ORCID Profile
0000-0002-2384-4826
Current Organisation
The University of Hong Kong
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Biochemistry and Cell Biology | Analytical Biochemistry | Nanobiotechnology | Nanomedicine | Protein Trafficking | Analytical Chemistry | Nanotechnology | Sensor Technology (Chemical aspects) | Immunological and Bioassay Methods | Receptors and Membrane Biology | Cell Metabolism
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in Technology | Expanding Knowledge in the Information and Computing Sciences |
Publisher: Elsevier BV
Date: 06-2016
Publisher: Proceedings of the National Academy of Sciences
Date: 22-06-2020
Abstract: Bromine is an essential trace element, required for the formation of sulfilimine cross-links in collagen IV, a basement membrane protein. Sulfilimine cross-link formation depends on the production of hypobromous acid by peroxidasin. Once the cross-links are formed, bromide is released, but we suspected that hypobromous acid might brominate bystander molecules in the basement membrane. NanoSIMS imaging of mouse kidneys revealed peroxidasin-dependent bromine enrichment in the basement membrane, and proteomics studies uncovered peroxidasin-dependent bromination of a specific tyrosine in collagen IV. Our studies show that bromine, an essential element, is largely restricted to basement membranes in mammalian tissues. Our studies also show that peroxidasin brominates bystander tyrosines in addition to promoting the formation of collagen IV sulfilimine cross-links.
Publisher: Proceedings of the National Academy of Sciences
Date: 13-05-2013
Abstract: Antimicrobial peptides are postulated to disrupt microbial phospholipid membranes. The prevailing molecular model is based on the formation of stable or transient pores although the direct observation of the fundamental processes is lacking. By combining rational peptide design with topographical (atomic force microscopy) and chemical (nanoscale secondary ion mass spectrometry) imaging on the same s les, we show that pores formed by antimicrobial peptides in supported lipid bilayers are not necessarily limited to a particular diameter, nor they are transient, but can expand laterally at the nano-to-micrometer scale to the point of complete membrane disintegration. The results offer a mechanistic basis for membrane poration as a generic physicochemical process of cooperative and continuous peptide recruitment in the available phospholipid matrix.
Publisher: Wiley
Date: 08-06-2017
Abstract: Binary encoding of peptide sequences into differential antimicrobial mechanisms is reported. Such sequences are random in composition, but controllable in chain length, are assembled from the same two amino acids, but differ in the stereochemistry of one. Regardless of chirality, the sequences lyse bacteria including the "superbugs" methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Sequences with the same chirality, so-called homochiral sequences, assemble into antimicrobial pores and form contiguous helices that are biologically promiscuous and hemolytic. By contrast, heterochiral sequences that lack such persistence selectively attack bacterial membranes without oligomerizing into visible pores. These results offer a mechanistic rationale for designing membrane-selective and sequence-independent antimicrobials.
Publisher: American Chemical Society (ACS)
Date: 03-10-2022
DOI: 10.1021/ACS.ANALCHEM.2C02770
Abstract: Subcellular partitioning of therapeutic agents is highly relevant to their interactions with target molecules and drug efficacy, but studying subcellular partitioning is an enormous challenge. Here, we describe the application of nanoscale secondary ion mass spectrometry (NanoSIMS) analysis to define the subcellular pharmacokinetics of a cytotoxic chemotherapy drug, arsenic trioxide (ATO). We reasoned that defining the partitioning of ATO would yield valuable insights into the mechanisms underlying ATO efficacy. NanoSIMS imaging made it possible to define the intracellular fate of ATO in a label-free manner─and with high resolution and high sensitivity. Our studies of ATO-treated cells revealed that arsenic accumulates in the nucleolus. After prolonged ATO exposure, ∼40 nm arsenic- and sulfur-rich protein aggregates appeared in the cell nucleolus, nucleus, and membrane-free compartments in the cytoplasm, and our studies suggested that the partitioning of nanoscale aggregates could be relevant to cell survival. All-trans retinoic acid increased intracellular ATO levels and accelerated the nanoscale aggregate formation in the nucleolus. This study yielded fresh insights into the subcellular pharmacokinetics of an important cancer therapeutic agent and the potential impact of drug partitioning and pharmacokinetics on drug activity.
Publisher: American Chemical Society (ACS)
Date: 19-11-2019
Abstract: Copper (Cu) is a key trace element for many biological processes, but there is little available information regarding its requirements and functions in critical life stages of marine bivalves, during which dramatic morphological and physiological changes occur. In this study, the ontogeny pattern of Cu accumulation across the life history of oysters was explored for the first time and the distributions of Cu in oysters at critical life stages (pe eliger and early settled spat) were in situ mapped by nanoscale secondary ion mass spectrometry (NanoSIMS) with high lateral resolution. We first demonstrated that the late pelagic stage to early settled stage was the critical stage requiring Cu during oyster development. NanoSIMS imaging revealed a significant elevation of intercellular Cu levels along with mitochondrial calcium overload and obvious structural degradation of mitochondria in velar cells at the pe eliger stage, implying the possible role of Cu in cell apoptosis of the velum during larval metamorphosis. Furthermore, an obvious enrichment of Cu together with calcium was observed in the nucleus and mitochondria of ciliated cells of gill tissue at the early settled stage. Their accumulation in the gill cells was significantly higher than that in the juveniles, indicating the potential role of Cu in sustaining the fast growth of the gill filament and the concomitant acceleration of energy metabolism during early benthic development. Our findings offer new insights into the understanding of the interactions between trace metals and marine bivalves.
Publisher: Elsevier BV
Date: 05-2016
Publisher: American Chemical Society (ACS)
Date: 08-12-2017
Abstract: Determining the in situ localization of trace elements at high lateral resolution levels in the biological system is very challenging, but critical for our understanding of metal sequestration and detoxification. Here, the cellular and subcellular distributions of Cu and Zn in contaminated oysters of Crassostrea hongkongensis were for the first time mapped using nanoscale secondary ion mass spectrometry (nanoSIMS). Three types of metal-containing cells were revealed in the gill and mantle of oysters, including Cu-specific hemocytes, Cu and Zn-containing granular hemocytes, and Cu and Zn-containing calcium cells. Obvious intercellular distribution of Cu was found in the gill tissue, indicating the potential role of hemolymph in the transportation of Cu in oysters. The distribution of Cu showed a strong colocalization with sulfur and nitrogen in Cu-specific hemocyte and intercellular hemolymph. In the Cu and Zn-containing granular hemocytes and calcium cells, the co-occurrence of Cu and Zn with phosphorus and calcium was also found. Different relationships of distributions between Cu/Zn and macronutrient elements (nitrogen, sulfur and phosphorus) implied the differential metal complexation in oysters. Interestingly, quantitative analysis of the ratios of
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6SC02925F
Abstract: A novel mechanism of monolayer poration leading to the rapid exfoliation and lysis of microbial membranes is reported.
Publisher: IOP Publishing
Date: 13-07-2009
DOI: 10.1088/0957-4484/20/31/315303
Abstract: A general sonochemical process is reported for the replication of photonic structures from Morpho butterfly wings in several hours. By selecting appropriate precursors, we can achieve exact replications of photonic structures in a variety of transparent metal oxides, such as titania, tin oxide and silica. The exact replications at the micro- and nanoscales were characterized by a combination of FE-SEM, TEM, EDX and Raman measurements. The optical properties of the replicas were investigated by using reflectance spectroscopy, and it was found that the interesting chromaticity of the reflected light could be adjusted simply by tuning the replica materials. An ultrasensitive SnO(2)-based chemical sensor was prepared from the SnO(2) replica. The sensor has a sensitivity of 35.3-50 ppm ethanol at 300 degrees C, accompanied by a rapid response and recovery (around 8-15 s), owing to its large surface area and photonic structure. Thus, this process could be developed to produce photonic structural ceramics which could be used in many passive and active infrared devices, especially high performance optical components and sensors.
Publisher: Elsevier BV
Date: 05-2014
Publisher: American Society for Clinical Investigation
Date: 19-10-2017
Publisher: Springer Science and Business Media LLC
Date: 27-03-2019
DOI: 10.1038/S41467-019-09111-2
Abstract: Myoglobin, encoded by MB , is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O 2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O 2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.
Publisher: Elsevier BV
Date: 10-2018
Publisher: Ivyspring International Publisher
Date: 2021
DOI: 10.7150/THNO.60902
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6CC08549K
Abstract: Correlative NanoSIMS and EM imaging of amiodarone-treated macrophages shows the internalisation of the drug at a sub-cellular level.
Publisher: Wiley
Date: 14-03-2021
Abstract: AlGaN‐based multiple quantum wells (MQWs) incorporating opposite polarity domains are grown by metal–organic chemical vapor deposition (MOCVD). A direct demonstration of the carrier localization effect is provided by a combination analysis of space‐resolved luminescence peak position and Ga/Al composition distribution. Furthermore, through Raman spectroscopy, it is found that compressive strain plays a key role in improving the optical properties of UV‐MQWs despite the inferior crystalline quality in the N‐polar domains. This suggests that incorporating sub‐micrometer‐scale polarity domains in the MQWs is promising for the development of efficient UV emitters.
Publisher: MDPI AG
Date: 20-11-2019
DOI: 10.3390/IJMS20235839
Abstract: The nuclei of cells may exhibit invaginations of the nuclear envelope under a variety of conditions. These invaginations form a branched network termed the nucleoplasmic reticulum (NR), which may be found in cells in pathological and physiological conditions. While an extensive NR is a hallmark of cellular senescence and shows associations with some cancers, very little is known about the formation of NR in physiological conditions, despite the presence of extensive nuclear invaginations in some cell types such as endometrial cells. Here we show that in these cells the NR is formed in response to reproductive hormones. We demonstrate that oestrogen and progesterone are sufficient to induce NR formation and that this process is reversible without cell ision upon removal of the hormonal stimulus. Nascent lamins and phospholipids are incorporated into the invaginations suggesting that there is a dedicated machinery for its formation. The induction of NR in endometrial cells offers a new model to study NR formation and function in physiological conditions.
Publisher: eLife Sciences Publications, Ltd
Date: 06-06-2019
DOI: 10.7554/ELIFE.47178
Abstract: GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1–LPL complex is crucial for the generation of lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent from the capillaries of the brain, which uses glucose for fuel however, GPIHBP1 is expressed in the capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We use NanoSIMS imaging to show that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells.
Publisher: American Chemical Society (ACS)
Date: 16-12-2020
Publisher: eLife Sciences Publications, Ltd
Date: 25-05-2019
Publisher: Proceedings of the National Academy of Sciences
Date: 23-10-2023
Publisher: The Optical Society
Date: 13-08-2019
Publisher: Springer Science and Business Media LLC
Date: 07-08-2017
DOI: 10.1038/S41598-017-07614-W
Abstract: Structure of interphase cell nuclei remains dynamic and can undergo various changes of shape and organisation, in health and disease. The double-membraned envelope that separates nuclear genetic material from the rest of the cell frequently includes deep, branching tubular invaginations that form a dynamic nucleoplasmic reticulum (NR). This study addresses mechanisms by which NR can form in interphase nuclei. We present a combination of Nanoscale Secondary Ion Mass Spectrometry (NanoSIMS) approach and light microscopy techniques to follow formation of NR by using pulse-chase experiments to examine protein and lipid delivery to nascent NR in cultured cells. Lamina protein incorporation was assessed using precursor accumulation (for lamin A) or a MAPLE3 photoconvertible tag (for lamin B1) and membrane phospholipid incorporation using stable isotope labelling with deuterated precursors followed by high resolution NanoSIMS. In all three cases, nascent molecules were selectively incorporated into newly forming NR tubules thus strongly suggesting that NR formation is a regulated process involving a focal assembly machine, rather than simple physical perturbation of a pre-existing nuclear envelope.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 28-06-2019
Abstract: Improving chemotherapies against intracellular pathogens requires understanding how antibiotic distribution within infected cells affects efficacy. Greenwood et al. developed an approach to visualize antibiotics in human macrophages infected with the tubercle bacillus (see the Perspective by Smith and Aldridge). They showed that the antitubercular (anti-TB) drug bedaquiline accumulated in host lipid droplets. Lipid droplets seemed to act as an antibiotic reservoir that could be transferred to bacteria during host lipid consumption. Indeed, alterations in host lipid droplet content affected the anti-TB activity of bedaquiline against intracellular bacilli. Science , this issue p. 1279 see also p. 1234
Publisher: Elsevier BV
Date: 07-2016
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.COPBIO.2016.06.006
Abstract: Nano-scale Secondary Ion Mass Spectrometry (NanoSIMS) is one of the most powerful in situ elemental and isotopic analysis techniques available to biologists. The combination of stable isotope probing with NanoSIMS (nanoSIP) has opened up new avenues for biological studies over the past decade. However, due to limitations inherent with any analytical methodology, additional information from correlative techniques is usually required to address real biological questions. Here we review recent developments in correlative analysis applied to complex biological systems: first, high-resolution tracking of molecules (e.g. peptides, lipids) by correlation with electron microscopy and atomic force microscopy second, identification of a specific microbial taxon with fluorescence in situ hybridization and quantification of its metabolic capacities and, third, molecular specific imaging with new probes.
Publisher: American Chemical Society (ACS)
Date: 25-05-2021
Publisher: Cold Spring Harbor Laboratory
Date: 05-08-2020
DOI: 10.1101/2020.08.05.237537
Abstract: Correlative light, electron and ion microscopy (CLEIM) offers huge potential to track the intracellular fate of antibiotics, with organelle-level resolution. However, a correlative approach that enables subcellular antibiotic visualisation in pathogen-infected tissue is lacking. Here, we developed CLEIM in tissue (CLEIMiT), and used it to identify the cell-type specific accumulation of an antibiotic in lung lesions of mice infected with Mycobacterium tuberculosis. Using CLEIMiT, we found that the anti-TB drug bedaquiline is localised not only in foamy macrophages in the lungs during infection but also accumulate in polymorphonuclear (PMN) cells.
Publisher: Oxford University Press (OUP)
Date: 04-12-2021
DOI: 10.1093/NAR/GKAA1112
Abstract: Nucleic acid therapeutics (NATs) have proven useful in promoting the degradation of specific transcripts, modifying gene expression, and regulating mRNA splicing. In each situation, efficient delivery of nucleic acids to cells, tissues and intracellular compartments is crucial—both for optimizing efficacy and reducing side effects. Despite successes in NATs, our understanding of their cellular uptake and distribution in tissues is limited. Current methods have yielded insights into distribution of NATs within cells and tissues, but the sensitivity and resolution of these approaches are limited. Here, we show that nanoscale secondary ion mass spectrometry (NanoSIMS) imaging can be used to define the distribution of 5-bromo-2′-deoxythymidine (5-BrdT) modified antisense oligonucleotides (ASO) in cells and tissues with high sensitivity and spatial resolution. This approach makes it possible to define ASO uptake and distribution in different subcellular compartments and to quantify the impact of targeting ligands designed to promote ASO uptake by cells. Our studies showed that phosphorothioate ASOs are associated with filopodia and the inner nuclear membrane in cultured cells, and also revealed substantial cellular and subcellular heterogeneity of ASO uptake in mouse tissues. NanoSIMS imaging represents a significant advance in visualizing uptake and distribution of NATs this approach will be useful in optimizing efficacy and delivery of NATs for treating human disease.
Publisher: Public Library of Science (PLoS)
Date: 31-12-2020
DOI: 10.1371/JOURNAL.PBIO.3000879
Abstract: Correlative light, electron, and ion microscopy (CLEIM) offers huge potential to track the intracellular fate of antibiotics, with organelle-level resolution. However, a correlative approach that enables subcellular antibiotic visualisation in pathogen-infected tissue is lacking. Here, we developed correlative light, electron, and ion microscopy in tissue (CLEIMiT) and used it to identify the cell type–specific accumulation of an antibiotic in lung lesions of mice infected with Mycobacterium tuberculosis . Using CLEIMiT, we found that the anti-tuberculosis (TB) drug bedaquiline (BDQ) is localised not only in foamy macrophages in the lungs during infection but also accumulate in polymorphonuclear (PMN) cells.
Publisher: American Chemical Society (ACS)
Date: 13-11-2017
Abstract: Increasing consumer use of engineered nanomaterials has led to significantly increased efforts to understand their potential impact on the environment and living organisms. Currently, no in idual technique can provide all the necessary information such as their size, distribution, and chemistry in complex biological systems. Consequently, there is a need to develop complementary instrumental imaging approaches that provide enhanced understanding of these "bio-nano" interactions to overcome the limitations of in idual techniques. Here we used a multimodal imaging approach incorporating dark-field light microscopy, high-resolution electron microscopy, and nanoscale secondary ion mass spectrometry (NanoSIMS). The aim was to gain insight into the bio-nano interactions of surface-functionalized silver nanoparticles (Ag-NPs) with the green algae Raphidocelis subcapitata, by combining the fidelity, spatial resolution, and elemental identification offered by the three techniques, respectively. Each technique revealed that Ag-NPs interact with the green algae with a dependence on the size (10 nm vs 60 nm) and surface functionality (tannic acid vs branched polyethylenimine, bPEI) of the NPs. Dark-field light microscopy revealed the presence of strong light scatterers on the algal cell surface, and SEM imaging confirmed their nanoparticulate nature and localization at nanoscale resolution. NanoSIMS imaging confirmed their chemical identity as Ag, with the majority of signal concentrated at the cell surface. Furthermore, SEM and NanoSIMS provided evidence of 10 nm bPEI Ag-NP internalization at higher concentrations (40 μg/L), correlating with the highest toxicity observed from these NPs. This multimodal approach thus demonstrated an effective approach to complement dose-response studies in nano-(eco)-toxicological investigations.
Publisher: Proceedings of the National Academy of Sciences
Date: 30-04-2020
Abstract: By ingesting apoptotic cells and other cellular debris, macrophages accumulate cholesterol. Some of the cholesterol is esterified and stored in cytosolic lipid droplets, mitigating the toxicity from free cholesterol. Eventually, however, macrophages must unload surplus cholesterol—a process often referred to as “cholesterol efflux.” Cholesterol efflux is an important physiologic process because it would be expected to retard the formation of cholesterol-rich macrophage foam cells in atherosclerotic plaques. Most studies of cholesterol efflux have focused on the ability of ABC transporters to export cholesterol onto high-density lipoproteins. The current study examines another mechanism. We found, using NanoSIMS imaging, that [ 13 C]cholesterol-loaded macrophages unload cholesterol directly into adjacent smooth muscle cells. This mechanism is potentially relevant to cholesterol efflux by tissue macrophages.
Publisher: Elsevier BV
Date: 05-2018
Publisher: Wiley
Date: 28-06-2019
Abstract: New anticancer platinum(II) compounds with distinctive modes of action are appealing alternatives to combat the drug resistance and improve the efficacy of clinically used platinum chemotherapy. Herein, we describe a rare ex le of an antitumor Pt
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 10-2018
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.COLSURFB.2018.11.036
Abstract: A wide range of small molecules are used in our daily hair products to improve the appearance of hair and to protect it from damage from the environment. In order to better design formulations of these products, an understanding of the partitioning and distributions of these small molecules in hair is critical. In this study, we used preferential extraction methods to measure the partitioning of active compounds commonly found in hair cosmetic products on the hair surface and inside hair, and investigated the use of stable isotope labelling, cryo-s le preparation and nanoscale secondary ion mass spectrometry (NanoSIMS) for high-resolution visualization of distributions of these compounds. With this approach, we quantified partitioning and directly visualized distributions at high-resolution of four molecules (e.g. resorcinol, salicylic acid, pentadecyl alcohol and pentadecanoic acid) in hair. This has not been achieved before and revealed distributions of high lipophilicity active compounds in the lipid-rich and hydrophobic cell membrane complex network in hair, while low lipophilicity ones distributed dispersedly.
Publisher: American Chemical Society (ACS)
Date: 09-05-2016
Abstract: Lead sulfide colloidal quantum dot (CQD) solar cells demonstrate extremely high short-circuit currents (Jsc) and are making decent progress in power conversion efficiencies. However, the low fill factors (FF) and open-circuit voltages have to be addressed with urgency to prevent the stalling of efficiency improvements. This paper highlights the importance of improving hole extraction, which received much less attention as compared to the electron-accepting component of the device architecture (e.g., TiO2 or ZnO). Here, we show the use of semiconducting polymer poly(3-hexylthiophene-2,5-diyl) to create efficient CQD devices by improving hole transport, removing interfacial barriers, and minimizing shunt pathways, thus resulting in an overall improvement in device performance stemming from better Jsc and FF.
Publisher: Proceedings of the National Academy of Sciences
Date: 20-08-2018
Abstract: Earlier studies suggested that particles are released from the macrophage plasma membrane, but the mechanism has been unclear. We found that filopodia of macrophages release large numbers of vesicular particles. Nanoscale secondary ion mass spectrometry revealed that these particles are enriched in cholesterol, including the “accessible” pool of cholesterol detectable by the cholesterol-binding protein. The cholesterol content of macrophage particles increased when the cells were loaded with cholesterol and could be depleted by incubating the cells with high-density lipoproteins. Our studies suggest that the release of particles by macrophages could be one mechanism for cholesterol efflux and that particles could be an intermediate in the movement of cholesterol to high-density lipoproteins.
Publisher: American Chemical Society (ACS)
Date: 11-08-2020
Publisher: Frontiers Media SA
Date: 22-01-2020
Publisher: SAGE Publications
Date: 03-2017
Abstract: Over the past few decades, several approaches have been used to image lipids in cells and tissues, but most have limited spatial resolution and sensitivity. Here, we discuss a relatively new approach, nanoscale secondary ion mass spectrometry imaging, that makes it possible to visualize lipids in cells and tissues in a quantitative fashion and with high spatial resolution and high sensitivity.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1194/JLR.M053363
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.ULTSONCH.2010.12.015
Abstract: Hierarchy structure of granum in chloroplast was replicated onto titania using a simple and tactical sonochemical method and calcination. The structures of TiO(2) replicas were characterized by XRD, FE-SEM and TEM and the pore structures were characterized by N(2) adsorption/desorption. As a comparison, the preparation without sonication by using impregnation then calcination method was conducted, which shows the efficiency of the ultrasound on the exact replication of granum from micrometers down to nanometers. The optical properties of the TiO(2) replica, the chloroplast and the commercial pure TiO(2) powder together with the compared replica were measured by absorbance spectroscopy. It was found that the absorbance intensity of the TiO(2) replica made by ultrasonication is much better than the soaked one, and is twice of that of the pure TiO(2) powder in ultraviolet - visible light range. The excellent light harvesting performance of the TiO(2) is attributed to the combination of the functionality from the inorganic oxide and the fine hierarchical biological structures.
Publisher: Wiley
Date: 11-2017
DOI: 10.1111/NPH.14878
Abstract: Soil acidity and waterlogging increase manganese (Mn) in leaf tissues to potentially toxic concentrations, an effect reportedly alleviated by increased silicon (Si) and phosphorus (P) supply. Effects of Si and P on Mn toxicity were studied in four plant species using synchrotron-based micro X-ray fluorescence (μ-XRF) and nanoscale secondary ion mass spectrometry (NanoSIMS) to determine Mn distribution in leaf tissues and using synchrotron-based X-ray absorption spectroscopy (XAS) to measure Mn speciation in leaves, stems and roots. A concentration of 30 μM Mn in solution was toxic to cowpea and soybean, with 400 μM Mn toxic to sunflower but not white lupin. Unexpectedly, μ-XRF analysis revealed that 1.4 mM Si in solution decreased Mn toxicity symptoms through increased Mn localization in leaf tissues. NanoSIMS showed Mn and Si co-localized in the apoplast of soybean epidermal cells and basal cells of sunflower trichomes. Concomitantly, added Si decreased oxidation of Mn(II) to Mn(III) and Mn(IV). An increase from 5 to 50 μM P in solution changed some Mn toxicity symptoms but had little effect on Mn distribution or speciation. We conclude that Si increases localized apoplastic sorption of Mn in cowpea, soybean and sunflower leaves thereby decreasing free Mn
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 07-2014
Publisher: Oxford University Press (OUP)
Date: 17-07-2019
DOI: 10.1093/AOB/MCY135
Publisher: eLife Sciences Publications, Ltd
Date: 02-09-2019
Publisher: Proceedings of the National Academy of Sciences
Date: 06-02-2017
Abstract: Biochemical studies have demonstrated that one pool of cholesterol in the plasma membrane is accessible to binding by bacterial cholesterol-binding proteins, whereas another pool is “sequestered” and inaccessible to binding by those proteins. Here, we used nanoscale secondary ion mass spectrometry (NanoSIMS) imaging, along with cholesterol-binding proteins that had been labeled with a stable isotope, to visualize and quantify the distribution of “accessible cholesterol” on the plasma membrane of mammalian cells. Our studies revealed that accessible cholesterol, as judged by cholesterol-binding proteins, is not evenly distributed on the plasma membrane but instead is enriched on the surface of microvilli. The accessible cholesterol on microvilli could be relevant to the movement of cholesterol away from the plasma membrane.
Publisher: Informa UK Limited
Date: 14-09-2020
DOI: 10.1128/MCB.00255-20
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1AN00363A
Abstract: Staining bacteria is made more informative with a probe that enables imaging using super-resolution microscopy, and ion nanoscopy.
Publisher: Public Library of Science (PLoS)
Date: 09-06-2014
Publisher: Proceedings of the National Academy of Sciences
Date: 02-01-2020
Abstract: Cysteine thiols of many cancer-associated proteins are attractive targets of anticancer agents. Herein, we unequivocally demonstrate a distinct thiol-targeting property of gold(III) mesoporphyrin IX dimethyl ester (AuMesoIX) and its anticancer activities. While the binding of cysteine thiols with metal complexes usually occurs via M–S bond formation, AuMesoIX is unique in that the meso -carbon atom of the porphyrin ring is activated by the gold(III) ion to undergo nucleophilic aromatic substitution with thiols. AuMesoIX was shown to modify reactive cysteine residues and inhibit the activities of anticancer protein targets including thioredoxin, peroxiredoxin, and deubiquitinases. Treatment of cancer cells with AuMesoIX resulted in the formation of gold-bound sulfur-rich protein aggregates, oxidative stress-mediated cytotoxicity, and accumulation of ubiquitinated proteins. Importantly, AuMesoIX exhibited effective antitumor activity in mice. Our study has uncovered a gold(III)-induced ligand scaffold reactivity for thiol targeting that can be exploited for anticancer applications.
Publisher: Springer Science and Business Media LLC
Date: 21-06-2021
DOI: 10.1038/S41467-021-24127-3
Abstract: To be effective, chemotherapy against tuberculosis (TB) must kill the intracellular population of the pathogen, Mycobacterium tuberculosis . However, how host cell microenvironments affect antibiotic accumulation and efficacy remains unclear. Here, we use correlative light, electron, and ion microscopy to investigate how various microenvironments within human macrophages affect the activity of pyrazinamide (PZA), a key antibiotic against TB. We show that PZA accumulates heterogeneously among in idual bacteria in multiple host cell environments. Crucially, PZA accumulation and efficacy is maximal within acidified phagosomes. Bedaquiline, another antibiotic commonly used in combined TB therapy, enhances PZA accumulation via a host cell-mediated mechanism. Thus, intracellular localisation and specific microenvironments affect PZA accumulation and efficacy. Our results may explain the potent in vivo efficacy of PZA, compared to its modest in vitro activity, and its critical contribution to TB combination chemotherapy.
Publisher: Springer Science and Business Media LLC
Date: 08-10-2018
DOI: 10.1038/S41565-018-0272-2
Abstract: Gold nanorods are one of the most widely explored inorganic materials in nanomedicine for diagnostics, therapeutics and sensing
Publisher: eLife Sciences Publications, Ltd
Date: 05-09-2019
DOI: 10.7554/ELIFE.50231
Abstract: Cultured mouse peritoneal macrophages release large numbers of ~30-nm cholesterol-rich particles. Here, we show that those particles represent fragments of the plasma membrane that are pulled away and left behind during the projection and retraction of filopodia and lamellipodia. Consistent with this finding, the particles are enriched in proteins found in focal adhesions, which attach macrophages to the substrate. The release of particles is abolished by blocking cell movement (either by depolymerizing actin with latrunculin A or by inhibiting myosin II with blebbistatin). Confocal microscopy and NanoSIMS imaging studies revealed that the plasma membrane–derived particles are enriched in ‘accessible cholesterol’ (a mobile pool of cholesterol detectable with the modified cytolysin ALO-D4) but not in sphingolipid-sequestered cholesterol [a pool detectable with ostreolysin A (OlyA)]. The discovery that macrophages release cholesterol-rich particles during cellular locomotion is likely relevant to cholesterol efflux and could contribute to extracellular cholesterol deposition in atherosclerotic plaques.
Publisher: Springer Science and Business Media LLC
Date: 26-11-2010
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6CC10226C
Abstract: Non-destructive & label-free nanoscale mapping of newly-synthesised phospholipid molecules inside a biological cell is demonstrated using tip-enhanced Raman spectroscopy for the first time.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 05-2018
End Date: 05-2021
Amount: $365,058.00
Funder: Australian Research Council
View Funded ActivityStart Date: 09-2022
End Date: 08-2025
Amount: $510,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 03-2023
End Date: 03-2027
Amount: $3,975,864.00
Funder: Australian Research Council
View Funded ActivityStart Date: 01-2021
End Date: 01-2024
Amount: $558,400.00
Funder: Australian Research Council
View Funded Activity