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Search Results: 1 - 10 of 33970 matches for " Hwee Cheng Tan? "
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Proteasome Inhibition Suppresses Dengue Virus Egress in Antibody Dependent Infection
Milly M. Choy?,Summer L. Zhang?,Vivian V. Costa?,Hwee Cheng Tan,Sophie Horrevorts?,Eng Eong Ooi
PLOS Neglected Tropical Diseases , 2015, DOI: 10.1371/journal.pntd.0004058
Abstract: The mosquito-borne dengue virus (DENV) is a cause of significant global health burden, with an estimated 390 million infections occurring annually. However, no licensed vaccine or specific antiviral treatment for dengue is available. DENV interacts with host cell factors to complete its life cycle although this virus-host interplay remains to be fully elucidated. Many studies have identified the ubiquitin proteasome pathway (UPP) to be important for successful DENV production, but how the UPP contributes to DENV life cycle as host factors remains ill defined. We show here that proteasome inhibition decouples infectious virus production from viral RNA replication in antibody-dependent infection of THP-1 cells. Molecular and imaging analyses in β-lactone treated THP-1 cells suggest that proteasome function does not prevent virus assembly but rather DENV egress. Intriguingly, the licensed proteasome inhibitor, bortezomib, is able to inhibit DENV titers at low nanomolar drug concentrations for different strains of all four serotypes of DENV in primary monocytes. Furthermore, bortezomib treatment of DENV-infected mice inhibited the spread of DENV in the spleen as well as the overall pathological changes. Our findings suggest that preventing DENV egress through proteasome inhibition could be a suitable therapeutic strategy against dengue.
Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes
Monica Poggianella?,José L. Slon Campos?,Kuan Rong Chan?,Hwee Cheng Tan,Marco Bestagno?,Eng Eong Ooi?,Oscar R. Burrone
PLOS Neglected Tropical Diseases , 2015, DOI: 10.1371/journal.pntd.0003947
Abstract: Dengue virus (DENV) infection is a major emerging disease widely distributed throughout the tropical and subtropical regions of the world affecting several millions of people. Despite constants efforts, no specific treatment or effective vaccine is yet available. Here we show a novel design of a DNA immunisation strategy that resulted in the induction of strong antibody responses with high neutralisation titres in mice against all four viral serotypes. The immunogenic molecule is an engineered version of the domain III (DIII) of the virus E protein fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII sequences were also codon-optimised for expression in mammalian cells. While DIII alone is very poorly secreted, the codon-optimised fusion protein is rightly expressed, folded and secreted at high levels, thus inducing strong antibody responses. Mice were immunised using gene-gun technology, an efficient way of intradermal delivery of the plasmid DNA, and the vaccine was able to induce neutralising titres against all serotypes. Additionally, all sera showed reactivity to a recombinant DIII version and the recombinant E protein produced and secreted from mammalian cells in a mono-biotinylated form when tested in a conformational ELISA. Sera were also highly reactive to infective viral particles in a virus-capture ELISA and specific for each serotype as revealed by the low cross-reactive and cross-neutralising activities. The serotype specific sera did not induce antibody dependent enhancement of infection (ADE) in non-homologous virus serotypes. A tetravalent immunisation protocol in mice showed induction of neutralising antibodies against all four dengue serotypes as well.
Dengue Virus Neutralization in Cells Expressing Fc Gamma Receptors
Tanu Chawla, Kuan Rong Chan, Summer L. Zhang, Hwee Cheng Tan, Angeline P. C. Lim, Brendon J. Hanson, Eng Eong Ooi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065231
Abstract: Activating Fc gamma receptors (FcγRs) in hematopoietic cells serve to remove antibody-opsonized antigens, including dengue virus (DENV), from systemic circulation. While neutralizing antibody concentrations provide humoral immunity, cross-reactive or sub-neutralizing levels of antibody can result in antibody-dependent enhancement of DENV infection that increases overall viral burden. Recently, it has been suggested that the antibody levels needed for DENV neutralization differs when different FcγR is engaged. If this is true, the threshold titer used to infer immunity should be influenced by FcγR usage. Here, using cells that express both activating and inhibitory FcγRs, we show that the type of FcγR engaged during phagocytosis can influence the antibody concentration requirement for DENV neutralization. We demonstrate that phagocytosis through FcγRI requires significantly less antibody for complete DENV neutralization compared to FcγRIIA. Furthermore, when DENV is opsonized with sub-neutralizing levels of antibody, FcγRI-mediated phagocytosis resulted in significantly reduced DENV titers compared to FcγRIIA. However, while FcγRI may remove antibody-opsonized DENV more efficiently, this receptor is only preferentially engaged by clustering when neutralizing, but not sub-neutralizing antibody concentrations, were used. Collectively, our study demonstrates that activating FcγR usage may influence antibody titers needed for DENV neutralization.
First Experimental In Vivo Model of Enhanced Dengue Disease Severity through Maternally Acquired Heterotypic Dengue Antibodies
Jowin Kai Wei Ng,Summer Lixin Zhang,Hwee Cheng Tan,Benedict Yan,Julia Maria Martinez Gomez,Wei Yu Tan,Jian Hang Lam,Grace Kai Xin Tan,Eng Eong Ooi,Sylvie Alonso
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004031
Abstract: Dengue (DEN) represents the most serious arthropod-borne viral disease. DEN clinical manifestations range from mild febrile illness to life-threatening hemorrhage and vascular leakage. Early epidemiological observations reported that infants born to DEN-immune mothers were at greater risk to develop the severe forms of the disease upon infection with any serotype of dengue virus (DENV). From these observations emerged the hypothesis of antibody-dependent enhancement (ADE) of disease severity, whereby maternally acquired anti-DENV antibodies cross-react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Although in vitro and in vivo experimental set ups have indirectly supported the ADE hypothesis, direct experimental evidence has been missing. Furthermore, a recent epidemiological study has challenged the influence of maternal antibodies in disease outcome. Here we have developed a mouse model of ADE where DENV2 infection of young mice born to DENV1-immune mothers led to earlier death which correlated with higher viremia and increased vascular leakage compared to DENV2-infected mice born to dengue na?ve mothers. In this ADE model we demonstrated the role of TNF-α in DEN-induced vascular leakage. Furthermore, upon infection with an attenuated DENV2 mutant strain, mice born to DENV1-immune mothers developed lethal disease accompanied by vascular leakage whereas infected mice born to dengue na?ve mothers did no display any clinical manifestation. In vitro ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice born to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice born to DENV1-immune mothers, thus reproducing epidemiological observations. Overall, this work provides direct in vivo demonstration of the role of maternally acquired heterotypic dengue antibodies in the enhancement of dengue disease severity and offers a unique opportunity to further decipher the mechanisms involved.
A Solution for Cross-docking Operations Planning, Scheduling and Coordination  [PDF]
Zhengping Li, Wei He, Cheng Hwee Sim, Chong Chuan Chen
Journal of Service Science and Management (JSSM) , 2012, DOI: 10.4236/jssm.2012.52014
Abstract: Crossdocking is defined as an operational strategy that moves items through consolidation centers or cross docks without putting them into storage. As the need to move inventory faster increases, more logistics managers are turning to crossdocking but the ability to execute such strategy well depends on good planning, dynamic scheduling and coordina-tion. This paper introduces our research and development work on cross docking solution in three aspects: optimized planning on container grouping, clustering, sequencing and allocating containers to docks; real-time scheduling handles the dynamics of container arrivals and actual pallet transfers; and cross-docking coordination conducts real-time task assignment/sequencing and resource management to deal with dynamic changes.
A Human PrM Antibody That Recognizes a Novel Cryptic Epitope on Dengue E Glycoprotein
Annie Hoi Yi Chan, Hwee Cheng Tan, Angelia Yee Chow, Angeline Pei Chiew Lim, Shee Mei Lok, Nicole J. Moreland, Subhash G. Vasudevan, Paul A. MacAry, Eng Eong Ooi, Brendon J. Hanson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033451
Abstract: Dengue virus (DENV) is a major mosquito-borne pathogen infecting up to 100 million people each year; so far no effective treatment or vaccines are available. Recently, highly cross-reactive and infection-enhancing pre-membrane (prM)-specific antibodies were found to dominate the anti-DENV immune response in humans, raising concern over vaccine candidates that contain native dengue prM sequences. In this study, we have isolated a broadly cross-reactive prM-specific antibody, D29, during a screen with a non-immunized human Fab-phage library against the four serotypes of DENV. The antibody is capable of restoring the infectivity of virtually non-infectious immature DENV (imDENV) in FcγR-bearing K562 cells. Remarkably, D29 also cross-reacted with a cryptic epitope on the envelope (E) protein located to the DI/DII junction as evidenced by site-directed mutagenesis. This cryptic epitope, while inaccessible to antibody binding in a native virus particle, may become exposed if E is not properly folded. These findings suggest that generation of anti-prM antibodies that enhance DENV infection may not be completely avoided even with immunization strategies employing E protein alone or subunits of E proteins.
Participatory Sensing for Government-Centric Applications: A Singapore Case Study
Ramgopal Venkat,Thirumoorthy Divagar,Tie Luo,Hwee Pink Tan
Computer Science , 2015,
Abstract: Singapore, an urbanized and populated country with high penetration of smartphones, provides an excellent base for citizen-centric participatory sensing applications. Mobile participatory sensing applications offer an efficient means of directing feedback to government agencies for timely identifying and solving problems of citizens' concern. While real deployments of such applications are on an uprising trend in Singapore, there is no concerted effort that studies the {\em user experience} of these applications. To fill this gap, we conduct a market study by analyzing the user reviews on the Google Play and Apple App Store for six major mobile crowdsourcing applications created by Singapore government agencies. This study was carried out for a period of 4 months during which we collected and analyzed 592 customer reviews. This was also supplemented by our personal use of the applications during the same period. This paper presents the methodology and findings of this study, as well as our recommendations of what improvements that these applications could incorporate. We classify user reviews into 8 major concerns, and recommend 9 features to enhance the applications' utility. The recommendations are presented in terms of user interface, incentive, and publicity.
Prooxidant/Antioxidant Ratio (ProAntidex) as a Better Index of Net Free Radical Scavenging Potential
Lai Teng Ling,Uma D Palanisamy,Hwee Ming Cheng
Molecules , 2010, DOI: 10.3390/molecules15117884
Abstract: The antioxidant activity of several Malaysian plant extracts was analyzed simultaneously with their pro-oxidant capacity. This ratio represents an index (ProAntidex) of the net free radical scavenging ability of whole plant extracts. We observed that ethanolic extracts of Nephelium lappaceum peel, Fragaria x ananassa leaf, Lawsonia inermis leaf, Syzygium aqueum leaf and grape seed had a lower Pro-Antidex than the commercially available Emblica? extract which is an antioxidant agent with very low pro-oxidant activity. Among the aqueous extracts, Lawsonia inermis leaf, Nephelium mutobile leaf and grape seed had lower pro-oxidant activity compared to the Emblica? extract. Among these extracts, aqueous extract of Nephelium mutobile leaf had a very low index of 0.05 compared to 0.69 for Emblica?. Most of the extracts had a far lower ProAntidex compared to the Vitamin C. The index enables us to identify extracts with high net free radical scavenging activity potential. The ProAntidex is beneficial as a screening parameter to the food industries and healthcare.
Tropical Plant Extracts as Potential Antihyperglycemic Agents
Thamilvaani Manaharan,Uma Devi Palanisamy,Cheng Hwee Ming
Molecules , 2012, DOI: 10.3390/molecules17055915
Abstract: Preliminary investigations on 14 plant extracts (obtained by ethanolic and aqueous extraction) identified those having high antioxidant and a significant total phenolic content. Antihyperglycemic, a-amylase and a-glucosidase inhibition activities were also observed. A correlation between the antihyperglycemic activity, total phenolic content and antioxidant (DPPH scavenging) activity was established. To further substantiate these findings, the possibility of tannins binding non-specifically to enzymes and thus contributing to the antihyperglycemic activity was also investigated. Our study clearly indicated that the antihyperglycemic activity observed in the plant extracts was indeed not due to non-specific tannin absorption.
Alpha-tocotrienol is the most abundant tocotrienol isomer circulated in plasma and lipoproteins after postprandial tocotrienol-rich vitamin E supplementation
Syed Fairus, Rosnah M Nor, Hwee M Cheng, Kalyana Sundram
Nutrition Journal , 2012, DOI: 10.1186/1475-2891-11-5
Abstract: Ten healthy volunteers (5 males and 5 females) were administered a single dose of vitamin E [526 mg palm tocotrienol-rich fraction (TRF) or 537 mg α-T] after 7-d pre-conditioning on a T3-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of T and T3 isomers in plasma, triacylglycerol-rich particles (TRP), LDL, and HDL were measured at each postprandial interval.After TRF supplementation, plasma α-T3 and γ-T3 peaked at 5 h (α-T3: 4.74 ± 1.69 μM; γ-T3: 2.73 ± 1.27 μM). δ-T3 peaked earlier at 4 h (0.53 ± 0.25 μM). In contrast, α-T peaked at 6 h (30.13 ± 2.91 μM) and 8 h (37.80 ± 3.59 μM) following supplementation with TRF and α-T, respectively. α-T was the major vitamin E isomer detected in plasma, TRP, LDL, and HDL even after supplementation with TRF (composed of 70% T3). No T3 were detected during fasted states. T3 are detected postprandially only after TRF supplementation and concentrations were significantly lower than α-T.Bio-discrimination between vitamin E isomers in humans reduces the rate of T3 absorption and affects their incorporation into lipoproteins. Although low absorption of T3 into circulation may impact some of their physiological functions in humans, T3 have biological functions well below concentration noted in this study.Vitamin E is the generic name for a group of 8 plant-derived, lipid soluble substances ("tocols") including four tocopherol (T) and four tocotrienol (T3) derivatives. T3 are similar to T in molecular structure, except that they have an isoprenoid tail with three unsaturation points instead of a saturated phytyl chain. Vitamin E is a recognized antioxidant and thought beneficial for human health. There have been several indications that T3 may result in superior therapeutic properties compared to T [1-8].The absorption and biokinetics of T3 in humans are however not fully understood. Inter alia, the above issues related to the absorption and biokinetics have been linke
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