Discovering novel SNPs that are correlated with patient outcome in a Singaporean cancer patient cohort treated with gemcitabine-based chemotherapy

Published date : 11 May 2018

Background
Single Nucleotide Polymorphisms (SNPs) can influence patient outcome such as drug response and toxicity after drug intervention. The purpose of this study is to develop a systematic pathway approach to accurately and efficiently predict novel non-synonymous SNPs (nsSNPs) that could be causative to gemcitabine-based chemotherapy treatment outcome in Singaporean non-small cell lung cancer (NSCLC) patients.

type
Journal Paper
journal
BMC Cancer (2018), 18:555, doi: 10.1186/s12885-018-4471-x
Impact Factor
3.288

Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH2

Published date : 11 May 2018

Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH2, with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 μM), the main causative pathogen of human skin infections with an unknown mechanism of action.

type
Journal Paper
journal
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2018, doi: 10.1016/j.bbamem.2018.05.004
Impact Factor
3.498

Role of the serotonergic pathway in uterotonic activity of Ananas comosus (L.) Merr. – An in vitro and in vivo study

Published date : 08 May 2018

Background
Ananas comosus (L.) Merr. has been used as a traditional medicine in inducing abortion in many countries. Our previous in vitro experiments showed that the aqueous fraction (F4) of A. comosus extract stimulated the rat and human uterine contractions.

Purpose
The aim of this study was to identify the bioactive compound and further investigate the molecular mechanism of F4 induced contraction and the in vivo uterotonic effect of F4.

type
Journal Paper
journal
Phytomedicine, Vol. 48, 15 Sept 2018, Pg 32-42, doi: 10.1016/j.phymed.2018.05.004
Impact Factor
3.610

Three-dimensional computational model of multiphase flow driven by a bed of active cilia

Published date : 02 May 2018

Micro-scale physiological fluid propulsion is often accomplished with arrays of beating cilia. It is well-known that cilia can spontaneously coordinate their beat patterns to form metachronal waves. While it is generally agreed upon that metachronal waves arise largely due to hydrodynamic coupling, their effects on fluid propulsion are not thoroughly explored. There are presently complex, nonlinear models where cilia motion mimics their internal mechanisms; however these models are often computationally challenging and expensive to perform.

type
Journal Paper
journal
Computers & Fluids, Vol. 170, 15 Jul 2018, Pg 222-235, doi: 10.1016/j.compfluid.2018.05.001
Impact Factor
2.221

Building predictive in vitro pulmonary toxicity assays using high-throughput imaging and artificial intelligence

Published date : 28 Apr 2018

Human lungs are susceptible to the toxicity induced by soluble xenobiotics. However, the direct cellular effects of many pulmonotoxic chemicals are not always clear, and thus, a general in vitro assay for testing pulmonotoxicity applicable to a wide variety of chemicals is not currently available. Here, we report a study that uses high-throughput imaging and artificial intelligence to build an in vitro pulmonotoxicity assay by automatically comparing and selecting human lung-cell lines and their associated quantitative phenotypic features most predictive of in vivo pulmonotoxicity.

type
Journal Paper
journal
Archives of Toxicology, April 2018, doi: 10.1007/s00204-018-2213-0
Impact Factor
5.901

Comparison of Charge Derivation Methods Applied to Amino Acid Parametrization

Published date : 27 Apr 2018

When using non-natural amino acids in computational simulations of proteins, it is necessary to ensure appropriate parameterization of the new amino acids toward the creation of appropriate input files. In particular, the charges on the atoms may have to be derived de novo and ad hoc for the new species. As there are many variables in the charge derivation process, an investigation was devised to compare different approaches and determine their effect on simulations. This was done with the purpose to identify the methods which produced results compatible with the existing parameters.

type
Journal Paper
journal
ACS Omega 2018, 3, Pg 4664-4673, doi: 10.1021/acsomega.8b00438

Human mesenchymal stem cell basal membrane bending on gratings is dependent on both grating width and curvature

Published date : 24 Apr 2018

The topography of the extracellular substrate provides physical cues to elicit specific downstream biophysical and biochemical effects in cells. An example of such a topographical substrate is periodic gratings, where the dimensions of the periodic gratings influence cell morphology and directs cell differentiation.

type
Journal Paper
journal
Scintific Reports 8, No. 6444, 2018, doi: 10.1038/s41598-018-24123-6
Impact Factor
4.122

Optimization of Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibitors for the treatment of Blast Crisis Leukemia

Published date : 23 Apr 2018

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by bcr-abl1, a constitutively active tyrosine kinase fusion gene responsible for an abnormal proliferation of leukemic stem cells (LSCs). Inhibition of BCR-ABL1 kinase activity offers long-term relief to CML patients. However, for a proportion of them, BCR-ABL1 inhibition will become ineffective at treating the disease, and CML will progress to blast crisis (BC) CML with poor prognosis.

type
Journal Paper
journal
Journal of Medicinal Chemistry, May 7 2018, doi: 10.1021/acs.jmedchem.7b01714
Impact Factor
6.259

Evidence that TLR4 Is Not a Receptor for Saturated Fatty Acids but Mediates Lipid-Induced Inflammation by Reprogramming Macrophage Metabolism

Published date : 19 Apr 2018

Chronic inflammation is a hallmark of obesity and is linked to the development of numerous diseases. The activation of toll-like receptor 4 (TLR4) by long-chain saturated fatty acids (lcSFAs) is an important process in understanding how obesity initiates inflammation. While experimental evidence supports an important role for TLR4 in obesity-induced inflammation in vivo, via a mechanism thought to involve direct binding to and activation of TLR4 by lcSFAs, several lines of evidence argue against lcSFAs being direct TLR4 agonists.

type
Journal Paper
journal
Cell Metabolism, Vol. 27, Issue 5, pg 1096-1110, 1 May 2018, doi: 10.1016/j.cmet.2018.03.014
Impact Factor
18.164

An Optical Technique for Mapping Microviscosity Dynamics in Cellular Organelles

Published date : 12 Apr 2018

Microscopic viscosity (microviscosity) is a key determinant of diffusion in the cell and defines the rate of biological processes occurring at the nanoscale, including enzyme-driven metabolism and protein folding. Here we establish a rotor-based organelle viscosity imaging (ROVI) methodology that enables real-time quantitative mapping of cell microviscosity. This approach uses environment-sensitive dyes termed molecular rotors, covalently linked to genetically encoded probes to provide compartment-specific microviscosity measurements via fluorescence lifetime imaging.

type
Journal Paper
journal
ACS Nano, 18 April 2018, doi: 10.1021/acsnano.8b00177
Impact Factor
13.942