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KHAN, MOHAMMAD ASİF

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MOHAMMAD ASİF
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KHAN
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Now showing 1 - 7 of 7
  • PublicationMetadata only
    Correlation of host inflammatory cytokines and immune-related metabolites, but not viral NS1 protein, with disease severity of dengue virus infection
    (2020-08-01T00:00:00Z) Soe, Hui Jen; Manikam, Rishya; Raju, Chandramathi Samudi; Khan, MOHAMMAD ASİF; Sekaran, Shamala Devi; KHAN, MOHAMMAD ASİF
    Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from patients with different disease severity. Cytokines and metabolites profiles were assessed using a multiplex cytokine assay and liquid chromatography mass spectrometry respectively. The findings showed that NS1 was able to induce the loss of barrier function in microvascular endothelium in a dose dependent manner, however, the level of NS1 in serum samples did not correlate with the extent of vascular leakage induced. Further assessment of host factors revealed that cytokines such as CCL2, CCL5, CCL20 and CXCL1, as well as adhesion molecule ICAM-1, that are involved in leukocytes infiltration were expressed higher in dengue patients in comparison to healthy individuals. In addition, metabolomics study revealed the presence of deregulated metabolites involved in the phospholipid metabolism pathway in patients with severe manifestations. In conclusion, disease severity in dengue virus infection did not correlate directly with NS1 level, but instead with host factors that are involved in the regulation of junctional integrity and phospholipid metabolism. However, as the studied population was relatively small in this study, these exploratory findings should be confirmed by expanding the sample size using an independent cohort to further establish the significance of this study.
  • PublicationOpen Access
    Avian Influenza H7N9 Virus Adaptation to Human Hosts
    (2021-05-01T00:00:00Z) Tan, Swan; Sjaugi, Muhammad Farhan; Fong, Siew Chinn; Chong, Li Chuin; Abd Raman, Hadia Syahirah; Nik Mohamed, Nik Elena; August, Joseph Thomas; Khan, Asif M.; KHAN, MOHAMMAD ASİF
    Avian influenza virus A (H7N9), after circulating in avian hosts for decades, was identified as a human pathogen in 2013. Herein, amino acid substitutions possibly essential for human adaptation were identified by comparing the 4706 aligned overlapping nonamer position sequences (1-9, 2-10, etc.) of the reported 2014 and 2017 avian and human H7N9 datasets. The initial set of virus sequences (as of year 2014) exhibited a total of 109 avian-to-human (A2H) signature amino acid substitutions. Each represented the most prevalent substitution at a given avian virus nonamer position that was selectively adapted as the corresponding index (most prevalent sequence) of the human viruses. The majority of these avian substitutions were long-standing in the evolution of H7N9, and only 17 were first detected in 2013 as possibly essential for the initial human adaptation. Strikingly, continued evolution of the avian H7N9 virus has resulted in avian and human protein sequences that are almost identical. This rapid and continued adaptation of the avian H7N9 virus to the human host, with near identity of the avian and human viruses, is associated with increased human infection and a predicted greater risk of human-to-human transmission.
  • PublicationMetadata only
    Developing critical thinking inSTEMeducation through inquiry-based writing in the laboratory classroom
    (2021-01-01T00:00:00Z) Jeon, Ah-Jung; Kellogg, David; Khan, MOHAMMAD ASİF; Tucker-Kellogg, Greg; KHAN, MOHAMMAD ASİF
    Laboratory pedagogy is moving away from step-by-step instructions and toward inquiry-based learning, but only now developing methods for integrating inquiry-based writing (IBW) practices into the laboratory course. Based on an earlier proposal (Science 2011;332:919), we designed and implemented an IBW sequence in a university bioinformatics course. We automatically generated unique, double-blinded, biologically plausible DNA sequences for each student. After guided instruction, students investigated sequences independently and responded through IBW writing assignments. IBW assignments were structured as condensed versions of a scientific research article, and because the sequences were double blinded, they were also assessed as authentic science and evaluated on clarity and persuasiveness. We piloted the approach in a seven-day workshop (35 students) at Perdana University in Malaysia. We observed dramatically improved student engagement and indirect evidence of improved learning outcomes over a similar workshop without IBW. Based on student feedback, initial discomfort with the writing component abated in favor of an overall positive response and increasing comfort with the high demands of student writing. Similarly, encouraging results were found in a semester length undergraduate module at the National University of Singapore (155 students).
  • PublicationOpen Access
    Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology
    (2022-01-01T00:00:00Z) Cuscino, Nicola; Fatima, Ayesha; Di Pilato, Vincenzo; Bulati, Matteo; Alfano, Caterina; Monaca, Elisa; Di Mento, Giuseppina; Di Carlo, Daniele; Cardinale, Francesca; Monaco, Francesco; Rossolini, Gian Maria; KHAN, MOHAMMAD ASİF; Conaldi, Pier Giulio; Douradinha, Bruno; FATIMA, AYESHA; KHAN, MOHAMMAD ASİF
    Klebsiella pneumoniae is a Gram-negative pathogen of clinical relevance, which can provoke serious urinary and blood infections and pneumonia. This bacterium is a major public health threat due to its resistance to several antibiotic classes. Using a reverse vaccinology approach, 7 potential antigens were identified, of which 4 were present in most of the sequences of Italian carbapenem-resistant K. pneumoniae clinical isolates. Bioinformatics tools demonstrated the antigenic potential of these bacterial proteins and allowed for the identification of T and B cell epitopes. This led to a rational design and in silico characterization of a multiepitope vaccine against carbapenem-resistant K. pneumoniae strains. As adjuvant, the mycobacterial heparin-binding hemagglutinin adhesin (HBHA), which is a Toll-like receptor 4 (TLR-4) agonist, was included, to increase the immunogenicity of the construct. The multiepitope vaccine candidate was analyzed by bioinformatics tools to assess its antigenicity, solubility, allergenicity, toxicity, physical and chemical parameters, and secondary and tertiary structures. Molecular docking binding energies to TLR-2 and TLR-4, two important innate immunity receptors involved in the immune response against K. pneumoniae infections, and molecular dynamics simulations of such complexes supported active interactions. A codon optimized multiepitope sequence cloning strategy is proposed, for production of recombinant vaccine in classical bacterial vectors. Finally, a 3 dose-immunization simulation with the multiepitope construct induced both cellular and humoral immune responses. These results suggest that this multiepitope construct has potential as a vaccination strategy against carbapenem-resistant K. pneumoniae and deserves further validation.
  • PublicationOpen Access
    Dynamics of Influenza A (H5N1) virus protein sequence diversity
    (2020-05-01T00:00:00Z) Abd Raman, Hadia Syahirah; Tan, Swan; August, Joseph Thomas; Khan, Asif M.; KHAN, MOHAMMAD ASİF
    Background. InfluenzaA(H5N1) virus is a global concern with potential as a pandemic threat. High sequence variability of influenza A viruses is a major challenge for effective vaccine design. A continuing goal towards this is a greater understanding of influenza A (H5N1) proteome sequence diversity in the context of the immune system (antigenic diversity), the dynamics of mutation, and effective strategies to overcome the diversity for vaccine design.
  • PublicationOpen Access
    Editorial: Bioinformatics and the Translation of Data-Driven Discoveries
    (2022-05-01T00:00:00Z) KHAN, MOHAMMAD ASİF; Ranganathan, Shoba; Suravajhala, Prashanth; KHAN, MOHAMMAD ASİF
  • PublicationMetadata only
    Absence of BapA type III effector protein affects Burkholderia pseudomallei intracellular lifecycle in human host cells
    (2021-09-01T00:00:00Z) Choh, Leang-Chung; Ong, Guang-Han; Chua, Eng-Guan; Vellasamy, Kumutha Malar; Mariappan, Vanitha; Khan, Asif M.; Wise, Micheal J.; Wong, Kum-Thong; Vadivelu, Jamuna; KHAN, MOHAMMAD ASİF
    The etiological agent of melioidosis, Burkholderia pseudomallei, utilises a type III secretion system cluster 3 (T3SS3) to deliver proteins termed type III effectors (T3SEs) into the host cytoplasm in order to establish an intracellular lifecycle in phagocytic and non-phagocytic cells, thus playing an important role in pathogenesis. To gain insight into possible functional roles for BapA, a putative T3SE with unknown function, in the intracellular lifecycle of B.pseudomallei, bapA gene knockout mutant was constructed. The effect of the knockout on virulence to the otherwise isogenic parental strain, K96243, was studied by cellular infection assays and Caenorhabditis elegans killing assay. The attachment and subsequent entry into A549 cells was significantly (P < 0.05) attenuated in the Delta bapA compared to K96243. However, intracellular replication was not affected. Furthermore, the cell-to-cell spreading capacity of Delta bapA was impaired although the mutant exhibited no evident defect in its actin tail formation. Additionally, phagocytosis and intracellular replication rates of Delta bapA in U937 macrophage cells were significantly reduced relative to K96243 without phagosomal escape being affected. Based on these observations, we conclude that the BapA T3SE could play an important role in B.pseudomallei intracellular lifecycle, especially, in the early stages of attachment and entry into the host cell.