131 research outputs found

    Minimum Resale Price Maintenance In South Africa: Rule of reason or per se prohibition?

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    Magister Legum - LLM (Mercantile and Labour Law)The field of competition law has in an unprecedented way experienced an incredibly vast geographical expansion within a short period of time and as such it is no longer the exclusive feature of developed countries only. Competition law as a body of legal rules aims at protecting the process of competition in the market. It deals with market imperfections with the desire to restore competition conditions in the market economy. Whilst specific competition law objectives may differ from jurisdiction to jurisdiction, it is settled between competition law scholars that, the general goals of competition law are to promote efficiency, adaptability and development of the economy together with the provision of consumer welfare

    Land-use diversity within an agricultural landscape promotes termite nutrient cycling services in a southern African savanna

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    CITATION: LeClare, S. K. et al. 2020. Land-use diversity within an agricultural landscape promotes termite nutrient cycling services in a southern African savanna. Global Ecology and Conservation, 21. doi:10.1016/j.gecco.2019.e00885The original publication is available at https://www.sciencedirect.com/journal/global-ecology-and-conservationSoil macrofauna provide key supporting ecosystem services by transporting nutrients against physical and chemical gradients. In the semi-arid savannas of southern Africa, termites are the dominant macrofauna whose foraging activities increase nutrient availability, soil aeration and water infiltration. With increasing land-use conversion, savanna landscapes are becoming surrounded by a matrix of agricultural landscapes. We tested how compositional and configurational landscape heterogeneity influenced the presence of soil sheetings, a termite foraging activity, within savanna habitat patches embedded in a heterogeneous agricultural landscape in north-east Eswatini. We found that landscape heterogeneity most strongly influenced termite foraging activity at smaller spatial scales (1- to 2-km surrounding the savanna patch). Within this spatial scale, high compositional heterogeneity, which was indicative of diverse habitat patches, promoted termite foraging activity, yet high configurational heterogeneity, indicative of a fragmented landscape, reduced termite foraging activity. At larger landscape scales (5-km), the heterogeneity of the landscape no longer influenced termite foraging activity, yet low to moderate proportions of sugarcane surrounding savanna patches promoted termite foraging activity within those patches. Our results provide novel insights in how the structure of the landscape affects termite foraging activity, demonstrating that diverse, intact landscapes are a critical buffer in maintaining positive nutrient cycling services within an agricultural landscape.https://www.sciencedirect.com/science/article/pii/S2351989419304408Publishers versio

    Intercolony variation in reproductive skipping in the African penguin

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    This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data underlying this article are available in the Dryad digital repository: https://doi.org/10.5061/dryad.0rxwdbs3z (Leith et al., 2022).In long-lived species, reproductive skipping is a common strategy whereby sexually mature animals skip a breeding season, potentially reducing population growth. This may be an adaptive decision to protect survival, or a non-adaptive decision driven by individual-specific constraints. Understanding the presence and drivers of reproductive skipping behavior can be important for effective population management, yet in many species such as the endangered African penguin (Spheniscus demersus), these factors remain unknown. This study uses multistate mark-recapture methods to estimate African penguin survival and breeding probabilities at two colonies between 2013 and 2020. Overall, survival (mean ± SE) was higher at Stony Point (0.82 ± 0.01) than at Robben Island (0.77 ± 0.02). Inter-colony differences were linked to food availability; under decreasing sardine (Sardinops sagax) abundance, survival decreased at Robben Island and increased at Stony Point. Additionally, reproductive skipping was evident across both colonies; at Robben Island the probability of a breeder becoming a nonbreeder was ~0.22, versus ~0.1 at Stony Point. Penguins skipping reproduction had a lower probability of future breeding than breeding individuals; this lack of adaptive benefit suggests reproductive skipping is driven by individual-specific constraints. Lower survival and breeding propensity at Robben Island places this colony in greater need of conservation action. However, further research on the drivers of inter-colony differences is needed.Association of Zoos and AquariumsBristol Zoological SocietyDepartment of Forestry, Fisheries, and the EnvironmentEarthwatch InstitutePew Charitable TrustsLeiden Conservation FoundationSANCCOBSan Diego Zoo Wildlife Allianc

    Nanoparticles and thin films of silver from complexes of derivatives of N-(diisopropylthiophosphoryl) thioureas

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    The derivatives of JV-(diisopropylthiophosphoryl)thiourea RC(S)NHP(S)(OiPr)2 (R = C5H11N, C5H6N2 or C10H7NH 2) followed by their complexation with silver are reported. All complexes are decomposed in hot hexadecylamine (HDA) to give HDA-capped silver nanoparticles. The absorption spectra of the HDA-capped silver nanoparticles exhibit surface plasmon resonance (SPR) absorption in the 400-420 nm region. Transmission electron microscopy (TEM) images of all particles are close to spherical in shape; with sizes ranging from 17 to 20 nm. The X-ray diffraction (XRD) patterns of the silver nanoparticles obtained from all three complexes could be indexed to face centered cubic silver. Scanning electron microscopy (SEM) image confirmed the spherical shape of the particles. The silver complex of 1-naphthylamine was also used to deposit thin films of silver by the aerosol-assisted chemical vapor deposition (AACVD). © 2009 American Chemical Society

    Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets

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    <p>Abstract</p> <p>Background:</p> <p><it>Mycobacterium tuberculosis </it>continues to be a major pathogen in the third world, killing almost 2 million people a year by the most recent estimates. Even in industrialized countries, the emergence of multi-drug resistant (MDR) strains of tuberculosis hails the need to develop additional medications for treatment. Many of the drugs used for treatment of tuberculosis target metabolic enzymes. Genome-scale models can be used for analysis, discovery, and as hypothesis generating tools, which will hopefully assist the rational drug development process. These models need to be able to assimilate data from large datasets and analyze them.</p> <p>Results:</p> <p>We completed a bottom up reconstruction of the metabolic network of <it>Mycobacterium tuberculosis </it>H37Rv. This functional <it>in silico </it>bacterium, <it>iNJ</it>661, contains 661 genes and 939 reactions and can produce many of the complex compounds characteristic to tuberculosis, such as mycolic acids and mycocerosates. We grew this bacterium <it>in silico </it>on various media, analyzed the model in the context of multiple high-throughput data sets, and finally we analyzed the network in an 'unbiased' manner by calculating the Hard Coupled Reaction (HCR) sets, groups of reactions that are forced to operate in unison due to mass conservation and connectivity constraints.</p> <p>Conclusion:</p> <p>Although we observed growth rates comparable to experimental observations (doubling times ranging from about 12 to 24 hours) in different media, comparisons of gene essentiality with experimental data were less encouraging (generally about 55%). The reasons for the often conflicting results were multi-fold, including gene expression variability under different conditions and lack of complete biological knowledge. Some of the inconsistencies between <it>in vitro </it>and <it>in silico </it>or <it>in vivo </it>and <it>in silico </it>results highlight specific loci that are worth further experimental investigations. Finally, by considering the HCR sets in the context of known drug targets for tuberculosis treatment we proposed new alternative, but equivalent drug targets.</p

    Genome-Scale Identification Method Applied to Find Cryptic Aminoglycoside Resistance Genes in Pseudomonas aeruginosa

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    BACKGROUND:The ability of bacteria to rapidly evolve resistance to antibiotics is a critical public health problem. Resistance leads to increased disease severity and death rates, as well as imposes pressure towards the discovery and development of new antibiotic therapies. Improving understanding of the evolution and genetic basis of resistance is a fundamental goal in the field of microbiology. RESULTS:We have applied a new genomic method, Scalar Analysis of Library Enrichments (SCALEs), to identify genomic regions that, given increased copy number, may lead to aminoglycoside resistance in Pseudomonas aeruginosa at the genome scale. We report the result of selections on highly representative genomic libraries for three different aminoglycoside antibiotics (amikacin, gentamicin, and tobramycin). At the genome-scale, we show significant (p<0.05) overlap in genes identified for each aminoglycoside evaluated. Among the genomic segments identified, we confirmed increased resistance associated with an increased copy number of several genomic regions, including the ORF of PA5471, recently implicated in MexXY efflux pump related aminoglycoside resistance, PA4943-PA4946 (encoding a probable GTP-binding protein, a predicted host factor I protein, a delta 2-isopentenylpyrophosphate transferase, and DNA mismatch repair protein mutL), PA0960-PA0963 (encoding hypothetical proteins, a probable cold shock protein, a probable DNA-binding stress protein, and aspartyl-tRNA synthetase), a segment of PA4967 (encoding a topoisomerase IV subunit B), as well as a chimeric clone containing two inserts including the ORFs PA0547 and PA2326 (encoding a probable transcriptional regulator and a probable hypothetical protein, respectively). CONCLUSIONS:The studies reported here demonstrate the application of new a genomic method, SCALEs, which can be used to improve understanding of the evolution of antibiotic resistance in P. aeruginosa. In our demonstration studies, we identified a significant number of genomic regions that increased resistance to multiple aminoglycosides. We identified genetic regions that include open reading frames that encode for products from many functional categories, including genes related to O-antigen synthesis, DNA repair, and transcriptional and translational processes

    Mycobacterial dihydrofolate reductase inhibitors identified using chemogenomic methods and in vitro validation.

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    The lack of success in target-based screening approaches to the discovery of antibacterial agents has led to reemergence of phenotypic screening as a successful approach of identifying bioactive, antibacterial compounds. A challenge though with this route is then to identify the molecular target(s) and mechanism of action of the hits. This target identification, or deorphanization step, is often essential in further optimization and validation studies. Direct experimental identification of the molecular target of a screening hit is often complex, precisely because the properties and specificity of the hit are not yet optimized against that target, and so many false positives are often obtained. An alternative is to use computational, predictive, approaches to hypothesize a mechanism of action, which can then be validated in a more directed and efficient manner. Specifically here we present experimental validation of an in silico prediction from a large-scale screen performed against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. The two potent anti-tubercular compounds studied in this case, belonging to the tetrahydro-1,3,5-triazin-2-amine (THT) family, were predicted and confirmed to be an inhibitor of dihydrofolate reductase (DHFR), a known essential Mtb gene, and already clinically validated as a drug target. Given the large number of similar screening data sets shared amongst the community, this in vitro validation of these target predictions gives weight to computational approaches to establish the mechanism of action (MoA) of novel screening hit

    Structural Insights into the Quinolone Resistance Mechanism of Mycobacterium tuberculosis DNA Gyrase

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    Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP) is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA

    Identification of a small molecule with activity against drug-resistant and persistent tuberculosis

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    A cell-based phenotypic screen for inhibitors of biofilm formation in mycobacteria identified the small molecule TCA1, which has bactericidal activity against both drug-susceptible and -resistant Mycobacterium tuberculosis (Mtb) and sterilizes Mtb in vitro combined with rifampicin or isoniazid. In addition, TCA1 has bactericidal activity against nonreplicating Mtb in vitro and is efficacious in acute and chronic Mtb infection mouse models both alone and combined with rifampicin or isoniazid. Transcriptional analysis revealed that TCA1 down-regulates genes known to be involved in Mtb persistence. Genetic and affinity-based methods identified decaprenyl-phosphoryl-beta-D-ribofuranose oxidoreductase DprE1 and MoeW, enzymes involved in cell wall and molybdenum cofactor biosynthesis, respectively, as targets responsible for the activity of TCA1. These in vitro and in vivo results indicate that this compound functions by a unique mechanism and suggest that TCA1 may lead to the development of a class of antituberculosis agents
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