Investigation of molecular mechanism of recognition between citral and MARK4: A newer therapeutic approach to attenuate cancer cell progression
- Naz, Farha, Khan, Faez I, Mohammad, Taj, Khan, Parvez, Manzoor, Saaliqa, Hasan, Gulam M, Lobb, Kevin A, Luqman, Suaib, Ahmad, Faizan, Hassan, M Imtaiyaz
- Authors: Naz, Farha , Khan, Faez I , Mohammad, Taj , Khan, Parvez , Manzoor, Saaliqa , Hasan, Gulam M , Lobb, Kevin A , Luqman, Suaib , Ahmad, Faizan , Hassan, M Imtaiyaz
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447967 , vital:74687 , xlink:href="https://doi.org/10.1016/j.ijbiomac.2017.10.143"
- Description: Microtubule affinity regulating kinase 4 (MARK4) is a member of AMP-activated protein kinase, found to be involved in apoptosis, inflammation and many other regulatory pathways. Since, its aberrant expression is directly associated with the cell cycle and thus cancer. Therefore, MARK4 is being considered as a potential drug target for cancer therapy. Here, we investigated the mechanism of inhibition of MARK4 activity by citral. Docking studies suggested that citral effectively binds to the active site cavity, and complex is stabilized by several interactions. We further performed molecular dynamics simulation of MARK4-citral complex under explicit water condition for 100 ns and observed that binding of citral to MARK4 was quite stable. Fluorescence binding studies suggested that citral strongly binds to MARK4 and thereby inhibits its enzyme activity which was measured by the kinase inhibition assay. We further performed MTT assay and observed that citral inhibits proliferation of breast cancer cell line MCF-7. This work provides a newer insight into the use of citral as novel cancer therapeutics through the MARK4 inhibition. Results may be employed to design novel therapeutic molecule using citral as a scaffold for MARK4 inhibition to fight related diseases.
- Full Text:
- Date Issued: 2018
- Authors: Naz, Farha , Khan, Faez I , Mohammad, Taj , Khan, Parvez , Manzoor, Saaliqa , Hasan, Gulam M , Lobb, Kevin A , Luqman, Suaib , Ahmad, Faizan , Hassan, M Imtaiyaz
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447967 , vital:74687 , xlink:href="https://doi.org/10.1016/j.ijbiomac.2017.10.143"
- Description: Microtubule affinity regulating kinase 4 (MARK4) is a member of AMP-activated protein kinase, found to be involved in apoptosis, inflammation and many other regulatory pathways. Since, its aberrant expression is directly associated with the cell cycle and thus cancer. Therefore, MARK4 is being considered as a potential drug target for cancer therapy. Here, we investigated the mechanism of inhibition of MARK4 activity by citral. Docking studies suggested that citral effectively binds to the active site cavity, and complex is stabilized by several interactions. We further performed molecular dynamics simulation of MARK4-citral complex under explicit water condition for 100 ns and observed that binding of citral to MARK4 was quite stable. Fluorescence binding studies suggested that citral strongly binds to MARK4 and thereby inhibits its enzyme activity which was measured by the kinase inhibition assay. We further performed MTT assay and observed that citral inhibits proliferation of breast cancer cell line MCF-7. This work provides a newer insight into the use of citral as novel cancer therapeutics through the MARK4 inhibition. Results may be employed to design novel therapeutic molecule using citral as a scaffold for MARK4 inhibition to fight related diseases.
- Full Text:
- Date Issued: 2018
Iron (iii) porphyrin electrocatalyzed enantioselective carbon-chloride bond cleavage of hexachlorocyclohexanes (HCHs): combined experimental investigation and theoretical calculations
- Liang, Xu, Li, Minzhi, Mack, John, Lobb, Kevin A, Zhu, Weihua
- Authors: Liang, Xu , Li, Minzhi , Mack, John , Lobb, Kevin A , Zhu, Weihua
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447979 , vital:74688 , xlink:href="https://pubs.rsc.org/en/content/articlehtml/2018/dt/c8dt02510j"
- Description: Enantioselective electrocatalysis of α-, β-, γ- and δ-hexachlorocyclohexanes (HCHs) by tetrakis-pentafluorophenyl-Fe(III)porphyrin is described. The first example of the combined use of electrochemical measurements and theoretical calculations to determine the mechanism of the enantioselective C–Cl bond cleavage of the electrocatalysis is reported. The electrochemical measurements demonstrate that the reactivity of the HCHs follows the order γ-HCH > α-HCH > δ-HCH > β-HCH. Steric considerations and a molecular orbital theory approach can be used to rationalize the enantioselective nature of the catalysis based on the ease of approach of each Cl atom to the central Fe(I) ion and a consideration of the nodes on the C–Cl bonds that weaken these bonds in a manner that results in bond cleavage and the formation of an Fe–Cl bond.
- Full Text:
- Date Issued: 2018
- Authors: Liang, Xu , Li, Minzhi , Mack, John , Lobb, Kevin A , Zhu, Weihua
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447979 , vital:74688 , xlink:href="https://pubs.rsc.org/en/content/articlehtml/2018/dt/c8dt02510j"
- Description: Enantioselective electrocatalysis of α-, β-, γ- and δ-hexachlorocyclohexanes (HCHs) by tetrakis-pentafluorophenyl-Fe(III)porphyrin is described. The first example of the combined use of electrochemical measurements and theoretical calculations to determine the mechanism of the enantioselective C–Cl bond cleavage of the electrocatalysis is reported. The electrochemical measurements demonstrate that the reactivity of the HCHs follows the order γ-HCH > α-HCH > δ-HCH > β-HCH. Steric considerations and a molecular orbital theory approach can be used to rationalize the enantioselective nature of the catalysis based on the ease of approach of each Cl atom to the central Fe(I) ion and a consideration of the nodes on the C–Cl bonds that weaken these bonds in a manner that results in bond cleavage and the formation of an Fe–Cl bond.
- Full Text:
- Date Issued: 2018
Isolation and Characterisation of Stigmasterol and β–Sitosterol from Anthocleista djalonensis A. Chev.
- Okoro, Ijeoma S, Tor-Anyiin, Terrumun A, Igoli, John O, Noundou, Xavier S, Krause, Rui W M
- Authors: Okoro, Ijeoma S , Tor-Anyiin, Terrumun A , Igoli, John O , Noundou, Xavier S , Krause, Rui W M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/126191 , vital:35857 , https://doi.org/10.9734/AJOCS/2017/37147
- Description: Aim: Anthocleista djalonensis A. Chev. is a plant with several chemical constituents whichaccounts for its ethno-pharmacological uses. The present study is aimed at identifying and characterizing the active principles from the roots of the plant. Place and Duration of Study: The study was carried out at the Department of Organic Chemistry,Rhodes University, Grahamstown, South Africa between March and July 2016. Methodology: The root powder was subjected to maceration with methanol to obtain the crude extract. The methanol extract was fractionated using hexane, ethyl acetate and acetone successively. The acetone extract was thereafter subjected to column chromatography to isolate any pure components. Results: White needle-like crystals were obtained which on spectral analysis(IR, 1H NMR, 13C NMR, 2D- NMR, and ESI-MS ) were identified as a mixture of stigmasterol and β-sitosterol. Conclusion: The compounds isolated were identified as stigmasterol and β-sitosterol.
- Full Text:
- Date Issued: 2018
- Authors: Okoro, Ijeoma S , Tor-Anyiin, Terrumun A , Igoli, John O , Noundou, Xavier S , Krause, Rui W M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/126191 , vital:35857 , https://doi.org/10.9734/AJOCS/2017/37147
- Description: Aim: Anthocleista djalonensis A. Chev. is a plant with several chemical constituents whichaccounts for its ethno-pharmacological uses. The present study is aimed at identifying and characterizing the active principles from the roots of the plant. Place and Duration of Study: The study was carried out at the Department of Organic Chemistry,Rhodes University, Grahamstown, South Africa between March and July 2016. Methodology: The root powder was subjected to maceration with methanol to obtain the crude extract. The methanol extract was fractionated using hexane, ethyl acetate and acetone successively. The acetone extract was thereafter subjected to column chromatography to isolate any pure components. Results: White needle-like crystals were obtained which on spectral analysis(IR, 1H NMR, 13C NMR, 2D- NMR, and ESI-MS ) were identified as a mixture of stigmasterol and β-sitosterol. Conclusion: The compounds isolated were identified as stigmasterol and β-sitosterol.
- Full Text:
- Date Issued: 2018
Jesus, Che, Luaty: on the relationship between a digital picture and an iconic image in political iconography in Angola
- Authors: Siegert, Nadine
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/145919 , vital:38478 , DOI: 10.2979/africatoday.65.1.04
- Description: This essay makes a close examination of a selection of images of the Angolan rapper Luaty Beirão, who became internationally known as a political activist during his imprisonment in June 2015, accused of staging a coup d'état. By analyzing and interpreting images that were highly mediatized during that period, this article shows how political iconography can be traced back to Christian iconography and other images. Such filiations of images and their mediatization invoke a power that contributes to the formation of political and popular icons. This article analyzes this nexus by deconstructing the transmutation of a photograph into a popular icon.
- Full Text:
- Date Issued: 2018
- Authors: Siegert, Nadine
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/145919 , vital:38478 , DOI: 10.2979/africatoday.65.1.04
- Description: This essay makes a close examination of a selection of images of the Angolan rapper Luaty Beirão, who became internationally known as a political activist during his imprisonment in June 2015, accused of staging a coup d'état. By analyzing and interpreting images that were highly mediatized during that period, this article shows how political iconography can be traced back to Christian iconography and other images. Such filiations of images and their mediatization invoke a power that contributes to the formation of political and popular icons. This article analyzes this nexus by deconstructing the transmutation of a photograph into a popular icon.
- Full Text:
- Date Issued: 2018
Kowieria alveoformis gen. nov. sp. nov., a new heterosporous lycophyte from the Latest Devonian of Southern Africa
- Gess, Robert W, Prestianni, Cyrille
- Authors: Gess, Robert W , Prestianni, Cyrille
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/73894 , vital:30239 , https://doi.org/10.1016/j.revpalbo.2017.10.002
- Description: A new lycopsid, Kowieria alveoformis gen. et sp. nov., is described from the FamennianWitpoort Formation, Grahamstown, South Africa. It possesses spirally arranged elongated falcate vegetative leaves. Terminal bisporangiate strobili are present and show loosely grouped micro- and megasporophylls. Sporophylls are similar in shape to the vegetative leaves though somewhat wider with a marked expansion to house the sporangium. One sporangium is attached directly to the adaxial surface of the lamina. Each megasporangium contains up to four heavily ornamented hologulate megaspores of the Lagenicula type. The combination of both basal and derived characters within this plant places it at an interesting position at the base of the phylogenetic tree of rhizomorphic lycopsids.
- Full Text:
- Date Issued: 2018
- Authors: Gess, Robert W , Prestianni, Cyrille
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/73894 , vital:30239 , https://doi.org/10.1016/j.revpalbo.2017.10.002
- Description: A new lycopsid, Kowieria alveoformis gen. et sp. nov., is described from the FamennianWitpoort Formation, Grahamstown, South Africa. It possesses spirally arranged elongated falcate vegetative leaves. Terminal bisporangiate strobili are present and show loosely grouped micro- and megasporophylls. Sporophylls are similar in shape to the vegetative leaves though somewhat wider with a marked expansion to house the sporangium. One sporangium is attached directly to the adaxial surface of the lamina. Each megasporangium contains up to four heavily ornamented hologulate megaspores of the Lagenicula type. The combination of both basal and derived characters within this plant places it at an interesting position at the base of the phylogenetic tree of rhizomorphic lycopsids.
- Full Text:
- Date Issued: 2018
Legitimation of knowers for access in science
- Authors: Ellery, Karen
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/70302 , vital:29643 , https://doi.org/10.1080/02602930701772788
- Description: Based on poor performance of students in the higher education science context, this paper questions the current focus on content knowledge and, in so doing, examines the role student knowers play in enabling epistemological access. Using Legitimation Code Theory, and drawing on data from interviews, course documents, observations, and critical reflections, the social relations of a science foundation course in the South African context are examined empirically to reveal the valuing of two kinds of knowers—learning-context knowers (or science learners) and production-context knowers (or scientists). Since being both kinds of knowers is necessary for access to powerful science knowledge, and home and educational contexts of certain groups of students are better in terms of enabling science knowers and learners than others, it is argued from a social justice perspective that science (and other) curricula account for knower attributes in enabling access for success for all students.
- Full Text:
- Date Issued: 2018
- Authors: Ellery, Karen
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/70302 , vital:29643 , https://doi.org/10.1080/02602930701772788
- Description: Based on poor performance of students in the higher education science context, this paper questions the current focus on content knowledge and, in so doing, examines the role student knowers play in enabling epistemological access. Using Legitimation Code Theory, and drawing on data from interviews, course documents, observations, and critical reflections, the social relations of a science foundation course in the South African context are examined empirically to reveal the valuing of two kinds of knowers—learning-context knowers (or science learners) and production-context knowers (or scientists). Since being both kinds of knowers is necessary for access to powerful science knowledge, and home and educational contexts of certain groups of students are better in terms of enabling science knowers and learners than others, it is argued from a social justice perspective that science (and other) curricula account for knower attributes in enabling access for success for all students.
- Full Text:
- Date Issued: 2018
Lesbian, gay, and bisexual (LGB) people's experiences of nursing health care: An emancipatory nursing practice integrative review
- Nhamo-Murire, Mercy, Macleod, Catriona I
- Authors: Nhamo-Murire, Mercy , Macleod, Catriona I
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/444357 , vital:74222 , xlink:href="https://doi.org/10.1111/ijn.12606"
- Description: To review current research on lesbian, gay, and bisexual (LGB) individuals' experience of nursing services from an emancipatory nursing practice framework.
- Full Text:
- Date Issued: 2018
- Authors: Nhamo-Murire, Mercy , Macleod, Catriona I
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/444357 , vital:74222 , xlink:href="https://doi.org/10.1111/ijn.12606"
- Description: To review current research on lesbian, gay, and bisexual (LGB) individuals' experience of nursing services from an emancipatory nursing practice framework.
- Full Text:
- Date Issued: 2018
Limitations of the random response technique and a call to implement the ballot box method for estimating recreational angler compliance using surveys:
- Bova, Christopher S, Aswani, Shankar, Farthing, Matthew W, Potts, Warren M
- Authors: Bova, Christopher S , Aswani, Shankar , Farthing, Matthew W , Potts, Warren M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/145359 , vital:38431 , DOI: 10.1016/j.fishres.2018.06.017
- Description: Accurate estimation of the levels of non-compliance to fishing regulations is crucial in ensuring that long term sustainability goals of fisheries are met. When requesting information regarding sensitive behaviour, such as an angler’s non-compliance to regulations through direct questioning methods (DQM), their responses can be influenced by social desirability bias (SDB). Literature in human dimensions research on methods for controlling this bias is limited. There has been an emerging prevalence in the use of the random response technique (RRT), which is a method aimed at reducing SDB in questions regarding sensitive behaviour, although it has never been validated against observed data in an environmental resource use context. An alternative to the RRT, the use of a ballot box method (BBM) has been successfully implemented to reduce SDB in contingent valuation studies and is introduced in this paper as a method for reducing SDB in face-to-face survey responses regarding sensitive behaviour.
- Full Text:
- Date Issued: 2018
- Authors: Bova, Christopher S , Aswani, Shankar , Farthing, Matthew W , Potts, Warren M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/145359 , vital:38431 , DOI: 10.1016/j.fishres.2018.06.017
- Description: Accurate estimation of the levels of non-compliance to fishing regulations is crucial in ensuring that long term sustainability goals of fisheries are met. When requesting information regarding sensitive behaviour, such as an angler’s non-compliance to regulations through direct questioning methods (DQM), their responses can be influenced by social desirability bias (SDB). Literature in human dimensions research on methods for controlling this bias is limited. There has been an emerging prevalence in the use of the random response technique (RRT), which is a method aimed at reducing SDB in questions regarding sensitive behaviour, although it has never been validated against observed data in an environmental resource use context. An alternative to the RRT, the use of a ballot box method (BBM) has been successfully implemented to reduce SDB in contingent valuation studies and is introduced in this paper as a method for reducing SDB in face-to-face survey responses regarding sensitive behaviour.
- Full Text:
- Date Issued: 2018
Literary cynics: Borges, Beckett, Coetzee
- Authors: Marais, Mike
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/144148 , vital:38315 , DOI: 10.1080/17533171.2018.1427849
- Description: Samuel Beckett’s last few plays were all written by invitation and performed before specialist audiences who were familiar with his work and knew what they could expect from him. Arthur Rose quite rightly points out that such expectation is constitutive in nature, that these audiences approached the plays with the baggage of a “preconceived Beckett” (112–13). He is also right when he argues that Beckett, in the plays in question, evinces an awareness of his reification as an author and of the authority of reputation.
- Full Text:
- Date Issued: 2018
- Authors: Marais, Mike
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/144148 , vital:38315 , DOI: 10.1080/17533171.2018.1427849
- Description: Samuel Beckett’s last few plays were all written by invitation and performed before specialist audiences who were familiar with his work and knew what they could expect from him. Arthur Rose quite rightly points out that such expectation is constitutive in nature, that these audiences approached the plays with the baggage of a “preconceived Beckett” (112–13). He is also right when he argues that Beckett, in the plays in question, evinces an awareness of his reification as an author and of the authority of reputation.
- Full Text:
- Date Issued: 2018
Local perceptions of environmental changes in fishing communities of southwest Madagascar:
- Lemahieu, Anne, Scott, Lucy E P, Malherbe, Willem, Mahatante, Paubert T, Randrianarimanana, José V, Aswani, Shankar
- Authors: Lemahieu, Anne , Scott, Lucy E P , Malherbe, Willem , Mahatante, Paubert T , Randrianarimanana, José V , Aswani, Shankar
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/145370 , vital:38432 , DOI: 10.1016/j.ocecoaman.2018.06.012
- Description: Southwest Madagascar is a region that is significantly impacted upon by climate change. As in a lot of developing countries, the livelihoods of many communities in this region are dependent on fishing. This makes these communities particularly vulnerable to climate-related changes. We conducted a survey in two coastal fishing communities in the Toliara Province, Ambola and Ambotsibotsike. Using a free listing exercise, semi-structured interviews and focus group methods, we documented local perceptions of environmental changes and responses to changes. Results were compared, taking into account the differences in the degree of remoteness, market exposure and religiosity. Time periods that respondents reported as having had a high degree of change were compared to time periods of historical records of cyclones occurring in Toliara Province.
- Full Text:
- Date Issued: 2018
- Authors: Lemahieu, Anne , Scott, Lucy E P , Malherbe, Willem , Mahatante, Paubert T , Randrianarimanana, José V , Aswani, Shankar
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/145370 , vital:38432 , DOI: 10.1016/j.ocecoaman.2018.06.012
- Description: Southwest Madagascar is a region that is significantly impacted upon by climate change. As in a lot of developing countries, the livelihoods of many communities in this region are dependent on fishing. This makes these communities particularly vulnerable to climate-related changes. We conducted a survey in two coastal fishing communities in the Toliara Province, Ambola and Ambotsibotsike. Using a free listing exercise, semi-structured interviews and focus group methods, we documented local perceptions of environmental changes and responses to changes. Results were compared, taking into account the differences in the degree of remoteness, market exposure and religiosity. Time periods that respondents reported as having had a high degree of change were compared to time periods of historical records of cyclones occurring in Toliara Province.
- Full Text:
- Date Issued: 2018
Low symmetric metallophthalocyanine modified electrode via click chemistry for simultaneous detection of heavy metals
- Fomo, Gertrude, Nwaji, Njemuwa, Nyokong, Tebello
- Authors: Fomo, Gertrude , Nwaji, Njemuwa , Nyokong, Tebello
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/187914 , vital:44709 , xlink:href="https://doi.org/10.1016/j.jelechem.2018.02.016"
- Description: Beside different methods and materials used to develop electrochemical sensors, the modification of the electrode using click reaction based on metallophthalocyanine (MPc) compounds are shown to improve the stability and sensitivity of the sensor. This work reported the development of electrochemical sensor for mercury (II), Lead (II), copper (II) and cadmium (II) ions detection based on the synthesized novel low symmetry alkyne terminated cobalt Phthalocyanine (CoPc) derivative. Differential pulse stripping voltammetry (DPSV) technique was employed for the first time in simultaneous determination of trace levels of the above metal ions using modified glassy carbon electrode (GCE) via click chemistry. Under the optimum experimental conditions, the anodic peak current is proportional to the concentrations of metal ions over a wide range of 0 to 0.1 mM with nanolevel detection limit of 81.94, 327.71, 55.87 and 347.06 nM and the sensitivity of 866.23 ± 5.48, 215.82 ± 2.16, 1979.48 ± 11.47 and 204.50 ± 1.10 μA/mM for Hg(II), Cu(II), Pb(II) and Cd(II), respectively. The selectivity of the clicked-CoPc modified GCE toward Hg(II), Cu(II), Pb(II), Cd(II) present no interference from these metals ions. The fabricated electrochemical sensor exhibited very good electrochemical properties such as good reproducibility, stability, reusability and is suitable for the detection of heavy metal ions in tap water in our laboratory.
- Full Text:
- Date Issued: 2018
- Authors: Fomo, Gertrude , Nwaji, Njemuwa , Nyokong, Tebello
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/187914 , vital:44709 , xlink:href="https://doi.org/10.1016/j.jelechem.2018.02.016"
- Description: Beside different methods and materials used to develop electrochemical sensors, the modification of the electrode using click reaction based on metallophthalocyanine (MPc) compounds are shown to improve the stability and sensitivity of the sensor. This work reported the development of electrochemical sensor for mercury (II), Lead (II), copper (II) and cadmium (II) ions detection based on the synthesized novel low symmetry alkyne terminated cobalt Phthalocyanine (CoPc) derivative. Differential pulse stripping voltammetry (DPSV) technique was employed for the first time in simultaneous determination of trace levels of the above metal ions using modified glassy carbon electrode (GCE) via click chemistry. Under the optimum experimental conditions, the anodic peak current is proportional to the concentrations of metal ions over a wide range of 0 to 0.1 mM with nanolevel detection limit of 81.94, 327.71, 55.87 and 347.06 nM and the sensitivity of 866.23 ± 5.48, 215.82 ± 2.16, 1979.48 ± 11.47 and 204.50 ± 1.10 μA/mM for Hg(II), Cu(II), Pb(II) and Cd(II), respectively. The selectivity of the clicked-CoPc modified GCE toward Hg(II), Cu(II), Pb(II), Cd(II) present no interference from these metals ions. The fabricated electrochemical sensor exhibited very good electrochemical properties such as good reproducibility, stability, reusability and is suitable for the detection of heavy metal ions in tap water in our laboratory.
- Full Text:
- Date Issued: 2018
LRP1 is required for novobiocin-mediated fibronectin turnover:
- Boel, Natasha M-E, Hunter, Morgan C, Edkins, Adrienne L
- Authors: Boel, Natasha M-E , Hunter, Morgan C , Edkins, Adrienne L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164896 , vital:41182 , DOI: 10.1038/s41598-018-29531-2
- Description: Fibronectin (FN) plays a major role in the stability and organization of the extracellular matrix (ECM). We have previously demonstrated that FN interacts directly with Hsp90, as well as showing that the Hsp90 inhibitor novobiocin results in FN turnover via a receptor mediated process. However, the receptor involved has not been previously identified. LRP1 is a ubiquitous receptor responsible for the internalisation of numerous ligands that binds both Hsp90 and FN, and therefore we investigated whether LRP1 was involved in novobiocin-mediated FN turnover.
- Full Text:
- Date Issued: 2018
- Authors: Boel, Natasha M-E , Hunter, Morgan C , Edkins, Adrienne L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164896 , vital:41182 , DOI: 10.1038/s41598-018-29531-2
- Description: Fibronectin (FN) plays a major role in the stability and organization of the extracellular matrix (ECM). We have previously demonstrated that FN interacts directly with Hsp90, as well as showing that the Hsp90 inhibitor novobiocin results in FN turnover via a receptor mediated process. However, the receptor involved has not been previously identified. LRP1 is a ubiquitous receptor responsible for the internalisation of numerous ligands that binds both Hsp90 and FN, and therefore we investigated whether LRP1 was involved in novobiocin-mediated FN turnover.
- Full Text:
- Date Issued: 2018
Mapping the field of Higher Education Research using PhD examination reports
- McKenna, Sioux, Quinn, Lynn, Vorster, Jo-Anne
- Authors: McKenna, Sioux , Quinn, Lynn , Vorster, Jo-Anne
- 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
- 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.
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- Date Issued: 2018
Marine resource management and conservation in the Anthropocene
- Aswani, Shankar, Basurto, Xavier, Ferse, Sebastian, Glaser, Marion, Campbell, Lisa, Cinner, Joshua E, Dalton, Tracey, Jenkins, Lekelia D, Miller, Marc L, Pollnac, Richard, McGill University, Christie, Patrick
- Authors: Aswani, Shankar , Basurto, Xavier , Ferse, Sebastian , Glaser, Marion , Campbell, Lisa , Cinner, Joshua E , Dalton, Tracey , Jenkins, Lekelia D , Miller, Marc L , Pollnac, Richard , McGill University , Christie, Patrick
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/124987 , vital:35716 , https://doi.10.1017/S0376892917000431
- Description: Because the Anthropocene by definition is an epoch during which environmental change is largely anthropogenic and driven by social, economic, psychological and political forces, environmental social scientists can effectively analyse human behaviour and knowledge systems in this context. In this subject review, we summarize key ways in which the environmental social sciences can better inform fisheries management policy and practice and marine conservation in the Anthropocene. We argue that environmental social scientists are particularly well positioned to synergize research to fill the gaps between: (1) local behaviours/needs/worldviews and marine resource management and biological conservation concerns; and (2) large-scale drivers of planetary environmental change (globalization, affluence, technological change, etc.) and local cognitive, socioeconomic, cultural and historical processes that shape human behaviour in the marine environment. To illustrate this, we synthesize the roles of various environmental social science disciplines in better understanding the interaction between humans and tropical marine ecosystems in developing nations where issues arising from human–coastal interactions are particularly pronounced. We focus on: (1) the application of the environmental social sciences in marine resource management and conservation; (2) the development of ‘new’ socially equitable marine conservation; (3) repopulating the seascape; (4) incorporating multi-scale dynamics of marine social–ecological systems; and (5) envisioning the future of marine resource management and conservation for producing policies and projects for comprehensive and successful resource management and conservation in the Anthropocene.
- Full Text:
- Date Issued: 2018
- Authors: Aswani, Shankar , Basurto, Xavier , Ferse, Sebastian , Glaser, Marion , Campbell, Lisa , Cinner, Joshua E , Dalton, Tracey , Jenkins, Lekelia D , Miller, Marc L , Pollnac, Richard , McGill University , Christie, Patrick
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/124987 , vital:35716 , https://doi.10.1017/S0376892917000431
- Description: Because the Anthropocene by definition is an epoch during which environmental change is largely anthropogenic and driven by social, economic, psychological and political forces, environmental social scientists can effectively analyse human behaviour and knowledge systems in this context. In this subject review, we summarize key ways in which the environmental social sciences can better inform fisheries management policy and practice and marine conservation in the Anthropocene. We argue that environmental social scientists are particularly well positioned to synergize research to fill the gaps between: (1) local behaviours/needs/worldviews and marine resource management and biological conservation concerns; and (2) large-scale drivers of planetary environmental change (globalization, affluence, technological change, etc.) and local cognitive, socioeconomic, cultural and historical processes that shape human behaviour in the marine environment. To illustrate this, we synthesize the roles of various environmental social science disciplines in better understanding the interaction between humans and tropical marine ecosystems in developing nations where issues arising from human–coastal interactions are particularly pronounced. We focus on: (1) the application of the environmental social sciences in marine resource management and conservation; (2) the development of ‘new’ socially equitable marine conservation; (3) repopulating the seascape; (4) incorporating multi-scale dynamics of marine social–ecological systems; and (5) envisioning the future of marine resource management and conservation for producing policies and projects for comprehensive and successful resource management and conservation in the Anthropocene.
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- Date Issued: 2018
Mbeki's African Renaissance Vision as Reflected in isiXhosa Written Poetry: 2005–2011
- Mona, Godfrey V, Kaschula, Russell H
- Authors: Mona, Godfrey V , Kaschula, Russell H
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/174705 , vital:42502 , ttps://doi.org/10.1080/18186874.2018.1457616
- Description: IsiXhosa literary critics have not yet interrogated literature that was produced during and after the tenure of Thabo Mvuyelwa Mbeki as deputy president and president of the Republic of South Africa in order to study the impact of his African Renaissance doctrine. This article analyses poetry that was produced from 2005 to 2011. The content of the isiXhosa written poetry is profoundly influenced by the context of former President Mbeki's African Renaissance philosophy, its implementation structures and philosophy of self-confidence and self-reliance. The selected poems analysed and interpreted in this article suggest that Mbeki's legacy of the African Renaissance empowered poets to develop a narrative that advances the building of a regenerated South African nation and the African continent.
- Full Text:
- Date Issued: 2018
- Authors: Mona, Godfrey V , Kaschula, Russell H
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/174705 , vital:42502 , ttps://doi.org/10.1080/18186874.2018.1457616
- Description: IsiXhosa literary critics have not yet interrogated literature that was produced during and after the tenure of Thabo Mvuyelwa Mbeki as deputy president and president of the Republic of South Africa in order to study the impact of his African Renaissance doctrine. This article analyses poetry that was produced from 2005 to 2011. The content of the isiXhosa written poetry is profoundly influenced by the context of former President Mbeki's African Renaissance philosophy, its implementation structures and philosophy of self-confidence and self-reliance. The selected poems analysed and interpreted in this article suggest that Mbeki's legacy of the African Renaissance empowered poets to develop a narrative that advances the building of a regenerated South African nation and the African continent.
- Full Text:
- Date Issued: 2018
Mechanisms and indicators for assessing the impact of biofuel feedstock production on ecosystem services
- Gasparatos, Alexandros, Romeu-Dalmau, Carla, von Maltitz, Graham P, Johnson, Francis X, Shackleton, Charlie M, Jarzebski, Marcin P, Jumbe, Charles, Ochieng, Caroline, Mudombi, Shakespear, Nyambane, Anne, Willis, Katherine J
- Authors: Gasparatos, Alexandros , Romeu-Dalmau, Carla , von Maltitz, Graham P , Johnson, Francis X , Shackleton, Charlie M , Jarzebski, Marcin P , Jumbe, Charles , Ochieng, Caroline , Mudombi, Shakespear , Nyambane, Anne , Willis, Katherine J
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/181368 , vital:43727 , xlink:href="https://doi.org/10.1016/j.biombioe.2018.01.024"
- Description: Biofuel feedstock production can be a significant driver of landscape modification, ecosystem change and biodiversity loss. There is growing body of literature that shows how biofuel landscapes provide various ecosystem services (e.g., feedstock for fuel, carbon sequestration) and compromise other ecosystem services (e.g., food, freshwater services). These effects are context-specific and depend largely on prior land use conditions and feedstock production practices. Changes in the flow of ecosystem services due to the conversion of natural and agricultural areas can have ripple effects on human wellbeing. Despite some recent attempts to apply to biofuel settings concepts and methods rooted in the ecosystem services literature, this is the exception rather than the rule within both the biofuel and the ecosystem services research communities. This paper synthesizes the current knowledge about the impact of biofuels on ecosystem services. It focuses especially on the feedstock production phase and outlines the main mechanisms through which landscape conversion affects the provisions of ecosystem services. It proposes conceptually coherent indicators to reflect these mechanisms and offers a critical discussion of key issues at the interface of biofuels and ecosystem services.
- Full Text:
- Date Issued: 2018
- Authors: Gasparatos, Alexandros , Romeu-Dalmau, Carla , von Maltitz, Graham P , Johnson, Francis X , Shackleton, Charlie M , Jarzebski, Marcin P , Jumbe, Charles , Ochieng, Caroline , Mudombi, Shakespear , Nyambane, Anne , Willis, Katherine J
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/181368 , vital:43727 , xlink:href="https://doi.org/10.1016/j.biombioe.2018.01.024"
- Description: Biofuel feedstock production can be a significant driver of landscape modification, ecosystem change and biodiversity loss. There is growing body of literature that shows how biofuel landscapes provide various ecosystem services (e.g., feedstock for fuel, carbon sequestration) and compromise other ecosystem services (e.g., food, freshwater services). These effects are context-specific and depend largely on prior land use conditions and feedstock production practices. Changes in the flow of ecosystem services due to the conversion of natural and agricultural areas can have ripple effects on human wellbeing. Despite some recent attempts to apply to biofuel settings concepts and methods rooted in the ecosystem services literature, this is the exception rather than the rule within both the biofuel and the ecosystem services research communities. This paper synthesizes the current knowledge about the impact of biofuels on ecosystem services. It focuses especially on the feedstock production phase and outlines the main mechanisms through which landscape conversion affects the provisions of ecosystem services. It proposes conceptually coherent indicators to reflect these mechanisms and offers a critical discussion of key issues at the interface of biofuels and ecosystem services.
- Full Text:
- Date Issued: 2018
Mechanistic insights into the urea-induced denaturation of kinase domain of human integrin linked kinase
- Syed, Sunayana B, Khan, Faez I, Khan, Sabab H, Srivastava, Saurabha, Hasan, Gulam M, Lobb, Kevin A, Islam, Asimul, Ahmad, Faizan, Hassan, M Imtaiyaz
- Authors: Syed, Sunayana B , Khan, Faez I , Khan, Sabab H , Srivastava, Saurabha , Hasan, Gulam M , Lobb, Kevin A , Islam, Asimul , Ahmad, Faizan , Hassan, M Imtaiyaz
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448013 , vital:74691 , xlink:href="https://doi.org/10.1016/j.ijbiomac.2017.12.164"
- Description: Integrin-linked kinase (ILK), a ubiquitously expressed intracellular Ser/Thr protein kinase, plays a major role in the oncogenesis and tumour progression. The conformational stability and unfolding of kinase domain of ILK (ILK193–446) was examined in the presence of increasing concentrations of urea. The stability parameters of the urea-induced denaturation were measured by monitoring changes in [θ]222 (mean residue ellipticity at 222 nm), difference absorption coefficient at 292 nm (Δε292) and intrinsic fluorescence emission intensity at pH 7.5 and 25 ± 0.1 °C. The urea-induced denaturation was found to be reversible. The protein unfolding transition occurred in the urea concentration range 3.0–7.0 M. A coincidence of normalized denaturation curves of optical properties ([θ]222, Δε292 and λmax, the wavelength of maximum emission intensity) suggested that ureainduced denaturation of kinase domain of ILK is a two-state process. We further performed molecular dynamics simulation for 100 ns to see the effect of urea on structural stability of kinase domain of ILK at atomic level. Structural changes with increasing concentrations of urea were analysed, and we observed a significant increase in the root mean square deviation, root mean square fluctuations, solvent accessible surface area and radius of gyration. A correlation was observed between in vitro and in silico studies.
- Full Text:
- Date Issued: 2018
- Authors: Syed, Sunayana B , Khan, Faez I , Khan, Sabab H , Srivastava, Saurabha , Hasan, Gulam M , Lobb, Kevin A , Islam, Asimul , Ahmad, Faizan , Hassan, M Imtaiyaz
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448013 , vital:74691 , xlink:href="https://doi.org/10.1016/j.ijbiomac.2017.12.164"
- Description: Integrin-linked kinase (ILK), a ubiquitously expressed intracellular Ser/Thr protein kinase, plays a major role in the oncogenesis and tumour progression. The conformational stability and unfolding of kinase domain of ILK (ILK193–446) was examined in the presence of increasing concentrations of urea. The stability parameters of the urea-induced denaturation were measured by monitoring changes in [θ]222 (mean residue ellipticity at 222 nm), difference absorption coefficient at 292 nm (Δε292) and intrinsic fluorescence emission intensity at pH 7.5 and 25 ± 0.1 °C. The urea-induced denaturation was found to be reversible. The protein unfolding transition occurred in the urea concentration range 3.0–7.0 M. A coincidence of normalized denaturation curves of optical properties ([θ]222, Δε292 and λmax, the wavelength of maximum emission intensity) suggested that ureainduced denaturation of kinase domain of ILK is a two-state process. We further performed molecular dynamics simulation for 100 ns to see the effect of urea on structural stability of kinase domain of ILK at atomic level. Structural changes with increasing concentrations of urea were analysed, and we observed a significant increase in the root mean square deviation, root mean square fluctuations, solvent accessible surface area and radius of gyration. A correlation was observed between in vitro and in silico studies.
- Full Text:
- Date Issued: 2018
Metabolic activity throughout early development of dusky kob Argyrosomus japonicus (Sciaenidae)
- Edworthy, Carla, James, Nicola C, Erasmus, B, Kemp, Justin O G, Kaiser, Horst, Potts, Warren M
- Authors: Edworthy, Carla , James, Nicola C , Erasmus, B , Kemp, Justin O G , Kaiser, Horst , Potts, Warren M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125159 , vital:35737 , https://doi.10.2989/1814232x.2018.1441907
- Description: Metabolism quantifies the energy-consuming activities of an organism (Nelson 2016) and is used as an indication of how organisms partition energy resources to activities that allow them to survive, grow and reproduce (Post and Lee 1996). The metabolic profile, which is a composition of the various metabolic rates of an individual, therefore gives an indication of the efficiency of energy transformation and allocation (Fry 1971; Brown et al. 2004). McKenzie et al. (2016) suggested that an organism’s physiology contributes towards its ability to survive under specific environmental conditions. As a result, physiological condition can be a reflection of the performance and fitness of an organism (Pörtner 2010). When combined with information on changing environmental conditions, physiological information can provide insight into species- and community-level responses (Pörtner and Farrell 2008). These kinds of data have served numerous ecological applications, including resource management, conservation (McKenzie et al. 2016) and climate-change assessments (Pörtner and Farrell 2008).
- Full Text:
- Date Issued: 2018
- Authors: Edworthy, Carla , James, Nicola C , Erasmus, B , Kemp, Justin O G , Kaiser, Horst , Potts, Warren M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125159 , vital:35737 , https://doi.10.2989/1814232x.2018.1441907
- Description: Metabolism quantifies the energy-consuming activities of an organism (Nelson 2016) and is used as an indication of how organisms partition energy resources to activities that allow them to survive, grow and reproduce (Post and Lee 1996). The metabolic profile, which is a composition of the various metabolic rates of an individual, therefore gives an indication of the efficiency of energy transformation and allocation (Fry 1971; Brown et al. 2004). McKenzie et al. (2016) suggested that an organism’s physiology contributes towards its ability to survive under specific environmental conditions. As a result, physiological condition can be a reflection of the performance and fitness of an organism (Pörtner 2010). When combined with information on changing environmental conditions, physiological information can provide insight into species- and community-level responses (Pörtner and Farrell 2008). These kinds of data have served numerous ecological applications, including resource management, conservation (McKenzie et al. 2016) and climate-change assessments (Pörtner and Farrell 2008).
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- Date Issued: 2018
MODE-TASK: Large-scale protein motion tools
- Ross, Caroline J, Nizami, B, Glenister, Michael, Amamuddy, Olivier S, Atilgan, Ali R, Atilgan, Canan, Tastan Bishop, Özlem
- Authors: Ross, Caroline J , Nizami, B , Glenister, Michael , Amamuddy, Olivier S , Atilgan, Ali R , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125206 , vital:35746 , http://dx.doi.org/10.1101/217505
- Description: Conventional analysis of molecular dynamics (MD) trajectories may not identify global motions of macromolecules. Normal Mode Analysis (NMA) and Principle Component Analysis (PCA) are two popular methods to quantify large-scale motions, and find the “essential motions”; and have been applied to problems such as drug resistant mutations (Nizami et al., 2016) and viral capsid expansion (Hsieh et al., 2016). MODE-TASK is an array of tools to analyse and compare protein dynamics obtained from MD simulations and/or coarse grained elastic network models. Users may perform standard PCA, kernel and incremental PCA (IPCA). Data reduction techniques (Multidimensional Scaling (MDS) and t-Distributed Stochastics Neighbor Embedding (t-SNE)) are implemented. Users may analyse normal modes by constructing elastic network models (ENMs) of a protein complex. A novel coarse graining approach extends its application to large biological assemblies.
- Full Text:
- Date Issued: 2018
- Authors: Ross, Caroline J , Nizami, B , Glenister, Michael , Amamuddy, Olivier S , Atilgan, Ali R , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125206 , vital:35746 , http://dx.doi.org/10.1101/217505
- Description: Conventional analysis of molecular dynamics (MD) trajectories may not identify global motions of macromolecules. Normal Mode Analysis (NMA) and Principle Component Analysis (PCA) are two popular methods to quantify large-scale motions, and find the “essential motions”; and have been applied to problems such as drug resistant mutations (Nizami et al., 2016) and viral capsid expansion (Hsieh et al., 2016). MODE-TASK is an array of tools to analyse and compare protein dynamics obtained from MD simulations and/or coarse grained elastic network models. Users may perform standard PCA, kernel and incremental PCA (IPCA). Data reduction techniques (Multidimensional Scaling (MDS) and t-Distributed Stochastics Neighbor Embedding (t-SNE)) are implemented. Users may analyse normal modes by constructing elastic network models (ENMs) of a protein complex. A novel coarse graining approach extends its application to large biological assemblies.
- Full Text:
- Date Issued: 2018
Modulation of human Hsp90α conformational dynamics by allosteric ligand interaction at the c-terminal domain:
- Penkler, David L, Tastan Bishop, Özlem
- Authors: Penkler, David L , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148402 , vital:38736 , DOI: 10.1101/386755
- Description: Recent years have seen heat shock protein 90 kDa (Hsp90) attract significant interest as a viable drug target, particularly for cancer. To date, designed inhibitors that target the ATPase domain demonstrate potent anti-proliferative effects, but have failed clinical trials due to high levels of associated toxicity. To circumvent this, the focus has shifted away from the ATPase domain. One option involves modulation of the protein through allosteric activation/inhibition. Here, we propose a novel approach: we use previously obtained information via residue perturbation scanning coupled with dynamic residue network analysis to identify allosteric drug targeting sites for inhibitor docking.
- Full Text:
- Date Issued: 2018
- Authors: Penkler, David L , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148402 , vital:38736 , DOI: 10.1101/386755
- Description: Recent years have seen heat shock protein 90 kDa (Hsp90) attract significant interest as a viable drug target, particularly for cancer. To date, designed inhibitors that target the ATPase domain demonstrate potent anti-proliferative effects, but have failed clinical trials due to high levels of associated toxicity. To circumvent this, the focus has shifted away from the ATPase domain. One option involves modulation of the protein through allosteric activation/inhibition. Here, we propose a novel approach: we use previously obtained information via residue perturbation scanning coupled with dynamic residue network analysis to identify allosteric drug targeting sites for inhibitor docking.
- Full Text:
- Date Issued: 2018