Lame dan lame? La main dans la main? Hand in Hand? Introduction

Anu Bissonauth-Bedford and Kumari Issur, Introduction, Lame dan lame? La main dans la main? Hand in Hand? Conference, University of Mauritius and University of Wollongong, 2019. The articles in this special issue of Research Online publication titled ‘Lame dan lame? La main dans la main? Hand in Hand?’ are drawn from presentations at the colloquium held at the University of Mauritius (UoM) on 13 September 2018. The colloquium itself was organised following discussions about the need to focus on the theme of lame dan lame adopted by the Mauritian government to mark its fifty years of independence from British rule and the spirit of a united Mauritian nation built made by walking hand in hand since 1968. This issue brings together articles by researchers from Australia,France and Mauritius who analyze the concept of lame dan lame, its challenges and opportunities across disciplinary fields of Linguistics, Education, Identity, Politics and History. The publication of this special issue expands on collaborative links built between academics at the Universities of Mauritius (UoM) and Wollongong (UOW) at the International Conference of the Mauritian Academic Diaspora (ICMAD) organized by UoMin February 2018to celebrate the fiftieth anniversary of Mauritian independence. Guest Editors Dr Anu Bissoonauth is Senior Lecturer in French in the Faculty of Law, Humanities and the Arts at the University of Wollongong. Her research interests include social, cultural and political challenges in multilingual and multicultural creolophone societies, where French comes in contact with local Creoles and/or migrant heritage languages as well as global English. Associate Professor Kumari R. Issur from the French department at the University of Mauritius, specialises in French literatures of the Indian Ocean and the Caribbean, Ecocriticism and Oceanic studies. She has published numerous articles and co-authored several books such as Revue Nouvelles Etudes Francophones, Revue Mosaïques , New forms of otherness in the Indian Ocean (2013), Spaces, memories and knowledge in the fiction of Ananda Devi (2017)

Structural definition of substrate recognition by model RNA capping enzymes and the identification of a novel class of viral RNA capping enzymes

The RNA cap structure is a fundamental feature of most known eukaryotic mRNAs and some viral RNAs, It is important for the stability, transport and translation of mRNAs. It is co-transcriptionally synthesized via the action of 3 consecutive enzymatic reactions: (1) A RNA triphosphatase which cleaves off the 5' terminal phosphate of nascent RNAs; (2) A RNA guanylyltransferase which transfers a GMP moiety onto the acceptor RNA; (3) A RNA (guanine-N7) methyltransferase which methylates the cap guanine at the N7 position. Through the end of the 1990's until now, the crystal structures of several capping enzymes have been solved. However, these structures, although very insightful in themselves, failed to provide any instructive information on several key issues regarding enzyme-substrate interactions. For instance, one of the first breakthrough crystallographic studies in RNA capping chemistry led to the elucidation of the yeast RNA triphosphatase structure (the Cet1 protein). However, in the crystal structure, the Cet1 protein was bound to a sulphate molecule, which was hypothesised to be mimicking the product of the RNA triphosphatase reaction- a phosphate molecule.The inability to capture the RNA triphosphatase in complex with its ligands is probably on account of the inherent thermodynamic instability of this protein when bound to RNA or a nucleotide. A structural definition of the active site of the yeast RNA triphosphatase in complex with an appropriate substrate is still lacking. In addition, the elucidation of the structure of the RNA guanylyltransferase of the Paramecium bursaria chlorella virus -1 (PBCV-1) in several different conformations has been a landmark study which greatly contributed towards the understanding of the catalytic pathway of this model enzyme. On the other hand, despite the presence of the natural substrate-GTP, within the active site of the enzyme, the rationale behind the GTP specificity of RNA guanylyltransferase remains poorly understood. Moreover, a molecular mechanism for the RNA guanylyltransferase reaction is still missing. Finally, the importance of the RNA cap for the process of eukaryotic translation is undisputable. However, the relationship between the RNA cap and translation has been mostly studied indirectly through proteins which bind to the cap structure. Most studies pertaining directly to the impact of the binding of the RNA cap structure have been restricted to investigating the inhibitory potential of various cap analogues on the translation process. Studies on the effects of modified RNA caps at the 5' ends of RNAs have only started in the last few years, and more importantly, the necessity of the N7-methyl group on RNA cap analogues had not been addressed. This thesis therefore aims to provide a structural insight into the structural dynamics of enzyme-ligand(s) interactions of the model S. cerevisiae's RNA triphosphatase and the PBCV-1 RNA guanylyltransferase. In addition, we show that purine analogues can be a useful tool for the study of several cellular processes, such as RNA translation. In the process we have uncovered a novel class of RNA capping enzyme in the flavivirus genus of the Flaviviridae family of RNA viruses, thus providing a more succinct insight into the flaviviral replication complex

Simulation of the Earth's radio leakage from mobile towers as seen from selected nearby stellar systems

Mobile communication towers represent a relatively new but growing contributor to the total radio leakage associated with planet Earth. We investigate the overall power contribution of mobile communication towers to the Earth\'s radio leakage budget, as seen from a selection of different nearby stellar systems. We created a model of this leakage using publicly available data of mobile tower locations. The model grids the planet's surface into small, computationally manageable regions, assuming a simple integrated transmission pattern for the mobile antennas. In this model, these mobile tower regions rise and set as the Earth rotates. In this way, a dynamic power spectrum of the Earth was determined, summed over all cellular frequency bands. We calculated this dynamic power spectrum from three different viewing points, HD 95735, Barnard star, and Alpha Centauri A. Our preliminary results demonstrate that the peak power leaking into space from mobile towers is $\sim 4$GW. This is associated with LTE mobile tower technology emanating from the East Coast of China as viewed from HD 95735. We demonstrate that the mobile tower leakage is periodic, direction dependent, and could not currently be detected by a nearby civilization located within 10 light years of the Earth, using instrumentation with a sensitivity similar to the Green Bank Telescope. We plan to extend our model to include more powerful 5G mobile systems, radar installations, ground based uplinks (including the Deep Space Network), and various types of satellite services, including low Earth orbit constellations such as Starlink and OneWeb

Nucleotide analogs and molecular modeling studies reveal key interactions involved in substrate recognition by the yeast RNA triphosphatase

RNA triphosphatases (RTPases) are involved in the addition of the distinctive cap structure found at the 5′ ends of eukaryotic mRNAs. Fungi, protozoa and some DNA viruses possess an RTPase that belongs to the triphosphate tunnel metalloenzyme family of enzymes that can also hydrolyze nucleoside triphosphates. Previous crystallization studies revealed that the phosphohydrolase catalytic core is located in a hydrophilic tunnel composed of antiparallel β-strands. However, all past efforts to obtain structural information on the interaction between RTPases and their substrates were unsuccessful. In the present study, we used computational molecular docking to model the binding of a nucleotide substrate into the yeast RTPase active site. In order to confirm the docking model and to gain additional insights into the molecular determinants involved in substrate recognition, we also evaluated both the phosphohydrolysis and the inhibitory potential of an important number of nucleotide analogs. Our study highlights the importance of specific amino acids for the binding of the sugar, base and triphosphate moieties of the nucleotide substrate, and reveals both the structural flexibility and complexity of the active site. These data illustrate the functional features required for the interaction of an RTPase with a ligand and pave the way to the use of nucleotide analogs as potential inhibitors of RTPases of pathogenic importance

Image plane detection of FRB121102 with the MeerKAT radio telescope

We present the analysis of radio interferometric 2-s images from a MeerKAT observation of the repeating fast radio burst FRB121102 on September 2019, during which 11 distinct pulses have been previously detected using high time and frequency resolution data cubes. In this work, we detected 6 out of the 11 bursts in the image plane at 1.48 GHz with a minimum peak signal-to-noise ratio (S/N) of 5 {\sigma} and a fluence detection limit of 0.512 Jy ms. These constitute the first detections of a fast radio burst (FRB) or a radio transient using 2-s timescale images with MeerKAT data. Analysis of the fitted burst properties revealed a weighted average precision of 1 arcsec in the localization of the bursts. The accurate knowledge of FRB positions is essential for identifying their host galaxy and understanding their mysterious nature which is still unresolved to this day. We also produced 2-s images at 1.09 GHz but yielded no detection which we attributed to the spectral structure of the pulses that are mostly higher in strength in the upper frequencies. We also explore a new approach to difference imaging analysis (DIA) to search for transients and find that our technique has the potential to reduce the number of candidates and could be used to automate the detection of FRBs in the image plane for future MeerKAT observations.Comment: The paper has already been accepted to MNRAS and we wait for proof of review from the publisher for final publicatio

Analysis of RNA Binding by the Dengue Virus NS5 RNA Capping Enzyme

Flaviviruses are small, capped positive sense RNA viruses that replicate in the cytoplasm of infected cells. Dengue virus and other related flaviviruses have evolved RNA capping enzymes to form the viral RNA cap structure that protects the viral genome and directs efficient viral polyprotein translation. The N-terminal domain of NS5 possesses the methyltransferase and guanylyltransferase activities necessary for forming mature RNA cap structures. The mechanism for flavivirus guanylyltransferase activity is currently unknown, and how the capping enzyme binds its diphosphorylated RNA substrate is important for deciphering how the flavivirus guanylyltransferase functions. In this report we examine how flavivirus NS5 N-terminal capping enzymes bind to the 5′ end of the viral RNA using a fluorescence polarization-based RNA binding assay. We observed that the KD for RNA binding is approximately 200 nM Dengue, Yellow Fever, and West Nile virus capping enzymes. Removal of one or both of the 5′ phosphates reduces binding affinity, indicating that the terminal phosphates contribute significantly to binding. RNA binding affinity is negatively affected by the presence of GTP or ATP and positively affected by S-adensyl methoninine (SAM). Structural superpositioning of the dengue virus capping enzyme with the Vaccinia virus VP39 protein bound to RNA suggests how the flavivirus capping enzyme may bind RNA, and mutagenesis analysis of residues in the putative RNA binding site demonstrate that several basic residues are critical for RNA binding. Several mutants show differential binding to 5′ di-, mono-, and un-phosphorylated RNAs. The mode of RNA binding appears similar to that found with other methyltransferase enzymes, and a discussion of diphosphorylated RNA binding is presented

Synthesis and biological evaluation of novel flexible nucleoside analogues that inhibit flavivirus replication in vitro

Flaviviruses, such as Dengue (DENV) and Zika (ZIKV) viruses, represent a severe health burden. There are currently no FDA-approved treatments, and vaccines against most flaviviruses are still lacking. We have developed several flexible analogues (“fleximers”) of the FDA-approved nucleoside Acyclovir that exhibit activity against various RNA viruses, demonstrating their broad-spectrum potential. The current study reports activity against DENV and YFV, particularly for compound 1. Studies to elucidate the mechanism of action suggest the flex-analogue triphosphates, especially 1-TP, inhibit DENV and ZIKV methyltransferases. The results of these studies are reported herein

Deciphering the molecular basis for nucleotide selection by the West Nile virus RNA helicase

The West Nile virus RNA helicase uses the energy derived from the hydrolysis of nucleotides to separate complementary strands of RNA. Although this enzyme has a preference for ATP, the bias towards this purine nucleotide cannot be explained on the basis of specific protein–ATP interactions. Moreover, the enzyme does not harbor the characteristic Q-motif found in other helicases that regulates binding to ATP. In the present study, we used structural homology modeling to generate a model of the West Nile virus RNA helicase active site that provides instructive findings on the interaction between specific amino acids and the ATP substrate. In addition, we evaluated both the phosphohydrolysis and the inhibitory potential of a collection of 30 synthetic purine analogs. A structure-guided alanine scan of 16 different amino acids was also performed to clarify the contacts that are made between the enzyme and ATP. Our study provides a molecular rationale for the bias of the enzyme for ATP by highlighting the specific functional groups on ATP that are important for binding. Moreover, we identified three new essential amino acids (Arg-185, Arg-202 and Asn-417) that are critical for phosphohydrolysis. Finally, we provide evidence that a region located upstream of motif I, which we termed the nucleotide specificity region, plays a functional role in nucleotide selection which is reminiscent to the role exerted by the Q-motif found in other helicases

Antiviral and Neuroprotective Role of Octaguanidinium Dendrimer-Conjugated Morpholino Oligomers in Japanese Encephalitis

Japanese encephalitis (JE) is caused by a flavivirus that is transmitted to humans by mosquitoes belonging to the Culex sp. The threat of JE looms over a vast geographical realm, encompassing approximately 10 billion people. The disease is feared because currently there are no specific antiviral drugs available. There have been reports where other investigators have shown that agents that block viral replication can be used as effective therapeutic countermeasures. Vivo-Morpholinos (MOs) are synthetically produced analogs of DNA or RNA that can be modified to bind with specific targeted regions in a genome. In this study the authors propose that in an animal model of JE, MOs specifically designed to bind with specific region of JE virus (JEV) genome, blocks virus production in cells of living organisms. This results in reduced mortality of infected animals. As the major target of JEV is the nerve cells, analysis of brain of experimental animals, post treatment with MOs, showed neuroprotection. Studies in cultured cells were also supportive of the antiviral role of the MOs. The potent anti-sense effect in animals and lack of obvious toxicity at the effective dosage make these MOs good research reagents with future therapeutic applications in JE