Central adiposity-induced plasma-free amino acid alterations are associated with increased insulin resistance in healthy Singaporean adults.

BACKGROUND/OBJECTIVES: Recent metabolomics technique reveals a plasma-free amino acid (PFAA)-based metabolite signature that is suggestive of altered PFAAs being an early manifestation of obesity-related insulin resistance. However, the PFAA profiles within non-obese, but more insulin-resistant Asians are not well researched. Compared with Caucasians, Asian populations have more central adiposity, which is generally regarded as metabolically more adverse, but the underlying mechanisms remain unclear. In the present study, we examined whether PFAA profiling was at least one important factor mediating central adiposity and insulin resistance, and aid in cardiovascular risk assessment in healthy Asians with normal body weight. SUBJECT/METHODS: This was a cross-sectional study. A total of 190 healthy men (n=87 with a mean±s.d. body mass index (BMI) of 23.5±3.5 kg/m2) and women (n=103 with a mean±s.d. BMI of 21.4±3.7 kg/m2) residing in Singapore took part in this study. PFAA levels were measured by using an amino acid analyzer. Basic anthropometric measurements, fasting blood glucose, fasting serum insulin and lipid profiles were obtained using standard protocols. RESULTS: Seven out of 18 amino acids were significantly correlated with measures of obesity (for example, waist circumference; waist-to-hip ratio and BMI) in current participants. Among them, the plasma concentrations of five amino acids, including Phe, Tyr, Met, Ala and His were positively associated with waist-to-hip ratio. With the exception of His, which had no association with insulin resistance, Phe, Tyr, Met and Ala were significantly associated with hyperinsulinemia and insulin resistance (P<0.05). In contrast, no associations were observed between circulating BCAAs (that is, Val, Leu, Ile), measures of obesity and insulin resistance. However, significant inverse associations were observed between BCAAs and total cholesterol and high-density lipoprotein. CONCLUSIONS: We found that central adiposity was associated with alterations of specific amino acids. As a result, PFAAs may serve as metabolite predictors of hyperglycemia, hyperinsulinemia and dyslipidemia in healthy participants.

Miniaturized power limiter metasurface based on Fano-type resonance and Babinet principle.

In this work, we present a miniaturize power limiter, a device with size smaller than that required by the working frequency, made of coupled self-complementary electric inductive-capacitive (CELC) resonator and original electric inductive-capacitive (ELC) structure. We also make use of Babinet principle to ensure both CELC and ELC are resonating at the same frequency. The CELC structure is loaded with a Schottky diode to achieve the effect of a nonlinear power limiter. The constructive interference of CELC and ELC structure produces a new Fano-type resonance peak at a lower frequency. The Fano peak is sharp and able to concentrate electric field at a region between the inner and outer metallic patch of the metastructure, hence enhancing the nonlinear properties of the loaded diode. The Fano peak enhances the maximum isolation of the power limiter due to the local field enhancement at where the diode is loaded. Numerical simulation and experiment are conducted in the S-band frequency to verify the power limiting effect of the device designed and to discuss the formation of Fano peak. The power limiter designed has a maximum isolation of 8.4 dB and a 3-dB isolation bandwidth of 6%.

Transcriptional analysis of antiviral small molecule therapeutics as agonists of the RLR pathway.

The recognition of pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRR) during viral infection initiates the induction of antiviral signaling pathways, including activation of the Interferon Regulator Factor 3 (IRF3). We identified small molecule compounds that activate IRF3 through MAVS, thereby inhibiting infection by viruses of the families Flaviviridae (West Nile virus, dengue virus and hepatitis C virus), Filoviridae (Ebola virus), Orthomyxoviridae (influenza A virus), Arenaviridae (Lassa virus) and Paramyxoviridae (respiratory syncytial virus, Nipah virus) (1). In this study, we tested a lead compound along with medicinal chemistry-derived analogs to compare the gene transcriptional profiles induced by these molecules to that of other known MAVS-dependent IRF3 agonists. Transcriptional analysis of these small molecules revealed the induction of specific antiviral genes and identified a novel module of host driven immune regulated genes that suppress infection of a range of RNA viruses. Microarray data can be found in Gene Expression Omnibus (GSE74047).

Metal nanocluster light-emitting devices with suppressed parasitic emission and improved efficiency: exploring the impact of photophysical properties.

Here we investigate the photophysical properties of Au(0)@Au(i)-thiolate nanoclusters by controlling the degree of aggregation, and measure electrochemical energy levels to design a metal nanocluster-based thin film LED (MNC-LED) structure. These efforts allow us to implement MNC-LEDs with luminance exceeding 40 cd m(-2) and external quantum efficiency exceeding 0.1% with clearly visible orange emission. It is also demonstrated that by varying the sizes of nanoclusters, the electroluminescence spectrum of the device can be tuned to the infrared emission, indicating the possibility of exploiting metal nanocluster emitters for use over a wide spectral range.

A novel Osmium-based compound targets the mitochondria and triggers ROS-dependent apoptosis in colon carcinoma.

Engagement of the mitochondrial-death amplification pathway is an essential component in chemotherapeutic execution of cancer cells. Therefore, identification of mitochondria-targeting agents has become an attractive avenue for novel drug discovery. Here, we report the anticancer activity of a novel Osmium-based organometallic compound (hereafter named Os) on different colorectal carcinoma cell lines. HCT116 cell line was highly sensitive to Os and displayed characteristic features of autophagy and apoptosis; however, inhibition of autophagy did not rescue cell death unlike the pan-caspase inhibitor z-VAD-fmk. Furthermore, Os significantly altered mitochondrial morphology, disrupted electron transport flux, decreased mitochondrial transmembrane potential and ATP levels, and triggered a significant increase in reactive oxygen species (ROS) production. Interestingly, the sensitivity of cell lines to Os was linked to its ability to induce mitochondrial ROS production (HCT116 and RKO) as HT29 and SW620 cell lines that failed to show an increase in ROS were resistant to the death-inducing activity of Os. Finally, intra-peritoneal injections of Os significantly inhibited tumor formation in a murine model of HCT116 carcinogenesis, and pretreatment with Os significantly enhanced tumor cell sensitivity to cisplatin and doxorubicin. These data highlight the mitochondria-targeting activity of this novel compound with potent anticancer effect in vitro and in vivo, which could have potential implications for strategic therapeutic drug design.

Prevalence and quantification of Listeria monocytogenes in chicken offal at the retail level in Malaysia.

A total of 216 chicken offal samples (chicken liver = 72; chicken heart = 72; chicken gizzard = 72) from wet markets and hypermarkets in Selangor, Malaysia, were examined for the presence and density of Listeria monocytogenes by using a combination of the most probable number and PCR method. The prevalence of L. monocytogenes in 216 chicken offal samples examined was 26.39%, and among the positive samples, the chicken gizzard showed the highest percentage at 33.33% compared with chicken liver (25.00%) and chicken heart (20.83%). The microbial load of L. monocytogenes in chicken offal samples ranged from <3 to 93.0 most probable number per gram. The presence of L. monocytogenes in chicken offal samples may indicate that chicken offal can act as a possible vehicle for the occurrence of foodborne listeriosis. Hence, there is a need to investigate the biosafety level of chicken offal in Malaysia.

Listeria monocytogenes in retailed raw chicken meat in Malaysia.

This study aimed to determine the prevalence Listeria monocytogenes in raw chicken meat samples at hypermarkets and wet markets. Chicken drumsticks, breasts, and thighs were randomly selected. The most probable number (MPN) PCR method was used to quantify the L. monocytogenes in the samples. Listeria monocytogenes was detected in 20% of the samples. Occurrence of L. monocytogenes was highest in breast (42.03%) followed by drumstick (11.27%) and thigh (7.14%). Samples from hypermarkets showed higher occurrence (25.71%) of L. monocytogenes compared with wet markets (14.29%). The density of L. monocytogenes found in samples ranged from <3.0 to 16 MPN•g(-1). The presence of L. monocytogenes in raw chicken meat is unwanted but unpreventable. Thus, further research on the processing method to reduce and eliminate this kind of bacteria in chicken meat before consumption is necessary. The presence of L. monocytogenes in chicken samples suggests the importance of this pathogen in chicken. Thus, more study is needed to find ways to eliminate this pathogen from poultry.

Dynamic character of charge transport parameters in disordered organic semiconductor field-effect transistors.

In this perspective article, we discuss the dynamic instability of charge carrier transport in a range of popular organic semiconductors. We observe that in many cases field-effect mobility, an important parameter used to characterize the performance of organic field-effect transistors (OFETs), strongly depends on the rate of the gate voltage sweep during the measurement. Some molecular systems are so dynamic that their nominal mobility can vary by more than one order of magnitude, depending on how fast the measurements are performed, making an assignment of a single mobility value to devices meaningless. It appears that dispersive transport in OFETs based on disordered semiconductors, those with a high density of localized trap states distributed over a wide energy range, is responsible for the gate voltage sweep rate dependence of nominal mobility. We compare such rate dependence in different materials and across different device architectures, including pristine and trap-dominated single-crystal OFETs, as well as solution-processed polycrystalline thin-film OFETs. The paramount significance given to a single mobility value in the organic electronics community and the practical importance of OFETs for applications thus suggest that such an issue, previously either overlooked or ignored, is in fact a very important point to consider when engaging in fundamental studies of charge carrier mobility in organic semiconductors or designing applied circuits with organic semiconductors.

Treatment of p-nitrophenol in an adsorbent-supplemented sequencing batch reactor.

The objective of this research was to evaluate the treatment ofp-nitrophenol (PNP) as a sole organic carbon source using a sequencing batch reactor (SBR) with the addition of adsorbent. Two types of adsorbents, namely powdered activated carbon (PAC) and pyrolysed rice husk (PRH) were used in this study. Two identical SBRs, each with a working volume of 10 L, were operated with fill, react, settle, draw and idle periods in the ratio of 2:8:1:0.75:0.25 for a cycle time of 12 h. The results showed that, without the addition of adsorbent, increasing the influent PNP concentration to 200 mg/L resulted in the deterioration of chemical oxygen demand (COD) removal efficiency and PNP removal efficiency in the SBRs. Improvement in the performance of the SBR was observed with the addition of PAC. When the dosage of 1.0 g PAC/cycle was applied, COD removal of 95% and almost complete removal of PNP were achieved at the influent PNP concentration of 300 mg/L. The kinetic study showed that the rates of COD and PNP removal can be described by the first-order kinetics. The enhancement of performance in the PAC-supplemented SBR was postulated to be due to the initial adsorption of PNP by the freshly added and the bioregenerated PAC, thus reducing the inhibition on the microorganisms. The PRH was found to be ineffective because of its relatively low adsorption capacity for PNP, compared with that of PAC.

Effect of bone to implant contact percentage on bone remodelling surrounding a dental implant.

Dental implants are an effective, safe and predictable solution for patients suffering from tooth loss, but implant placement changes the normal mechanical environment of the jawbone leading to bone density redistribution and 'remodelling', in order to adapt to the new environment. Many bone remodelling theories assume the presence of 100% contact between bone and implant, which is inconsistent with clinical reality. About 50-80% bone-implant contact is commonly seen with clinically successful implants. The influence of different percentages of bone-implant contact on bone remodelling has not been investigated adequately. This study aims to evaluate this influence using a newly proposed remodelling algorithm through a 2D finite element model. Four different degrees of bone-implant contact (25, 50, 75 and 100%) are considered and their influences on the density distribution of the jawbone are evaluated. The predicted results indicate that no matter what the initial percentage of bone-implant contact (25-100%), the final outcome is about 58-60% contact when an equilibrium state is reached by bone remodelling. The results are consistent with clinical observations and findings.

Impact of a fall prevention programme in acute hospital settings in Singapore.

INTRODUCTION: This study aimed to develop a multifaceted strategy using tailored interventions to implement a fall prevention programme, and to achieve a change in fall prevention practices and a reduction in fall incidence at an acute care hospital in Singapore. METHODS: A comparative study was conducted at two acute care hospitals (intervention and control) in Singapore. Pre-intervention, post-intervention and six-month follow-up knowledge assessments of 641 nursing staff, and audits of fall rates and fall prevention practices were performed to determine the effectiveness of a multifaceted strategy with targeted interventions in supporting the implementation of a fall prevention programme. RESULTS: The mean post-knowledge test scores at six months were statistically significantly higher (t[516] is -3.3, p-value is less than 0.01) at the intervention hospital (10.3 +/- 2.3) compared to the scores at the control hospital (9.8 +/- 1.8). Increased compliance with the use of fall risk assessment tools was evident in 99.4 percent and 99.3 percent of all patient records at the control and intervention hospitals, respectively. Following the implementation strategy for a fall prevention programme, there was a non-significant reduction in fall rates from 1.44 to 1.09 per 1,000 patient days at the intervention hospital. No reduction in the fall rate was observed at the control hospital. CONCLUSION: A multifaceted strategy for the implementation of a fall prevention programme was effective in increasing nurses' knowledge and the use of the fall risk assessment, but did not have a statistically significant impact on a reduction in the fall rate. The increase in nurses' knowledge and change in nursing practice were important markers of success in terms of fall prevention at the acute hospitals.

Viral regulation and evasion of the host response.

The type I interferons (IFN) are cytokines produced by mammalian cells in response to virus infection or other stressors. IFNs exert antiviral function by binding to the IFNalpha/beta receptors on the cell surface, with the major effect of triggering the JAK-STAT signaling cascade and inducing the expression of interferon-stimulated genes. The resulting innate antiviral response is a first line of immune defense against virus infection. Recent studies demonstrate that many viruses, including hepatitis C virus, direct processes to control the host response to infection. We provide a review of the virus/host processes involved in IFN signaling and regulation of innate immune defenses.

Application of the finite element method in dental implant research.

This article provides a review of the achievements and advancements in dental technology brought about by computer-aided design and the all powerful finite element method (FEM) of analysis. The scope of the review covers dental implants, jawbone surrounding the implant and the biomechanical implant and jawbone interaction. Prevailing assumptions made in the published finite element analysis (FEA) and their limitations are discussed in some detail which helps identify the gaps in research as well as future research direction.

A pilot study of a biotrickling filter for the treatment of odorous sewage air.

The nuisance impact of air pollutant emissions from wastewater treatment plants (WWTPs) is a major issue of concern to Singapore and to many developing cities worldwide. Existing chemical and physical treatment methods are efficient but costly, and may generate secondary pollutants. Biotreatment, on the other hand, is a proven control technology for effectively removing hydrogen sulphide (H2S), the principal odour component of sewage air. The biotechnology is cost-effective to remove low-concentrations of biodegradable compounds from a large flow of waste gases. A pilot-scale biotrickling filter, packed with pall rings, was set up at a WWTP in Singapore to investigate its effectiveness for treatment of odorous sewage air. A series of experiments were conducted to assess the performance of the biotrickling filter under various operating scenarios. Results indicated that even at 5 second gas retention time, the biotrickling filter could remove 95% of the inlet H2S. The behaviour of the biotrickling filter under various operating scenarios are presented and discussed in this paper.

The majority of human replication protein A remains complexed throughout the cell cycle.

Replication Protein A (RPA), the replicative single-strand DNA binding protein from eukaryotic cells, is a stable heterotrimeric complex consisting of three polypeptides. Cytological studies have investigated the subcellular distribution and association characteristics of the three RPA subunits during different stages of the cell cycle with varying results. In this study, various HeLa cell fractions were subjected to separation by either immunoprecipitation or velocity sedimentation. These separations were evaluated by immunoblotting for specific RPA subunits to determine whether the RPA in these fractions retains its heterotrimeric association. Immunoprecipitation of either the large (RPA70) or middle-sized (RPA32) subunit of RPA followed by immunoblotting for the other subunits demonstrate that RPA remains complexed throughout the G(1), S and G(2) phases of the cell cycle. Immunoprecipitation and sedimentation separations of both the nucleosolic and chromatin-bound RPA populations from both cycling and nocodazole-blocked cells showed that the majority of RPA remains complexed under all conditions examined. Consistent with previous reports, hypotonic extracts from 293 cells were shown to contain some RPA32 not complexed with RPA70. These results indicate that in some cell types, extracts may contain small amounts of RPA32 free of RPA70; however, in HeLa cells the majority of RPA clearly remains complexed as a heterotrimer throughout the cell cycle.

Interactions of the papovavirus DNA replication initiator proteins, bovine papillomavirus type 1 E1 and simian virus 40 large T antigen, with human replication protein A.

Papovaviruses utilize predominantly cellular DNA replication proteins to replicate their own viral genomes. To appropriate the cellular DNA replication machinery, simian virus 40 (SV40) large T antigen (Tag) binds to three different cellular replication proteins, the DNA polymerase alpha-primase complex, the replication protein A (RPA) complex, and topoisomerase I. The functionally similar papillomavirus E1 protein has also been shown to bind to the DNA polymerase alpha-primase complex. Enzyme-linked immunoassay-based protein interaction assays and protein affinity pull-down assays were used to show that the papillomavirus E1 protein also binds to the cellular RPA complex in vitro. Furthermore, SV40 Tag was able to compete with bovine papillomavirus type 1 E1 for binding to RPA. Each of the three RPA subunits was individually overexpressed in Escherichia coli as a soluble fusion protein. These fusion proteins were used to show that the E1-RPA and Tag-RPA interactions are primarily mediated through the 70-kDa subunit of RPA. These results suggest that different viruses have evolved similar mechanisms for taking control of the cellular DNA replication machinery.

Effect of feeding clofibrate-containing diet on the hepatic NAD+ level in rats.

Feeding rats with a diet containing 0.25% clofibrate for 2 weeks elevated the hepatic NAD+ and total nicotinate levels significantly. Other peroxisome proliferators, such as 2-(4-chlorophenoxy)propionic acid and di(2-ethylhexyl)phthalate, had similar effects. When rats were fed the control diet without clofibrate for 1 week after 2 weeks of the clofibrate diet, the hepatic NAD+ level returned to the control value. Muscular NAD+ content was not affected by the peroxisome proliferators. The results were discussed in relation to induction of peroxisomal beta-oxidation enzymes by the peroxisome proliferators.

Cerebral biochemical abnormalities in experimental maternal phenylketonuria: gangliosides and sialoglycoproteins.

The present study sought a biochemical explanation for retarded brain development in the heterozygous offspring of the phenylketonuric (PKU) mother. Two rat models of simulated maternal PKU, one induced by p-chlorophenylalanine and phenylalanine and the other by phenylacetate, were employed in this investigation. Maternal PKU had no influence on cerebral concentrations of DNA, protein, and cholesterol, which were normal in the 2 d old pup. However, there was a noticeable disruption of the normal ganglioside pattern and a significant reduction of sialoglycoproteins. Concomitant with a delayed drop in the gangliosides Q1b and D3, was a slower rise in M1 and D1a. At least 66% of sialoglycoproteins located on SDS-PAGE gel chromatograms, by radioactivity incorporated in vivo from radiolabeled N-acetylmannosamine and by (3H) sialic acid released by Neuraminidase from periodate-(3H)borohydride labeled glycoproteins, have mobilities of the cell adhesion molecules N-CAM and D-CAM. Whether the reduction of the sialoglycoproteins induced by maternal PKU is mainly in these cell adhesion molecules requires further investigation. Interference with the function of gangliosides and certain sialoglycoproteins during cerebral development may contribute to the brain dysfunction observed in the offspring of PKU mothers not on diet control during pregnancy.

A biochemical explanation of phenyl acetate neurotoxicity in experimental phenylketonuria.

The in vivo formation of [1-14C]acetyl-coenzyme A from D-[3-14C]3-hydroxybutyrate in the brain of the suckling rat was not affected by postnatal exposure to phenyl acetate. However, utilization of the generated acetyl-coenzyme A was significantly inhibited in certain metabolic reactions, namely synthesis of fatty acids and of sterols, but not in others as the Krebs cycle reactions that lead to the production of dicarboxylic amino acids. The incorporation of D-[U-14C]glucosamine into N-acetylneuraminic acid bound to glycoproteins was appreciably diminished in the rat pup previously exposed to maternal phenylketonuria induced by phenyl acetate. During the period of very rapid development of the brain, interference by phenyl acetate and/or its metabolites with certain critical biosynthetic pathways that require acetyl-coenzyme A would significantly contribute to retarded maturation of the brain that occurs in phenylketonuria.