ORCID Profile
0000-0001-5934-6047
Current Organisations
University of Sydney
,
University of Technology Sydney
,
Sydney Girls High School
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Medical Biotechnology | Medical Biotechnology Diagnostics (incl. Biosensors) | Nanotechnology | Biomedical Instrumentation | Nanotechnology | Biosensor Technologies | Biochemistry and Cell Biology | Optical Physics Not Elsewhere Classified | Toxicology (Incl. Clinical Toxicology) | Physical Chemistry Not Elsewhere Classified | Computational Heat Transfer | Protein Targeting And Signal Transduction | Materials Engineering | Heat and Mass Transfer Operations | Materials Engineering Not Elsewhere Classified | Invertebrate Biology | Diagnostic Applications | Interdisciplinary Engineering | Biomedical Engineering not elsewhere classified | Nanobiotechnology |
ANZSRC Socio-Economic Objective (SEO)
Higher education | Expanding Knowledge in Technology | Diagnostic Methods | Medical instrumentation | Diagnostic methods | Control of pests and exotic species | Scientific instrumentation | Agricultural chemicals | Veterinary Diagnostics | Expanding Knowledge in Engineering | Disease distribution and transmission | Scientific Instruments | Expanding Knowledge in the Biological Sciences | Computer hardware and electronic equipment not elsewhere classified
Related Links
Publications
Regulation of the Membrane Insertion and Conductance Activity of the Metamorphic Chloride Intracellular Channel Protein CLIC1 by Cholesterol
Publisher: Public Library of Science (PLoS)
Date: 14-02-2013
Effects of Components of Ischemia on the Kv4.3 Current Stably Expressed in Chinese Hamster Ovary Cells
Publisher: Elsevier BV
Date: 02-2002
In Vivo Study of Spherical Gold Nanoparticles: Inflammatory Effects and Distribution in Mice
Publisher: Public Library of Science (PLoS)
Date: 28-02-2013
Gold nanoparticles improve metabolic profile of mice fed a high-fat diet
Publisher: Springer Science and Business Media LLC
Date: 06-02-2018
Dispersion stability and biocompatibility of four ligand-exchanged NaYF4: Yb, Er upconversion nanoparticles
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.ACTBIO.2019.11.048
Abstract: Surface modification to obtain high dispersion stability and biocompatibility is a key factor for bio-application of upconversion nanoparticles (UCNPs). A systematic study of UCNPs modified with four hydrophilic molecules separately, comparing their dispersion stability in biological buffers and cellular biocompatibility is reported here. The results show that carboxyl-functionalized UCNPs (modified by 3,4-dihydrocinnamic acid (DHCA) or poly(monoacryloxyethyl phosphate (MAEP)) with negative surface charge have superior even-distribution in biological buffers compared to amino-functionalized UCNPs (modified by (aminomethyl)phosphonic (AMPA) or (3-Aminopropyl)triethoxysilane (APTES)) with positive surface charge. Subsequent investigation of cellular interactions revealed high levels of non-targeted cellular uptake of the particles modified with either of the three small molecules (AMPA, APTES, DHCA) and high levels of cytotoxicity when used at high concentrations. The particles were seen to be trapped as particle-aggregates within the cellular cytoplasm, leading to reduced cell viability and cell proliferation, along with dysregulation of the cell cycle as assessed by DNA content measurements. The dramatically reduced proportion of cells in G
Crystal Structure of a Soluble Form of the Intracellular Chloride Ion Channel CLIC1 (NCC27) at 1.4-Å Resolution
Publisher: Elsevier BV
Date: 11-2001
Exonuclease III-Assisted Upconversion Resonance Energy Transfer in a Wash-Free Suspension DNA Assay
Publisher: American Chemical Society (ACS)
Date: 19-12-2018
DOI: 10.1021/ACS.ANALCHEM.7B04240
Abstract: Sensitivity is the key in optical detection of low-abundant analytes, such as circulating RNA or DNA. The enzyme Exonuclease III (Exo III) is a useful tool in this regard its ability to recycle target DNA molecules results in markedly improved detection sensitivity. Lower limits of detection may be further achieved if the detection background of autofluorescence can be removed. Here we report an ultrasensitive and specific method to quantify trace amounts of DNA analytes in a wash-free suspension assay. In the presence of target DNA, the Exo III recycles the target DNA by selectively digesting the dye-tagged sequence-matched probe DNA strand only, so that the amount of free dye removed from the probe DNA is proportional to the number of target DNAs. Remaining intact probe DNAs are then bound onto upconversion nanoparticles (energy donor), which allows for upconversion luminescence resonance energy transfer (LRET) that can be used to quantify the difference between the free dye and tagged dye (energy acceptor). This scheme simply avoids both autofluorescence under infrared excitation and many tedious washing steps, as the free dye molecules are physically located away from the nanoparticle surface, and as such they remain "dark" in suspension. Compared to alternative approaches requiring enzyme-assisted lification on the nanoparticle surface, introduction of probe DNAs onto nanoparticles only after DNA hybridization and signal lification steps effectively avoids steric hindrance. Via this approach, we have achieved a detection limit of 15 pM in LRET assays of human immunodeficiency viral DNA.
Ion Channel Proteins that Spontaneously Insert into Lipid Bilayer Membranes: An Impedance Spectroscopy Study Employing Tethered Membranes
Publisher: Elsevier BV
Date: 2012
CLIC proteins, ezrin, radixin, moesin and the coupling of membranes to the actin cytoskeleton: A smoking gun?
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.BBAMEM.2013.05.025
Abstract: The CLIC proteins are a highly conserved family of metazoan proteins with the unusual ability to adopt both soluble and integral membrane forms. The physiological functions of CLIC proteins may include enzymatic activity in the soluble form and anion channel activity in the integral membrane form. CLIC proteins are associated with the ERM proteins: ezrin, radixin and moesin. ERM proteins act as cross-linkers between membranes and the cortical actin cytoskeleton. Both CLIC and ERM proteins are controlled by Rho family small GTPases. CLIC proteins, ERM and Rho GTPases act in a concerted manner to control active membrane processes including the maintenance of microvillar structures, phagocytosis and vesicle trafficking. All of these processes involve the interaction of membranes with the underlying cortical actin cytoskeleton. The relationships between Rho GTPases, CLIC proteins, ERM proteins and the membrane:actin cytoskeleton interface are reviewed. Speculative models are proposed involving the formation of localised multi-protein complexes on the membrane surface that assemble via multiple weak interactions. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé.
The antipsychotic agents thioridazine, chlorpromazine and clozapine block the human-ether-a-go-go-related gene (HERG) potassium channel: Cellular mechanism for proarrhythmia
Publisher: Wiley
Date: 12-2000
A study of Functional ion Transport Using Tethered Membranes
Publisher: Elsevier BV
Date: 02-2011
Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene
Publisher: Wiley
Date: 2010
DOI: 10.1002/DVG.20590
Abstract: CLIC1 belongs to a family of highly conserved and widely expressed intracellular chloride ion channel proteins existing in both soluble and membrane integrated forms. To study the physiological and biological role of CLIC1 in vivo, we undertook conditional gene targeting to engineer Clic1 gene knock-out mice. This represents creation of the first gene knock-out of a vertebrate CLIC protein family member. We first generated a Clic1 Knock-in (Clic1(FN)) allele, followed by Clic1 knock-out (Clic1(-/-)) mice by crossing Clic1(FN) allele with TNAP-cre mice, resulting in germline gene deletion through Cre-mediated recombination. Mice heterozygous or homozygous for these alleles are viable and fertile and appear normal. However, Clic1(-) (/-) mice show a mild platelet dysfunction characterized by prolonged bleeding times and decreased platelet activation in response to adenosine diphosphate stimulation linked to P2Y(12) receptor signaling.
Clozapine and Sudden Death
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2001
Inhibition of the human ether‐a‐go‐go‐related gene (HERG) potassium channel by cisapride: affinity for open and inactivated states
Publisher: Wiley
Date: 09-1999
A golden bullet? Selective targeting of toxoplasma gondii tachyzoites using antibody-functionalized gold nanorods
Publisher: American Chemical Society (ACS)
Date: 23-11-2007
DOI: 10.1021/NL072377+
Abstract: Conjugates of gold nanoparticles and antibodies have useful functionalities. Here, we show how they can be used to selectively target and destroy parasitic protozoans. Gold nanorods were conjugated with an anti-Toxoplasma gondii antibody and used to target the extracellular tachyzoite which is an infectious form of an obligate parasite Toxoplasma gondii. Subsequent laser irradiation was used to kill the targeted protozoans. This concept provides a new paradigm for the treatment of parasitic protozoans.
Destruction and control of Toxoplasma gondii tachyzoites using gold nanosphere/antibody conjugates
Publisher: Wiley
Date: 22-04-2009
The Janus-faced atracotoxins are specific blockers of invertebrate K Ca channels
Publisher: Wiley
Date: 28-07-2008
DOI: 10.1111/J.1742-4658.2008.06545.X
Abstract: The Janus-faced atracotoxins are a unique family of excitatory peptide toxins that contain a rare vicinal disulfide bridge. Although lethal to a wide range of invertebrates, their molecular target has remained enigmatic for almost a decade. We demonstrate here that these toxins are selective, high-affinity blockers of invertebrate Ca(2+)-activated K(+) (K(Ca)) channels. Janus-faced atracotoxin (J-ACTX)-Hv1c, the prototypic member of this toxin family, selectively blocked K(Ca) channels in cockroach unpaired dorsal median neurons with an IC(50) of 2 nm, but it did not significantly affect a wide range of other voltage-activated K(+), Ca(2+) or Na(+) channel subtypes. J-ACTX-Hv1c blocked heterologously expressed cockroach large-conductance Ca(2+)-activated K(+) (pSlo) channels without a significant shift in the voltage dependence of activation. However, the block was voltage-dependent, indicating that the toxin probably acts as a pore blocker rather than a gating modifier. The molecular basis of the insect selectivity of J-ACTX-Hv1c was established by its failure to significantly inhibit mouse mSlo currents (IC(50) approximately 10 mum) and its lack of activity on rat dorsal root ganglion neuron K(Ca) channel currents. This study establishes the Janus-faced atracotoxins as valuable tools for the study of invertebrate K(Ca) channels and suggests that K(Ca) channels might be potential insecticide targets.
Targeted destruction of murine macrophage cells with bioconjugated gold nanorods
Publisher: Springer Science and Business Media LLC
Date: 13-02-2007
Recombinant CLIC1 (NCC27) Assembles in Lipid Bilayers via a pH-dependent Two-state Process to Form Chloride Ion Channels with Identical Characteristics to Those Observed in Chinese Hamster Ovary Cells
Publisher: Elsevier BV
Date: 07-2002
Comparative effects of azimilide and ambasilide on the human ether-a-go-go-related gene (HERG) potassium channel
Publisher: Oxford University Press (OUP)
Date: 10-2000
DOI: 10.1016/S0008-6363(00)00155-3
Abstract: To evaluate the effects of azimilide and ambasilide on the biophysical properties of the human-ether-a-go-go-related (HERG) channel. HERG was stably transfected into Chinese hamster ovary (CHO-K1) cells and currents were measured using a whole cell, voltage-cl technique. Azimilide had a 'dual effect', inhibiting current at voltage steps above -40 mV and augmenting current at -40 and -50 mV. Tail current inhibition following a step to +30 mV did not vary with temperature (IC(50) 610 nM at 22 degrees C and 560 nM at 37 degrees C). The agonist effect at -50 mV was concentration-dependent and correlated with a hyperpolarizing shift in the V(1/2) of activation (r=0.98, P<0.05). Time constants of inactivation were faster and there was a -10 mV shift in the V(1/2) of steady state inactivation suggestive of open and inactivated state binding. By comparison, ambasilide inhibited HERG channels with lower potency (IC(50) 3.6 microM), in a voltage- and time-dependent but frequency-independent manner (0.03-1 Hz). Ambasilide had no effect on activation or inactivation gating but prolonged both fast and slow components of deactivation consistent with unbinding from the open state. The net effect of both drugs was similar during a voltage r which simulated a cardiac action potential. Inhibition of HERG channels by azimilide and ambasilide exhibits a similar time and voltage-dependence. While both exhibit affinity for the open state, azimilide also binds to inactivated channels.
The effect of surface chemistry modification of titanium alloy on signalling pathways in human osteoblasts
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1016/J.BIOMATERIALS.2005.05.024
Abstract: Establishing and maintaining mature bone at the bone-device interface is critical to the long-term success of prosthesis. Poor cell adhesion to orthopaedic and dental implants results in implant failure. Considerable effort has been devoted to alter the surface characteristics of these biomaterials in order to improve the initial interlocking of the device and skeleton. We investigated the effect of surface chemistry modification of titanium alloy (Ti-6Al-4V) with zinc, magnesium or alkoxide-derived hydroxy carbonate apatite (CHAP) on the regulation of key intracellular signalling proteins in human bone-derived cells (HBDC) cultured on these modified Ti-6Al-4V surfaces. Western blotting demonstrated that modifying Ti-6Al-4V with CHAP or Mg results in modulation of key intracellular signalling proteins. We showed an enhanced activation of Shc, a common point of integration between integrins and the Ras/Mapkinase pathway. Mapkinase pathway was also upregulated, suggesting its role in mediating osteoblastic cell interactions with biomaterials. The signalling pathway involving c-fos (member of the activated protein-1) was also shown to be upregulated in osteoblasts cultured on the Mg and CHAP modified Ti-6Al-4V. Thus surface modification with CHAP or Mg may contribute to successful osteoblast function and differentiation at the skeletal tissue-device interface.
Versatile multicolor nanodiamond probes for intracellular imaging and targeted labeling
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB00508G
Abstract: We report on the first demonstration of FNDs containing either silicon or nitrogen vacancy color centers for multi-color bio-imaging.
A conserved GXXXG motif in the transmembrane domain of CLIC proteins is essential for their cholesterol-dependant membrane interaction
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.BBAGEN.2019.04.020
Abstract: Sterols have been reported to modulate conformation and hence the function of several membrane proteins. One such group is the Chloride Intracellular Ion Channel (CLIC) family of proteins. The CLIC protein family consists of six evolutionarily conserved protein members in vertebrates. These proteins exist as both monomeric soluble proteins and as membrane bound proteins. To date, the structure of their membrane-bound form remains unknown. In addition to several studies indicating cellular redox environment and pH as facilitators of CLIC1 insertion into membranes, we have also demonstrated that the spontaneous membrane insertion of CLIC1 is regulated by membrane cholesterol. We have performed Langmuir-film, Impedance Spectroscopy and Molecular Docking Simulations to study the role of this GXXXG motif in CLIC1 interaction with cholesterol. Unlike CLIC1-wild-type protein, the G18A and G22A mutants, that form part of the GXXXG motif, showed much slower initial kinetics and lower ion channel activity compared to the native protein. This difference can be attributed to the significantly reduced membrane interaction and insertion rate of the mutant proteins and/or slower formation of the final membrane configuration of the mutant proteins once in the membrane. In this study, our findings uncover the identification of a GXXXG motif in CLIC1, which likely serves as the cholesterol-binding domain, that facilitates the protein's membrane interaction and insertion. Furthermore, we were able to postulate a model by which CLIC1 can autonomously insert into membranes to form functional ion channels. Members of the CLIC family of proteins demonstrate unusual structural and dual functional properties - as ion channels and enzymes. Elucidating how the CLIC proteins' interact with membranes, thus allowing them to switch between their soluble and membrane form, will provide key information as to a mechanism of moonlighting activity and a novel regulatory role for cholesterol in such a process.
The effects of spring versus summer heat events on two arid zone plant species under field conditions
Publisher: CSIRO Publishing
Date: 21-04-2023
DOI: 10.1071/FP22135
Abstract: Heatwaves are increasingly occurring out-of-season, which may affect plants not primed for the event. Further, heat stress often coincides with water and/or nutrient stress, impairing short-term physiological function and potentially causing downstream effects on reproductive fitness. We investigated the response of water-stressed arid-zone Solanum oligacanthum and Solanum orbiculatum to spring vs summer heat stress under differing nutrient conditions. Heat stress events were imposed in open-topped chambers under in situ desert conditions. To assess short-term impacts, we measured leaf photosystem responses (Fv/Fm) and membrane stability long-term effects were compared via biomass allocation, visible damage, flowering and fruiting. Plants generally fared more poorly following summer than spring heat stress, with the exception of Fv/Fm. Summer heat stress caused greater membrane damage, reduced growth and survival compared with spring. Nutrient availability had a strong influence on downstream effects of heat stress, including species-specific outcomes for reproductive fitness. Overall, high temperatures during spring posed a lower threat to fitness than in severe arid summer conditions of high temperature and low water availability, which were more detrimental to plants in both the short and longer term. Our study highlights the importance of considering ecologically relevant, multiple-stressor events to understand different species responses to extreme heat.
The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle
Publisher: Wiley
Date: 12-2000
DOI: 10.1111/J.1469-7793.2000.00541.X
Abstract: NCC27 is a nuclear chloride ion channel, identified in the PMA-activated U937 human monocyte cell line. NCC27 mRNA is expressed in virtually all cells and tissues and the gene encoding NCC27 is also highly conserved. Because of these factors, we have examined the hypothesis that NCC27 is involved in cell cycle regulation. Electrophysiological studies in Chinese hamster ovary (CHO-K1) cells indicated that NCC27 chloride conductance varied according to the stage of the cell cycle, being expressed only on the plasma membrane of cells in G2/M phase. We also demonstrate that Cl- ion channel blockers known to block NCC27 led to arrest of CHO-K1 cells in the G2/M stage of the cell cycle, the same stage at which this ion channel is selectively expressed on the plasma membrane. These data strongly support the hypothesis that NCC27 is involved, in some as yet undetermined manner, in regulation of the cell cycle.
Gold nanoparticles with organic linkers for applications in biomedicine
Publisher: CRC Press
Date: 03-10-2017
X-ray and Neutron Reflectivity Study Shows That CLIC1 Undergoes Cholesterol-Dependent Structural Reorganization in Lipid Monolayers
Publisher: American Chemical Society (ACS)
Date: 20-10-2017
DOI: 10.1021/ACS.LANGMUIR.7B02872
Abstract: CLIC1 belongs to the ubiquitous family of chloride intracellular ion channel proteins that are evolutionarily conserved across species. The CLICs are unusual in that they exist mainly as soluble proteins but possess the intriguing property of spontaneous conversion from the soluble to an integral membrane-bound form. This conversion is regulated by the membrane lipid composition, especially by cholesterol, together with external factors such as oxidation and pH. However, the precise physiological mechanism regulating CLIC1 membrane insertion is currently unknown. In this study, X-ray and neutron reflectivity experiments were performed to study the interaction of CLIC1 with different phospholipid monolayers prepared using POPC, POPE, or POPS with and without cholesterol in order to better understand the regulatory role of cholesterol in CLIC1 membrane insertion. Our findings demonstrate for the first time two different structural orientations of CLIC1 within phospholipid monolayers, dependent upon the absence or presence of cholesterol. In phospholipid monolayers devoid of cholesterol, CLIC1 was unable to insert into the lipid acyl chain region. However, in the presence of cholesterol, CLIC1 showed significant insertion within the phospholipid acyl chains occupying an area per protein molecule of 6-7 nm
Terminating polyelectrolyte in multilayer films influences growth and morphology of adhering cells
Publisher: Institution of Engineering and Technology (IET)
Date: 2010
DOI: 10.1049/IET-NBT.2009.0016
Abstract: Polyelectrolyte films of anionic poly(sodium 4-styrenesulphonate) (PSS) and cationic poly (allylamine hydrochloride) (PAH) were constructed using layer-by-layer assembly. The authors examined the cytocompatibility of these films for future use in nanobiotechnology applications. Cell lines HEK-293 and 3T3-L1 were cultured on these films and the initial attachment, adhesion, proliferation and cytotoxicity of the cells were measured using a propidium iodide assay. The morphology and spread of the cells were measured by phase-contrast microscopy. The actin cytoskeleton was observed using fluorescent microscopy. Neither the PAH-terminated nor the PSS-terminated polyelectrolyte films were cytotoxic. The PAH-terminated polyelectrolyte films improved the initial attachment and subsequent adhesion of the cells, in addition to enhancing the production of extracellular matrix and the modelling of the actin filaments. The PSS-terminated film enhanced the proliferation of the cells compared to the PAH-terminated film. That was despite the cell cycle, the spreading or the cytotoxicity of both cell types being similar for either the PSS-terminated surfaces or the PAH-terminated surfaces. Cell behaviour can be modulated by the final surface charge of the polyelectrolyte film and the results are useful in guiding the choice of substrates and/or coatings for potential biomedical applications (e.g. implants) as well as cell biology research.
The heart of psychotropic drug therapy
Publisher: Elsevier BV
Date: 05-2000
Stereoselective synthesis of perdeuterated phytanic acid, its phospholipid derivatives and their formation into lipid model membranes for neutron reflectivity studies
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.CHEMPHYSLIP.2014.04.004
Abstract: We describe a straightforward method, for synthesis of large scale (gram quantities) of highly deuterated phytanic acid from commercially available phytol while preserving the stereochemistry around the chiral centres. The subsequent synthesis of tail-deuterated analogues of the archeabacterial membrane lipids 1,2-di(3RS,7R,11R-phytanyl)-sn-glycero-3-phosphocholine (DPEPC) and 1,2-di(3RS,7R,11R-phytanoyl)-sn-glycero-3-phosphocholine (DPhyPC) from perdeuterated phytanic acid is also described. Both lipids were employed in construction of two different model membranes, namely Langmuir monolayers and a tethered bilayer membrane (TBM) on a solid substrate, characterised by pressure area isotherm and neutron reflectometry techniques. At 10 mN/m pressure the head-group thickness of both monolayers was similar while the thickness of the tail region was significantly larger for tail-deuterated DPhyPC, which was evident from a smaller area per molecule. At 20 mN/m the thickness of the head and tail regions in both lipids was comparable, yet the area per molecule of tail-deuterated DPhyPC was 10% smaller than tail-deuterated DPEPC. In the TBM bilayer model membrane, the thickness of the lipid tails in both inner and outer leaflets was 8.2 Å, giving a total of 16.4 Å. Deuteration enabled unambiguous determination of the relative proportion of the hydrogenous tether, phospholipid and subphase.
Members of the Chloride Intracellular Ion Channel Protein Family Demonstrate Glutaredoxin-Like Enzymatic Activity
Publisher: Public Library of Science (PLoS)
Date: 12-01-2015
Novel Engineered Ion Channel Provides Controllable Ion Permeability for Polyelectrolyte Microcapsules Coated with a Lipid Membrane
Publisher: Wiley
Date: 08-01-2009
Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity
Publisher: Springer Science and Business Media LLC
Date: 15-02-2017
DOI: 10.1038/NCOMMS14206
Abstract: The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2). CLIC3 acts as a glutathione-dependent oxidoreductase that reduces TGM2 and regulates TGM2 binding to its cofactors. Finally, CLIC3 is also secreted by cancer cells, is abundant in the stromal and tumour compartments of aggressive ovarian cancers and its levels correlate with poor clinical outcome. This work reveals a previously undescribed invasive mechanism whereby the secretion of a glutathione-dependent oxidoreductase drives angiogenesis and cancer progression by promoting TGM2-dependent invasion.
Versatile multicolor nanodiamond probes for intracellular imaging and targeted labeling
Publisher: Cold Spring Harbor Laboratory
Date: 15-02-2018
DOI: 10.1101/108720
Abstract: Diamond nanoparticles that host bright luminescent centers are attracting attention for applications in bio-labeling and bio-sensing. Beyond their unsurpassed photostability, diamond can host multiple color centers, from the blue to the near infra-red spectral range. While nanodiamonds hosting nitrogen vacancy defects have been widely employed as bio-imaging probes, production and fabrication of nanodiamonds with other color centers is a challenge. In this work, a large scale production of fluorescent nanodiamonds (FNDs) containing a near infrared (NIR) color center – namely the silicon vacancy (SiV) defect, is reported. More importantly, a concept of application of different color centers for multi-color bio-imaging to investigate intercellular processes is demonstrated. Furthermore, two types of FNDs within cells can be easily resolved by their specific spectral properties, where data shows that SiV FNDs initially dispersed throughout the cell interior while NV FNDs localized in a close proximity to nucleus. The reported results are the first demonstration of multi-color labeling with FNDs that can pave the way for the wide-ranging use of FNDs in applications, including bio-sensing, bio-imaging and drug delivery applications.
X-Ray Mapping of Minerals Incorporated into Liposomes
Publisher: Oxford University Press (OUP)
Date: 07-2009
DOI: 10.1017/S1431927609092502
Abstract: Extended abstract of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009
In Vitro Enzymatic Studies Reveal pH and Temperature Sensitive Properties of the CLIC Proteins
Publisher: MDPI AG
Date: 15-09-2023
DOI: 10.3390/BIOM13091394
Inhibition of HERG channels stably expressed in a mammalian cell line by the antianginal agent perhexiline maleate
Publisher: Wiley
Date: 05-1999
Real-time monitoring of heat transfer between gold nanoparticles and tethered bilayer lipid membranes
Publisher: Elsevier BV
Date: 09-2020
Soluble Structure of CLIC and S100 Proteins Investigated by Atomic Force Microscopy
Publisher: Scientific Research Publishing, Inc.
Date: 2011
MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily
Publisher: Proceedings of the National Academy of Sciences
Date: 14-10-1997
Abstract: Macrophages play a key role in both normal and pathological processes involving immune and inflammatory responses, to a large extent through their capacity to secrete a wide range of biologically active molecules. To identify some of these as yet not characterized molecules, we have used a subtraction cloning approach designed to identify genes expressed in association with macrophage activation. One of these genes, designated macrophage inhibitory cytokine 1 (MIC-1), encodes a protein that bears the structural characteristics of a transforming growth factor β (TGF-β) superfamily cytokine. Although it belongs to this superfamily, it has no strong homology to existing families, indicating that it is a ergent member that may represent the first of a new family within this grouping. Expression of MIC-1 mRNA in monocytoid cells is up-regulated by a variety of stimuli associated with activation, including interleukin 1β, tumor necrosis factor α (TNF-α), interleukin 2, and macrophage colony-stimulating factor but not interferon γ, or lipopolysaccharide (LPS). Its expression is also increased by TGF-β. Expression of MIC-1 in CHO cells results in the proteolytic cleavage of the propeptide and secretion of a cysteine-rich dimeric protein of M r 25 kDa. Purified recombinant MIC-1 is able to inhibit lipopolysaccharide -induced macrophage TNF-α production, suggesting that MIC-1 acts in macrophages as an autocrine regulatory molecule. Its production in response to secreted proinflammatory cytokines and TGF-β may serve to limit the later phases of macrophage activation.
Targeting and dissolution characteristics of bone forming and antibacterial drugs by harnessing the structure of microspherical shells from coral beach sand
Publisher: Wiley
Date: 02-11-2011
Prospects for gold nanorod particles in diagnostic and therapeutic applications
Publisher: Informa UK Limited
Date: 2008
DOI: 10.5661/BGER-25-93
Abstract: Rod-shaped gold nanoparticles ('nanorods') have recently attracted widespread attention due to their unique optical properties and facile synthesis. In particular, they can support a longitudinal surface plasmon, which results in suspensions of them having a strong extinction peak in the upper visible or near-infrared parts of the spectrum. The position of this peak can be readily tuned by controlling the shape of the rods. In addition, the surface of the nanorods can be functionalized by a very wide variety of molecules. This has led to interest in their use as selective biomarkers in biodiagnostics or for selective targeting in photothermal thearapeutics. Here, we review the recent advances in the use of gold nanorods in these applications. Additionally, the information available regarding their biocompatibility is discussed.
The enigma of the CLIC proteins: Ion channels, redox proteins, enzymes, scaffolding proteins?
Publisher: Wiley
Date: 18-01-2010
DOI: 10.1016/J.FEBSLET.2010.01.027
Abstract: Chloride intracellular channel proteins (CLICs) are distinct from most ion channels in that they have both soluble and integral membrane forms. CLICs are highly conserved in chordates, with six vertebrate paralogues. CLIC-like proteins are found in other metazoans. CLICs form channels in artificial bilayers in a process favoured by oxidising conditions and low pH. They are structurally plastic, with CLIC1 adopting two distinct soluble conformations. Phylogenetic and structural data indicate that CLICs are likely to have enzymatic function. The physiological role of CLICs appears to be maintenance of intracellular membranes, which is associated with tubulogenesis but may involve other substructures.
Applications of protein-based capacitive Biosensors for the detection of heavy-metal ions
Publisher: IEEE
Date: 2006
Are calcifying matrix vesicles in atherosclerotic lesions of cellular origin?
Publisher: Springer Science and Business Media LLC
Date: 12-2006
DOI: 10.1007/S00395-006-0637-9
Abstract: Over recent years, the role of matrix vesicles in the initial stages of arterial calcification has been recognized. Matrix calcifying vesicles have been isolated from atherosclerotic arteries and the biochemical composition of calcified vesicles has been studied. No studies have yet been carried out to examine the fine structure of matrix vesicles in order to visualize the features of the consequent stages of their calcification in arteries. In the present work, a high resolution ultrastructural analysis has been employed and the study revealed that matrix vesicles in human atherosclerotic lesions are heterogeneous with two main types which we classified. Type I calcified vesicles were presented by vesicles surrounded by two electron-dense layers and these vesicles were found to be resistant to the calcification process in atherosclerotic lesions in situ. Type II matrix vesicles were presented by vesicles surrounded by several electron-dense layers and these vesicles were found to represent calcifying vesicles in atherosclerotic lesions. To test the hypothesis that calcification of matrix vesicles surrounded by multilayer sheets may occur simply as a physicochemical process, independently from the cell regulation, we produced multilamellar liposomes and induced their calcification in vitro in a manner similar to that occurring in matrix vesicles in atherosclerotic lesions in situ.
Comparative study of His- and Non-His-tagged CLIC proteins, reveals changes in their enzymatic activity
Publisher: Elsevier BV
Date: 07-2021
Sterol Structural Features' Impact on the Spontaneous Membrane Insertion of CLIC1 into Artificial Lipid Membranes
Publisher: American Chemical Society (ACS)
Date: 23-02-2023
Gold nanoparticles as cell regulators: Beneficial effects of gold nanoparticles on the metabolic profile of mice with pre-existing obesity
Publisher: Springer Science and Business Media LLC
Date: 03-11-2018
Blockade by N‐3 polyunsaturated fatty acid of the Kv4.3 current stably expressed in Chinese hamster ovary cells
Publisher: Wiley
Date: 06-1999
Evidence of the Key Role of H3 O+ in Phospholipid Membrane Morphology
Publisher: American Chemical Society (ACS)
Date: 04-10-2016
DOI: 10.1021/ACS.LANGMUIR.6B01988
Abstract: This study explains the importance of the phosphate moiety and H
A novel family of insect-selective peptide neurotoxins targeting insect large-conductance calcium-activated K+ channels isolated from the venom of the theraphosid spider Eucratoscelus constrictus
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 29-03-2011
Abstract: Spider venoms are actively being investigated as sources of novel insecticidal agents for biopesticide engineering. After screening 37 theraphosid spider venoms, a family of three new "short-loop" inhibitory cystine knot insecticidal toxins (κ-TRTX-Ec2a, κ-TRTX-Ec2b, and κ-TRTX-Ec2c) were isolated and characterized from the venom of the African tarantula Eucratoscelus constrictus. Whole-cell patch-cl recordings from cockroach dorsal unpaired median neurons revealed that, despite significant sequence homology with other theraphosid toxins, these 29-residue peptides lacked activity on insect voltage-activated sodium and calcium channels. It is noteworthy that κ-TRTX-Ec2 toxins were all found to be high-affinity blockers of insect large-conductance calcium-activated K(+) (BK(Ca)) channel currents with IC(50) values of 3 to 25 nM. In addition, κ-TRTX-Ec2a caused the inhibition of insect delayed-rectifier K(+) currents, but only at significantly higher concentrations. κ-TRTX-Ec2a and κ-TRTX-Ec2b demonstrated insect-selective effects, whereas the homologous κ-TRTX-Ec2c also resulted in neurotoxic signs in mice when injected intracerebroventricularly. Unlike other theraphosid toxins, κ-TRTX-Ec2 toxins induce a voltage-independent channel block, and therefore, we propose that these toxins interact with the turret and/or loop region of the external entrance to the channel and do not project deeply into the pore of the channel. Furthermore, κ-TRTX-Ec2a and κ-TRTX-Ec2b differ from other theraphotoxins at the C terminus and positions 5 to 6, suggesting that these regions of the peptide contribute to the phyla selectivity and are involved in targeting BK(Ca) channels. This study therefore establishes these toxins as tools for studying the role of BK(Ca) channels in insects and lead compounds for the development of novel insecticides.
Gramicidin ion channel-based biosensors: Construction, Stochastic dynamical models, and statistical detection algorithms
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 09-2007
Tethered Bilayer Lipid Membranes to Monitor Heat Transfer between Gold Nanoparticles and Lipid Membranes
Publisher: MyJove Corporation
Date: 08-12-2020
DOI: 10.3791/61851
An in vitro study of the effects of exposure to a GSM signal in two human cell lines: Monocytic U937 and neuroblastoma SK-N-SH
Publisher: Wiley
Date: 10-2006
DOI: 10.1016/J.CELLBI.2006.06.001
Abstract: The use of mobile phones is increasing, which also increases the population's exposure to global system of mobile communications (GSM) signals. Questions of safety and possible biological effects are of concern and to date, remain largely unanswered. In order to examine possible biological effects of a GSM-like signal at a cellular level, we exposed two human cell lines (one of neuronal (SK-N-SH) and the other of monocytoid (U937) origin) to a 900 MHz RF signal, pulsed at 217 Hz, producing a specific absorption rate (SAR) of 0.2 W/kg. Putative effects were assessed by comparing radiofrequency-exposed cells to sham-exposed cells using a variety of assay techniques. For the cell line SK-N-SH, effects were specifically assessed by gene microarray, followed by real-time PCR of the genes of interest, Western blot analysis was used to measure heat shock protein levels, and flow cytometry to measure cell cycle distributions and apoptosis. Effects of radiofrequency on the cell line U937 were assessed by cell viability and cell cycle analysis. From our study of these two cell lines, we found no significant difference between sham-exposed versus radiofrequency-exposed cells in any of the assays or conditions examined.
Current Challenges and Opportunities for Improved Cannabidiol Solubility
Publisher: MDPI AG
Date: 25-09-2023
Elucidating the structure and function of S100 proteins in membranes
Publisher: SPIE
Date: 28-12-2006
DOI: 10.1117/12.638873
Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene
Publisher: Wiley
Date: 2010
DOI: 10.1002/DVG.20616
Structural properties of liposomes from digital holographic microscopy
Publisher: SPIE
Date: 28-12-2006
DOI: 10.1117/12.638823
Therapeutic possibilities of plasmonically heated gold nanoparticles
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.TIBTECH.2005.12.004
Abstract: Nanoparticles of gold, which are in the size range 10-100 nm, undergo a plasmon resonance with light. This is a process whereby the electrons of the gold resonate in response to incoming radiation causing them to both absorb and scatter light. This effect can be harnessed to either destroy tissue by local heating or release payload molecules of therapeutic importance. Gold nanoparticles can also be conjugated to biologically active moieties, providing possibilities for targeting to particular tissues. Here, we review the progress made in the exploitation of the plasmon resonance of gold nanoparticles in photo-thermal therapeutic medicine.
Cholesterol promotes interaction of the protein CLIC1 with phospholipid monolayers at the air–water interface
Publisher: MDPI AG
Date: 11-02-2016
Gold Nanoparticles with Organic Linkers for Applications in Biomedicine
Publisher: CRC Press
Date: 03-10-2018
Molecular cloning and expression of a chloride ion channel of cell nuclei
Publisher: Elsevier BV
Date: 05-1997
Preparing Ion Channel Switch Membrane-Based Biosensors
Publisher: Springer US
Date: 02-12-2022
DOI: 10.1007/978-1-0716-1843-1_2
Abstract: Monitoring the changes in membrane conductance using electrical impedance spectroscopy is the platform of membrane-based biosensors in order to detect a specific target molecule. These biosensors represent the amalgamation of an electrical conductor such as gold and a chemically tethered bilayer lipid membrane with specific incorporated ion channels such as gramicidin-A that is further functionalized with detector molecules of interest.
Strontium- and magnesium-enriched biomimetic β-TCP macrospheres with potential for bone tissue morphogenesis
Publisher: Hindawi Limited
Date: 27-07-2014
DOI: 10.1002/TERM.1576
Abstract: During the last two decades, biogenic mineral ions have become important additives in treatments for bone regeneration and repair. Prominent among these is strontium, which is a potent suppressor of osteoclast bone resorption. Another is magnesium, which has a key influence in mineralization processes. The shells of benthic foraminiferans, hydrothermally converted into β-TCP, have been shown to effectively release a number of bone-promoting drugs at clinically relevant levels. In this study we characterized the effects of converted foraminiferan calcium dissolution and the concomitant release profile of intrinsic strontium and magnesium. We tested the effects of strontium- and magnesium-enriched macrospheres on human osteoblast (SaOS-2) and monocytoid (U937) cell lines, which can be induced to express equivalent phagocytic activities to osteoclasts. On dissolution in a biomimetic physiological solution, the macrospheres released biologically significant quantities of calcium and phosphate ions in the first 18 days. At 3 days, during which biogenic mineral ions are released, the number of U937 osteoclast-like monocyte cells decreased, while 4 days later the osteoblast cell number increased. These results show that strontium and magnesium naturally enriched macrospheres are capable of altering the metabolic activities of the cells regulating bone homeostasis. These unique macrospheres are natural origin bone void filler particles that resorb, and release physiologically significant levels of incorporated strontium, magnesium and calcium, which together make a uniquely multifunctional in situ remedy for bone regeneration and repair and the treatment of bone-wasting diseases.
Functionalised gold nanoparticles for controlling pathogenic bacteria
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.TIBTECH.2009.12.004
Abstract: The increasing number of bacterial strains that are resistant to available pharmaceutical compounds is a vital issue for public health. Innovative approaches will be required to improve the methods for both diagnosis and destruction of these organisms. Here, we consider the possible role that can be played by technologies based on gold nanoparticles. Gold nanoparticles generally are considered to be biologically inert but can be engineered to possess chemical or photothermal functionality. A growing body of research is devoted to the potential use of these nanoparticles in the diagnosis and treatment of bacterial infections. The results are both promising and intriguing, and suggest a range of new strategies to identify, target or destroy pathogenic organisms.
Computational Analysis of the Soluble Form of the Intracellular Chloride Ion Channel Protein CLIC1
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/170586
Abstract: The chloride intracellular channel (CLIC) family of proteins has the remarkable property of maintaining both a soluble form and an integral membrane form acting as an ion channel. The soluble form is structurally related to the glutathione-S-transferase family, and CLIC can covalently bind glutathione via an active site cysteine. We report approximately 0.6 μ s of molecular dynamics simulations, encompassing the three possible ligand-bound states of CLIC1, using the structure of GSH-bound human CLIC1. Noncovalently bound GSH was rapidly released from the protein, whereas the covalently ligand-bound protein remained close to the starting structure over 0.25 μ s of simulation. In the unliganded state, conformational changes in the vicinity of the glutathione-binding site resulted in reduced reactivity of the active site thiol. Elastic network analysis indicated that the changes in the unliganded state are intrinsic to the protein architecture and likely represent functional transitions. Overall, our results are consistent with a model of CLIC function in which covalent binding of glutathione does not occur spontaneously but requires interaction with another protein to stabilise the GSH binding site and/or transfer of the ligand. The results do not indicate how CLIC1 undergoes a radical conformational change to form a transmembrane chloride channel but further elucidate the mechanism by which CLICs are redox controlled.
In vitro testing and efficacy of poly-lactic acid coating incorporating antibiotic loaded coralline bioceramic on Ti6Al4V implant against Staphylococcus aureus
Publisher: Hindawi Limited
Date: 07-10-2022
DOI: 10.1002/TERM.3353
Abstract: Biofilm formation on an implant surface is most commonly caused by the human pathogenic bacteria Staphylococcus aureus, which can lead to implant related infections and failure. It is a major problem for both implantable orthopedic and maxillofacial devices. The current antibiotic treatments are typically delivered orally or in an injectable form. They are not highly effective in preventing or removing biofilms, and they increase the risk of antibiotic resistance of bacteria and have a dose-dependent negative biological effect on human cells. Our aim was to improve current treatments via a localized and controlled antibiotic delivery-based implant coating system to deliver the antibiotic, gentamicin (Gm). The coating contains coral skeleton derived hydroxyapatite powders (HAp) that act as antibiotic carrier particles and have a biodegradable poly-lactic acid (PLA) thin film matrix. The system is designed to prevent implant related infections while avoiding the deleterious effects of high concentration antibiotics in implants on local cells including primary human adipose derived stem cells (ADSCs). Testing undertaken in this study measured the rate of S. aureus biofilm formation and determined the growth rate and proliferation of ADSCs. After 24 h, S. aureus biofilm formation and the percentage of live cells found on the surfaces of all 5%-30% (w/w) PLA-Gm-(HAp-Gm) coated Ti6Al4V implants was lower than the control s les. Furthermore, Ti6Al4V implants coated with up to 10% (w/w) PLA-Gm-(HAp-Gm) did not have noticeable Gm related adverse effect on ADSCs, as assessed by morphological and surface attachment analyses. These results support the use and application of the antibacterial PLA-Gm-(HAp-Gm) thin film coating design for implants, as an antibiotic release control mechanism to prevent implant-related infections.
Elucidating the Mechanism for Sterol Regulation of Chloride Intracellular Ion Channel Protein Interactions with Lipid Membranes
Publisher: Elsevier BV
Date: 02-2016
Investigating Sterol and Redox Regulation of the Ion Channel Activity of CLIC1 Using Tethered Bilayer Membranes
Publisher: MDPI AG
Date: 08-12-2016
High order accurate dual-phase-lag numerical model for microscopic heating in multiple domains
Publisher: Elsevier BV
Date: 11-2016
Novel Intra- and Inter-molecular Sulfinamide Bonds in S100A8 Produced by Hypochlorite Oxidation
Publisher: Elsevier BV
Date: 09-2001
Soluble Structure of CLIC and S100 Proteins Investigated by Atomic Force Microscopy
Publisher: Scientific Research Publishing, Inc.
Date: 2011
Antibiotic delivery potential of nano-and micro-porous marine structure-derived β-tricalcium phosphate spheres for medical applications
Publisher: Future Medicine Ltd
Date: 06-2014
DOI: 10.2217/NNM.13.116
Abstract: Aims: This study gives a detailed evaluation of the antibiotic potential of a marine structure-based new drug delivery system produced by hydrothermally converting foraminifera exoskeletons to β-tricalcium phosphate (β-TCP) to treat clinical strain Staphylococcus aureus (MW2). Materials & methods: Foraminifera precursor materials were hydrothermally converted at 250°C for 48 h to produce β-TCP and loaded with gentamicin sulfate by adsorption for 24 h. The physicochemical properties of the material were characterized by scanning electron microscopy, powder x-ray diffraction and for pore size distribution profiles. The antibacterial efficacy of the system was tested for inhibition of S. aureus growth and in vitro cellular behavior were tested with human osteoblast cells (MG63) for cell viability. Discussion: Pore size distribution profiles showed that the structure allows the uniform distribution of nanopores of 1.5 nm and micropores of approximately 5 µm. The in vitro release profile indicates an initial burst release of 5% of total incorporated gentamicin. A time-delayed antibacterial efficacy test was designed to introduce the bacteria at predetermined time intervals from 0 to 60 min and showed that gentamicin prevents S. aureus grown in the same culture within 30 min, with no evidence of bacterial regrowth within 24 h. Human osteoblast cell (MG63) studies showed no detrimental effect on cell viability. Conclusion: In the light of these results nano- and micro-pores containing β-TCP spheres show promise as potential bone void filler particles with antibacterial effects. Original submitted 7 February 2013 Revised submitted 9 May 2013
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