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Heat shock protein inhibitors: success stories

- McAlpine, Shelli R, Edkins, Adrienne L

Authors: McAlpine, Shelli R , Edkins, Adrienne L
Date: 2016
Language: English
Type: text , book
Identifier: http://hdl.handle.net/10962/66359 , vital:28940 , https://doi.org/10.1007/978-3-319-32607-8
Description: publisher version , Introduction: Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors. , This work is based on the research supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant No 98566), the Cancer Association of South Africa (CANSA), Medical Research Council South Africa (MRC-SA) and Rhodes University. The views expressed are those of the authors and should not be attributed to the DST, NRF, CANSA, MRC-SA or Rhodes University. We apologize if we have inadvertently missed any important contributions to the field.
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Date Issued: 2016

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Hsp40 Co-chaperones as drug targets: towards the development of specific inhibitors

- Pesce, Eva-Rachele, Blatch, Gregory L, Edkins, Adrienne L

Authors: Pesce, Eva-Rachele , Blatch, Gregory L , Edkins, Adrienne L
Date: 2016
Language: English
Type: text , article
Identifier: http://hdl.handle.net/10962/66335 , vital:28937 , https://doi.org/10.1007/7355_2015_92
Description: publisher version , The heat shock protein 40 (Hsp40/DNAJ) family of co-chaperones modulates the activity of the major molecular chaperone heat shock protein 70 (Hsp70) protein group. Hsp40 stimulates the basal ATPase activity of Hsp70 and hence regulates the affinity of Hsp70 for substrate proteins. The number of Hsp40 genes in most organisms is substantially greater than the number of Hsp70 genes. Therefore, different Hsp40 family members may regulate different activities of the same Hsp70. This fact, along with increasing knowledge of the function of Hsp40 in diseases, has led to certain Hsp40 isoforms being considered promising drug targets. Here we review the role of Hsp40 in human disease and recent developments towards the creation of Hsp40-specific inhibitors.
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Date Issued: 2016

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Hsp90 co-chaperones as drug targets in cancer: current perspectives

- Edkins, Adrienne L

Authors: Edkins, Adrienne L
Date: 2016
Language: English
Type: text , article
Identifier: http://hdl.handle.net/10962/66347 , vital:28938 , https://doi.org/10.1007/7355_2015_99
Description: publisher version , Hsp90 is a molecular chaperone that regulates the function of numerous oncogenic transcription factors and signalling intermediates in the cell. Inhibition of Hsp90 is sufficient to induce the proteosomal degradation of many of these proteins, and as such, the Hsp90 chaperone has been regarded as a promising drug target. The appropriate functioning of the Hsp90 chaperone is dependent on its ATPase activity and interactions with a cohort of non-substrate accessory proteins known as co-chaperones. Co-chaperones associate with Hsp90 at all stages of the chaperone cycle and regulate a range of Hsp90 functions, including ATP hydrolysis and client protein binding and release. Given the ability of co-chaperones to organise the function of the Hsp90 molecular machine, these proteins are now regarded as potential drug targets. Herein the role of selected Hsp90 co-chaperones Hop, Cdc37, p23 and Aha1 as possible drug targets is discussed with a focus on cancer. , This work is based on the research supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant No 98566), the Cancer Association of South Africa (CANSA), Medical Research Council South Africa (MRC-SA) and Rhodes University. The views expressed are those of the authors and should not be attributed to the DST, NRF, CANSA, MRC-SA or Rhodes University. We apologize if we have inadvertently missed any important contributions to the field.
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Date Issued: 2016

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Indolyl-3-ethanone-α-thioethers: a promising new class of non-toxic antimalarial agents

- Svogie, Archibald L, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D, Veale, Clinton G L

Authors: Svogie, Archibald L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Veale, Clinton G L
Date: 2016
Language: English
Type: text , article
Identifier: http://hdl.handle.net/10962/66233 , vital:28920 , https://doi.org/10.1016/j.ejmech.2016.02.056
Description: publisher version , The success of chemotherapeutics in easing the burden of malaria is under continuous threat from ever-evolving parasite resistance, including resistance to artemisinin combination therapies. Therefore, the discovery of new classes of antimalarials which inhibit new biological targets is imperative to controlling malaria. Accordingly, we report here the discovery of indolyl-3-ethanone-α-thioethers, a new class of antimalarial compounds with encouraging activity. Synthesis of a focused library of compounds revealed important insight into the SAR of this class of compounds, including critical information regarding the position and chemical nature of substituents on both the thiophenol and indole rings. This investigation ultimately led to the discovery of two hit compounds (16 and 27) which exhibited nano molar in vitro antimalarial activity coupled to no observable toxicity against a HeLa cell line.
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Date Issued: 2016

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Influence of argon-implantation on conventional and phototransferred thermoluminescence of synthetic quartz

- Nsengiyumva, S, Chithambo, Makaiko L, Pichon, L

Authors: Nsengiyumva, S , Chithambo, Makaiko L , Pichon, L
Date: 2016
Language: English
Type: text , article
Identifier: http://hdl.handle.net/10962/124732 , vital:35656 , DOI: 10.1080/10420150.2016.1194412
Description: Conventional and phototransferred thermoluminescence of crystalline synthetic quartz implanted with 70 keV Ar ions at fluences in the range 1 × 1014–5 × 1015 ions/cm2 is reported. The glow curves, recorded at 5°C/s from beta-irradiated samples of similar mass, show a prominent peak between 100°C and 120°C. The thermoluminescence intensity of all implanted samples was greater than that of the unimplanted one. The increase in sensitivity is attributed to a corresponding increase in the concentration of point defects, as a result of the implantation, which act as electron traps or recombination centres. Kinetic analysis carried out using the peak shape, whole glow-peak and curve-fitting methods produced values of the activation energy, frequency factor and order of kinetics that are generally independent of implantation fluence. This result suggests that implantation did not necessarily affect the nature of the electron traps. With respect to phototransferred thermoluminescence, it was observed that it only appeared in the sample implanted at the highest fluence of 5 × 1015 ions/cm2. This may be so because the concentration of deep traps produced as a result of implantation at low fluence is too low to give rise to phototransferred thermoluminescence. The intensity of the phototransferred thermoluminescence goes through a peak with illumination time. We attribute this behaviour to the relative concentration of holes at recombination centres and phototransferred electrons at shallow traps.
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Date Issued: 2016

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Influences on the struggle over content: considering two fine art studio practice curricula in developing/ed contexts

- Belluigi, Dina Z

Authors: Belluigi, Dina Z
Date: 2016
Language: English
Type: article , text
Identifier: http://hdl.handle.net/10962/59809 , vital:27653 , http://dx.doi.org/10.1080/13562517.2016.1183617
Description: This paper considers the influences of curricula content on the nuances of teaching and learning practices, and the ways in such influences are complicated by the contexts within which they are situated. Generated data from within the particularity of two fine art schools, one operating from the developed world in the global ‘north’ and another the developing world in the ‘south’, considers how they have negotiated the contemporary push from the professional community of practice, led by ‘western’ artmaking, towards the discourse-interest of contextualism in fine art practice education, compared to the focus on skills and mastery of more out-dated formalism. Particular emphasis is placed on the significance of such influences and pressures on the structures and cultures of teaching and learning.
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Date Issued: 2016

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Knowledge-building: educational studies in Legitimation Code Theory

- Clarence, Sherran

Authors: Clarence, Sherran
Date: 2016
Language: English
Type: book review , text
Identifier: http://hdl.handle.net/10962/61300 , vital:28013 , http://dx.doi.org/10.1080/14703297.2016.1231751
Description: A challenge facing higher education researchers, especially those new to the craft of research, is that of moving between theory and data effectively in order to mediate research findings clearly to readers. For postgraduate students and academics publishing their research, working with data and designing effective and fit-for-purpose methodologies can be a challenge. Moreover, this is not necessarily an easy area for supervisors and research mentors to assist with. In addition to researchers, practitioners working in academic development also need ways of using research – either empirical or conceptual – to augment their work with lecturers to improve teaching and learning. There are many handbooks that detail the differences between qualitative, quantitative and mixed-methods research. There are many theoretical texts to choose from. But there are few texts that offer researchers and those mentoring researchers insight into how methodology and theory connect in research studies, as well as practical tools to navigate the chaos of research, bringing theory and data into conversation in relevant and problem-oriented ways that can influence practice effectively. Karl Maton, in his introduction to this edited collection, argues that in spite of many claims within educational and social research for the need to connect research with theory more effectively, ‘the two frequently remain divorced or, at best, not on speaking terms’ (p. 1). The central premise of the book flows from this: we need to move beyond calls for more theory-informed research into education and society towards generating ways of demonstrating enactments of research that bring theory and research together meaningfully. The need for the research we publish to make clear its theoretical and methodological underpinning and enactments is crucial for effecting sustainable and meaningful change in practice within the field. This text, located within the growing field of Legitimation Code Theory (LCT) research, within the broader field of sociology of education, takes a generous step in that direction. Building on Maton’s 2014 text, Knowledge and knowers. Towards a realist sociology of education, this text delves into how LCT concepts – particularly in the dimensions of Specialisation and Semantics – can be enacted within educational research and practice.
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Date Issued: 2016

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Latrunculid sponges, their microbial communities and secondary metabolites: connecting conserved bacterial symbionts to pyrroloiminoquinone production

- Dorrington, Rosemary A, Hilliar, Storm Hannah, Kalinski, Jarmo-Charles J, Krause, Rui W M, McPhail, Kerry L, Parker-Nance, Shirley, Wlalmsley, Tara A, Waterworth, Samantha C

Authors: Dorrington, Rosemary A , Hilliar, Storm Hannah , Kalinski, Jarmo-Charles J , Krause, Rui W M , McPhail, Kerry L , Parker-Nance, Shirley , Wlalmsley, Tara A , Waterworth, Samantha C
Date: 2016
Language: English
Type: text , article
Identifier: http://hdl.handle.net/10962/65915 , vital:28858 , https://doi.org/10.1055/s-0036-1596655
Description: publisher version , The Latrunculiidae are cold water sponges known for their production of bioactive pyrroloiminoquinone alkaloids (e.g. makaluvamines, discorhabdins and tsitsikammamines). Since pyrroloiminoquinones have also been isolated from sponges belonging to other families, ascidians and microorganisms, the biosynthetic origin of these alkaloids in latrunculid sponges is likely microbial. This study focuses on the secondary metabolites produced by closely-related Tsitsikamma species and Cyclacanthia bellae, all latrunculid sponges endemic to Algoa Bay on the South African southeast coast. The sponges produced suites of related pyrroloiminoquinones, including tsitsikammine A and B, and discohabdin C and V, the combination and relative abundance of which is species-specific. Characterisation of the diversity of sponge-associated bacterial communities revealed the unprecedented conservation of two dominant bacterial species. The first, a Betaproteobacterium, is also found in other latrunculids and related sponge families, representing a novel clade of sponge endosymbionts that have co-evolved with their hosts. The second conserved bacterial symbiont is a spirochaete found only in Cyclacanthia and Tsitsikamma species that is likely to have been recruited from free-living spirochaetes in the environment. This study sheds new light on the interactions between latrunculid sponges, their dominant bacterial symbionts, and the potential involvement of these bacteria in pyrroloiminoquinone biosynthesis.
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Date Issued: 2016

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LCT and systemic functional linguistics: Enacting complimentary theories for explanatory power

- Maton, Karl, Martin, James R, Matruglio, Erika S

Authors: Maton, Karl , Martin, James R , Matruglio, Erika S
Date: 2016
Language: English
Type: text , book
Identifier: http://hdl.handle.net/10962/66491 , vital:28955
Description: publisher version , Interdisciplinarity is the future. Such is the thrust of pronouncements repeatedly heard across the social sciences and humanities. Interdisciplinarity is often equated with intellectually and socially progressive stances and greater responsiveness to business and workplace needs. Yet such axiological and economic benefits are more often assumed or proclaimed than evidenced or demonstrated (Moore 2011). Moreover，what is declared to be 'interdisciplinary' often comprises the appropriation by literary or philosophical discourses of ideas from other fields rather than genuinely interdisciplinary dialogue. Nonetheless，to highlight the vacuity of much written in its name is not to dismiss the potential of interdisciplinarity itself. There are serious ontological and epistemological arguments for bringing disciplines together in substantive research (Bhaskar and Danermark 2006). Simply put，the social world comprises more than the phenomena addressed by any one discipline. Education，for example，involves at least knowledges， knowers， knowing， and the known, implicating insights from, among others，sociology，linguistics，psychology，and philosophy (Maton 2014b: 212-13). This is not to suggest a single study must encompass the disciplinary map in order to recreate reality in its entirety, Rather，it highlights that drawing on more than one disciplinary approach may offer greater explanatory power when exploring a specific problem-situation.
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Date Issued: 2016

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LCT in mixed-methods research: evolving an instrument for quantitative data

- Maton, Karl, Howard, Sarah Katherine

Authors: Maton, Karl , Howard, Sarah Katherine
Date: 2016
Language: English
Type: text , book
Identifier: http://hdl.handle.net/10962/66479 , vital:28954
Description: publisher version , A mantra of social science declares a fundamental divide between the quantitative and the qualitative that involves more than methods. According to this depiction, the two methodologies are intrinsically associated with a range of ontological, epistemological, political and moral stances. Each of these constellations of stances is strongly integrated, such that choice of method is held to involve a series of associated choices. Each constellation is also strongly opposed to the other, along axes labelled positivism/constructivism, scientism/humanism, conservative/critical, old/new, among others. These ‘binary constellations’ (Maton 2014b: 148-70) offer a forced choice between two tightly-knit sets of practices that are portrayed as jointly exhaustive and mutually exclusive. So widespread is this methodological binarism that many scholars ‘are left with the impression that they have to pledge allegiance to one research school of thought or the other’ (Johnson and Onwuegbuzie 2004: 14). A competing mantra disclaims this divide. Distinctions underpinning the picture of binary constellations have been regularly dissolved. Arguments that one deals with numbers, the other with words, one studies behaviour, the other reveals meanings, one is hypothetico-deductive, the other inductive, one enables generalization, the other explores singular depth, among others, have been repeatedly undermined (e.g. Hammersley 1992). Indeed, the death of the divide is frequently declared. Calls for ‘transcending’ (Salomon 1991) or ‘getting over’ (Howe 1992) the quantitative-qualitative debate and arguments for mixed-methods research (Brannen 2005; Johnson and Onwuegbuzie 2004) are recurrent. These calls highlight how the methodologies offer complementary insights for research and demonstrate that eschewing either methodology on principle is unnecessarily renouncing potential explanatory power. However, the call to mixed-methods research remains more breached than honoured. Methodological monotheism remains dominant – studies of education and society typically adopt either quantitative or qualitative methods. As we shall discuss, the former is typically associated with the influence of psychology and the latter is often claimed as emblematic of sociology. Studies utilizing the sociological frameworks on which Legitimation Code Theory (LCT) builds have echoed this pattern by overwhelmingly adopting qualitative methods. Accordingly, Part I of this volume begins by exploring how LCT concepts can be enacted in qualitative research (Chapter 2). However, LCT is not limited to one methodology and a growing body of mixed-methods research is engaging with both qualitative and quantitative data. In this chapter we illustrate how this research works and the gains it offers. For resolutely qualitative researchers, the prospect of reading anything quantitative, even in mixed-methods research, may be unenticing. However, it would be a mistake to pass over this chapter, for several reasons. First, we offer insights into research practice that might surprise such scholars. As Bourdieu argued, ‘methodological indictments are too often no more than a disguised way of making a virtue out of necessity, of feigning to dismiss, to ignore in an active way, what one is ignorant of in fact’ (Bourdieu and Wacquant 1992: 226). Our aim is to contribute towards removing this reason for one-sidedness. We show, for example, how quantitative methods confound their common portrayal as neat, straightforward and procedural; they are complex and involved and require craft work and judgement. Our focus is, therefore, more practical than metaphysical. We shall not enter seemingly endless debates over whether the ‘quantitative-qualitative divide’ refers to paradigms, epistemologies or methods and whether these are complementary or incommensurable. Rather, we discuss the development of an instrument for enacting LCT concepts in quantitative methods and ground this account in real examples of mixed-methods research. Specifically, we trace the evolution of an instrument for embedding specialization codes within questionnaires through its creation for research into school music and then its development within studies of educational technology. Given that mathematics can be off-putting to the noviciate, we minimize discussion of statistics and explain measures in lay terms. Second, this is much more than a story of quantitative methods. The evolution of the instrument both shaped qualitative methods and was shaped by the data they generated, offering insights into how qualitative research can more fully engage with LCT. Its development also involved intimate dialogue with theory that shed fresh light on LCT itself, making explicit the ‘gaze’ embodied by the framework (Chapter 1, this volume). We shall highlight wider lessons learned about the craft of enacting LCT in research, lessons of direct relevance for studies using any methods. Third, we shall illustrate the explanatory power offered by using quantitative and qualitative methods together, such as providing a robust basis for detailed findings, identifying wider-scale trends typically inaccessible to qualitative methods that provide a context for their data, and facilitating knowledge-building through greater replicability across contexts and over time. For example, the technology studies built directly on the music studies to cumulatively develop the instrument and generated probably the largest data set in code sociology: 97,386 responses (83,937 student and 13,449 staff surveys) on the organizing principles of academic subjects, alongside 20 in-depth qualitative case studies of secondary schools. This offers a foundation of substantial breadth and depth for making claims about knowledge practices across the disciplinary map and a firm basis on which future research into disciplinary differences can build. Moreover, the quantitative instrument itself can be adopted or adapted in new studies, further enabling cumulative knowledge-building. Given these substantive, methodological and theoretical gains, it is perhaps surprising there exists any temptation to skip past discussion of mixed-methods research. This reflects the methodological character of the fields in which LCT emerged. We thus begin by briefly illustrating how the sociological frameworks on which the theory builds have become distanced from quantitative methods.
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Date Issued: 2016

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Learning style of Chinese event management students

- Louw, Mattheus J, Louw, Lynette, Li, Yanxia

Authors: Louw, Mattheus J , Louw, Lynette , Li, Yanxia
Date: 2016
Language: English
Type: text , book
Identifier: http://hdl.handle.net/10962/69167 , vital:29438 , https://doi.org/10.1515/9783110366778-028
Description: There is a demand for social development in China by establishing, inter alia, a framework focusing on the employability of university graduates and developing self-directed learners. The key to achieving this would be to gain a better understanding of how learning styles, as one of the cognitive factors, contribute towards academic performance in order to provide meaningful learning experiences.
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Date Issued: 2016

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Legal ethics education in South Africa: possibilities, challenges and opportunities

- Robertson, Michael, Kruuse, Helen

Authors: Robertson, Michael , Kruuse, Helen
Date: 2016
Language: English
Type: text , article
Identifier: http://hdl.handle.net/10962/68941 , vital:29341 , http://dx.doi.org/10.1080/02587203.2016.1210934
Description: Publisher version , The South African legal profession has been subject to harsh criticism in the last few years, leading to what some have called ‘an ethical crisis.’ Although this perception may or may not be warranted, there have been numerous calls for improved ethical legal practices by South African lawyers. This article seeks to contribute to a discussion about the importance of implementing legal ethics education in South African law schools. The authors (a) explore the meaning of ‘ethical legal practice’ by reference to the international literature; (b) examine the way in which legal ethics has so far been presented in the limited South African literature on the topic; (c) argue the need for a more thorough and critical literature on South African lawyers’ ethics, coupled with a commitment to developing a stronger legal ethics culture within the profession and the legal academia; and (d) suggest a possible approach for South African legal ethics education in the future, with reference to recent developments in other countries.
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Date Issued: 2016

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Linking the ‘know-that’ and ‘know-how’ knowledge through games: a quest to evolve the future for science and engineering education

- Vahed, Anisa, McKenna, Sioux, Singh, S

Authors: Vahed, Anisa , McKenna, Sioux , Singh, S
Date: 2016
Language: English
Type: text , article
Identifier: http://hdl.handle.net/10962/66785 , vital:28993 , ISSN 1573-174X , https://doi.org/10.1007/s10734-015-9956-9
Description: Publisher version , This paper responds to Muller’s notions of ‘knowing-that’ and ‘knowing how’. The paper addresses how educational interventions that are designed in line with targeted discipline-specific subjects can enhance the balance between professional practice and disciplinary knowledge in professionally accredited programmes at universities of technology. The context is a Dental Technology programme at a University of Technology in South Africa. Teaching through discipline-specific games, conceptualised from a game literacies perspective, is proposed as an engaging, interactive pedagogy for learning disciplinary knowledge that potentially encourages access to a particular affinity group. The authors use concepts from Bernstein and Maton to investigate whether epistemic relations or social relations are emphasised through board and digital games designed for two Dental Technology subjects. This paper offers valuable insight into alternative pedagogies that can be adopted into science, technology, engineering, and mathematics education with the aim of paving a pathway towards Muller’s Scenario 3.
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Date Issued: 2016

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