Investigating musical copyright infringement: Examining International Understandings of Musical Copyright Infringement for Potential Adaptation into South African Copyright Law

This thesis examines international approaches to musical work copyright infringement law for the purpose of establishing an approach that can be utilised effectively under the South African copyright infringement framework. In doing so, the importance of the various interactive elements of musical works is investigated as well as the modes of assessment in infringement scenarios. The findings are used to create a robust middle-ground approach to be adapted into the South African copyright infringement framework. Further considerations that impact infringement outcomes are addressed to the extent that they are contextually relevant. These include a discussion of research undertaken on the continent regarding the relationship between creators and the music-related copyright regime as well as the role that exceptions and limitations play in infringement outcomes

SALT Spectropolarimetry and Self-Consistent SED and Polarization Modeling of Blazars

We report on recent results from a target-of-opportunity program to obtain spectropolarimetry observations with the Southern African Large Telescope (SALT) on flaring gamma-ray blazars. SALT spectropolarimetry and contemporaneous multi-wavelength spectral energy distribution (SED) data are being modelled self-consistently with a leptonic single-zone model. Such modeling provides an accurate estimate of the degree of order of the magnetic field in the emission region and the thermal contributions (from the host galaxy and the accretion disk) to the SED, thus putting strong constraints on the physical parameters of the gamma-ray emitting region. For the specific case of the $\gamma$-ray blazar 4C+01.02, we demonstrate that the combined SED and spectropolarimetry modeling constrains the mass of the central black hole in this blazar to $M_{\rm BH} \sim 10^9 \, M_{\odot}$.Comment: Submitted to Galaxies - Proceedings of "Polarized Emission from Astrophysical Jets", Ierapetra, Crete, June 12 - 16, 201

The EGF Receptor Hokey-Cokey

In cancer, the epidermal growth factor (EGF) receptor (EGFR) can be activated by mutations that disrupt the inactive conformation and allow the active conformation to predominate. Structural studies have elucidated the molecular events that lead to EGFR activation and shown that small-molecule anti-EGFR drugs can bind to either the inactive or the active conformation of the kinase domain. In this issue of Cancer Cell, Yun et al. present 12 crystal structures of the wild-type or mutant forms of the EGFR kinase domain bound to four different ligands. This study will prove invaluable to those developing novel anti-EGFR drugs

Monitoring CD27 expression to evaluate Mycobacterium tuberculosis activity in HIV-1 infected individuals in vivo.

The level of bacterial activity is only poorly defined during asymptomatic Mycobacterium tuberculosis (MTB) infection. The objective was to study the capacity of a new biomarker, the expression of the T cell maturation marker CD27 on MTB-specific CD4 T cells, to identify active tuberculosis (TB) disease in subjects from a MTB and HIV endemic region. The frequency and CD27 expression of circulating MTB-specific CD4 T cells was determined in 96 study participants after stimulation with purified protein derivative (PPD) using intracellular cytokine staining for IFNgamma (IFNγ). Subjects were then stratified by their TB and HIV status. Within PPD responders, a CD27(-) phenotype was associated with active TB in HIV(-) (p = 0.0003) and HIV(+) (p = 0.057) subjects, respectively. In addition, loss of CD27 expression preceded development of active TB in one HIV seroconverter. Interestingly, in contrast to HIV(-) subjects, MTB-specific CD4 T cell populations from HIV(+) TB-asymptomatic subjects were often dominated by CD27(-) cells. These data indicate that down-regulation of CD27 on MTB-specific CD4 T cell could be used as a biomarker of active TB, potentially preceding clinical TB disease. Furthermore, these data are consistent with the hypothesis that late, chronic HIV infection is frequently associated with increased mycobacterial activity in vivo. The analysis of T cell maturation and activation markers might thus be a useful tool to monitor TB disease progression

Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells

BRAF inhibitors can extend progression-free and overall survival in melanoma patients whose tumors harbor mutations in BRAF. However, the majority of patients eventually develop resistance to these drugs. Here we show that BRAF mutant melanoma cells that have developed acquired resistance to BRAF inhibitors display increased oxidative metabolism and increased dependency on mitochondria for survival. Intriguingly, the increased oxidative metabolism is associated with a switch from glucose to glutamine metabolism and an increased dependence on glutamine over glucose for proliferation. We show that the resistant cells are more sensitive to mitochondrial poisons and to inhibitors of glutaminolysis, suggesting that targeting specific metabolic pathways may offer exciting therapeutic opportunities to treat resistant tumors, or to delay emergence of resistance in the first-line setting

Sunglasses to hide behind may also prevent melanoma of the eyes

From Springer Nature via Jisc Publications RouterHistory: received 2021-02-05, rev-recd 2021-02-26, accepted 2021-03-02, registration 2021-03-04, pub-electronic 2021-04-06, online 2021-04-06, pub-print 2021-08-17Publication status: PublishedFunder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289; Grant(s): A27412 and A22902Summary: In 1967, Sandy Posey pronounced that sunglasses are essential beachwear (https://www.youtube.com/watch?v=4HVBEb-GA1Y). Now, whole-genome sequencing reveals that ultraviolet radiation (UVR) can contribute to melanomas in the iris and conjunctiva, data that provide a molecular explanation for why it is important to protect our eyes from exposure to UVR

Calmodulin prevents activation of Ras by PKC in 3T3 fibroblasts

We have shown previously (Villalonga, P., López- Alcalá, C., Bosch, M., Chiloeches, A., Rocamora, N., Gil, J., Marais, R., Marshall, C. J., Bachs, O., and Agell, N. (2001) Mol. Cell. Biol. 21, 7345-7354) that calmodulin negatively regulates Ras activation in fibroblasts. Hence, anti-calmodulin drugs (such as W13, trifluoroperazine, or W7) are able to induce Ras/ERK pathway activation under low levels of growth factors. We show here that cell treatment with protein kinase C (PKC) inhibitors abolishes W13-induced activation of Ras, Raf-1, and ERK. Consequently, PKC activity is essential for achieving the synergism between calmodulin inhibition and growth factors to activate Ras. Furthermore, whereas the activation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) does not induce Ras activation in 3T3 cells, activation is observed if calmodulin is simultaneously inhibited. This indicates that calmodulin is preventing Ras activation by PKC. Treatment of cells with epidermal growth factor receptor or platelet-derived growth factor receptor tyrosine kinase inhibitors does not abrogate the activation of Ras by calmodulin inhibition. This implies that epidermal growth factor receptor and platelet-derived growth factor receptor tyrosine kinase activities are dispensable for the activation of Ras by TPA plus W13, and, therefore, Ras activation is not a consequence of the transactivation of those receptors by the combination of the anti-calmodulin drug plus TPA. Furthermore, K-Ras, the isoform previously shown to bind to calmodulin, is the only one activated by TPA when calmodulin is inhibited. These data suggest that direct interaction between K-Ras and calmodulin may account for the inability of PKC to activate Ras in 3T3 fibroblasts. In vitro experiments showed that the phosphorylation of K-Ras by PKC was inhibited by calmodulin, suggesting that calmodulin-dependent modulation of K-Ras phosphorylation by PKC could be the mechanism underlying K-Ras activation in fibroblasts treated with TPA plus W13