ORCID Profile
0000-0003-3608-5440
Current Organisation
University of Technology Sydney
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Medical Biotechnology | Biomedical Instrumentation | Medical Biotechnology Diagnostics (incl. Biosensors) | Biomaterials | Biomedical Engineering
Diagnostic Methods | Expanding Knowledge in the Chemical Sciences | Scientific Instruments | Expanding Knowledge in the Biological Sciences | Veterinary Diagnostics |
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.EJMECH.2017.10.066
Abstract: Antimicrobial peptides (AMPs) and their synthetic mimics have received recent interest as new alternatives to traditional antibiotics in attempts to overcome the rise of antibiotic resistance in many microbes. AMPs are part of the natural defenses of most living organisms and they also have a unique mechanism of action against bacteria. Herein, a new series of short hiphilic cationic peptidomimetics were synthesized by incorporating the 3'-amino-[1,1'-biphenyl]-3-carboxylic acid backbone to mimic the essential properties of natural AMPs. By altering hydrophobicity and charge, we identified the most potent analogue 25g that was active against both Gram-positive Staphylococcus aureus (MIC = 15.6 μM) and Gram-negative Escherichia coli (MIC = 7.8 μM) bacteria. Cytoplasmic permeability assay results revealed that 25g acts primarily by depolarization of lipids in cytoplasmic membranes. The active compounds were also investigated for their cytotoxicity to human cells, lysis of lipid bilayers using tethered bilayer lipid membranes (tBLMs) and their activity against established biofilms of S. aureus and E. coli.
Publisher: Humana Press
Date: 07-11-2013
DOI: 10.1007/978-1-62703-245-2_23
Abstract: Ion channel studies have been focused on ion channels from animal and human cells over many years. Based on the knowledge acquired, predominantly over the last 20 years, a large ersity of ion channels exists in cellular membranes of prokaryotes as well. Paradoxically, most of what is known about the structure of eukaryotic ion channels is based on the structure of bacterial channels. This is largely due to the suitability of bacterial cells for functional and structural studies of biological macromolecules in a laboratory environment. Development of the "giant spheroplast" preparation from E. coli cells was instrumental for functional studies of ion channels in the bacterial cell membrane. Here we describe detailed protocols used for the preparation of giant spheroplasts as well as protocols used for the patch-cl recording of native or heterologously expressed ion channels in E. coli spheroplast membrane.
Publisher: Springer Science and Business Media LLC
Date: 24-06-2021
Publisher: Wiley
Date: 30-10-2000
DOI: 10.1002/9780470027318.A9354
Abstract: Fluorescence spectroscopy has, over the last two decades, been frequently used for studies of biological cells and their molecular components. In combination with molecular biological methods that allow introduction of fluorescent labeling in vivo and in vitro , fluorescence spectroscopy methods, such as Förster resonance energy transfer ( FRET ), have made membrane proteins accessible to studies of their molecular structure and dynamics. In this article, we describe a variety of fluorescence spectroscopy techniques and focus on their use in the studies of the physiological role ion channels play, and the conformational rearrangements involved in the gating of ion channels, whose function as gated membrane pores underlies numerous cellular processes essential for the survival of living cells and organisms.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.TOXICON.2018.11.432
Abstract: Microcystin-LR (MC-LR) is a potent cyanobacterial toxin responsible for animal and human poisonings worldwide. MC-LR is found in organisms throughout the foodweb, however there is conjecture regarding whether it biomagnifies. Few studies have investigated how MC-LR interacts with lipid membranes, a determinant of biomagnification potential. We tested whether 1 μM MC-LR irreversibly associates with lipid bilayers or causes the creation of pore defects upon short and long-term exposure. Using tethered bilayer lipid membranes (tBLMs), we observed an increase in membrane conduction in tBLMs, representing an interaction of microcystin-LR with the lipid bilayer and a change in membrane packing properties. However, there were minimal changes in membrane capacitance upon short and long-term exposure, and MC-LR exhibited a rapid off-rate. Upon 24 h exposure to the toxin, no lipophilic multimeric complexes were detected capable of altering the toxin's off-rate. There was no evidence of the creation of new pores. This study demonstrates that MC-LR does not irreversibly imbed itself into lipids membranes after short or long-term exposure and suggests MC-LR does not biomagnify through the food web via lipid storage.
Publisher: Springer New York
Date: 22-09-2015
DOI: 10.1007/978-1-4939-1752-5_4
Abstract: Because they are firmly held in place, tethered bilayer lipid membranes (tBLMs) are considerably more robust than supported lipid bilayers such as black lipid membranes (BLMs) (Cornell et al. Nature 387(6633): 580-583, 1997). Here we describe the procedures required to assemble and test tethered lipid bilayers that can incorporate various lipid species, peptides, and ion channel proteins.
Publisher: Public Library of Science (PLoS)
Date: 13-10-2016
Publisher: Springer Netherlands
Date: 2012
Publisher: Elsevier BV
Date: 07-2022
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7CP06776C
Abstract: This work studies the mechanisms by which hydronium ions modulate the structure of phospholipid bilayers.
Publisher: Elsevier BV
Date: 2013
Publisher: Wiley
Date: 24-04-2017
Publisher: MDPI AG
Date: 21-12-2022
DOI: 10.3390/IJMS24010067
Abstract: The Na+, K+-ATPase is an integral membrane protein which uses the energy of ATP hydrolysis to pump Na+ and K+ ions across the plasma membrane of all animal cells. It plays crucial roles in numerous physiological processes, such as cell volume regulation, nutrient reabsorption in the kidneys, nerve impulse transmission, and muscle contraction. Recent data suggest that it is regulated via an electrostatic switch mechanism involving the interaction of its lysine-rich N-terminus with the cytoplasmic surface of its surrounding lipid membrane, which can be modulated through the regulatory phosphorylation of the conserved serine and tyrosine residues on the protein’s N-terminal tail. Prior data indicate that the kinases responsible for phosphorylation belong to the protein kinase C (PKC) and Src kinase families. To provide indications of which particular enzyme of these families might be responsible, we analysed them for evidence of coevolution via the mirror tree method, utilising coevolution as a marker for a functional interaction. The results obtained showed that the most likely kinase isoforms to interact with the Na+, K+-ATPase were the θ and η isoforms of PKC and the Src kinase itself. These theoretical results will guide the direction of future experimental studies.
Publisher: Springer Science and Business Media LLC
Date: 15-09-2018
Publisher: Springer Science and Business Media LLC
Date: 02-2022
Publisher: American Chemical Society (ACS)
Date: 19-07-2022
DOI: 10.1021/ACSCHEMBIO.1C00807
Abstract: Targeting the cancer cell mitochondrion is a promising approach for developing novel anticancer agents. The experimental anticancer agent
Publisher: SPIE-Intl Soc Optical Eng
Date: 2007
DOI: 10.1117/1.2756102
Abstract: The development of miniaturized nonlinear optical microscopy or endoscopy is essential to complement the current imaging modalities for diagnosis and monitoring of cancers. We report on a nonlinear optical endoscope based on a double-clad photonic crystal fiber and a two-dimensional (2-D) microelectromechanical system mirror, enabling the three-dimensional (3-D) nonlinear optical imaging through in vitro gastrointestinal tract tissue and human breast cancer tissue with a penetration depth of approximately 100 mum and axial resolution of 10 mum. The 3-D high-resolution and high-sensitive imaging ability of the nonlinear optical endoscope facilitates the visualization of 3-D morphologic and cell nuclei arrangement within tissue, and therefore will be important for histopathologic interpretation without the need of tissue excision.
Publisher: Springer Berlin Heidelberg
Date: 2013
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9SC05686F
Abstract: The mobility of hydrophobic moieties at a peptide nanofibre surface determines its suitability as a scaffold for sensitive primary cells.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2SM00272H
Abstract: Extremely small shifts in pH could have impacted the ability of fatty-acid-based primitive cells to thrive, with survival under osmotic stress and the ability to retain encapsulated material severely impacted at higher pHs.
Publisher: Research Square Platform LLC
Date: 05-07-2022
DOI: 10.21203/RS.3.RS-1772694/V1
Abstract: Cardiovascular disease (CVD) is a leading cause of mortality worldwide, with cigarette smoking being a major preventable risk factor. Smoking cessation can be difficult due to the addictive nature of nicotine and the withdrawal symptoms following cessation. Electronic cigarettes (e-Cigs) have emerged as an alternative smoking cessation device, which has been increasingly used by non-smokers however, the cardiovascular effects surrounding the use of e-Cigs remains unclear. This study aimed to investigate the effects of e-Cig aerosol condensate (EAC) (0mg and 18mg nicotine) in-vitro on human coronary artery endothelial cells (HCAEC) and in-vivo on the cardiovascular system using a mouse model of ‘e-vaping’. The results show a decrease in cell viability of HCAEC when exposed to EAC either directly or after exposure to conditioned lung cell media ( p 0.005). Reactive oxygen species and ICAM-1 expression were increased in HCAEC when exposed to EAC directly ( p 0.0005). ICAM-1 mRNA expression was increased (18mg vs control, p 0.05), and immunostaining revealed upregulated anti-angiogenic markers, FKBPL, and endothelial cell marker, CD31, in murine hearts following exposure to electronic cigarette aerosol treatment. This study showed that even though e-Cigs are widely used for tobacco smoking cessation, these can negatively impact on endothelial cell health with a potential to lead to the development of cardiovascular disease. This process is visualised in Supplementary File 1.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2019
Publisher: Proceedings of the National Academy of Sciences
Date: 14-05-2012
Abstract: Mechanosensitive (MS) channels of small (MscS) and large (MscL) conductance are the major players in the protection of bacterial cells against hypoosmotic shock. Although a great deal is known about structure and function of these channels, much less is known about how membrane lipids may influence their mechanosensitivity and function. In this study, we use liposome coreconstitution to examine the effects of different types of lipids on MscS and MscL mechanosensitivity simultaneously using the patch-cl technique and confocal microscopy. Fluorescence lifetime imaging (FLIM)-FRET microscopy demonstrated that coreconstitution of MscS and MscL led to clustering of these channels causing a significant increase in the MscS activation threshold. Furthermore, the MscL/MscS threshold ratio dramatically decreased in thinner compared with thicker bilayers and upon addition of cholesterol, known to affect the bilayer thickness, stiffness and pressure profile. In contrast, application of micromolar concentrations of lysophosphatidylcholine (LPC) led to an increase of the MscL/MscS threshold ratio. These data suggest that differences in hydrophobic mismatch and bilayer stiffness, change in transbilayer pressure profile, and close proximity of MscL and MscS affect the structural dynamics of both channels to a different extent. Our findings may have far-reaching implications for other types of ion channels and membrane proteins that, like MscL and MscS, may coexist in multiple molecular complexes and, consequently, have their activation characteristics significantly affected by changes in the lipid environment and their proximity to each other.
Publisher: OSA
Date: 2006
DOI: 10.1364/BIO.2006.WF1
Publisher: IOP Publishing
Date: 21-12-2009
DOI: 10.1088/0957-4484/21/5/055501
Abstract: In this study, we describe the design of new ratiometric fluorescent nanosensors, whose architecture is based on a gold core surrounded by a poly(vinyl alcohol)-polyacetal shell. To the gold core, indicator dyes and reference dyes are attached via a cysteine linker. This nanosensor architecture is flexible with regards to the number and types of fluorophore linkages possible. The robust poly(vinyl alcohol)-polyacetal shell protects the fluorophores linked to the core from non-specific interactions with intracellular proteins. The nanosensors developed in this way are biocompatible and can be easily incorporated into mammalian cells without the use of transfection agents. Here, we show the application of these nanosensors for intracellular pH and sodium ion measurements.
Publisher: Oxford University Press (OUP)
Date: 28-08-2019
Abstract: Maternal smoking is currently a public health concern and has been associated with a number of complications in the offspring. E-cigarettes are gaining popularity as a “safer” alternative to tobacco cigarettes during pregnancy, however, there are a limited number of studies to suggest that it is actually “safe.” Balb/C female mice were exposed to ambient air (n = 8 Sham), or tobacco cigarette smoke (n = 8 SE) before gestation, during gestation and lactation. A third group was exposed to cigarette smoke before gestation followed by e-cigarette aerosols during gestation and lactation (n = 8 Switch). Male offspring (12-week old, n = 10–14/group) underwent behavioral assessments to investigate short-term memory, anxiety, and activity using the novel object recognition and elevated plus maze tests. Brains were collected at postnatal day (P)1, P20, and Week 13 for global DNA methylation, epigenetic gene expression, and neuronal cell counts. The offspring from mothers switching to e-cigarettes exhibited no change in exploration/activity but showed a decrease in global DNA methylation, Aurora Kinase (Aurk) A and AurkB gene expression and a reduction in neuronal cell numbers in the cornu ammonis 1 region of the dorsal hippoc us compared with the SE group. Continuous tobacco cigarette smoke exposure during pregnancy resulted in marked neurological deficits in the offspring. Switching to e-cigarettes during pregnancy reduced these neurological deficits compared with cigarette smoke exposure. However, neurological changes were still observed, so we therefore conclude that e-cigarette use during pregnancy is not advised.
Publisher: Elsevier BV
Date: 2012
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 09-2014
Publisher: CRC Press
Date: 24-10-2014
DOI: 10.1201/B17566-38
Publisher: Elsevier BV
Date: 2014
Publisher: SPIE
Date: 11-02-2010
DOI: 10.1117/12.849742
Publisher: MDPI AG
Date: 19-11-2020
DOI: 10.3390/IJMS21228745
Abstract: Statins are a class of drugs used to lower low-density lipoprotein cholesterol and are amongst the most prescribed medications worldwide. Most statins work as a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), but statin intolerance from pleiotropic effects have been proposed to arise from non-specific binding due to poor enzyme-ligand sensitivity. Yet, research into the physicochemical properties of statins, and their interactions with off-target sites, has not progressed much over the past few decades. Here, we present a concise perspective on the role of statins in lowering serum cholesterol levels, and how their reported interactions with phospholipid membranes offer a crucial insight into the mechanism of some of the more commonly observed pleiotropic effects of statin administration. Lipophilicity, which governs hepatoselectivity, is directly related to the molecular structure of statins, which dictates interaction with and transport through membranes. The structure of statins is therefore a clinically important consideration in the treatment of hypercholesterolaemia. This review integrates the recent biophysical studies of statins with the literature on the physiological effects and provides new insights into the mechanistic cause of statin pleiotropy, and prospective means of understanding the cholesterol-independent effects of statins.
Publisher: American Chemical Society (ACS)
Date: 08-07-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7OB00053G
Abstract: Novel antibacterial peptidomimetics that inhibit the growth of planktonic cells and reduce biofilm formation in both Gram-positive and Gram-negative bacteria.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0SM00320D
Abstract: The incorporation of polar amino acids into the Fmoc-FF motif yields tetrapeptide hydrogels whose biocompatibility in the gel state is inversely proportional to their biocompatibility in the solution state.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2OB02049A
Abstract: Aryl-carbamate substituted fatty acids are protonophores that uncouple mitochondrial oxidative phosphorylation. The proton transport cycle requires self-assembly into membrane permeable dimers. The findings demonstrate the anion transport capability of the carbamate group.
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
Publisher: Mary Ann Liebert Inc
Date: 20-02-2014
Abstract: Sensations of touch and hearing are manifestations of mechanical contact and air pressure acting on touch receptors and hair cells of the inner ear, respectively. In bacteria, osmotic pressure exerts a significant mechanical force on their cellular membrane. Bacteria have evolved mechanosensitive (MS) channels to cope with excessive turgor pressure resulting from a hypo-osmotic shock. MS channel opening allows the expulsion of osmolytes and water, thereby restoring normal cellular turgor and preventing cell lysis. As biological force-sensing systems, MS channels have been identified as the best ex les of membrane proteins coupling molecular dynamics to cellular mechanics. The bacterial MS channel of large conductance (MscL) and MS channel of small conductance (MscS) have been subjected to extensive biophysical, biochemical, genetic, and structural analyses. These studies have established MscL and MscS as model systems for mechanosensory transduction. In recent years, MS ion channels in mammalian cells have moved into focus of mechanotransduction research, accompanied by an increased awareness of the role they may play in the pathophysiology of diseases, including cardiac hypertrophy, muscular dystrophy, or Xerocytosis. A recent exciting development includes the molecular identification of Piezo proteins, which function as nonselective cation channels in mechanosensory transduction associated with senses of touch and pain. Since research on Piezo channels is very young, applying lessons learned from studies of bacterial MS channels to establishing the mechanism by which the Piezo channels are mechanically activated remains one of the future challenges toward a better understanding of the role that MS channels play in mechanobiology.
Publisher: American Chemical Society (ACS)
Date: 20-07-2020
Publisher: Elsevier BV
Date: 2014
Publisher: Elsevier BV
Date: 10-2023
Publisher: Hindawi Limited
Date: 2006
Abstract: A study demonstrating how ultrafast laser radiation stimulates osteoblasts is presented. The study employed a custom made optical system that allowed for simultaneous confocal cell imaging and targeted femtosecond pulse laser irradiation. When femtosecond laser light was focused onto a single cell, a rise in intracellular Ca 2 + levels was observed followed by contraction of the targeted cell. This contraction caused deformation of neighbouring cells leading to a heterogeneous strain field throughout the monolayer. Quantification of the strain fields in the monolayer using digital image correlation revealed local strains much higher than threshold values typically reported to stimulate extracellular bone matrix production in vitro. This use of point targeting with femtosecond pulse lasers could provide a new method for stimulating cell activity in orthopaedic tissue engineering.
Publisher: Hindawi Limited
Date: 2006
Abstract: We have demonstrated a combined imaging system, where the physiology of biological specimens can be imaged and profiled at 10–20 frames per second whilst undergoing femtosecond laser irradiation. In idual GH3 cells labeled with the calcium fluorophore Fluo-3 were stimulated using a counter-propagating focused femtosecond beam with respect to the imaging system. As a result of the stimulation, calcium waves can be generated in COS cells, and laser-induced calcium oscillations are initiated in the GH3 cells. Single-photon fluorescence images and intensity profiles of the targeted specimens are s led in real-time using a modified PerkinElmer UltraView LCI microscope.
Publisher: MDPI AG
Date: 21-04-2022
DOI: 10.3390/IJMS23094623
Abstract: There is a significant and urgent need for the development of novel antibacterial agents to tackle the increasing incidence of antibiotic resistance. Cholic acid-based small molecular antimicrobial peptide mimics are reported as potential new leads to treat bacterial infection. Here, we describe the design, synthesis and biological evaluation of cholic acid-based small molecular antimicrobial peptide mimics. The synthesis of cholic acid analogues involves the attachment of a hydrophobic moiety at the carboxyl terminal of the cholic acid scaffold, followed by the installation of one to three amino acid residues on the hydroxyl groups present on the cholic acid scaffold. Structure–activity relationship studies suggest that the tryptophan moiety is important for high antibacterial activity. Moreover, a minimum of +2 charge is also important for antimicrobial activity. In particular, analogues containing lysine-like residues showed the highest antibacterial potency against Gram-positive S. aureus. All di-substituted analogues possess high antimicrobial activity against both Gram-positive S. aureus as well as Gram-negative E. coli and P. aeruginosa. Analogues 17c and 17d with a combination of these features were found to be the most potent in this study. These compounds were able to depolarise the bacterial membrane, suggesting that they are potential antimicrobial pore forming agents.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2019
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 09-2003
Abstract: The interaction of mobile phone RF emissions with biogenic magnetite in the human brain has been proposed as a potential mechanism for mobile phone bioeffects. This is of particular interest in light of the discovery of magnetite in human brain tissue. Previous experiments using magnetite-containing bacteria exposed directly to emissions from a mobile phone have indicated that these emissions might be causing greater levels of cell death in these bacterial populations when compared to sham exposures. A repeat of these experiments examining only the radio frequency (RF) global system for mobile communication (GSM) component of the mobile phone signal in a well-defined waveguide system (REFLEX), shows no significant change in cell mortality compared to sham exposures. A nonmagnetite containing bacterial cell strain (CC-26) with similar genotype and phenotype to the magnetotactic bacteria was used as a control. These also showed no significant change in cell mortality between RF and sham exposed s les. Results indicate that the RF components of mobile phone exposure do not appear to be responsible for previous findings indicating cell mortality as a result of direct mobile phone exposure. A further mobile phone emission component that should be investigated is the 2-Hz magnetic field pulse generated by battery currents during periods of discontinuous transmission.
Publisher: MDPI AG
Date: 16-09-2020
DOI: 10.3390/IJMS21186789
Abstract: There has been an increasing interest in the development of antimicrobial peptides (AMPs) and their synthetic mimics as a novel class of antibiotics to overcome the rapid emergence of antibiotic resistance. Recently, phenylglyoxamide-based small molecular AMP mimics have been identified as potential leads to treat bacterial infections. In this study, a new series of biphenylglyoxamide-based small molecular AMP mimics were synthesised from the ring-opening reaction of N-sulfonylisatin bearing a biphenyl backbone with a diamine, followed by the conversion into tertiary ammonium chloride, quaternary ammonium iodide and guanidinium hydrochloride salts. Structure–activity relationship studies of the analogues identified the octanesulfonyl group as being essential for both Gram-positive and Gram-negative antibacterial activity, while the biphenyl backbone was important for Gram-negative antibacterial activity. The most potent analogue was identified to be chloro-substituted quaternary ammonium iodide salt 15c, which possesses antibacterial activity against both Gram-positive (MIC against Staphylococcus aureus = 8 μM) and Gram-negative bacteria (MIC against Escherichia coli = 16 μM, Pseudomonas aeruginosa = 63 μM) and disrupted 35% of pre-established S. aureus biofilms at 32 μM. Cytoplasmic membrane permeability and tethered bilayer lipid membranes (tBLMs) studies suggested that 15c acts as a bacterial membrane disruptor. In addition, in vitro toxicity studies showed that the potent compounds are non-toxic against human cells at therapeutic dosages.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0SC02777D
Abstract: A new mitochondrial uncoupler that forms membrane permeable dimers through interactions of remote acidic and anion receptor groups.
Publisher: Elsevier BV
Date: 02-2023
Publisher: Elsevier BV
Date: 02-2021
Publisher: CRC Press
Date: 14-10-2014
DOI: 10.1201/B17566-46
Publisher: MyJove Corporation
Date: 08-12-2020
DOI: 10.3791/61851
Publisher: Wiley
Date: 10-02-2019
DOI: 10.1002/ECE3.4962
Publisher: Elsevier BV
Date: 03-2021
Publisher: Informa UK Limited
Date: 2001
DOI: 10.1080/09553000110083960
Abstract: To test whether exposure to simulated GSM mobile phone signals (915 MHz, 2 W x kg(-1)) influences the concentration of calcium or calcium signalling patterns in a human lymphocyte cell line. The radiofrequency (RF) energy was delivered via a coaxial applicator to a perfused chamber where cells adherent to a thin glass coverslip were imaged by laser scanning confocal microscopy. Cell calcium concentration, estimated from Fluo-3 fluorescence, was monitored over two 10-min periods control followed by exposed/sham, with exposure status assigned in a blind and randomized fashion. Both continuous wave (CW) and pulsed wave (PW) RF (on both phytohaemagglutanin-activated and unactivated cells) were studied (with an equal number of sham exposures) on 100 cells per category (total 800 cells). No significant changes were noted for the following: regression slope of calcium fluorescence mean calcium concentration number of calcium 'spikes' in each 10 min or mean height of these 'spikes'. The average frequency from Fourier spectra of these periods showed significant alteration in one category only: PW exposure of activated cells. There is no clear indication that RF emissions from mobile phones are associated with any changes in calcium levels or calcium signalling in lymphocytes.
Publisher: American Chemical Society (ACS)
Date: 21-06-2017
DOI: 10.1021/ACS.LANGMUIR.7B01642
Abstract: Cyclotides are cyclic disulfide-rich peptides that are chemically and thermally stable and possess pharmaceutical and insecticidal properties. The activities reported for cyclotides correlate with their ability to target phosphatidylethanolamine (PE)-phospholipids and disrupt cell membranes. However, the mechanism by which this disruption occurs remains unclear. In the current study we examine the effect of the prototypic cyclotides, kalata B1 (kB1) and kalata B2 (kB2), on tethered lipid bilayer membranes (tBLMs) using swept frequency electrical impedance spectroscopy. We confirmed that kB1 and kB2 bind to bilayers only if they contain PE-phospholipids. We hypothesize that the increase in membrane conduction and capacitance observed upon addition of kB1 or kB2 is unlikely to result from ion channel like pores but is consistent with the formation of lipidic toroidal pores. This hypothesis is supported by the concentration dependence of effects of kB1 and kB2 being suggestive of a critical micelle concentration event rather than a progressive increase in conduction arising from increased channel insertion. Additionally, conduction behavior is readily reversible when the peptide is rinsed from the bilayer. Our results support a mechanism by which kB1 and kB2 bind to and disrupt PE-containing membranes by decreasing the overall membrane critical packing parameter, as would a surfactant, which then opens or increases the size of existing membrane defects. The cyclotides need not participate directly in the conductive pore but might exert their effect indirectly through altering membrane packing constraints and inducing purely lipidic conductive pores.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Springer US
Date: 02-12-2021
DOI: 10.1007/978-1-0716-1843-1_7
Abstract: Swept frequency electrical impedance spectroscopy (EIS) can be used in conjunction with tethered bilayer lipid membranes to monitor the membrane permeability of ions in real-time (Deplazes et al. J Phys Chem Lett 11:6353-6358, 2020). Conductance readings, as determined by EIS, are a measure of the ability of ions to be transported across membranes. Recording the change in conductance as a function of cation concentration and a comparison between a range of cations permits conclusions to be made about the specificity of cation transport through pores. An estimate for upper pore size and cation selectivity of ion channels can be established using this method.
Publisher: CRC Press
Date: 24-10-2014
DOI: 10.1201/B17566
Publisher: Springer Science and Business Media LLC
Date: 20-01-2016
DOI: 10.1038/SREP19352
Abstract: Mutation, irregular expression and sustained activation of the Transient Receptor Potential Channel, type Melastatin 4 (TRPM4), have been linked to various cardiovascular diseases. However, much remains unknown about the structure of this important ion channel. Here, we have purified a heterologously expressed TRPM4-eGFP fusion protein and investigated the oligomeric state of TRPM4-eGFP in detergent micelles using crosslinking, native gel electrophoresis, multi-angle laser light scattering and electron microscopy. Our data indicate that TRPM4 is tetrameric, like other TRP channels studied to date. Furthermore, the functionality of liposome reconstituted TRPM4-eGFP was examined using electrophysiology. Single-channel recordings from TRPM4-eGFP proteoliposomes showed inhibition of the channel using Flufenamic acid, a well-established inhibitor of TRPM4, suggesting that the channels are functional upon reconstitution. Our characterisation of the oligomeric structure of TRPM4 and the ability to reconstitute functional channels in liposomes should facilitate future studies into the structure, function and pharmacology of this therapeutically relevant channel.
Publisher: Springer US
Date: 02-12-2022
DOI: 10.1007/978-1-0716-1843-1_3
Abstract: Because they are firmly anchored to a noble metal substrate, tethered bilayer lipid membranes (tBLMs) are considerably more robust than supported lipid bilayers such as black lipid membranes (BLMs) (Cranfield et al. Biophys J 106:182-189, 2014). The challenge to rapidly create asymmetrical tBLMs that include a lipopolysaccharide outer leaflet for bacterial model membrane research can be overcome by the use of a Langmuir-Schaefer deposition protocol. Here, we describe the procedures required to assemble and test asymmetric lipopolysaccharide (LPS) tethered lipid bilayers.
Publisher: Springer Berlin Heidelberg
Date: 2018
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.
Publisher: American Chemical Society (ACS)
Date: 18-12-2014
DOI: 10.1021/LA504057Z
Abstract: The nanoscale spacing between a tethered lipid bilayer membrane (tBLM) and its supporting gold electrode can be utilized to determine the polarity selectivity of the conduction of ion channels and ion carriers embedded in a membrane. The technique relies upon a bias voltage sequestering or eliminating ions, of a particular polarity, into or out of the aqueous electrolyte region between the gold electrode and the tethered membrane. A demonstration is given, using ac swept frequency impedance spectrometry, of the bias polarity dependence of the ionophore conductance of gramicidin A, a cationic selective channel, and valinomycin, a potassium ion selective carrier. We further use pulsed erometry to show that the intrinsic voltage dependence of the ion conduction is actually selective of the polarity of the transported ion and not simply of the direction of the ionic current flow.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6OB00298F
Abstract: The synthesis of novel glyoxamide-based antimicrobial peptide mimics is described.
Publisher: The Royal Society
Date: 07-12-2004
Publisher: Optica Publishing Group
Date: 06-02-2006
DOI: 10.1364/OE.14.001027
Abstract: Two-photon fluorescence and second harmonic generation microscopy have enabled functional and morphological in vivo imaging. However, in vivo applications of those techniques to living animals are limited by bulk optics on a bench top. Fortunately, growing functionality of fiber-optic devices and miniaturization of scanning mirrors stimulate the race to develop nonlinear optical endoscopy. In this paper, we report on a prototype of a nonlinear optical endoscope based on a double-clad photonic crystal fiber to improve the detection efficiency and a MEMS mirror to steer the light at the fiber tip. The miniaturized fiber-optic nonlinear microscope is characterized by rat esophagus imaging. Line profiles from the rat tail tendon and esophagus prove the potential of the technology in in vivo applications.
Publisher: MDPI AG
Date: 28-03-2023
DOI: 10.3390/IJMS24076378
Abstract: Cardiovascular disease (CVD) is a leading cause of mortality worldwide, with cigarette smoking being a major preventable risk factor. Smoking cessation can be difficult due to the addictive nature of nicotine and the withdrawal symptoms following cessation. Electronic cigarettes (e-Cigs) have emerged as an alternative smoking cessation device, which has been increasingly used by non-smokers however, the cardiovascular effects surrounding the use of e-Cigs remains unclear. This study aimed to investigate the effects of e-Cig aerosol condensate (EAC) (0 mg and 18 mg nicotine) in vitro on human coronary artery endothelial cells (HCAEC) and in vivo on the cardiovascular system using a mouse model of ‘e-vaping’. In vitro results show a decrease in cell viability of HCAEC when exposed to EAC either directly or after exposure to conditioned lung cell media (p 0.05 vs. control). Reactive oxygen species were increased in HCAEC when exposed to EAC directly or after exposure to conditioned lung cell media (p 0.0001 vs. control). ICAM-1 protein expression levels were increased after exposure to conditioned lung cell media (18 mg vs. control, p 0.01). Ex vivo results show an increase in the mRNA levels of anti-angiogenic marker, FKBPL (p 0.05 vs. sham), and endothelial cell adhesion molecule involved in barrier function, ICAM-1 (p 0.05 vs. sham) in murine hearts following exposure to electronic cigarette aerosol treatment containing a higher amount of nicotine. Immunohistochemistry also revealed an upregulation of FKBPL and ICAM-1 protein expression levels. This study showed that despite e-Cigs being widely used for tobacco smoking cessation, these can negatively impact endothelial cell health with a potential to lead to the development of cardiovascular disease.
Publisher: American Chemical Society (ACS)
Date: 09-09-2020
Publisher: Elsevier BV
Date: 02-2021
Publisher: MDPI AG
Date: 30-01-2019
DOI: 10.3390/ANTIBIOTICS8010012
Abstract: This review identifies the ways in which tethered bilayer lipid membranes (tBLMs) can be used for the identification of the actions of antimicrobials against lipid bilayers. Much of the new research in this area has originated, or included researchers from, the southern hemisphere, Australia and New Zealand in particular. More and more, tBLMs are replacing liposome release assays, black lipid membranes and patch-cl electrophysiological techniques because they use fewer reagents, are able to obtain results far more quickly and can provide a uniformity of responses with fewer artefacts. In this work, we describe how tBLM technology can and has been used to identify the actions of numerous antimicrobial agents.
Publisher: American Chemical Society (ACS)
Date: 04-06-2018
DOI: 10.1021/ACS.CHEMRESTOX.8B00084
Abstract: Electronic cigarette (e-cigarette) use is on the rise worldwide and is particularly attractive to young people and as a smoking substitute by pregnant woman. There is a perception in pregnant women and women of child-bearing age that the use of e-cigarettes (vaping) is safer than smoking tobacco cigarettes during pregnancy. However, there is little evidence to support this perception. Here, we examined the offspring from mouse dams that had been exposed during and after pregnancy to ambient air (sham) ( n = 8), e-cigarette aerosols with nicotine ( n = 8), or e-cigarette aerosols without nicotine ( n = 8). Offspring underwent cognitive testing at 12 weeks of age and epigenetic testing of brain tissues at 1 day, 20 days, and 13 weeks after birth. The findings showed deficits in short-term memory, reduced anxiety, and hyperactivity in offspring following maternal e-cigarette exposure using the novel object recognition and elevated plus maze tests. In addition, global DNA methylation was increased in the brains of offspring soon after birth. Using a quantitative-PCR array specific to chromatin modification enzymes on genomic DNA and histones,13 key genes were identified to be significantly altered in the offspring brains from the e-cigarette groups compared to the nonexposed groups. The changes to genes Aurka, Aurkb, Aurkc, Kdm5c, Kdm6b, Dnmt3a, Dnmt3b, and Atf2, all associated with modulating neurological activity, were validated using RT-qPCR. In conclusion, in a mouse model, maternal exposure to e-cigarette aerosols resulted in both cognitive and epigenetic changes in offspring. This suggests that the use of e-cigarettes during pregnancy may have hitherto undetected neurological consequences on newborns.
Publisher: American Chemical Society (ACS)
Date: 16-11-2021
DOI: 10.1021/ACS.LANGMUIR.1C02016
Abstract: Calcium ions (Ca
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 03-2003
Abstract: Ferromagnetic transduction models have been proposed as a potential mechanism for mobile phone bioeffects. These models are based on the coupling of RF and pulsed electromagnetic emissions to biogenic magnetite (Fe3O4) present in the human brain via either ferromagnetic resonance or mechanical activation of cellular ion channels. We have tested these models experimentally for the first time using a bacterial analogue (Magnetospirillum magnetotacticum) which produces intracellular biogenic magnetite similar to that present in the human brain. Experimental evaluation revealed that exposure to mobile phone emissions resulted in a consistent and significantly higher proportion of cell death in exposed cultures versus sham exposure (p = 0.037). Though there appears to be a repeatable trend toward higher cell mortality in magnetite-producing bacteria exposed to mobile phone emissions, it is not yet clear that this would extrapolate to a deleterious health effect in humans.
Publisher: American Chemical Society (ACS)
Date: 17-08-2018
DOI: 10.1021/ACS.LANGMUIR.8B01701
Abstract: Melimine and its derivatives are synthetic chimeric antimicrobial agents based on protamine and melittin. The binding of solubilized melimine and its derivative, with a cysteine on N-terminus, (cys-melimine) on tethered bilayer lipid membranes (tBLMs) was examined using ac electrical impedance spectroscopy. The addition of melimine and cys-melimine initially increased membrane conduction, which subsequently falls over time. The results were obtained for tBLMs comprising zwitterionic phosphatidylcholine, anionic phosphatidylglycerol, or tBLMs made using purified lipids from Escherichia coli. The effect on conduction is more marked with the cysteine variant than the noncysteine variant. The variation in membrane conduction most probably arises from in idual melimines inducing increased ionic permeability, which is then reduced as the melimines aggregate and phase-separate within the membrane. The actions of these antimicrobials are modeled in terms of altering the critical packing parameter (CPP) of the membranes. The variations in the peptide length of cys-melimine were compared with a truncated version of the peptide, cys-mel4. The results suggest that the smaller molecule impacts the membrane by a mechanism that increases the average CPP, reducing membrane conduction. Alternatively, an uncharged alanine-replacement version of melimine still produced an increase in membrane conduction, further supporting the CPP model of geometry-induced toroidal pore alterations. All the data were then compared to their antimicrobial effectiveness for the Gram-positive and Gram-negative strains of bacteria, and their fusogenic properties were examined using dynamic light scattering in 1-oleoyl-2-hydroxy- sn-glycero-3-phosphocholine lipid spheroids. We conclude that a degree of correlation exists between the antimicrobial effectiveness of the peptides studied here and their modulation of membrane conductivity.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2007
End Date: 2008
Funder: Enterprise Ireland
View Funded ActivityStart Date: Start date not available
End Date: 2022
Funder: Australian Research Council
View Funded ActivityStart Date: 2016
End Date: 12-2018
Amount: $392,500.00
Funder: Australian Research Council
View Funded ActivityStart Date: 03-2017
End Date: 12-2023
Amount: $3,708,510.00
Funder: Australian Research Council
View Funded Activity