Preformulation studies of efavirenz with lipid excipients using thermal and spectroscopic techniques
- Authors: Makoni, Pedzisai A , Kasongo, Kasongo W , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183253 , vital:43934 , xlink:href=" https://doi.org/10.1691/ph.2020.0053"
- Description: Investigation and identification of potential lipids for the manufacture of efavirenz loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) was undertaken. Polymorphic modification and characteristics of the lipids with the best solubilising potential for efavirenz was explored using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and Wide-angle X-ray Scattering (WAXS). Lipid screening revealed that EFV is highly soluble in solid and liquid lipids, with glyceryl monostearate (GM) and Transcutol® HP (THP) exhibiting the best solubilising potential for EFV. GM exists in a stable β-polymorphic modification prior to exposure to heat, but exists in an α-polymorphic modification following exposure to heat. However, it was established that the addition of THP to GM revealed the co-existence of the α- and β'-polymorphic modifications of the lipid. EFV (60% w/w) exists in a crystalline state in a 70:30 mixture of GM and THP. Investigation of binary mixtures of EFV/GM and GM/THP, in addition to eutectic mixtures of EFV, GM and THP using FT-IR, DSC and WAXS revealed no potential interactions between EFV and the lipids selected for the production of the nanocarriers.
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Prioritising African perspectives in psychiatric genomics research
- Authors: Kamaara, Eunice , Kong, Camillia , Campbell, Megan M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/302520 , vital:58204 , xlink:href="https://doi.org/10.1111/dewb.12248"
- Description: Psychiatric genomics research with African populations comes with a range of practical challenges around translation of psychiatric genomics research concepts, procedures, and nosology. These challenges raise deep ethical issues particularly around legitimacy of informed consent, a core foundation of research ethics. Through aconsideration of the constitutive function of language, the paper problematises like‐for‐like, designative translations which often involve the ‘indigenization’ of English terms or use of metaphors which misrepresent the risks and benefits of research. This paper argues that effective translation of psychiatric genomics research terminology in African contexts demands substantive engagement with African conceptual schemas and values. In developing attenuated forms of translational thinking, researchers may recognise the deeper motivational reasons behind participation in research, highlighting the possibility that such reasons may depart from the original meaning implied within informed consent forms. These translational issues might be ameliorated with a critical re-examination of how researchers develop and present protocols to institutional ethics review boards.
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Prospects for the biological control of Iris pseudacorus L(Iridaceae)
- Authors: Minuti, Gianmarco , Coetzee, Julie A , Ngxande-Koza, Samella W , Hill, Martin P , Stiers, Iris
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/417776 , vital:71485 , xlink:href="https://doi.org/10.1080/09583157.2020.1853050"
- Description: Native to Europe, North Africa and western Asia, Iris pseudacorus L. (Iridaceae) has invaded natural and human-modified wetlands worldwide. This species is considered a noxious weed in several countries including Argentina, South Africa and New Zealand. Its broad ecological tolerance, high resilience and reproductive potential make current mechanical and chemical control measures cost-ineffective, and biological control is considered a suitable alternative. In order to prioritise candidate biocontrol agents, a list of organisms reported to attack the plant within its native range has been assembled, and information about their host-range and damaging potential gathered from the literature. Furthermore, surveys for natural enemies of the plant were conducted in Belgium and northern Italy. The insect fauna associated with I. pseudacorus at the sites surveyed comprised mostly incidental visitors and polyphagous feeders, with the exception of the sawfly Rhadinoceraea micans Klug (Hymenoptera: Tenthredinidae), the seed weevil Mononychus punctumalbum Herbst (Coleoptera: Curculionidae), and the flea beetle Aphthona nonstriata Goeze (Coleoptera: Chrysomelidae). The potential of these species for biocontrol was evaluated, and A. nonstriata was given highest priority. A population of this species was imported to quarantine in South Africa, where it is currently undergoing host-specificity testing. Importation of the two remaining candidates is expected shortly. In conclusion, the prospects for the biological control of I. pseudacorus appear promising.
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Rational design and regioselective synthesis of conformationally restricted furan-derived ligands as potential anti-malarial agents
- Authors: Mutorwa, Marius K , Nokalipa, Iviwe , Tanner, Delia C , Blatch, Gregory L , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447170 , vital:74589 , xlink:href="https://doi.org/10.24820/ark.5550190.p011.281"
- Description: Substituted 3-furanomethyl phosphate esters and their corresponding phosphoric acids have been prepared as conformationally restricted analogues of DOXP, the natural substrate for Plasmodium falciparum 1-deoxyD-xylulose-5-phosphate reductoisomerase (PfDXR), and fosmidomycin, an established inhibitor. Saturation Transfer Difference (STD) NMR analysis and in silico docking data suggest the potential of such compounds as PfDXR inhibitors.
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Regularly drinking desert birds have greater evaporative cooling capacity and higher heat tolerance limits than non‐drinking species
- Authors: Czenze, Zenon J , Kemp, Ryno , van Jaarsveld, Barry , Freeman, Marc T , Smit, Ben , Wolf, Blair O , McKechnie, Andrew
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/441585 , vital:73900 , https://doi.org/10.1111/1365-2435.13573
- Description: Surface water is a critical resource for many birds inhabiting arid re-gions, but the implications of regular drinking and dependence on sur-face water for the evolution of thermal physiology remain largely unex-plored. We hypothesized that avian thermoregulation in the heat has evolved in tandem with the use of surface water and predicted that (a) regularly drinking species have a greater capacity to elevate rates of evaporative water loss (EWL) compared to non‐drinking species, and (b) heat tolerance limits (HTLs) are higher among drinking species. To test these predictions, we quantified thermoregulatory responses to high air temperature (Ta) in 12 species of passerines from the South African arid zone and combined these with values for an additional five species. We categorized each species as either: (a) water‐dependent, regularly drinking, or (b) water‐independent, occasional‐/non‐drinking.
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Reimagining academic identities in response to research demands at Universities of Technology
- Authors: Gumbi, Thobani , McKenna, Sioux
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/185897 , vital:44446 , xlink:href="https://doi.org/10.14426/cristal.v8i1.234"
- Description: In the last volume of this journal, Garraway and Winberg called for a reimagination of Universities of Technology (UoT) within the South African higher education system. This article continues that conversation by looking at the implications that the formation of the UoT had for academics’ identities. Technikon lecturers’ identities were closely tied to workplace expertise, but demands for research in UoTs have changed this. A social realist analysis of interviews with fifteen academics at three UoTs finds that research remains a contested issue. Interviewees understood research to take the form of acquiring postgraduate qualifications, rather than as an ongoing activity tied to their identities. Echoing Garraway and Winberg’s study, the bureaucratic nature of the institutional culture was referred to as a constraint. There was also a view that for this programme, Dental Technology, a demand for research was needed from industry if this was to be a valued aspect of academics’ identities.
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Rejection of the genetic implications of the “Abundant Centre Hypothesis” in marine mussels
- Authors: Ntuli, Noxolo N , Nicastro, Katy R , Zardi, Gerardo I , Assis, Jorge , McQuaid, Christopher D , Teske, Peter R
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/444839 , vital:74302 , https://www.nature.com/articles/s41598-020-57474-0
- Description: The ‘Abundant-Centre Hypothesis’ is a well-established but controversial hypothesis stating that the abundance of a species is highest at the centre of its range and decreases towards the edges, where conditions are unfavourable. As genetic diversity depends on population size, edge populations are expected to show lower intra-population genetic diversity than core populations, while showing high inter-population genetic divergence. Here, the genetic implications of the Abundant-Centre Hypothesis were tested on two coastal mussels from South Africa that disperse by means of planktonic larvae, the native Perna perna and the invasive Mytilus galloprovincialis. Genetic structure was found within P. perna, which, together with evidence from Lagrangian particle simulations, points to significant reductions in gene flow between sites. Despite this, the expected diversity pattern between centre and edge populations was not found for either species. We conclude that the genetic predictions of the Abundant-Centre Hypothesis are unlikely to be met by high-dispersal species with large population sizes, and may only become evident in species with much lower levels of connectivity.
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Relational hubs for collaborative landscape stewardship
- Authors: Cockburn, Jessica J , Cundill, Georgina , Shackleton, Sheona E , Cele, Ayanda , Cornelius, Susanna F , Koopman, Vaughan , Le Roux, Jean-Pierre , McLeod, Nicky , Rouget, Mathieu , Schroder, Samantha , Van den Broek, Dieter , Wright, Dale R , Zwinkelse, Marijn
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/392748 , vital:68789 , xlink:href="https://doi.org/10.1080/08941920.2019.1658141"
- Description: Landscape stewardship is considered an important place-based approach to addressing sustainability challenges. Working at landscape-level requires collaboration between diverse landscape stakeholders. In this study, we partnered with local stewardship practitioners across six cases in South Africa to investigate how they facilitate collaboration towards social-ecological sustainability outcomes. We found that practitioners facilitate collaboration among stakeholders by operating as relational hubs in the landscape. Through these hubs, they build new inter-personal relationships among stakeholders, creating social networks which enable stewardship practice. The hubs deepen human-nature relationships by creating enabling conditions for stewards to put stewardship ethics into action. Drawing on insights from these cases, we call for a relational approach to landscape stewardship which focuses on human-to-human and human-to-nature relationships. Moreover, we argue that landscape stewardship initiatives need to re-focus stewardship on stewards, recognizing them as key agents of change in addressing the conflict between agriculture and conservation inherent in many landscapes.
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Resisting abortion stigma in situ: South African womxn's and healthcare providers' accounts of the pre-abortion counselling healthcare encounter
- Authors: Mavuso, Jabulile M-J J , Macleod, Catriona I
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/443749 , vital:74149 , xlink:href="https://doi.org/10.1080/13691058.2019.1674922"
- Description: Abortion providers and pregnant people who undergo abortion potentially face significant stigma. Researchers have started to explore how womxn respond to abortion stigma, usually focusing on individual strategies in managing or reducing stigma effects. Drawing on narrative data from research conducted on womxn’s and healthcare providers’ experiences of the pre-abortion healthcare encounter in the South African public health sector, we highlight how stigma may be resisted in social ways within this context. Everyday chatter and informal social support amongst womxn in the waiting room provided a counterpoint for health service providers’ ascription of shame to the womxn, and a sense of solidarity amongst the womxn. Health service providers narrated their decision to do abortion work through the socially affirming hero canonical narrative, and womxn described their counselling as helpful. These social and discursive practices resist the awfulisation of abortion and provide relief for the womxn and the healthcare providers in particular contexts.
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Screening for small molecule modulators of Trypanosoma brucei Hsp70 chaperone activity based upon alcyonarian coral-derived natural products
- Authors: Andreassend, Sarah K , Bentley, Stephen , Blatch, Gregory L , Boshoff, Aileen , Keyzers, Robert A
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/426045 , vital:72309 , xlink:href="https://doi.org/10.3390/md18020081"
- Description: The Trypanosoma brucei Hsp70/J-protein machinery plays an essential role in survival, differentiation, and pathogenesis of the protozoan parasite, and is an emerging target against African Trypanosomiasis. This study evaluated a set of small molecules, inspired by the malonganenones and nuttingins, as modulators of the chaperone activity of the cytosolic heat inducible T. brucei Hsp70 and constitutive TbHsp70.4 proteins. The compounds were assessed for cytotoxicity on both the bloodstream form of T. b. brucei parasites and a mammalian cell line. The compounds were then investigated for their modulatory effect on the aggregation suppression and ATPase activities of the TbHsp70 proteins. A structure–activity relationship for the malonganenone-class of alkaloids is proposed based upon these results.
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Screening of ectomycorrhizal and other associated fungi in South African forest nurseries
- Authors: Chartier FitzGerald, Veronique C , Dames, Joanna F , Hawley, Greer L
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/426058 , vital:72310 , xlink:href="https://hdl.handle.net/10520/ejc-soufor-v82-n4-a8"
- Description: The South African forestry industry covers approximately 1.3 million hectares and is dependent on exotic pine and eucalypt species. Nursery seedlings are not inoculated with ectomycorrhizal (ECM) fungi. This investigation assessed levels of naturally occurring ECM colonisation of Pinus patula seedlings from 10 different South African forestry nurseries using a grid line intersect method. Fungi from colonised roots were identified using morphological characteristics and Illumina sequencing. Colonisation of seedlings in production nurseries was low (2-21%). Morphologically, the ECM fungi Thelophora terrestris, Suillus sibiricus, and the genera Russula and Pseudotomentella were identified. Molecularly, the ECM fungi T. terrestris, Inocybe jacobi and the genus Sphaerosporella, as well as several other ECM-containing families were identified, along with many saprotrophic/ endophytic fungi belonging to genera such as Penicillium, Ramasonia and Talaromyces. As can be seen, a combination of both molecular and morphological identification techniques are needed as neither is able to give a full picture of the species present in isolation. This study reveals an initial insight into the root microbiome community associated with Pinus patula seedlings, which should be taken into account when inoculation with beneficial microbes is considered. It determined that natural ECM fungal root colonisation levels are very low throughout the South African nurseries investigated, indicating the need for ECM fungal inoculation, which can increase seedling growth, viability and resistance to pathogens.
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Seeking Faculty Jobs Exploring the Relationship Between Academic’ s Social Class of Origin and Hiring Networks in Chilean Universities
- Authors: Chiappa, Roxana
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/439508 , vital:73602 , https://doi.org/10.31619/caledu.n52.760
- Description: This research consisted of a qualitative case study on how a group of early-career doctorate holders in engineering (N=10) found academic positions in the Chilean academia. The analysis particularly explored how their social class of origin and their academic networks influenced their opportunities of getting an academic job. Findings show that social class of origin mediates the academic network configuration of academic-job seekers through unequal opportunities of completing their undergraduate degrees in prestigious Chilean universities with high research capacity, and subsequently, the unequal opportunities of studying a doctorate degree at top-ranked foreign universities. Only upper social class candidates who received their doctorate degrees from foreign highly prestigious universities were capable of securing positions at the top research-intensive Chilean universities. Overall, findings show that academic networks with professors who are knowledgeable of hiring processes are crucial at the moment of seeking academic jobs in the Chilean higher education system.
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Sn (iv) N-confused porphyrins as photosensitizer dyes for photodynamic therapy in the near IR region
- Authors: Babu, Balaji , Mack, John , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186648 , vital:44521 , xlink:href="https://doi.org/10.1039/D0DT03296D"
- Description: The utility of Sn(IV) N-confused porphyrin (SnNCP) for use as photosensitizer dyes in photodynamic therapy is investigated. SnNCP has an unusually high singlet oxygen quantum yield of 0.72 in DMSO. IC50 values of 1.6 and 12.8 μM were obtained against MCF-7 cells upon irradiation with 660 and 780 nm LEDs.
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Social and structural barriers related to menstruation across diverse schools in the Eastern Cape
- Authors: Macleod, Catriona I , Du Toit, Ryan , Paphitis, Sharli A , Kelland, Lindsay
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/444385 , vital:74224 , xlink:href="https://hdl.handle.net/10520/ejc-educat-v40-n3-a9"
- Description: The barriers to education associatedwith menstruation vary from country to countryand within countries. We report on a cross-sectional survey conducted in diverse schools in 2districts of the Eastern Cape, South Africa. Using multi-stage sampling(stratified random sampling of schools, and purposive sampling of Grade 11 female-identifiediilearners), we accessed1,035 respondents with an average age of 17.2 years. Respondents completed a questionnaire developed from previous questionnaires and our readings of the literature. We report here on results pertaining to the social and structural barriers relatedto menstruation. Just over one fifth of young womeniiiacross the whole sample reported missing an average of 1.8 days of school per menstrual cycle, while a significant minority reportedrestrictions related to sporting and classroom activities. Results show, contrary to expectations, that young womenattending under-resourced schools report missing fewer days than young womenattending resourced schools, despite young womenin under-resourced schools experiencing inadequate sanitationfacilities and feeling unsafeusingthese facilities. This research indicates the importance of recognising social as well as structural features when considering the gendered barriers to education that menstruation may represent.
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SoTL: A mechanism for understanding and finding solutions to teaching and learning challenges
- Authors: Vorster, Jo-Anne E
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/445727 , vital:74419 , https://doi.org/10.36615/sotls.v4i2.149
- Description: The paper argues that the Scholarship of Teaching and Learning (SoTL) is a necessary strategy for mitigating the many teaching and learning challenges in South African higher education that prevent a large proportion of students from achieving academic success. Research suggests that well-structured and coordinated educational practices that are valued and supported by institutions are crucial for student success. While there exists a very useful body of scholarship on teaching and learning in higher education in South Africa, the persistently high levels of student failure and dropout across the system points to the need for more research into teaching and learning dilemmas in diverse institutional, disciplinary and classroom contexts. I argue that if more academics are to conduct SoTL, it has to be valued and supported by institutions and academic leaders. Even though more SoTL is needed to contribute to solving the many pedagogic dilemmas South African academics encounter, it is counter-productive to expect all academics to conduct SoTL. Rigorous SoTL requires immersion in educational ideas, concepts, theories and research processes. Many academics may not have the time or inclination to work in the area of SoTL, but I suggest that all must be scholarly teachers of their disciplines.
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Substituent effect on the photophysical and nonlinear optical characteristics of Si phthalocyanine–Detonated nanodiamond conjugated systems in solution
- Authors: Matshitse, Refilwe , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186293 , vital:44482 , xlink:href="https://doi.org/10.1016/j.ica.2020.119447"
- Description: This work reports on the photophysical, nonlinear absorption and optical limiting properties of detonation nanodiamonds (DNDs)-silicon phthalocyanine nanoconjugate systems. Si(IV) hydroxide phthalocyanines employed are: 2,9(10),16(17),23(24)-tetrakis-(4-pyridyloxy) phthalocyaninato (Si(OH)2TPPc), 2,9(10),16(17),23(24)-tetrakis-(4-tert-butyl) phthalocyanato (Si(OH)2TBPc) and phthalocyanato(Si(OH)2Pc). Pcs were covalently linked to nanondiamonds and investigated using 532 nm laser excitation at 7 ns pulses for their optical limiting properties. Si(OH)2TBPc and Si(OH)2Pc gave larger triplet quantum yields when linked to DNDs, while the value decreased for Si(OH)2TPPc in the presence of DNDs due to aggregation. However all Pcs showed enhanced nonlinear optical properties in the presence of DNDs. DNDs-Si(OH)2TPPc and DNDs-Si (OH)2TBPc gave the highest imaginary third-order susceptibility (Im[X(3)]) and hyperpolarizability (γ) at 5.19 × 10−8 and 3.85 × 10−8 esu and 2.66 × 10−27 and 1.97 × 10−27 esu, respectively. DNDs-Si(OH)2TBPc nanoconjugates showed lowest limiting threshold (Ilim) value of 0.01 J.cm−2 relative to 0.09 for DNDs-Si (OH)2TPPc.
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Susceptibility of Staphylococcus aureus to porphyrin-silver nanoparticle mediated photodynamic antimicrobial chemotherapy
- Authors: Shabangu, Samuel M , Babu, Balaji , Soy, Rodah C , Ovim, James , Amuhaya, Edith K , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186262 , vital:44479 , xlink:href="https://doi.org/10.1016/j.jlumin.2020.117158"
- Description: Photodynamic antimicrobial chemotherapy (PACT) is employed against multi drug resistant Staphylococcus aureus using porphyrins combined with silver nanoparticles to bring about a combined photodynamic effect. We employ Zn-meso-5,10,15,20-tetra(4-pyridyl) (1), Zn-meso-5,10,15,20-tetrathienyl (2), and Zn-meso-5-(4- hydroxyphenyl)- 10,15,20-tris(2-thienyl)(3) porphyrins and their self-assembled conjugates with silver nanoparticles for PACT against Staphylococcus aureus. Complex 3 with nanoparticles was found to perform better resulting in 0% bacterial viability at 60 min.
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Synergistic effects of temperature and plant quality, on development time, size and lipid in Eccritotarsus eichhorniae
- Authors: Ismail, Mohannad , Brooks, Margot , Van Baaren, Joan , Albittar, Loulou
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/426078 , vital:72312 , xlink:href="https://doi.org/10.1111/jen.12841"
- Description: Body size is an important biotic factor in evolutionary ecology, since it affects all aspects of insect physiology, life history and, consequently, fitness in ectothermic insects and how species adapt with their environment. It has been linked to tem-perature, with lower temperatures resulting in larger size. In this study, we tested the combined impact of temperature and plant quality on the body size, and de-velopment time from egg to adult of Eccritotarsus eichhorniae (Hemiptera: Miridae), an herbivorous insect used as a biological control agent against the invasive aquatic weed, water hyacinth Eichhornia crassipes (Pontederiaceae). We quantified insect size in individuals exposed to three temperatures (20, 25 and 30°C) combined with three qualities of host plant (high, medium and low) by calculating development time and measuring four traits: tibia length, forewing length, dry body mass and lipid con-tent, and we also determined the wing loading index. The development time, dry body mass and lipid content decreased linearly with increasing temperature and de-creasing plant quality. The decrease in size was the greatest when high temperature interacted with low plant quality. Smaller individuals had proportionately less lipid content. Wing loading decreased significantly with lower quality of host plant, result-ing in individuals likely to have theoretically higher flight ability. The results support the temperature-size rule (TSR) and that plant quality could influence the relationship between development time and the TSR. Results also provide novel evidence for a possible food quality-size rule for both sexes.
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Synthesis and anti-parasitic activity of N-benzylated phosphoramidate Mg2+-chelating ligands
- Authors: Adeyemi, Christiana M , Hoppe, Heinrich C , Isaacs, Michelle , Mnkandhla, Dumisani , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/451171 , vital:75025 , xlink:href="https://doi.org/10.1016/j.bioorg.2020.104280"
- Description: A series of N-benzylated phosphoramidate esters, containing a 3,4-dihydroxyphenyl Mg2+-chelating group, has been synthesised in five steps as analogues of fosmidomycin, a Plasmodium falciparum 1-deoxy-1-D-xylulose-5- phosphate reductoisomerase (PfDXR) inhibitor. The 3,4-dihydroxyphenyl group effectively replaces the Mg2+- chelating hydroxamic acid group in fosmidomycin. The compounds showed very encouraging anti-parasitic activity with IC50 values of 5.6–16.4 µM against Plasmodium falciparum parasites and IC50 values of 5.2 – 10.2 µM against Trypanosoma brucei brucei (T.b.brucei). Data obtained from in silico docking of the ligands in the PfDXR receptor cavity (3AU9)5 support their potential as PfDXR inhibitors.
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Synthesis and biological evaluation of bis-N2, N2′-(4-hydroxycoumarin-3-yl) ethylidene]-2, 3-dihydroxysuccinodihydrazides
- Authors: Manyeruke, Meloddy H , Tshiwawa, Tendamudzimu , Hoppe, Heinrich C , Isaacs, Michelle , Seldon, Ronnett , Warner, Digby F , Krause, Rui W M , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193430 , vital:45331 , xlink:href="https://doi.org/10.1016/j.bmcl.2019.126911"
- Description: A series of N2,N2′-bis[4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccino-hydrazides, containing 4-hydroxycoumarin, hydrazine and tartaric acid moieties, have been prepared and examined for possible biological activity. Several of these compounds exhibit promising HIV-1 integrase inhibition (IC50 = 3.5 μM), and anti-T. brucei (32% viability) and anti-mycobacterial (Visual MIC90 = 15.63 μM) activity.
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