journalism in South Africa?
- Full Text:
- Date Issued: 2010
Oxford dictionary of journalism:
- Authors: Amner, Roderick J
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/142656 , vital:38099 , DOI: 10.1080/23743670.2015.1041305
- Description: Tony Harcup is a self-confessed ‘hackademic’, a term which he defines in his Oxford dictionary of journalism as ‘a journalist who goes on to work in journalism education where they combine the roles of journalism (hack) and academic’ (p. 121). Harcup explains that hackademics perform this balancing act in the ‘hackademy’, a curious space within academe where journalism training intersects with Journalism Studies (a field of study which is nowadays often granted ‘upper case’ status), ‘sometimes with mutual respect and insight, sometimes with mutual suspicion and hostility’ (ibid.). And this tension is never far from the surface in many of the 1 300 definitions in this useful and absorbing dictionary.
- Full Text:
- Date Issued: 2015
- Authors: Amner, Roderick J
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/142656 , vital:38099 , DOI: 10.1080/23743670.2015.1041305
- Description: Tony Harcup is a self-confessed ‘hackademic’, a term which he defines in his Oxford dictionary of journalism as ‘a journalist who goes on to work in journalism education where they combine the roles of journalism (hack) and academic’ (p. 121). Harcup explains that hackademics perform this balancing act in the ‘hackademy’, a curious space within academe where journalism training intersects with Journalism Studies (a field of study which is nowadays often granted ‘upper case’ status), ‘sometimes with mutual respect and insight, sometimes with mutual suspicion and hostility’ (ibid.). And this tension is never far from the surface in many of the 1 300 definitions in this useful and absorbing dictionary.
- Full Text:
- Date Issued: 2015
Paper bridges: a critical examination of the Daily Dispatch's ‘community dialogues’
- Authors: Amner, Roderick J
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/142645 , vital:38098 , https://doi.org/10.1080/02560054.2011.545564
- Description: A series of town-hall-like meetings called the ‘community dialogues’ were conducted in 2009 by the Daily Dispatch newspaper in East London, under the banner of public/civic journalism, a global journalistic reform movement begun in the United States in the late 1980s. the editorial leadership of the newspaper imagined a number of core journalistic and civic purposes for the dialogues and succeeded in achieving some of these. However, the newspaper's claim that the dialogues could help to build ‘horizontal bridges’ between diverse communities in East London is critically examined through the example of two community dialogues which took place in neighbouring locations - the predominantly white, middle-class suburb of Beacon Bay, and the informal African settlement of Nompumelelo - on consecutive days in 2009. This article argues that social inequalities, particularly acute in the South African context, may preclude the emergence of a shared vision of the common good, and that joint deliberation between diverse social groups in the pursuit of consensus may not be realistic or even an appropriate goal, especially if it means ratifying an unjust status quo.
- Full Text:
- Date Issued: 2011
- Authors: Amner, Roderick J
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/142645 , vital:38098 , https://doi.org/10.1080/02560054.2011.545564
- Description: A series of town-hall-like meetings called the ‘community dialogues’ were conducted in 2009 by the Daily Dispatch newspaper in East London, under the banner of public/civic journalism, a global journalistic reform movement begun in the United States in the late 1980s. the editorial leadership of the newspaper imagined a number of core journalistic and civic purposes for the dialogues and succeeded in achieving some of these. However, the newspaper's claim that the dialogues could help to build ‘horizontal bridges’ between diverse communities in East London is critically examined through the example of two community dialogues which took place in neighbouring locations - the predominantly white, middle-class suburb of Beacon Bay, and the informal African settlement of Nompumelelo - on consecutive days in 2009. This article argues that social inequalities, particularly acute in the South African context, may preclude the emergence of a shared vision of the common good, and that joint deliberation between diverse social groups in the pursuit of consensus may not be realistic or even an appropriate goal, especially if it means ratifying an unjust status quo.
- Full Text:
- Date Issued: 2011
Azawan: precolonial musical culture and Saharawi nationalism in the refugee camps of the Hamada Desert in Algeria
- Authors: Amoros, Luis Gimenez
- Date: 2015
- Language: English
- Type: article , text
- Identifier: http://hdl.handle.net/10962/59710 , vital:27641 , http://dx.doi.org/10.21504/amj.v10i1.1225
- Description: This article analyses Saharawi music as performed for the refugee community in the camps. I argue that the construction and evolution of Saharawi music in the camps is divided into two main areas: nationalism in relation to the decolonisation of Western Sahara, and maintenance of cultural values in Saharawi music found in the historical retention of the Haul modal system originating in precolonial Saharawi culture. Local audiences use the term Azawan to define the combination of nationalist sentiments and retention of their precolonial musical culture in Saharawi music.
- Full Text:
- Date Issued: 2015
- Authors: Amoros, Luis Gimenez
- Date: 2015
- Language: English
- Type: article , text
- Identifier: http://hdl.handle.net/10962/59710 , vital:27641 , http://dx.doi.org/10.21504/amj.v10i1.1225
- Description: This article analyses Saharawi music as performed for the refugee community in the camps. I argue that the construction and evolution of Saharawi music in the camps is divided into two main areas: nationalism in relation to the decolonisation of Western Sahara, and maintenance of cultural values in Saharawi music found in the historical retention of the Haul modal system originating in precolonial Saharawi culture. Local audiences use the term Azawan to define the combination of nationalist sentiments and retention of their precolonial musical culture in Saharawi music.
- Full Text:
- Date Issued: 2015
Pragmatic research design
- Amos, Trevor L, Pearse, Noel J
- Authors: Amos, Trevor L , Pearse, Noel J
- Date: 2008
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270943 , vital:54494 , xlink:href="https://academic-publishing.org/index.php/ejbrm/article/view/1230/1193"
- Description: The creation of wealth is an important issue in any society, and entrepreneurship is regarded as an important catalyst in the creation of new wealth. This presents a challenge to develop entrepreneurship successfully. An important site for the development of entrepreneurship is higher education. The challenge however, is that there is a lack of a general understanding on how to educate students for entrepreneurship. In addition, current thought and practice on entrepreneurship education is historically biased, implying that graduates are essentially prepared for the past instead of for the future. From the perspective of higher education, the problem is how to develop current students to be entrepreneurial in the future. What is needed is to project into the future and then to develop an understanding of what should be taught as well as how it should be taught today. A versatile research technique that can assist in achieving this objective is the Delphi technique, as it is used to conduct futures research or research into areas where knowledge is incomplete. The Delphi method is a type of group interview, using the collective opinion of knowledgeable experts. The technique makes use of several rounds of data collection and feedback to create a consensus of opinion. Making use of the Delphi technique, research is being designed that will formulate expert‑based strategic guidelines on entrepreneurial education within the South African higher education sector. The aim of this paper is to illustrate the research design considerations that arise in the use of the Delphi technique for this purpose and how they are addressed. The main characteristics of the Delphi are presented and arguments for the use of the Delphi within a constructivist paradigm are discussed. Practical issues related to the design of the Delphi, panel‑member selection, and the formulation of panel questions, are examined. In illustrating these design considerations, the paper demonstrates a pragmatic approach to research design as well as the importance of creating coherence between the research question, the research paradigm, the research method and its use, encouraging research practitioners to adopt a more systematic, deliberate and philosophically‑based approach to research design.
- Full Text:
- Date Issued: 2008
- Authors: Amos, Trevor L , Pearse, Noel J
- Date: 2008
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270943 , vital:54494 , xlink:href="https://academic-publishing.org/index.php/ejbrm/article/view/1230/1193"
- Description: The creation of wealth is an important issue in any society, and entrepreneurship is regarded as an important catalyst in the creation of new wealth. This presents a challenge to develop entrepreneurship successfully. An important site for the development of entrepreneurship is higher education. The challenge however, is that there is a lack of a general understanding on how to educate students for entrepreneurship. In addition, current thought and practice on entrepreneurship education is historically biased, implying that graduates are essentially prepared for the past instead of for the future. From the perspective of higher education, the problem is how to develop current students to be entrepreneurial in the future. What is needed is to project into the future and then to develop an understanding of what should be taught as well as how it should be taught today. A versatile research technique that can assist in achieving this objective is the Delphi technique, as it is used to conduct futures research or research into areas where knowledge is incomplete. The Delphi method is a type of group interview, using the collective opinion of knowledgeable experts. The technique makes use of several rounds of data collection and feedback to create a consensus of opinion. Making use of the Delphi technique, research is being designed that will formulate expert‑based strategic guidelines on entrepreneurial education within the South African higher education sector. The aim of this paper is to illustrate the research design considerations that arise in the use of the Delphi technique for this purpose and how they are addressed. The main characteristics of the Delphi are presented and arguments for the use of the Delphi within a constructivist paradigm are discussed. Practical issues related to the design of the Delphi, panel‑member selection, and the formulation of panel questions, are examined. In illustrating these design considerations, the paper demonstrates a pragmatic approach to research design as well as the importance of creating coherence between the research question, the research paradigm, the research method and its use, encouraging research practitioners to adopt a more systematic, deliberate and philosophically‑based approach to research design.
- Full Text:
- Date Issued: 2008
Transformational leadership and organisational effectiveness in the administration of cricket in South Africa
- Authors: Amos, Trevor L
- Date: 1999
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270958 , vital:54495 , xlink:href="https://hdl.handle.net/10520/EJC-682622887"
- Description: After years of isolation from the international sporting arena, South African sports teams have recently achieved much success. This article is concerned specifically with managing for organisational effectiveness in South African cricket According to the theory of transformational leadership, there should be a positive relationship between this style of leadership and organisational effectiveness. The Multifactor Leadership Questionnaire was used to collect information about leadership while data for organisational effectiveness, the dependent variable, was collected using the Effectiveness Survey for Cricket Administration. Most of the results regarding the relationship of the transformational leadership factors and organisational effectiveness were significant. On the other hand, most of the results regarding the relationship of the transactional leadership factors and organisational effectiveness were not significant. The overall results provide general support of Bass' (1990) argument of the universal application of the transformational leadership theory.
- Full Text:
- Date Issued: 1999
- Authors: Amos, Trevor L
- Date: 1999
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270958 , vital:54495 , xlink:href="https://hdl.handle.net/10520/EJC-682622887"
- Description: After years of isolation from the international sporting arena, South African sports teams have recently achieved much success. This article is concerned specifically with managing for organisational effectiveness in South African cricket According to the theory of transformational leadership, there should be a positive relationship between this style of leadership and organisational effectiveness. The Multifactor Leadership Questionnaire was used to collect information about leadership while data for organisational effectiveness, the dependent variable, was collected using the Effectiveness Survey for Cricket Administration. Most of the results regarding the relationship of the transformational leadership factors and organisational effectiveness were significant. On the other hand, most of the results regarding the relationship of the transactional leadership factors and organisational effectiveness were not significant. The overall results provide general support of Bass' (1990) argument of the universal application of the transformational leadership theory.
- Full Text:
- Date Issued: 1999
Management education and training
- Authors: Amos, Trevor L , Quinn, Lynn
- Date: 1997
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270902 , vital:54490 , xlink:href="https://hdl.handle.net/10520/AJA10113487_559"
- Description: The paper outlines the role of language in leaming and cognitive development and argues that management education and training needs to be integrated with language development to enable students to cope with the demands made of them at university as well as with those of careers in the business world. An integrated language developmEint project developed by the Depanment of Management and academic language practitioners at Rhodes Uhlvetsity is descriptionbed and suggestions are outlined as to how university Management departments can integrate language development in their mainstream teaching.
- Full Text:
- Date Issued: 1997
- Authors: Amos, Trevor L , Quinn, Lynn
- Date: 1997
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270902 , vital:54490 , xlink:href="https://hdl.handle.net/10520/AJA10113487_559"
- Description: The paper outlines the role of language in leaming and cognitive development and argues that management education and training needs to be integrated with language development to enable students to cope with the demands made of them at university as well as with those of careers in the business world. An integrated language developmEint project developed by the Depanment of Management and academic language practitioners at Rhodes Uhlvetsity is descriptionbed and suggestions are outlined as to how university Management departments can integrate language development in their mainstream teaching.
- Full Text:
- Date Issued: 1997
Integrating the development of academic literacy into mainstream teaching and learning
- Authors: Amos, Trevor L
- Date: 1999
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270891 , vital:54489 , xlink:href="https://hdl.handle.net/10520/AJA10113487_947"
- Description: Higher education is challenged to develop effective and independent learners of students who experience learning difficulties. These students are however, (potentially) able to engage in and do not necessarily lack the the inherent bstract cognitive capability necessary for academic success. The aim of this article is to be done in practice to integrate the development of academic literacy into mainstream teaching and learning.
- Full Text:
- Date Issued: 1999
- Authors: Amos, Trevor L
- Date: 1999
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270891 , vital:54489 , xlink:href="https://hdl.handle.net/10520/AJA10113487_947"
- Description: Higher education is challenged to develop effective and independent learners of students who experience learning difficulties. These students are however, (potentially) able to engage in and do not necessarily lack the the inherent bstract cognitive capability necessary for academic success. The aim of this article is to be done in practice to integrate the development of academic literacy into mainstream teaching and learning.
- Full Text:
- Date Issued: 1999
Understanding and responding to student learning difficulties within the higher education context
- Amos, Trevor L, Fischer, Sarah
- Authors: Amos, Trevor L , Fischer, Sarah
- Date: 1998
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270972 , vital:54497 , xlink:href="https://hdl.handle.net/10520/AJA10113487_570"
- Description: Higher education in South Africa is challenged to promote the academic success of students through quality teaching and learning. This article provides a sound theoretical understanding of student learning difficulties as difficulties of accessing and mastering the cognitive processes entailed in the groundrules of the specific academic disciplines within higher education Based on this theoretical groundwork. the article argues for the integration of academic development into the mainstream teaching and learning activities of specific disciplines where the tutorial system is used to develop the specific academic literacy required for success within the discipline.
- Full Text:
- Date Issued: 1998
- Authors: Amos, Trevor L , Fischer, Sarah
- Date: 1998
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270972 , vital:54497 , xlink:href="https://hdl.handle.net/10520/AJA10113487_570"
- Description: Higher education in South Africa is challenged to promote the academic success of students through quality teaching and learning. This article provides a sound theoretical understanding of student learning difficulties as difficulties of accessing and mastering the cognitive processes entailed in the groundrules of the specific academic disciplines within higher education Based on this theoretical groundwork. the article argues for the integration of academic development into the mainstream teaching and learning activities of specific disciplines where the tutorial system is used to develop the specific academic literacy required for success within the discipline.
- Full Text:
- Date Issued: 1998
Factors Influencing the Entrepreneurial Orientation of Students
- Amos, Trevor L, Louw, L, Baxter, Jeremy
- Authors: Amos, Trevor L , Louw, L , Baxter, Jeremy
- Date: 2001
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270879 , vital:54488 , xlink:href="https://scialert.net/abstract/?doi=jas.2001.329.334"
- Description: With entrepreneurship being an important catalyst in wealth creation, it is imperative that entrepreneurs be developed. The aim of this exploratory research is to contribute to our understanding of the development of entrepreneurs and to encourage further research in the area. This paper proposes a model of entrepreneurship and tests the influencing factors on this model. Based on the findings of this research, it appears that entrepreneurial activity of family members influences the development of entrepreneurship more than gender, race, age or education. With education being a logical site for the development of entrepreneurship within society, this finding raises more questions than it provides answers, highlighting the need for educators to critically review the educational process if entrepreneurship is to be a realistic outcome.
- Full Text:
- Date Issued: 2001
- Authors: Amos, Trevor L , Louw, L , Baxter, Jeremy
- Date: 2001
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/270879 , vital:54488 , xlink:href="https://scialert.net/abstract/?doi=jas.2001.329.334"
- Description: With entrepreneurship being an important catalyst in wealth creation, it is imperative that entrepreneurs be developed. The aim of this exploratory research is to contribute to our understanding of the development of entrepreneurs and to encourage further research in the area. This paper proposes a model of entrepreneurship and tests the influencing factors on this model. Based on the findings of this research, it appears that entrepreneurial activity of family members influences the development of entrepreneurship more than gender, race, age or education. With education being a logical site for the development of entrepreneurship within society, this finding raises more questions than it provides answers, highlighting the need for educators to critically review the educational process if entrepreneurship is to be a realistic outcome.
- Full Text:
- Date Issued: 2001
Establishing computational approaches towards identifying malarial allosteric modulators: a case study of plasmodium falciparum hsp70s
- Amusengeri, Arnold, Astl, Lindy, Lobb, Kevin A, Verkhivker, Gennady M, Tastan Bishop, Özlem
- Authors: Amusengeri, Arnold , Astl, Lindy , Lobb, Kevin A , Verkhivker, Gennady M , Tastan Bishop, Özlem
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163000 , vital:41003 , https://doi.org/10.3390/ijms20225574
- Description: Combating malaria is almost a never-ending battle, as Plasmodium parasites develop resistance to the drugs used against them, as observed recently in artemisinin-based combination therapies. The main concern now is if the resistant parasite strains spread from Southeast Asia to Africa, the continent hosting most malaria cases. To prevent catastrophic results, we need to find non-conventional approaches. Allosteric drug targeting sites and modulators might be a new hope for malarial treatments. Heat shock proteins (HSPs) are potential malarial drug targets and have complex allosteric control mechanisms. Yet, studies on designing allosteric modulators against them are limited. Here, we identified allosteric modulators (SANC190 and SANC651) against P. falciparum Hsp70-1 and Hsp70-x, affecting the conformational dynamics of the proteins, delicately balanced by the endogenous ligands. Previously, we established a pipeline to identify allosteric sites and modulators. This study also further investigated alternative approaches to speed up the process by comparing all atom molecular dynamics simulations and dynamic residue network analysis with the coarse-grained (CG) versions of the calculations. Betweenness centrality (BC) profiles for PfHsp70-1 and PfHsp70-x derived from CG simulations not only revealed similar trends but also pointed to the same functional regions and specific residues corresponding to BC profile peaks.
- Full Text:
- Date Issued: 2019
- Authors: Amusengeri, Arnold , Astl, Lindy , Lobb, Kevin A , Verkhivker, Gennady M , Tastan Bishop, Özlem
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163000 , vital:41003 , https://doi.org/10.3390/ijms20225574
- Description: Combating malaria is almost a never-ending battle, as Plasmodium parasites develop resistance to the drugs used against them, as observed recently in artemisinin-based combination therapies. The main concern now is if the resistant parasite strains spread from Southeast Asia to Africa, the continent hosting most malaria cases. To prevent catastrophic results, we need to find non-conventional approaches. Allosteric drug targeting sites and modulators might be a new hope for malarial treatments. Heat shock proteins (HSPs) are potential malarial drug targets and have complex allosteric control mechanisms. Yet, studies on designing allosteric modulators against them are limited. Here, we identified allosteric modulators (SANC190 and SANC651) against P. falciparum Hsp70-1 and Hsp70-x, affecting the conformational dynamics of the proteins, delicately balanced by the endogenous ligands. Previously, we established a pipeline to identify allosteric sites and modulators. This study also further investigated alternative approaches to speed up the process by comparing all atom molecular dynamics simulations and dynamic residue network analysis with the coarse-grained (CG) versions of the calculations. Betweenness centrality (BC) profiles for PfHsp70-1 and PfHsp70-x derived from CG simulations not only revealed similar trends but also pointed to the same functional regions and specific residues corresponding to BC profile peaks.
- Full Text:
- Date Issued: 2019
Understanding the Pyrimethamine drug resistance mechanism via combined molecular dynamics and dynamic residue network analysis:
- Amusengeri, Arnold, Tata, Rolland B, Tastan Bishop, Özlem
- Authors: Amusengeri, Arnold , Tata, Rolland B , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163022 , vital:41005 , https://doi.org/10.3390/molecules25040904
- Description: In this era of precision medicine, insights into the resistance mechanism of drugs are integral for the development of potent therapeutics. Here, we sought to understand the contribution of four point mutations (N51I, C59R, S108N, and I164L) within the active site of the malaria parasite enzyme dihydrofolate reductase (DHFR) towards the resistance of the antimalarial drug pyrimethamine. Homology modeling was used to obtain full-length models of wild type (WT) and mutant DHFR. Molecular docking was employed to dock pyrimethamine onto the generated structures. Subsequent all-atom molecular dynamics (MD) simulations and binding free-energy computations highlighted that pyrimethamine’s stability and affinity inversely relates to the number of mutations within its binding site and, hence, resistance severity.
- Full Text:
- Date Issued: 2020
- Authors: Amusengeri, Arnold , Tata, Rolland B , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163022 , vital:41005 , https://doi.org/10.3390/molecules25040904
- Description: In this era of precision medicine, insights into the resistance mechanism of drugs are integral for the development of potent therapeutics. Here, we sought to understand the contribution of four point mutations (N51I, C59R, S108N, and I164L) within the active site of the malaria parasite enzyme dihydrofolate reductase (DHFR) towards the resistance of the antimalarial drug pyrimethamine. Homology modeling was used to obtain full-length models of wild type (WT) and mutant DHFR. Molecular docking was employed to dock pyrimethamine onto the generated structures. Subsequent all-atom molecular dynamics (MD) simulations and binding free-energy computations highlighted that pyrimethamine’s stability and affinity inversely relates to the number of mutations within its binding site and, hence, resistance severity.
- Full Text:
- Date Issued: 2020