22 results match your criteria: "Centre for Translational Medicine (MD6)[Affiliation]"

Splenic marginal zone B cells restrict Mycobacterium tuberculosis infection by shaping the cytokine pattern and cell-mediated immunity.

Cell Rep

July 2024

Center for Discovery and Innovation (CDI), Hackensack Meridian Health, 111 Ideation Way, Nutley, NJ 07110, USA; Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA. Electronic address:

Understanding the role of B cells in tuberculosis (TB) is crucial for developing new TB vaccines. However, the changes in B cell immune landscapes during TB and their functional implications remain incompletely explored. Using high-dimensional flow cytometry to map the immune landscape in response to Mycobacterium tuberculosis (Mtb) infection, our results show an accumulation of marginal zone B (MZB) cells and other unconventional B cell subsets in the lungs and spleen, shaping an unconventional B cell landscape.

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The long saphenous vein is routinely used for coronary bypass graft (CABG) surgery, and two primary techniques are commonly utilized: endoscopic vessel harvesting (EVH) and open vessel harvesting (OVH). The aim of this study was to compare the clinical outcomes of the EVH and OVH techniques used for CABG within the confines of a tertiary hospital. The clinical data of all patients subjected to either EVH or OVH for CABG surgery between 2014 and 2018 were retrospectively analyzed.

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Plasma osteopontin as a biomarker of Alzheimer's disease and vascular cognitive impairment.

Sci Rep

February 2021

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Unit 09-01, Centre for Translational Medicine (MD6), 14 Medical Drive, Singapore, 117599, Singapore.

Cerebrovascular disease (CeVD) and neurodegenerative dementia such as Alzheimer's disease (AD) are frequently associated comorbidities in the elderly, sharing common risk factors and pathophysiological mechanisms including neuroinflammation. Osteopontin (OPN) is an inflammatory marker found upregulated in vascular diseases as well as in AD. However, its involvement in vascular dementia (VaD) and pre-dementia stages, namely cognitive impairment no dementia (CIND), both of which fall under the spectrum of vascular cognitive impairment (VCI), has yet to be examined.

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Improved amyloid burden quantification with nonspecific estimates using deep learning.

Eur J Nucl Med Mol Imaging

June 2021

Clinical Imaging Research Centre, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Translational Medicine (MD6), 14 Medical Drive, #B1-01, Singapore, 117599, Singapore.

Purpose: Standardized uptake value ratio (SUVr) used to quantify amyloid-β burden from amyloid-PET scans can be biased by variations in the tracer's nonspecific (NS) binding caused by the presence of cerebrovascular disease (CeVD). In this work, we propose a novel amyloid-PET quantification approach that harnesses the intermodal image translation capability of convolutional networks to remove this undesirable source of variability.

Methods: Paired MR and PET images exhibiting very low specific uptake were selected from a Singaporean amyloid-PET study involving 172 participants with different severities of CeVD.

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Langendorff-Free Isolation and Propagation of Adult Mouse Cardiomyocytes.

Methods Mol Biol

July 2019

Cardiovascular Research Institute, Centre for Translational Medicine MD6, National University Health System, Singapore, Singapore.

Isolation of healthy, intact cardiomyocytes from the adult mouse heart for cardiac research is challenging. Traditional protocols depend upon specialized Langendorff apparatus, which requires extensive training and presents significant technical and logistical barriers. Described here is a much simplified technique, introducing optimized dissociation buffers to the heart by direct needle injection into the left ventricle, allowing deep myocardial perfusion and the isolation of high yields of viable, rod-shaped cardiomyocytes, using only standard surgical and laboratory equipment.

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Applications of Resting-State Functional Connectivity to Neurodegenerative Disease.

Neuroimaging Clin N Am

November 2017

Center for Cognitive Neuroscience, Neuroscience and Behavioral Disorders Programme, Duke-National University of Singapore Medical School, 8 College Road, #06-15, Singapore 169857, Singapore.

Neurodegenerative diseases target specific large-scale neuronal networks, leading to distinct behavioral and cognitive dysfunctions. Resting-state functional magnetic resonance imaging (rsfMR imaging)-based functional connectivity method maps symptoms-associated functional network deterioration in vivo. This article summarizes accumulating functional connectivity findings supporting the network-based neurodegeneration hypothesis.

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Brain plasticity following MI-BCI training combined with tDCS in a randomized trial in chronic subcortical stroke subjects: a preliminary study.

Sci Rep

August 2017

Singapore Bioimaging Consortium, Agency for Science Technology and Research, 11 Biopolis Way, #02-02 Helios, Singapore, 138667, Singapore.

Brain-computer interface-assisted motor imagery (MI-BCI) or transcranial direct current stimulation (tDCS) has been used in stroke rehabilitation, though their combinatory effect is unknown. We investigated brain plasticity following a combined MI-BCI and tDCS intervention in chronic subcortical stroke patients with unilateral upper limb disability. Nineteen patients were randomized into tDCS and sham-tDCS groups.

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An iTRAQ-based proteomic analysis reveals dysregulation of neocortical synaptopodin in Lewy body dementias.

Mol Brain

August 2017

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Unit 09-01, Centre for Translational Medicine (MD6), 14 Medical Drive, Kent Ridge, Singapore 117599, Singapore.

Lewy body dementias are the second most common cause of neurodegenerative dementia in the elderly after Alzheimer's disease (AD). The two clinical subgroups of Lewy body dementias, namely, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), are differentiated by the chronology of cognitive symptoms relative to parkinsonism. At present, there remains a debate on whether DLB and PDD are separate disease entities, or fall within the same spectrum of Lewy body dementias.

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Background: The use of radiolabeled choline as a positron emission tomography (PET) agent for imaging primary tumors in the prostate has been evaluated extensively over the past two decades. There are, however, conflicting reports of its sensitivity and the relationship between choline PET imaging and disease staging is not fully understood. Moreover, relatively few studies have investigated the correlation between tracer uptake and histological tumor grade.

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Selective induction of alternatively spliced FynT isoform by TNF facilitates persistent inflammatory responses in astrocytes.

Sci Rep

March 2017

Department of Clinical Translational Research, Singapore General Hospital, The Academia, Level 9, Discovery Tower, 20 College Road, 169856, Singapore.

Fyn tyrosine kinase has been implicated in the pathogenesis of Alzheimer's disease (AD). We have previously reported that upregulation of the FynT isoform in AD brains was partly associated with astrocyte activation. In this study, we demonstrated selective FynT induction in murine cortex and primary astrocyte culture after prolonged exposure to inflammatory stimulants, suggesting that FynT may mediate persistent neuroinflammation.

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Andrographolide induces Nrf2 and heme oxygenase 1 in astrocytes by activating p38 MAPK and ERK.

J Neuroinflammation

September 2016

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Unit 09-01, Centre for Translational Medicine (MD6), 14 Medical Drive, Kent Ridge, 117599, Singapore.

Background: Andrographolide is the major labdane diterpenoid originally isolated from Andrographis paniculata and has been shown to have anti-inflammatory and antioxidative effects. However, there is a dearth of studies on the potential therapeutic utility of andrographolide in neuroinflammatory conditions. Here, we aimed to investigate the mechanisms underlying andrographolide's effect on the expression of anti-inflammatory and antioxidant heme oxygenase-1 (HO-1) in primary astrocytes.

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Deciphering Noncoding RNA and Chromatin Interactions: Multiplex Chromatin Interaction Analysis by Paired-End Tag Sequencing (mChIA-PET).

Methods Mol Biol

January 2018

Cancer Science Institute of Singapore, Centre for Translational Medicine (MD6), National University of Singapore, 14 Medical Drive, #12-01 (Bench 7), Singapore, 117599, Singapore.

Genomic DNA is dynamically associated with protein factors and folded to form chromatin fibers. The 3-dimensional (3D) configuration of the chromatin will enable the distal genetic elements to come into close proximity, allowing transcriptional regulation. Noncoding RNA can mediate the 3D structure of chromatin.

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Automatic basal slice detection for cardiac analysis.

J Med Imaging (Bellingham)

July 2016

York University , Lassonde School of Engineering, Department of Electrical Engineering and Computer Science, 4700 Keele Street, Toronto, Ontario M3J 1P3, Canada.

Identification of the basal slice in cardiac imaging is a key step to measuring the ejection fraction of the left ventricle. Despite all the effort placed on automatic cardiac segmentation, basal slice identification is routinely performed manually. Manual identification, however, suffers from high interobserver variability.

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Increased phosphorylation of collapsin response mediator protein-2 at Thr514 correlates with β-amyloid burden and synaptic deficits in Lewy body dementias.

Mol Brain

September 2016

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Unit 09-01, Centre for Translational Medicine (MD6), 14 Medical Drive, Kent Ridge, 117599, Singapore.

Collapsin response mediator protein-2 (CRMP2) regulates axonal growth cone extension, and increased CRMP2 phosphorylation may lead to axonal degeneration. Axonal and synaptic pathology is an important feature of Lewy body dementias (LBD), but the state of CRMP2 phosphorylation (pCRMP2) as well as its correlations with markers of neurodegeneration have not been studied in these dementias. Hence, we measured CRMP2 phosphorylation at Thr509, Thr514 and Ser522, as well as markers of β-amyloid (Aβ), tau-phosphorylation, α-synuclein and synaptic function in the postmortem neocortex of a longitudinally assessed cohort of LBD patients characterized by low (Parkinson's disease dementia, PDD) and high (dementia with Lewy bodies, DLB) burden of Alzheimer type pathology.

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A Simplified, Langendorff-Free Method for Concomitant Isolation of Viable Cardiac Myocytes and Nonmyocytes From the Adult Mouse Heart.

Circ Res

September 2016

From the Cardiovascular Research Institute, Centre for Translational Medicine MD6, National University Health System, Singapore (M.A.-J., P.Y.L., R.S.F.); Genome Institute of Singapore (M.A.-J., R.S.F.); and Institute of Cardiovascular Sciences, University of Birmingham, UK (A.P.H., S.-M.O., D.P.).

Rationale: Cardiovascular disease represents a global pandemic. The advent of and recent advances in mouse genomics, epigenomics, and transgenics offer ever-greater potential for powerful avenues of research. However, progress is often constrained by unique complexities associated with the isolation of viable myocytes from the adult mouse heart.

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Chemically sulfated natural galactomannans with specific antiviral and anticoagulant activities.

Int J Biol Macromol

August 2016

Department of Bio and Environmental Chemistry, Kitami Institute of Technology, 165 Koen-cho Kitami 090-8507, Hokkaido, Japan. Electronic address:

Naturally occurring galactomannans were sulfated to give sulfated galactomannans with degrees of substitution of 0.7-1.4 per sugar unit and molecular weights of M¯n=0.

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SALL4, the missing link between stem cells, development and cancer.

Gene

June 2016

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, New Research Building Room 652D, Boston, MA 02115, USA. Electronic address:

There is a growing body of evidence supporting that cancer cells share many similarities with embryonic stem cells (ESCs). For example, aggressive cancers and ESCs share a common gene expression signature that includes hundreds of genes. Since ESC genes are not present in most adult tissues, they could be ideal candidate targets for cancer-specific diagnosis and treatment.

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Altered relaxin family receptors RXFP1 and RXFP3 in the neocortex of depressed Alzheimer's disease patients.

Psychopharmacology (Berl)

February 2016

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Unit 09-01, Centre for Translational Medicine (MD6), 14 Medical Drive, Kent Ridge, 117599, Singapore.

Rationale: The G-protein-coupled relaxin family receptors RXFP1 and RXFP3 are widely expressed in the cortex and are involved in stress responses and memory and emotional processing. However, the identification of these receptors in human cortex and their status in Alzheimer's disease (AD), which is characterized by both cognitive impairments and neuropsychiatric behaviours, have not been reported.

Objectives: In this study, we characterized RXFP receptors for immunoblotting and measured RXFP1 and RXFP3 immunoreactivities in the postmortem neocortex of AD patients longitudinally assessed for depressive symptoms.

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Cancellers - Exploring the Possibility of Receptor Decoy Traps As a Superior Anti-Retroviral Strategy.

Curr Drug Targets

December 2016

Translational ID Lab, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, #15-02 Centre for Translational Medicine (MD6), Singapore 117599, Singapore.

The global Human Immunodeficiency Virus (HIV) pandemic is still spreading due to the lack of ideal anti-retroviral measures and their availability. Till date, all attempts to produce an efficient vaccine have ended with unsatisfactory results. The highly active anti-retroviral therapy (HAART) is the only effective weapon currently available and is widely being used for curtailing the HIV pandemic.

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Experimental heart failure modelled by the cardiomyocyte-specific loss of an epigenome modifier, DNMT3B.

J Mol Cell Cardiol

May 2015

Division of Cardiovascular Medicine, Addenbrooke's Centre for Clinical Investigation Building, University of Cambridge, Cambridge CB2 0QQ, UK; Cardiovascular Research Institute, Centre for Translational Medicine MD6, National University Health System, 117599 Singapore; Genome Institute of Singapore, 60 Biopolis Street, 138672 Singapore. Electronic address:

Differential DNA methylation exists in the epigenome of end-stage failing human hearts but whether it contributes to disease progression is presently unknown. Here, we report that cardiac specific deletion of Dnmt3b, the predominant DNA methyltransferase in adult mouse hearts, leads to an accelerated progression to severe systolic insufficiency and myocardial thinning without a preceding hypertrophic response. This was accompanied by widespread myocardial interstitial fibrosis and myo-sarcomeric disarray.

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