Plasma fatty acid esters of hydroxy fatty acids and surrogate fatty acid esters of hydroxy fatty acids hydrolysis activity in children with or without obesity and in adults with or without coronary artery disease.

Aim: Fatty acid esters of hydroxy fatty acids (FAHFA) are a class of bioactive lipids with anti-inflammatory, antidiabetic and cardioprotective properties. FAHFA hydrolysis into its fatty acid (FA) and hydroxy fatty acid (HFA) constituents can affect the bioavailability of FAHFA and its subsequent biological effects. We aimed to investigate FAHFA levels and FAHFA hydrolysis activity in children with or without obesity, and in adults with or without coronary artery disease (CAD).

Trans-interaction of risk loci 6p24.1 and 10q11.21 is associated with endothelial damage in coronary artery disease.

Background And Aims: Single nucleotide polymorphism rs6903956 has been identified as one of the genetic risk factors for coronary artery disease (CAD). However, rs6903956 lies in a non-coding locus on chromosome 6p24.1.

A combination of two novel VARS2 variants causes a mitochondrial disorder associated with failure to thrive and pulmonary hypertension.

The VARS2 gene encodes a mitochondrial valyl-transfer RNA synthetase which is used in mitochondrial translation. To date, several patients with VARS2 pathogenic variants have been described in the literature. These patients have features of lactic acidosis with encephalomyopathy.

Fish and marine fatty acids intakes, the genotypes and long-term weight gain: a prospective cohort study.

Objective: We tested whether genetic variants near fatty acid desaturases gene () cluster, which were recently identified to be signatures of adaptation to fish-rich and n-3 polyunsaturated fatty acids (PUFAs)-rich diet, interacted with these dietary factors on change in body mass index (BMI).

Design: Three variants were examined for gene-diet interactions on long-term (~10 years) changes in BMI and body weight in four prospective cohort studies.

Setting: Population based study.

Differences in AMY1 Gene Copy Numbers Derived from Blood, Buccal Cells and Saliva Using Quantitative and Droplet Digital PCR Methods: Flagging the Pitfall.

Introduction: The human salivary (AMY1) gene, encoding salivary α-amylase, has variable copy number variants (CNVs) in the human genome. We aimed to determine if real-time quantitative polymerase chain reaction (qPCR) and the more recently available Droplet Digital PCR (ddPCR) can provide a precise quantification of the AMY1 gene copy number in blood, buccal cells and saliva samples derived from the same individual.

Methods: Seven participants were recruited and DNA was extracted from the blood, buccal cells and saliva samples provided by each participant.

In-vitro function of upstream visfatin polymorphisms that are associated with adverse cardiometabolic parameters in obese children.

Background: Visfatin is an adipokine associated with glucose and lipid metabolism. We previously reported two visfatin upstream single nucleotide polymorphisms (SNPs), c.-3187G > A (rs11977021) and c.

New loci and coding variants confer risk for age-related macular degeneration in East Asians.

Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.

Functional characterization of variants in MC4R gene promoter region found in obese children.

Context: Mutations in the MC4R gene are the most common cause of monogenic obesity, and there are few studies on mutations in the promoter region.

Objective: The objective of the study was to sequence the promoter region of the MC4R gene in a cohort of obese children to identify rare variants.

Design, Setting, And Patients: A region 1500 bp upstream of the MC4R gene was sequenced in 267 unrelated local children younger than 10 years, with body weight of at least 150% of ideal.

Metabolomics-based identification of apoptosis-inducing metabolites in recombinant fed-batch CHO culture media.

A liquid chromatography-mass spectrometry (LC-MS) based metabolomics platform was previously established to identify and profile extracellular metabolites in culture media of mammalian cells. This presented an opportunity to isolate novel apoptosis-inducing metabolites accumulating in the media of antibody-producing Chinese hamster ovary (CHO mAb) fed-batch bioreactor cultures. Media from triplicate cultures were collected daily for the metabolomics analysis.

Metabolomics-driven approach for the improvement of Chinese hamster ovary cell growth: overexpression of malate dehydrogenase II.

We have established a liquid chromatography-mass spectrometry based metabolomics platform to identify extracellular metabolites in the medium of recombinant Chinese hamster ovary (CHO) fed-batch reactor cultures. Amongst the extracellular metabolites identified, malate accumulation was the most significant. The contributing factors to malate efflux were found to be the supply of aspartate from the medium, and an enzymatic bottleneck at malate dehydrogenase II (MDH II) in the tricarboxylic acid cycle.

Comprehensive mutation scanning of KCNQ1 in 111 Han Chinese patients with lone atrial fibrillation.

Objective: To determine the extent to which genetic variation in the potassium channel gene KCNQ1 causes atrial fibrillation (AF).

Design: Case-control study.

Setting: National University Hospital, Singapore.

Metabolomics profiling of extracellular metabolites in recombinant Chinese Hamster Ovary fed-batch culture.

A metabolomics-based approach was used to time profile extracellular metabolites in duplicate fed-batch bioreactor cultures of recombinant Chinese Hamster Ovary (CHO) cells producing monoclonal IgG antibody. Culture medium was collected and analysed using a high-performance liquid chromatography (HPLC) system in tandem with an LTQ-Orbitrap mass spectrometer. An in-house software was developed to pre-process the LC/MS data in terms of filtering and peak detection.

Absence of the toll-like receptor 4 gene polymorphisms Asp299Gly and Thr399Ile in Singaporean Chinese.

Toll-like receptor 4 (TLR4) is the transuding subunit of lipopolysaccharide receptor and an important intracellular signal pathway of the innate immune response. Published data about the relationship between TLR4 mutations and atopy/asthma are not consistent. This study was performed to detect two commonly reported Asp299Gly and Thr399Ile polymorphisms in TLR4 gene in Singaporean Chinese and their possible association with atopy-related phenotypes.

Silicon-based microfilters for whole blood cell separation.

This paper reports on the comparison analysis of four main types of silicon-based microfilter for isolation of white blood cells (WBCs) from red blood cells (RBCs) in a given whole blood. The microfilter designs, namely, weir, pillar, crossflow, and membrane, all impose the same cut-off size of 3.5 mum to selectively trap WBCs.

Targeting early apoptotic genes in batch and fed-batch CHO cell cultures.

Based on the transcriptional profiling of CHO cell culture using microarray, four key early apoptosis signaling genes, Fadd, Faim, Alg-2, and Requiem, were identified and CHO GT (Gene Targeted) cell lines were developed by targeting these four genes. Two were CHO GT(O) cell lines overexpressing anti-apoptotic genes, Faim and Fadd DN and two were CHO GT(KD) cell lines involving knockdown of Alg-2 and Requiem which are pro-apoptotic genes using small interfering RNA (siRNA) technology. Comparisons of these CHO GT cell lines with the parental cell line in batch culture (BC) and fed-batch culture (FBC) were performed.

CD14 promoter polymorphisms have no functional significance and are not associated with atopic phenotypes.

Objectives: A polymorphism at CD14/-159 has been reported to be associated with atopic phenotypes in several studies. However, conflicting results from association studies in different populations have been reported. This study aimed to investigate the relationship between CD14 promoter polymorphisms and atopic phenotypes in Singaporean Chinese and the biological characterization of these polymorphisms.

Reduced transcriptional activity in individuals with IL-18 gene variants detected from functional but not association study.

Genetic polymorphisms of IL-18 and its receptor were reported to be associated with elevated serum IgE levels, atopy, and/or asthma. However, conflicting results were observed in various association studies and functional activity of these polymorphisms remains unclear. A total of 393 unrelated subjects were involved in this study.

Association of Leu125Val polymorphism of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene & soluble level of PECAM-1 with coronary artery disease in Asian Indians.

Background & Objectives: Platelet endothelial cell adhesion molecule-1 (PECAM-1) plays a key role in the transendothelial migration of circulating leukocytes (diapedesis) during vascular inflammation. We hypothesized that genetic variation and the level of soluble PECAM-1 could be associated with the development of atherosclerosis and conducted a study on gene polymorphisms of PECAM-1 and soluble PECAM-1 levels in Asian Indian patients with coronary artery disease (CAD) in Singapore.

Methods: Of the 137 angiographically confirmed patients (> or =70% stenosis) of CAD and 110 controls in Asian Indian population, two single nucleotide polymorphisms (SNPs) of PECAM-1 gene, C+373G (Leu125Val) at exon 3 and G+1688A (Ser563Asn) at exon 8 were analyzed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) strategy.

Schizosaccharomyces pombe cells deficient in triacylglycerols synthesis undergo apoptosis upon entry into the stationary phase.

Triacylglycerols (TAG) are important energy storage molecules for nearly all eukaryotic organisms. In this study, we found that two gene products (Plh1p and Dga1p) are responsible for the terminal step of TAG synthesis in the fission yeast Schizosaccharomyces pombe through two different mechanisms: Plh1p is a phospholipid diacylglycerol acyltransferase, whereas Dga1p is an acyl-CoA:diacylglycerol acyltransferase. Cells with both dga1+ and plh1+ deleted (DKO cells) lost viability upon entry into the stationary phase and demonstrated prominent apoptotic markers.