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Search Results: 1 - 10 of 4257 matches for " Eng-Tat Ang "
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Is there an optimal environment in which to learn clinical anatomy? One man’s view  [PDF]
Eng-Tat Ang, Peter Abrahams, Seow Choon Sheong, Mikael Hartman
Forensic Medicine and Anatomy Research (FMAR) , 2014, DOI: 10.4236/fmar.2014.21004
Abstract: Learning anatomy is essential in medical schools, and even more so for budding surgeons. Much has been discussed regarding the updated curriculum, and whether the pedagogies should be based upon cadaveric, and/or multimedia, or hybrid approaches. Much debate has also been centered on who is best qualified to teach. While all these are important, the setting is also critically important for the medical students and surgical trainees. Therefore the overarching issue is whether all these activities should be held in the dissection room, the operating theatre or the classical “Theatrum Anatomicum” ? What are the key experiential learning differences in picking up anatomical knowledge in the various venues listed above? This paper will provide some insights for teachers and students of human anatomy, and some ideas for the future planners and developers of anatomy learning centers internationally.
Neurodegenerative diseases: exercising towards neurogenesis and neuroregeneration
Eng-Tat Ang,Yee-Kit Tai,Shun-Qiang Lo,Raymond Seet,Tuck-Wah Soong
Frontiers in Aging Neuroscience , 2010, DOI: 10.3389/fnagi.2010.00025
Abstract: Currently, there is still no effective therapy for neurodegenerative diseases (NDD) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) despite intensive research and on-going clinical trials. Collectively, these diseases account for the bulk of health care burden associated with age-related neurodegenerative disorders. There is therefore an urgent need to further research into the molecular pathogenesis, histological differentiation, and clinical management of NDD. Importantly, there is also an urgency to understand the similarities and differences between these two diseases so as to identify the common or different upstream and downstream signaling pathways. In this review, the role iron play in NDD will be highlighted, as iron is key to a common underlying pathway in the production of oxidative stress. There is increasing evidence to suggest that oxidative stress predisposed cells to undergo damage to DNA, protein and lipid, and as such a common factor involved in the pathogenesis of AD and PD. The challenge then is to minimize elevated and uncontrolled oxidative stress levels while not affecting basal iron metabolism, as iron plays vital roles in sustaining cellular function. However, overload of iron results in increased oxidative stress due to the Fenton reaction. We discuss evidence to suggest that sustained exercise and diet restriction may be ways to slow the rate of neurodegeneration, by perhaps promoting neurogenesis or antioxidant-related pathways. It is also our intention to cover NDD in a broad sense, in the context of basic and clinical sciences to cater for both clinician’s and the scientist’s needs, and to highlight current research investigating exercise as a therapeutic or preventive measure.
Hypoxia-ischemia and retinal ganglion cell damage
Charanjit Kaur,Wallace S Foulds,Eng-Ang Ling
Clinical Ophthalmology , 2008,
Abstract: Charanjit Kaur1, Wallace S Foulds2, Eng-Ang Ling11Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Singapore Eye Research Institute, SingaporeAbstract: Retinal hypoxia is the potentially blinding mechanism underlying a number of sight-threatening disorders including central retinal artery occlusion, ischemic central retinal vein thrombosis, complications of diabetic eye disease and some types of glaucoma. Hypoxia is implicated in loss of retinal ganglion cells (RGCs) occurring in such conditions. RGC death occurs by apoptosis or necrosis. Hypoxia-ischemia induces the expression of hypoxia inducible factor-1α and its target genes such as vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS). Increased production of VEGF results in disruption of the blood retinal barrier leading to retinal edema. Enhanced expression of NOS results in increased production of nitric oxide which may be toxic to the cells resulting in their death. Excess glutamate release in hypoxic-ischemic conditions causes excitotoxic damage to the RGCs through activation of ionotropic and metabotropic glutamate receptors. Activation of glutamate receptors is thought to initiate damage in the retina by a cascade of biochemical effects such as neuronal NOS activation and increase in intracellular Ca2+ which has been described as a major contributing factor to RGC loss. Excess production of proinflammatory cytokines also mediates cell damage. Besides the above, free-radicals generated in hypoxic-ischemic conditions result in RGC loss because of an imbalance between antioxidant- and oxidant-generating systems. Although many advances have been made in understanding the mediators and mechanisms of injury, strategies to improve the damage are lacking. Measures to prevent neuronal injury have to be developed.Keywords: retinal hypoxia, retinal ganglion cells, glutamate receptors, neuronal injury, retina
Dexamethasone inhibits the Nox-dependent ROS production via suppression of MKP-1-dependent MAPK pathways in activated microglia
Yingqian Huo, Parakalan Rangarajan, Eng-Ang Ling, S Thameem Dheen
BMC Neuroscience , 2011, DOI: 10.1186/1471-2202-12-49
Abstract: The present study showed that the increased ROS production and NO release in activated BV-2 microglial cells by LPS were associated with increased expression of Nox-2 and iNOS. Dex suppressed the upregulation of Nox-2 and iNOS, as well as the subsequent ROS production and NO synthesis in activated BV-2 cells. This inhibition caused by Dex appeared to be mediated by upregulation of MAPK phosphatase-1 (MKP-1), which antagonizes the activity of mitogen-activated protein kinases (MAPKs). Dex induced-suppression of Nox-2 and -upregulation of MKP-1 was also evident in the activated microglia from corpus callosum of postnatal rat brains. The overexpression of MKP-1 or inhibition of MAPKs (by specific inhibitors of JNK and p38 MAPKs), were found to downregulate the expression of Nox-2 and iNOS and thereby inhibit the synthesis of ROS and NO in activated BV-2 cells. Moreover, Dex was unable to suppress the LPS-induced synthesis of ROS and NO in BV-2 cells transfected with MKP-1 siRNA. On the other hand, knockdown of Nox-2 in BV-2 cells suppressed the LPS-induced ROS production and NO release.In conclusion, it is suggested that downregulation of Nox-2 and overexpression of MKP-1 that regulate ROS and NO may form the potential therapeutic strategy for the treatment of neuroinflammation in neurodegenerative diseases.An inflammatory process in the central nervous system (CNS) is considered to be a prominent feature in a number of neurodegenerative diseases and is mediated by the activated microglia, the resident immune cells of the CNS. The microglia normally respond to neuronal damage and remove the damaged cells by phagocytosis [1]. The chronic activation of these cells appears to cause neuronal damage through enhanced release of potentially cytotoxic molecules such as proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), nitric oxide (NO), reactive oxygen intermediates, proteinases and complement proteins [2-5]. Moreover, microglia-de
Runx1t1 (Runt-Related Transcription Factor 1; Translocated to, 1) Epigenetically Regulates the Proliferation and Nitric Oxide Production of Microglia
Nimmi Baby, Yali Li, Eng-Ang Ling, Jia Lu, S. Thameem Dheen
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089326
Abstract: Background Microglia, the resident immune cells of the brain, undergo rapid proliferation and produce several proinflammatory molecules and nitric oxide (NO) when activated in neuropathological conditions. Runx1t1 (Runt-related transcription factor 1, translocated to 1) has been implicated in recruiting histone deacetylases (HDACs) for transcriptional repression, thereby regulating cell proliferation. In the present study, Runx1t1 expression was shown to localize in amoeboid microglial cells of the postnatal rat brain, being hardly detectable in ramified microglia of the adult brain. Moreover, a marked expression of Runx1t1was induced and translocated to nuclei in activated microglia in vitro and in vivo. In view of these findings, it was hypothesized that Runx1t1 regulates microglial functions during development and in neuropathological conditions. Methods and Findings siRNA-mediated knockdown of Runx1t1 significantly decreased the expression level of cell cycle-related gene, cyclin-dependent kinase 4 (Cdk4) and proliferation index in activated BV2 microglia. It was also shown that HDAC inhibitor (HDACi) treatment mimics the effects of Runx1t1 knockdown on microglial proliferation, confirming that microglial proliferation is associated with Runx1t1 expression and HDACs activity. Further, Runx1t1 and HDACs were shown to promote neurotoxic effect of microglia by repressing expression of LAT2, L-aminoacid transporter-2 (cationic amino acid transporter, y+ system), which normally inhibits NO production. This was confirmed by chromatin immunoprecipitation (ChIP) assay, which revealed that Runx1t1 binds to the promoter region of LAT2 and this binding increased upon microglial activation. However, the enhanced binding of Runx1t1 to the LAT2 promoter could not repress the LAT2 expression when the BV2 microglia cells were treated with HDACi, indicating that Runx1t1 requires HDACs to transcriptionally repress the expression of LAT2. Conclusion/Interpretation In conclusion, it is suggested that Runx1t1 controls proliferation and the neurotoxic effect of microglia by epigenetically regulating Cdk4 and LAT2 via its interaction with HDACs.
Low Level Primary Blast Injury in Rodent Brain
Enci Mary Kan,Eng-Ang Ling,Mui Hong Tan,Jia Lu
Frontiers in Neurology , 2011, DOI: 10.3389/fneur.2011.00019
Abstract: The incidence of blast attacks and resulting traumatic brain injuries has been on the rise in recent years. Primary blast is one of the mechanisms in which the blast wave can cause injury to the brain. The aim of this study was to investigate the effects of a single sub-lethal blast over pressure (BOP) exposure of either 48.9 kPa (7.1 psi) or 77.3 kPa (11.3 psi) to rodents in an open-field setting. Brain tissue from these rats was harvested for microarray and histopathological analyses. Gross histopathology of the brains showed that cortical neurons were “darkened” and shrunken with narrowed vasculature in the cerebral cortex day 1 after blast with signs of recovery at day 4 and day 7 after blast. TUNEL-positive cells were predominant in the white matter of the brain at day 1 after blast and double-labeling of brain tissue showed that these DNA-damaged cells were both oligodendrocytes and astrocytes but were mainly not apoptotic due to the low caspase-3 immunopositivity. There was also an increase in amyloid precursor protein immunoreactive cells in the white matter which suggests acute axonal damage. In contrast, Iba-1 staining for macrophages or microglia was not different from control post-blast. Blast exposure altered the expression of over 5786 genes in the brain which occurred mostly at day 1 and day 4 post-blast. These genes were narrowed down to 10 overlapping genes after time-course evaluation and functional analyses. These genes pointed toward signs of repair at day 4 and day 7 post-blast. Our findings suggest that the BOP levels in the study resulted in mild cellular injury to the brain as evidenced by acute neuronal, cerebrovascular, and white matter perturbations that showed signs of resolution. It is unclear whether these perturbations exist at a milder level or normalize completely and will need more investigation. Specific changes in gene expression may be further evaluated to understand the mechanism of blast-induced neurotrauma.
Recursive Asymptotic Hybrid Matrix Method for Acoustic Waves in Multilayered Piezoelectric Media  [PDF]
Eng Leong Tan
Open Journal of Acoustics (OJA) , 2011, DOI: 10.4236/oja.2011.12004
Abstract: This paper presents the recursive asymptotic hybrid matrix method for acoustic waves in multilayered piezoelectric media. The hybrid matrix method preserves the numerical stability and accuracy across large and small thicknesses. For discussion and comparison, the scattering matrix method is also presented in physics-based form and coherent form. The latter form resembles closely that of hybrid matrix method and helps to highlight their relationship and distinction. For both scattering and hybrid matrix methods, their formulations in terms of eigenwaves solution are provided concisely. Making use of the hybrid matrix, the recursive asymptotic method without eigenwaves solution is described and discussed. The method bypasses the intricacies of eigenvalue-eigenvector approach and requires only elementary matrix operations along with thin- layer asymptotic approximation. It can be used to determine Green’s function matrix readily and facilitates the trade-off between computation efficiency and accuracy.
CD137 ligand activated microglia induces oligodendrocyte apoptosis via reactive oxygen species
Yee Andy Yeo, Julia M Martínez Gómez, J Ludovic Croxford, Stephan Gasser, Eng-Ang Ling, Herbert Schwarz
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-173
Abstract:
Expression of sphingosine kinase 1 in amoeboid microglial cells in the corpus callosum of postnatal rats
Haiyan Lin, Nimmi Baby, Jia Lu, Charanjit Kaur, Chuansen Zhang, Jiajun Xu, Eng-Ang Ling, S Thameem Dheen
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-13
Abstract: Sphingosine kinase (SphK) is an enzyme that phosphorylates sphingosine to sphingosine-1-phosphate (S1P). SphK has two isoforms, SphK1 and SphK2, that have different properties and subcellular localizations [1,2]. While much has been reported on the expression and roles of SphK1 in different cells and its participation in distinct biological functions [1], the biological functions of SphK2 are not yet clearly defined. This study focused on SphK1 in view of its potential role in the central nervous system (CNS) [1]. SphK1 is mainly and abundantly expressed in cytosol of hippocampal neurons, endothelial cells, cerebellar granule cells and astrocytes of rat brain; and in cultured oligodendrocytes and murine BV2 cells [3-7]. SphK1 is also expressed in other tissues including heart, lungs, and kidneys [8,9]. SphK1 overexpression enhances cell survival and cell proliferation [10]. Studies of expression and functions of SphK1 in several types of human cancer tissues [11,12], primary human astrocytes [13], various glioblastoma cell lines [14,15], and cultured brain endothelial cells [6] have shown that it may serve as a novel and useful prognostic marker for astrocytoma and, furthermore, it may play an important role during the development and progression of neoplastic diseases [16,17]. Despite this, however, there is only a modicum of information on the role of SphK1 in the brain, especially in regard to its localization in microglia in vivo. This is particularly so in amoeboid microglial cells (AMC) in the developing brain, which are considered to be the nascent brain macrophages [18]. Indeed, as far as can be ascertained, expression of S1P receptors has been reported in microglia only in culture [5,19]. In this connection, it is relevant to note that SphK 1 is highly expressed in blood monocytes [20], the precuror cells of AMC [18].We have reported recently that AMC, when challenged with LPS or exposed to hypoxia, release large amounts of inflammatory cytokines including
Notch-1 Signaling Regulates Microglia Activation via NF-κB Pathway after Hypoxic Exposure In Vivo and In Vitro
Linli Yao, Enci Mary Kan, Charanjit Kaur, S. Thameem Dheen, Aijun Hao, Jia Lu, Eng-Ang Ling
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0078439
Abstract: Neuroinflammation mediated by the activated microglia is suggested to play a pivotal role in the pathogenesis of hypoxic brain injury; however, the underlying mechanism of microglia activation remains unclear. Here, we show that the canonical Notch signaling orchestrates microglia activation after hypoxic exposure which is closely associated with multiple pathological situations of the brain. Notch-1 and Delta-1 expression in primary microglia and BV-2 microglial cells was significantly elevated after hypoxia. Hypoxia-induced activation of Notch signaling was further confirmed by the concomitant increase in the expression and translocation of intracellular Notch receptor domain (NICD), together with RBP-Jκ and target gene Hes-1 expression. Chemical inhibition of Notch signaling with N-[N-(3,5-difluorophenacetyl)-1-alany1- S-phenyglycine t-butyl ester (DAPT), a γ-secretase inhibitor, effectively reduced hypoxia-induced upregulated expression of most inflammatory mediators. Notch inhibition also reduced NF-κB/p65 expression and translocation. Remarkably, Notch inhibition suppressed expression of TLR4/MyD88/TRAF6 pathways. In vivo, Notch signaling expression and activation in microglia were observed in the cerebrum of postnatal rats after hypoxic injury. Most interestingly, hypoxia-induced upregulation of NF-κB immunoexpression in microglia was prevented when the rats were given DAPT pretreatment underscoring the interrelationship between Notch signaling and NF-κB pathways. Taken together, we conclude that Notch signaling is involved in regulating microglia activation after hypoxia partly through the cross talk between TLR4/MyD88/TRAF6/NF-κB pathways. Therefore, Notch signaling may serve as a prospective target for inhibition of microglia activation known to be implicated in brain damage in the developing brain.
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