Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.
To reduce undesirable charging effects in scanning electron microscope images, Rayleigh contrast stretching is developed and employed. First, re-scaling is performed on the input image histograms with Rayleigh algorithm. Then, contrast stretching or contrast adjustment is implemented to improve the images while reducing the contrast charging artifacts. This technique has been compared to some existing histogram equalization (HE) extension techniques: recursive sub-image HE, contrast stretching dynamic HE, multipeak HE and recursive mean separate HE. Other post processing methods, such as wavelet approach, spatial filtering, and exponential contrast stretching, are compared as well. Overall, the proposed method produces better image compensation in reducing charging artifacts.
Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies.
Three new alkaloids were isolated from the bark extract of the Malayan Kopsia arborea, viz., arbophyllidine (1), an unusual pentacyclic, monoterpenoid indole characterized by an absence of oxygen atoms and incorporating a new carbon-nitrogen skeleton, and arbophyllinines A (2) and B (3), two pentacyclic corynanthean alkaloids incorporating a hydroxyethyl-substituted tetrahydrofuranone ring. The structures of the alkaloids were deduced based on analysis of the MS and NMR data and confirmed by X-ray diffraction analyses. The absolute configuration of arbophyllidine (1) was established based on experimental and calculated ECD data, while that of arbophyllinine A was based on X-ray diffraction analysis (Cu Kα). A reasonable biosynthetic route to arbophyllidine (1) from a pericine precursor is presented. Arbophyllidine (1) showed pronounced in vitro growth inhibitory activity against the HT-29 human cancer cell line with IC50 6.2 μM.
Enterobacter cloacae is a versatile bacterial species inhabiting a wide variety of niches and is capable of metabolising a wide variety of substances as energy resources. The fermentation culture of this bacterial species has successfully yielded one new compound, Rimboxa (1) and three known compounds, i.e. indole-3-carboxaldehyde (2), indole-3-acetic acid (3) and 3,4-di-t-butylaniline (4). Rimboxa (1) is shown to possess the 1,2-oxathiolane core structure. 3,4-Di-t-butylaniline (4) is isolated for the first time from a natural resource. These compounds were isolated and characterised using extensive chromatographic and spectroscopic methods, and were subjected to cytotoxicity evaluations.
Enterobacter cloacae is a highly pathogenic Gram-negative proteobacterium which is responsible for a wide array of infections. In the present study, the fermentation culture of E. cloacae has yielded one new oxolane compound, Rimboxo (1) in addition to three known compounds, i.e. Maculosine (2), phenylacetic acid (3) and methyl myristate (4). These compounds were isolated and characterised using extensive chromatographic and spectroscopic methods, and were subjected to cytotoxicity evaluations.
Eleven new indole alkaloids (1-11) comprising seven aspidofractinine and four eburnane alkaloids, were isolated from the stem-bark extract of Kopsia pauciflora occurring in Malaysian Borneo. The aspidofractinine alkaloids include a ring-contracted, an additional ring-fused, a paucidactine regioisomer, two paucidactine, and one kopsine alkaloid. The structures of several of these alkaloids were also confirmed by X-ray diffraction analyses. The bisindole alkaloids isolated, norpleiomutine and kopsoffinol, showed in vitro growth inhibitory activity against human PC-3, HCT-116, MCF-7, and A549 cells and moderate effects in reversing multidrug-resistance in vincristine-resistant human KB cells.
A methanol extract of the stem bark of the Malayan Alstonia penangiana provided seven new bisindole alkaloids, comprising six macroline-sarpagine alkaloids (angustilongines E-K, 1-6) and one macroline-pleiocarpamine bisindole alkaloid (angustilongine L, 7). Analysis of the spectroscopic data (NMR and MS) of these compounds led to the proposed structures of these alkaloids. The macroline-sarpagine alkaloids (1-6) showed in vitro growth inhibitory activity against a panel of human cancer cell lines, inclusive of KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells (IC50 values: 0.02-9.0 μM).
Image processing is introduced to remove or reduce the noise and unwanted signal that deteriorate the quality of an image. Here, a single level two-dimensional wavelet transform is applied to the image in order to obtain the wavelet transform sub-band signal of an image. An estimation technique to predict the noise variance in an image is proposed, which is then fed into a Wiener filter to filter away the noise from the sub-band of the image. The proposed filter is called adaptive tuning piecewise cubic Hermite interpolation with Wiener filter in the wavelet domain. The performance of this filter is compared with four existing filters: median filter, Gaussian smoothing filter, two level wavelet transform with Wiener filter and adaptive noise Wiener filter. Based on the results, the adaptive tuning piecewise cubic Hermite interpolation with Wiener filter in wavelet domain has better performance than the other four methods.
An ecologically important tropical freshwater microalga, Scenedesmus quadricauda, was exposed to Ni toxicity under two temperature regimes, 25 and 35 °C to investigate the interactive effects of warming and different Ni concentrations (0.1, 1.0 and 10.0 ppm). The stress responses were assessed from the growth, photosynthesis, reactive oxygen species (ROS) generation and metabolomics aspects to understand the effects at both the physiological and biochemical levels. The results showed that the cell densities of the cultures were higher at 35 °C compared to 25 °C, but decreased with increasing Ni concentrations at 35 °C. In terms of photosynthetic efficiency, the maximum quantum yield of photosystem II (Fv/Fm) of S. quadricauda remained consistent across different conditions. Nickel concentration at 10.0 ppm affected the maximum rate of relative electron transport (rETRm) and saturation irradiance for electron transport (Ek) in photosynthesis. At 25 °C, the increase of non-photochemical quenching (NPQ) values in cells exposed to 10.0 ppm Ni might indicate the onset of thermal dissipation process as a self-protection mechanism against Ni toxicity. The combination of warming and Ni toxicity induced a strong oxidative stress response in the cells. The ROS level increased significantly by 40% after exposure to 10.0 ppm of Ni at 35 °C. The amount of Ni accumulated in the biomass was higher at 25 °C compared to 35 °C. Based on the metabolic profile, temperature contributed the most significant differentiation among the samples compared to Ni treatment and the interaction between the two factors. Amino acids, sugars and organic acids were significantly regulated by the combined factors to restore homeostasis. The most affected pathways include sulphur, amino acids, and nitrogen metabolisms. Overall, the results suggest that the inhibitory effect of Ni was lower at 35 °C compared to 25 °C probably due to lower metal uptake and primary metabolism restructuring. The ability of S. quadricauda to accumulate substantial amount of Ni and thrive at 35 °C suggests the potential use of this strain for phycoremediation and outdoor wastewater treatment.