180 research outputs found
Towards the Discovery of Inhibitors Against FtsZ, an Essential Cell Division Protein from Mycobacterium Tuberculosis, a Potential Antimycobacterial Target
No full textTuberculosis (TB) is a bacterial infection responsible for more than 1.5 million deaths per year. The emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) poses an urgent need for novel antituberculosis drugs. Filamentous temperature-sensitive protein Z (FtsZ) is a bacterial homologue of mammalian tubulin. During bacterial cell division, FtsZ first polymerises into protofilaments in a GTP-dependent manner to form a highly dynamic cytokinetic structure, namely the Z-ring, at a cell midpoint. The Z-ring contracts resulting in septum formation and cell division. Thus, the FtsZ function is essential; indeed, its inhibition leads to the disruption of cell division and eventually bacterial cell death. The development of Mycobacterium tuberculosis FtsZ inhibitors has been hampered by a lack of structural data that could be exploited for structure-based drug design with a strong possibility of identifying false positive inhibitors using traditional drug discovery approaches. Through attempts to advance structural biology and the development of M. tuberculosis FtsZ inhibitors, first, we determined various crystal structures of M. tuberculosis FtsZ in complex with coumarin analogues (well established FtsZ inhibitors), revealing that coumarins exclusively bind to two novel cryptic pockets in nucleotide-free FtsZ, but not to binary FtsZ-GTP or -GDP complexes. Second, NMR-based fragment screening to identify novel FtsZ inhibitors was carried out in collaboration with our partners at Monash University, resulting in 38 fragments hits. These were further validated by biophysical and biochemical assays as well as X-ray crystallography to rank them for further development as lead compounds. Two fragments, A11 and B2, were selected for this development using structure-based drug design. A11 and B2 were successfully crystallised in complexes with FtsZ, in which transient binding pockets in M. tuberculosis FtsZ were further confirmed. Overall, the results of these studies help in our understanding of the mechanism of the cryptic pocket formation of M. tuberculosis FtsZ and also in advancing the development of M. tuberculosis FtsZ inhibitors using structure-based drug design
Does Reassessment of Risk Improve Predictions? A Framework and Examination of the SAVRY and YLS/CMI
No full textAuthor NoteJodi L. Viljoen, Andrew L. Gray, Catherine Shaffer, Aisha Bhanwer, Donna Tafreshi, and Kevin S. Douglas, Department of Psychology, Simon Fraser University.This research was supported by a grant from the Social Sciences and Humanities Research Council of Canada, and a Career Investigator Award for the first author from the Michael Smith Foundation for Health Research.Correspondence concerning this article should be address to Jodi Viljoen, Department of Psychology, Simon Fraser University, Burnaby, BC V5A 1S6. Contact: [email protected]
THE CULTURAL REPRESENTATION OF AMERICAN AND PAKISTANI AS SEEN IN AISHA SAEED’S WRITTEN IN THE STARS
No full textRepresentation of culture is portrayed in literary works. The representation of culture brings the reproduction of the said culture into public eyes. When the representation of a culture is wrongly done, the country whose culture is being presented takes its burden. This problem is depicted in Aisha Saeed’s Written in the Stars. Regarding the issue, this research is intended to analyze the cultural representation of two cultures presented by the author in the story using Stuart Halls representation theory. Furthermore, this is qualitative research in which the researcher comprehends social problems based on detailed information in its natural setting on the novel. Based on the analysis, the representation of two cultures, which are Pakistan and America, varies from each other. The cultural representation of Pakistan emphasizes the condition of a third-world country with issues of how women are unfairly treated. In contrast, the cultural representation of America explains the country, aside from their sexes, treats individuals fairly
Early presynaptic and late postsynaptic components contribute independently to Brain-Derived Neurotrophic Factor-induced synaptic plasticity
No full textTrophin-induced synaptic plasticity consists of both presynaptic and postsynaptic processes. The potential interdependence of these mechanisms and their temporal relationships are undefined. The synaptic vesicle protein Rab3A is required for the early, initial 10 min phase, but not for the later phase of BDNF-enhanced transmission. We now examine the temporal distinction and mechanistic relationships between these phases of BDNF action. Rab3A mutant cells did not exhibit increased mEPSC frequency in response to BDNF in cell culture, indicating absence of the presynaptic component. In contrast, BDNF enhanced post-synaptic glutamate-induced current in the mutant neurons as in the wildtype, indicating that the postsynaptic component of the response was intact. Finally, the postsynaptic NMDA receptor subunit NR2B was phosphorylated at Tyr1472 by BDNF in Rab3A knockouts, as previously shown in wildtype. Our results are the first to demonstrate that presynaptic and postsynaptic components of BDNF-enhanced synaptic activity are independent and temporally distinct.Peer reviewe
Intercultural Teaching Competence: A Multicultural Framework for Instructor Reflection
No full textNot peer reviewe
Intercultural Teaching Competence: A Multicultural Framework for Instructor Reflection
No full textNot peer reviewe
The Grammatical Phenomenon in Character Description in Aisha Al-Mahmoud’s Watan Mozawwar Novel
No full textThis research aims to analyze the manifestations of grammatical phenomena in describing the main character in Aisha Al-Mahmoud’s Watan Mozawwar (Forged Homeland). The author relies on several grammatical phenomena in presenting the character in a detailed and accurate way that enables one to understand the psychological dimensions of the character and to have guided impressions on the recipient’s or reader’s mind who is clearly present in the creative process. The research focuses on the grammatical phenomena that have emerged in describing the main character, specifically, around which events and narration are centered. The research concludes that the sentence lengthening phenomenon dominates the grammatical phenomena in the character description, and this is because of this phenomenon’s expansion through different methods it uses including the length of dependency, the length of multiplicity, and the different grammatical functions and styles. Moreover, the conjunction has formed a remarkable phenomenon in the style of the writer, and it has been well used by adding elements and other related things that increase its expansion even though it is in itself a method of lengthening the sentence
Authorship Attribution Dataset in Bangla 2
No full textA dataset consisting of text samples from 6 authors with 350 samples per author and total word count of 2.3+ million
BAAD6: Bangla Authorship Attribution Dataset
No full textA dataset consisting of text samples from 6 authors with 350 samples per author and total word count of 2.3+ million
Authorship Attribution Dataset in Bangla 2
No full textA dataset consisting of text samples from 6 authors with 350 samples per author and total word count of 2.3+ million
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