Science Collected Works - Research Publications
Now showing items 1-12 of 81
Using singscore to predict mutation status in acute myeloid leukemia from transcriptomic signatures.
(F1000 Research Ltd, 2019)
Advances in RNA sequencing (RNA-seq) technologies that measure the transcriptome of biological samples have revolutionised our ability to understand transcriptional regulatory programs that underpin diseases such as cancer. We recently published singscore - a single sample, rank-based gene set scoring method which quantifies how concordant the transcriptional profile of individual samples are relative to specific gene sets of interest. Here we demonstrate the application of singscore to investigate transcriptional profiles associated with specific mutations or genetic lesions in acute myeloid leukemia. Using matched genomic and transcriptomic data available through the TCGA we show that scoring of appropriate signatures can distinguish samples with corresponding mutations, reflecting the ability of these mutations to drive aberrant transcriptional programs involved in leukemogenesis. We believe the singscore method is particularly useful for studying heterogeneity within a specific subsets of cancers, and as demonstrated, we show the ability of singscore to identify where alternative mutations appear to drive similar transcriptional programs.
Novel Insights Into Bacterial Dimethylsulfoniopropionate Catabolism in the East China Sea
(FRONTIERS MEDIA SA, 2018-12-21)
The compatible solute dimethylsulfoniopropionate (DMSP), made by many marine organisms, is one of Earth's most abundant organosulfur molecules. Many marine bacteria import DMSP and can degrade it as a source of carbon and/or sulfur via DMSP cleavage or DMSP demethylation pathways, which can generate the climate active gases dimethyl sulfide (DMS) or methanthiol (MeSH), respectively. Here we used culture-dependent and -independent methods to study bacteria catabolizing DMSP in the East China Sea (ECS). Of bacterial isolates, 42.11% showed DMSP-dependent DMS (Ddd+) activity, and 12.28% produced detectable levels of MeSH. Interestingly, although most Ddd+ isolates were Alphaproteobacteria (mainly Roseobacters), many gram-positive Actinobacteria were also shown to cleave DMSP producing DMS. The mechanism by which these Actinobacteria cleave DMSP is unknown, since no known functional ddd genes have been identified in genome sequences of Ddd+Microbacterium and Agrococcus isolates or in any other sequenced Actinobacteria genomes. Gene probes to the DMSP demethylation gene dmdA and the DMSP lyase gene dddP demonstrated that these DMSP-degrading genes are abundant and widely distributed in ECS seawaters. dmdA was present in relatively high proportions in both surface (19.53% ± 6.70%) and bottom seawater bacteria (16.00% ± 8.73%). In contrast, dddP abundance positively correlated with chlorophyll a, and gradually decreased with the distance from land, which implies that the bacterial DMSP lyase gene dddP might be from bacterial groups that closely associate with phytoplankton. Bacterial community analysis showed positive correlations between Rhodobacteraceae abundance and concentrations of DMS and DMSP, further confirming the link between this abundant bacterial class and the environmental DMSP cycling.
Novel insights into the Thaumarchaeota in the deepest oceans: their metabolism and potential adaptation mechanisms
BACKGROUND: Marine Group I (MGI) Thaumarchaeota, which play key roles in the global biogeochemical cycling of nitrogen and carbon (ammonia oxidizers), thrive in the aphotic deep sea with massive populations. Recent studies have revealed that MGI Thaumarchaeota were present in the deepest part of oceans-the hadal zone (depth > 6000 m, consisting almost entirely of trenches), with the predominant phylotype being distinct from that in the "shallower" deep sea. However, little is known about the metabolism and distribution of these ammonia oxidizers in the hadal water. RESULTS: In this study, metagenomic data were obtained from 0-10,500 m deep seawater samples from the Mariana Trench. The distribution patterns of Thaumarchaeota derived from metagenomics and 16S rRNA gene sequencing were in line with that reported in previous studies: abundance of Thaumarchaeota peaked in bathypelagic zone (depth 1000-4000 m) and the predominant clade shifted in the hadal zone. Several metagenome-assembled thaumarchaeotal genomes were recovered, including a near-complete one representing the dominant hadal phylotype of MGI. Using comparative genomics, we predict that unexpected genes involved in bioenergetics, including two distinct ATP synthase genes (predicted to be coupled with H+ and Na+ respectively), and genes horizontally transferred from other extremophiles, such as those encoding putative di-myo-inositol-phosphate (DIP) synthases, might significantly contribute to the success of this hadal clade under the extreme condition. We also found that hadal MGI have the genetic potential to import a far higher range of organic compounds than their shallower water counterparts. Despite this trait, hadal MDI ammonia oxidation and carbon fixation genes are highly transcribed providing evidence they are likely autotrophic, contributing to the primary production in the aphotic deep sea. CONCLUSIONS: Our study reveals potentially novel adaptation mechanisms of deep-sea thaumarchaeotal clades and suggests key functions of deep-sea Thaumarchaeota in carbon and nitrogen cycling. Video Abstract.
Alterations in Gastric Microbiota After H. Pylori Eradication and in Different Histological Stages of Gastric Carcinogenesis
(NATURE PUBLISHING GROUP, 2017-03-21)
The role of bacteria other than Helicobacter pylori (HP) in the stomach remains elusive. We characterized the gastric microbiota in individuals with different histological stages of gastric carcinogenesis and after receiving HP eradication therapy. Endoscopic gastric biopsies were obtained from subjects with HP gastritis, gastric intestinal metaplasia (IM), gastric cancer (GC) and HP negative controls. Gastric microbiota was characterized by Illumina MiSeq platform targeting the 16 S rDNA. Apart from dominant H. pylori, we observed other Proteobacteria including Haemophilus, Serratia, Neisseria and Stenotrophomonas as the major components of the human gastric microbiota. Although samples were largely converged according to the relative abundance of HP, a clear separation of GC and other samples was recovered. Whilst there was a strong inverse association between HP relative abundance and bacterial diversity, this association was weak in GC samples which tended to have lower bacterial diversity compared with other samples with similar HP levels. Eradication of HP resulted in an increase in bacterial diversity and restoration of the relative abundance of other bacteria to levels similar to individuals without HP. In conclusion, HP colonization results in alterations of gastric microbiota and reduction in bacterial diversity, which could be restored by antibiotic treatment.
Proliferation of hydrocarbon-degrading microbes at the bottom of the Mariana Trench
BACKGROUND: The Mariana Trench is the deepest known site in the Earth's oceans, reaching a depth of ~ 11,000 m at the Challenger Deep. Recent studies reveal that hadal waters harbor distinctive microbial planktonic communities. However, the genetic potential of microbial communities within the hadal zone is poorly understood. RESULTS: Here, implementing both culture-dependent and culture-independent methods, we perform extensive analysis of microbial populations and their genetic potential at different depths in the Mariana Trench. Unexpectedly, we observed an abrupt increase in the abundance of hydrocarbon-degrading bacteria at depths > 10,400 m in the Challenger Deep. Indeed, the proportion of hydrocarbon-degrading bacteria at > 10,400 m is the highest observed in any natural environment on Earth. These bacteria were mainly Oleibacter, Thalassolituus, and Alcanivorax genera, all of which include species known to consume aliphatic hydrocarbons. This community shift towards hydrocarbon degraders was accompanied by increased abundance and transcription of genes involved in alkane degradation. Correspondingly, three Alcanivorax species that were isolated from 10,400 m water supplemented with hexadecane were able to efficiently degrade n-alkanes under conditions simulating the deep sea, as did a reference Oleibacter strain cultured at atmospheric pressure. Abundant n-alkanes were observed in sinking particles at 2000, 4000, and 6000 m (averaged 23.5 μg/gdw) and hadal surface sediments at depths of 10,908, 10,909, and 10,911 m (averaged 2.3 μg/gdw). The δ2H values of n-C16/18 alkanes that dominated surface sediments at near 11,000-m depths ranged from - 79 to - 93‰, suggesting that these sedimentary alkanes may have been derived from an unknown heterotrophic source. CONCLUSIONS: These results reveal that hydrocarbon-degrading microorganisms are present in great abundance in the deepest seawater on Earth and shed a new light on potential biological processes in this extreme environment.
Stability study of solution-processed zinc tin oxide thin-film transistors
(Springer Science and Business Media LLC, 2015-11)
In this study, the environmental dependence of the electrical stability of solution-processed n-channel zinc tin oxide (ZTO) thin-film transistors (TFTs) is reported. Under a prolonged negative gate bias stress, a negative shift in threshold voltage occurs in atmospheric air, whereas a negligible positive shift in threshold voltage occurs under vacuum. In the positive bias-stress experiments, a positive shift in threshold voltage was invariably observed both in atmospheric air and under vacuum. In this study, the negative gate-bias-stress-induced instability in atmospheric air is explained through an internal potential in the ZTO semiconductor, which can be generated owing to the interplay between H2O molecules and majority carrier electrons at the surface of the ZTO film. The positive bias-stress-induced instability is ascribed to electron-trapping phenomenon in and around the TFT channel region, which can be further augmented in the presence of air O2 molecules. These results suggest that the interaction between majority carriers and air molecules will have crucial implications for a reliable operation of solution-processed ZTO TFTs.
Effect of copper(II) species on the photooxidation of arsenite under UV-C irradiation
(Elsevier BV, 2019-08)
The effect of Cu(II) on the photooxidation of arsenite (As(III)) to arsenate (As(V)) under UV-C (254 nm) irradiation and the role of Cu(II) in the As(III) oxidation processes were mechanistically investigated. The presence of Cu(II) enhanced the oxidation of As(III), and the positive effect of Cu(II) increased with increasing Cu(II) concentration and pH. However, other metal ions, such as Al(III), Cr(III), Ni(II), and Mn(II), had little effect on the photooxidation kinetics of As(III). The UV absorption spectra of the As(III) and Cu(II) solutions indicated that not only As(III), but also Cu(II), can absorb 254 nm light. The absorption of 254 nm light by Cu(II) can induce electron transfer from Cu(II) to oxygen, which accelerates the production of hydroxyl radicals (radical dotOH) as a primary oxidant for As(III) oxidation and generates Cu(III) as another primary oxidant. The photooxidation of As(III) in the absence of Cu(II) was limited under anoxic conditions, but was observed in the presence of Cu(II). This result suggests another role of Cu(II) as an alternative electron acceptor, which enhances the production of radical dotOH and Cu(III) by mediating electron transfer from As(III) (or Cu(II)) to oxygen. Therefore, both radical dotOH and Cu(III) are involved in the oxidation of As(III) to As(V) as primary oxidants in the presence of Cu(II). The photooxidation of As(III) with Cu(II) was not completely inhibited in the presence of excess tert-butyl alcohol (TBA, an radical dotOH scavenger), in contrast with the case without Cu(II). This result confirms the generation of Cu(III) and its involvement in the As(III) oxidation processes in the presence of Cu(II). The present results imply that Cu(II) can act as both a UV-C photosensitizer and an electron acceptor in photochemical water treatment processes under UV-C irradiation and significantly affect the kinetics of pollutant oxidation.
The Assembly of Individual Chaplin Peptides from Streptomyces coelicolor into Functional Amyloid Fibrils
(PUBLIC LIBRARY SCIENCE, 2011-04-19)
The self-association of proteins into amyloid fibrils offers an alternative to the natively folded state of many polypeptides. Although commonly associated with disease, amyloid fibrils represent the natural functional state of some proteins, such as the chaplins from the soil-dwelling bacterium Streptomyces coelicolor, which coat the aerial mycelium and spores rendering them hydrophobic. We have undertaken a biophysical characterisation of the five short chaplin peptides ChpD-H to probe the mechanism by which these peptides self-assemble in solution to form fibrils. Each of the five chaplin peptides produced synthetically or isolated from the cell wall is individually surface-active and capable of forming fibrils under a range of solution conditions in vitro. These fibrils contain a highly similar cross-β core structure and a secondary structure that resembles fibrils formed in vivo on the spore and mycelium surface. They can also restore the growth of aerial hyphae to a chaplin mutant strain. We show that cysteine residues are not required for fibril formation in vitro and propose a role for the cysteine residues conserved in four of the five short chaplin peptides.
Annihilation events topology and their generated sound in turbulent premixed flames
The Combustion Institute This paper studies the contribution of flame annihilation events to the sound radiated by turbulent, premixed flames. Previously published direct numerical simulation (DNS) datasets of stoichiometric and lean (ϕ=0.7) flames (Haghiri et al. 2018) are first examined using an efficient formulation of the method of Griffiths et al. (2015) to identify the annihilation events. Four classes of annihilation event are observed. Three of these - pocket burn-out, tunnel closure and tunnel formation - were defined by Griffiths et al. A ‘multi-feature’ event is also defined in this paper as any combination of the other three annihilation events occurring close enough such that their radiated sound can be considered as originating from a single event. Further post-processing of these stoichiometric and lean datasets shows that the fluctuations in heat release rate associated with these 4 observed types of annihilation events are responsible for the broadband sound radiated by both flames. This, in turn, suggests that flame annihilation is the physical mechanism by which air-fuel ratio affects the radiated sound amplitude at high frequencies. This result is supported by previous works which have shown that the sound radiated from individual annihilation events scales with the laminar flame speed and the temperature ratio.
Embryonic Toxin Expression in the Cone Snail Conus victoriae PRIMED TO KILL OR DIVERGENT FUNCTION?
(American Society for Biochemistry and Molecular Biology, 2011)
Predatory marine cone snails (genus Conus) utilize complex venoms mainly composed of small peptide toxins that target voltage- and ligand-gated ion channels in their prey. Although the venoms of a number of cone snail species have been intensively profiled and functionally characterized, nothing is known about the initiation of venom expression at an early developmental stage. Here, we report on the expression of venom mRNA in embryos of Conus victoriae and the identification of novel α- and O-conotoxin sequences. Embryonic toxin mRNA expression is initiated well before differentiation of the venom gland, the organ of venom biosynthesis. Structural and functional studies revealed that the embryonic α-conotoxins exhibit the same basic three-dimensional structure as the most abundant adult toxin but significantly differ in their neurological targets. Based on these findings, we postulate that the venom repertoire of cone snails undergoes ontogenetic changes most likely reflecting differences in the biotic interactions of these animals with their prey, predators, or competitors. To our knowledge, this is the first study to show toxin mRNA transcripts in embryos, a finding that extends our understanding of the early onset of venom expression in animals and may suggest alternative functions of peptide toxins during development.
Characterization of aerosols over the Great Barrier Reef: The influence of transported continental sources
The rapid environmental changes in Australia prompt a more thorough investigation of the influence of transportation, local emissions, and optical-chemical properties on aerosol production across the region. A month-long intensive measurement campaign was conducted during spring 2016 at Mission Beach, a remote coastal site west of the Great Barrier Reef (GBR) on the north-east coast of Australia. One aerosol pollution episode was investigated in early October. This event was governed by meteorological conditions and characterized by the increase in black carbon (BC) mass concentration (averaged value of 0.35 ± 0.20 μg m-3). Under the influence of the continental transportation, a new layer of nucleation-mode aerosols with an initial size diameter of 20 nm was observed and aerosol number concentrations reached the peak of 6733 cm-3 at a diameter of 29 nm. The averaged aerosol extinction coefficient at the height of 2 km was 150 Mm-1, with a small depolarized ratio (3.5-5%). Simultaneously, the boundary layer height presented a fall-rise trend in the presence of these enhanced aerosol concentrations and became stable in a later stage of the episode. We did not observe clear boundary layer height diurnal variations from the LiDAR observations or from the Weather Research and Forecasting (WRF) model outputs, except in an earlier stage of the aerosol episode for the former. Although the sea breeze may have been responsible for these particles, on the balance of available data, we suggest that the aerosol properties at the GBR surface during this period are more likely influenced by regional transportation of continental sources, including biomass-burning aerosols.
A first evaluation of the contribution of aeolian sand transport to lagoon island accretion in the Maldives
Aeolian sedimentation and dune development have not been reported from coral atolls at equatorial latitudes. This study presents high-frequency measurements of incident and near surface wind flow and aeolian sand transport on a lagoon sand cay (Maaodegalaa) in the Maldives. Sonic anemometers and Wenglor™ particle counters were operated at 1 Hz for 8 days during the Iruvai monsoon in February 2018. Sand traps were deployed to estimate sand flux and island topography and vegetation cover were surveyed using UAV (un-manned aerial vehicle) photogrammetry and a laser level (in 2017 and 2018). Flow over beach scarps is 10 modelled using computational fluid dynamics. Maaodegalaa sand cay reaches just 0.9m above the highest spring high tides. Nebkha, between 0.10 and 0.40 m high, are widespread and are associated with Scaevola taccada and Cyperus conglomeratus. Between 2017 and 2018 the eastern section of the sand cay accreted 0.3 m following Cyperus colonisation. Reptation and aeolian ripple development occurred during fieldwork when near-surface flows exceeded 6 ms-1. Saltation occurred at higher wind speeds (8 ms-1). The highest rates of sand transport occurred during north-east incident winds of 12 ms-1 (at 6 m), that were probably generated by surface-based density currents under cumulonimbus clouds. Spatially, higher rates of sand transport were recorded downwind of a beach scarp, probably forced by flow acceleration. We propose a conceptual model of lagoon island formation, with both over-wash and aeolian sedimentation contributing to island accretion. A period of aeolian sedimentation may be critical to the emergence of sand cays.