ORCID Profile
0000-0003-1656-7215
Current Organisation
University of New South Wales
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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)
Diagnostic Applications | Bioprocessing, Bioproduction and Bioproducts | Oncology and Carcinogenesis | Biochemistry and Cell Biology | Immunology Not Elsewhere Classified | Biotechnology Not Elsewhere Classified | Numerical Computation | Agricultural Biotechnology | Industrial Biotechnology | Medical Biochemistry: Proteins And Peptides | Environmental Biotechnology | Oncology And Carcinogenesis | Protein Targeting And Signal Transduction | Polymers and Plastics | Materials Engineering | Genetic Engineering And Enzyme Technology | Water Treatment Processes | Bioremediation | Bacteriology
ANZSRC Socio-Economic Objective (SEO)
Polymeric Materials (e.g. Paints) | Immune system and allergy | Organic Industrial Chemicals (excl. Resins, Rubber and Plastics) | Cancer and related disorders | Diagnostic methods | Rehabilitation of Degraded Urban and Industrial Environments | Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in Engineering | Management of Solid Waste from Manufacturing Activities | Expanding Knowledge in the Biological Sciences | Diagnostics | Treatments (e.g. chemicals, antibiotics) |
Related Links
Publications
Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease
Publisher: Oxford University Press (OUP)
Date: 22-09-2011
DOI: 10.1093/NDT/GFR575
Abstract: Elevated macrophage inhibitory cytokine-1 (MIC-1/GDF15) levels in serum mediate anorexia and weight loss in some cancer patients and similarly elevated levels occur in chronic kidney disease (CKD). Serum MIC-1/GDF15 is also elevated in chronic inflammatory diseases and predicts atherosclerotic events independently of traditional risk factors. The relationship between chronic inflammation, decreasing body mass index (BMI) and increased mortality in CKD is not well understood and is being actively investigated. MIC-1/GDF15 may link these features of CKD. Cohorts of incident dialysis patients from Sweden (n = 98) and prevalent hemodialysis patients from the USA (n = 381) had serum MIC-1/GDF15, C-reactive protein (CRP) levels and BMI measured at study entry. Additional surrogate markers of nutritional adequacy, body composition and inflammation were assessed in Swedish patients. Patients were followed for all-cause mortality. In the Swedish cohort, serum MIC-1/GDF15 was associated with decreasing BMI, measures of nutrition and markers of oxidative stress and inflammation. Additionally, high serum MIC-1/GDF15 levels identified patients with evidence of protein-energy wasting who died in the first 3 years of dialysis. The ability of serum MIC-1/GDF15 to predict mortality in the first 3 years of dialysis was confirmed in the USA cohort. In both cohorts, serum MIC-1/GDF15 level was an independent marker of mortality when adjusted for age, CRP, BMI, history of diabetes mellitus and/or cardiovascular disease and glomerular filtration rate or length of time on dialysis at study entry. MIC-1/GDF15 is a novel independent serum marker of mortality in CKD capable of significantly improving the mortality prediction of other established markers. MIC-1/GDF15 may mediate protein-energy wasting in CKD and represent a novel therapeutic target for this fatal complication.
Protein Release from Biodegradable PolyHPMA–Lysozyme Conjugates Resulting in Bioactivity Enhancement
Publisher: Wiley
Date: 17-03-2011
Abstract: A novel biodegradable thiazolidine-2-thione functional chain transfer agent was synthesized and employed as a reversible additional fragmentation chain transfer agent to prepare well-defined semitelechelic poly-N-(2-hydroxypropyl) methacrylamides (polyHPMAs) with predetermined molecular weights and narrow polydispersities. The protein reactive group, thiazolidine-2-thione, was located at the polymer chain ends fixed by biodegradable disulfide bonds. The functional polyHPMA chains were subsequently conjugated to protein (lysozyme) by exploiting reactions between the thiazolidine-2-thione functionality and amine residues on the protein surface to form covalent amide linkages. The in vitro bioactivities of the lysozyme-polyHPMA conjugates were assessed by using Micrococcus lysodeikticus cells as substrates. The lysozyme bioactivity was significantly reduced following the conjugation procedure. However, cleavage of the polymer chains from the bioconjugates (under reducing conditions) yielded free protein and a remarkable recovery of bioactivity. In vivo tests were performed by subcutaneous injection into mice and clearly demonstrated decreased proteolytic degradation for the protein-polymer conjugate when compared with native protein, indicating effective protein protection through a conjugation strategy. This bioreversible approach to conjugation allows for a balance to be made between protein protection and effective bioactivity maintenance.
Cytotoxic origin of copper(II) oxide nanoparticles: Comparative studies with micron-sized particles, leachate, and metal salts
Publisher: American Chemical Society (ACS)
Date: 12-08-2011
DOI: 10.1021/NN2020248
Abstract: The work investigates the source of toxicity of copper oxide nanoparticles (CuO NPs) with respect to its leaching characteristic and speciation. Complexation-mediated leaching of CuO NPs by amino acids was identified as the source of toxicity toward Escherichia coli, the model microorganism used in the current study. The leached copper-peptide complex induces a multiple-fold increase in intracellular reactive oxygen species generation and reduces the fractions of viable cells, resulting in the overall inhibition of biomass growth. The cytotoxicity of the complex leachate is however different from that of equivalent soluble copper salts (nitrates and sulfates). A pH-dependent copper speciation during the addition of copper salts gives rise to uncoordinated copper ions, which in turn result in greater toxicity and cell lysis, the latter of which was not observed for CuO NPs even at comparable pH. Since leaching did not occur with micrometer-sized CuO, no cytotoxicty effect was observed, thus highlighting the prominence of materials toxicity at the nanoscale.
Effects of serum adsorption on cellular uptake profile and consequent impact of titanium dioxide nanoparticles on human lung cell lines
Publisher: American Chemical Society (ACS)
Date: 02-05-2012
DOI: 10.1021/NN3004845
Abstract: Exposure to fetal bovine serum (FBS) is shown herein to reduce the aggregate size of titanium dioxide (TiO(2)) nanoparticles, affecting uptake and consequent effect on A549 and H1299 human lung cell lines. Initially, the cellular uptake of the FBS-treated TiO(2) was lower than that of non-FBS-treated TiO(2). Expulsion of particles was then observed, followed by a second phase of uptake of FBS-treated TiO(2), resulting in an increase in the cellular content of FBS-treated TiO(2), eventually exceeding the amount by cells exposed to non-FBS-treated TiO(2). Surface adsorbed vitronectin and the clathrin-mediated endocytosis pathway were shown to regulate the uptake of TiO(2) into A549 cells, while the endocytosis mechanism responsible remains elusive for H1299. Intriguingly, nystatin treatment was shown to have the unexpected effect of increasing nanoparticle uptake into the A549 cells via an alternate endocytic pathway. The surface adsorbed serum components were found to provide some protection from the cytotoxic effect of endocytosed TiO(2) nanoparticles.
Dependency of engine combustion on blending ratio variations of lipase-catalysed coconut oil biodiesel and petroleum diesel
Publisher: Elsevier BV
Date: 04-2016
TGF-b Superfamily Cytokine MIC-1/GDF15 Is a Physiological Appetite and Body Weight Regulator
Publisher: Public Library of Science (PLoS)
Date: 28-02-2013
Nanoparticle-protein corona complexes govern the biological fates and functions of nanoparticles
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3TB21526A
One-pot synthesis of high molecular weight synthetic heteroprotein dimers driven by charge complementarity electrostatic interactions
Publisher: American Chemical Society (ACS)
Date: 30-09-2014
DOI: 10.1021/JO501713T
Abstract: Despite the importance of protein dimers and dimerization in biology, the formation of protein dimers through synthetic covalent chemistry has not found widespread use. In the case of maleimide-cysteine-based dimerization of proteins, we show here that when the proteins have the same charge, dimerization appears to be inherently difficult with yields around 1% or less, regardless of the nature of the spacer used or whether homo- or heteroprotein dimers are targeted. In contrast, if the proteins have opposing (complementary) charges, the formation of heteroprotein dimers proceeds much more readily, and in the case of one high molecular weight (>80 kDa) synthetic dimer between cytochrome c and bovine serum albumin, a 30% yield of the purified, isolated dimer was achieved. This represents at least a 30-fold increase in yield for protein dimers formed from proteins with complementary charges, compared to when the proteins have the same charge, under otherwise similar conditions. These results illustrate the role of ionic supramolecular interactions in controlling the reactivity of proteins toward bis-functionalized spacers. The strategy here for effective synthetic dimerization of proteins could be very useful for developing novel approaches to study the important role of protein-protein interactions in chemical biology.
Modified Longmire procedure: a novel approach to bile duct injury repair
Publisher: Wiley
Date: 22-10-2018
DOI: 10.1111/ANS.14901
Diabetes Adversely Influences Postoperative Outcomes After Oesophagectomy: An Analysis of the National Surgical Quality Improvement Program Database
Publisher: Cureus, Inc.
Date: 24-01-2022
DOI: 10.7759/CUREUS.21559
Growth differentiation factor-15 slows the growth of murine prostate cancer by stimulating tumor immunity
Publisher: Public Library of Science (PLoS)
Date: 05-06-2020
Asian gastric cancer patients show superior survival: the experiences of a single Australian center
Publisher: Springer Science and Business Media LLC
Date: 25-05-2014
DOI: 10.1007/S10120-014-0383-X
Abstract: Survival after curative gastrectomy for gastric cancer varies depending on region. The 5-year survival rates in Western trials reach 36-47% compared with 40-60% in Japanese studies. We analyzed the outcomes of Asian and non-Asian patients at a single Australian institution. We analyzed a prospectively kept database of patients following gastric resection between 1994 and 2010 at a tertiary Australian hospital. Overall survival was the primary endpoint. A total of 160 patients underwent a R0 gastrectomy with curative intent, of whom 26 (16%) were of Asian descent. Asian patients had a significantly younger age at diagnosis (60 ± 16 vs. 70 ± 11, p < 0.05) and longer overall survival (log-rank p = 0.018). Poor prognostic factors common to both groups included increased tumor length, higher T-score, higher LN ratio, poor tumor differentiation, and the presence of perineural or perivascular invasion. Multivariate analysis showed that non-Asian patients, higher T-score, higher N-score, and perivascular involvement were all independent predictors of poorer outcome. This study shows superior overall survival in Asian patients despite similar clinicopathological and treatment data. The younger age at diagnosis in Asian patients may suggest a different disease process between ethnicities. Targeted therapies based on population-specific tumor biology may potentially be beneficial.
Single-cell DNA methylation sequencing by combinatorial indexing and enzymatic DNA methylation conversion.
Publisher: Springer Science and Business Media LLC
Date: 04-01-2023
DOI: 10.1186/S13578-022-00938-9
Abstract: DNA methylation is a critical molecular mark involved in cellular differentiation and cell-specific processes. Single-cell whole genome DNA methylation profiling methods hold great potential to resolve the DNA methylation profiles of in idual cell-types. Here we present a method that couples single-cell combinatorial indexing (sci) with enzymatic conversion (sciEM) of unmethylated cytosines. The sciEM method facilitates DNA methylation profiling of single-cells that is highly correlated with single-cell bisulfite-based workflows (r 2 0.99) whilst improving sequencing alignment rates, reducing adapter contamination and over-estimation of DNA methylation levels (CpG and non-CpG). As proof-of-concept we perform sciEM analysis of the temporal lobe, motor cortex, hippoc us and cerebellum of the human brain to resolve single-cell DNA methylation of all major cell-types. To our knowledge sciEM represents the first non-bisulfite single-cell DNA methylation sequencing approach with single-base resolution.
Zinc oxide nanoparticles induce cell filamentation in escherichia coli
Publisher: Wiley
Date: 28-02-2013
Purification of recombinant human growth hormone from CHO cell culture supernatant by Gradiflow preparative electrophoresis technology
Publisher: Elsevier BV
Date: 11-2003
Genomic, transcriptomic and proteomic analyses of Dehalobacter UNSWDHB in response to chloroform
Publisher: Wiley
Date: 10-08-2016
Abstract: Organohalide respiring bacteria (ORB) are capable of utilising organohalides as electron acceptors for the generation of cellular energy and consequently play an important role in the turnover of natural and anthropogenically-derived organohalides. In this study, the response of a Dehalobacter sp. strain UNSWDHB to the addition of trichloromethane (TCM) after a 50 h period of its absence (suffocation) was evaluated from a transcriptomic and proteomic perspective. The up-regulation of TCM reductive dehalogenase genes (tmrABC) and their gene products (TmrABC) was confirmed at both transcriptional and proteomic levels. Other findings include the upregulation of various hydrogenases (membrane-associated Ni-Fe hydrogenase complexes and soluble Fe-Fe hydrogenases), formate dehydrogenases, complex I and a pyrophosphate-energized proton pump. The elevated expression of enzymes associated with carbon metabolism, including complete Wood Ljungdahl pathway, during TCM respiration raises interesting questions on possible fates of intracellular formate and its potential role in the physiology of this bacterium. Overall, the findings presented here provide a broader view on the bioenergetics and general physiology of Dehalobacter UNSWDHB cells actively respiring with TCM.
Large retroperitoneal isolated fibrous cyst in absence of preceding trauma or acute pancreatitis
Publisher: Springer Science and Business Media LLC
Date: 14-03-2015
In vitro coronal protein signatures and biological impact of silver nanoparticles synthesized with different natural polymers as capping agents
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0NA01013H
Abstract: Biopolymer-capped silver nanoparticle synthesis. Compositional and stability analysis of synthesised particles. Proteomic analysis of particles following serum exposure. In vitro hemolytic assays. Organ distribution following administration in mice.
Development of Super-CHO protein-free medium based on a statistical design
Publisher: Wiley
Date: 05-2007
DOI: 10.1002/JCTB.1670
Comparison of the efficiency of Moloney Murine Leukaemia Virus (M-MuLV) reverse transcriptase, RNase H--M-MuLV reverse transcriptase and Avian Myeloblastoma Leukaemia Virus (AMV) reverse transcriptase for the amplification of human immunoglobulin genes
Publisher: Springer Science and Business Media LLC
Date: 1998
Biosynthesis of protein products by animal cells. Are growth and non-growth associated concepts valid or useful?
Publisher: Springer Science and Business Media LLC
Date: 06-1996
DOI: 10.1007/BF02215663
Polyethylenimine based magnetic iron-oxide vector: The effect of vector component assembly on cellular entry mechanism, intracellular localization, and cellular viability
Publisher: American Chemical Society (ACS)
Date: 16-08-2010
DOI: 10.1021/BM100748P
Abstract: The order of assembly of a magnetic nanoparticle (MNP) vector comprised of the same components (MNP, PEI, and plasmid DNA) on entry mechanism, intracellular localization, and viability of BHK21 cells was investigated. Cellular uptake measurements under four different uptake inhibiting conditions, such as low temperature, depleted cellular ATP, nystatin treatment, and hypertonic environment, show that the cellular entry mechanism of the MNP vector was mediated via clathrin endocytosis. Despite different vector component assembly, all MNP vectors were taken up by the cells through the same mechanism. Labeling and intracellular tracking of the MNP vectors using epi-fluorescence and confocal laser scanning microscopy showed localization of MNP vector within the lysosomes when DNA was assembled on the outer layer of vector. Conversely, when PEI was on the surface of the vector, such that it enclosed both magnetic nanoparticles and the DNA, vector localization in the cell nucleus was observed. The microscopy results demonstrated that the configuration of the MNP vectors dictate the vector's final intracellular target location, and thus the efficiency of transfection. The cellular viability assessment using three different assays further showed that the cellular viability of MNP vector was dose-dependent and varied with the assembly of vector component. All viability assays found negligible toxicity when DNA was on the outer layer of MNP vector except at the highest vector loading. In contrast, attachment of PEI on MNP vector surface induced a significant decrease in cellular viability, due to the ability of PEI on the MNP vector to rupture the lysosomal vesicles.
The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains
Publisher: The Royal Society
Date: 05-09-2015
Abstract: The human and mouse antibody repertoires are formed by identical processes, but like all small animals, mice only have sufficient lymphocytes to express a small part of the potential antibody repertoire. In this study, we determined how the heavy chain repertoires of two mouse strains are generated. Analysis of IgM- and IgG-associated VDJ rearrangements generated by high-throughput sequencing confirmed the presence of 99 functional immunoglobulin heavy chain variable (IGHV) genes in the C57BL/6 genome, and inferred the presence of 164 IGHV genes in the BALB/c genome. Remarkably, only five IGHV sequences were common to both strains. Compared with humans, little N nucleotide addition was seen in the junctions of mouse VDJ genes. Germline human IgG-associated IGHV genes are rare, but many murine IgG-associated IGHV genes were unmutated. Together these results suggest that the expressed mouse repertoire is more germline-focused than the human repertoire. The apparently ergent germline repertoires of the mouse strains are discussed with reference to reports that inbred mouse strains carry blocks of genes derived from each of the three subspecies of the house mouse. We hypothesize that the germline genes of BALB/c and C57BL/6 mice may originally have evolved to generate distinct germline-focused antibody repertoires in the different mouse subspecies.
A Comparative Analysis on Engine Performance of a Conventional Diesel Fuel and 10% Biodiesel Blends Produced from Coconut Oils
Publisher: SAE International
Date: 06-09-2015
DOI: 10.4271/2015-24-2489
Treatment with the TGF-b superfamily cytokine MIC-1/GDF15 reduces the adiposity and corrects the metabolic dysfunction of mice with diet-induced obesity
Publisher: Springer Science and Business Media LLC
Date: 05-12-2017
DOI: 10.1038/IJO.2017.258
Abstract: To test the potential efficacy of recombinant macrophage inhibitory cytokine-1 (MIC-1/GDF15) as an obesity therapeutic. Male C57BL/6 J mice, either fed on normal chow or high-fat diet for 16 weeks to induce diet-induced obesity, were infused with either recombinant MIC-1/GDF15 or vehicle for 34 days by osmotic minipump. During the experimental period metabolic parameters were measured. Blood and tissue were collected for analysis of inflammatory markers. MIC-1/GDF15 decreased food intake and body weight of high-fat-fed and chow-fed mice compared with their vehicle-treated control mice. MIC-1/GDF15 reduced body weight, accompanied by greater reduction in fat mass in high-fat-fed mice compared to its effect on chow-fed mice. Further, whilst MIC-1/GDF15-treated chow-fed mice lost lean as well as fat mass, MIC-1/GDF15-treated high-fat-fed mice lost fat mass alone. This reduction in body weight and adiposity was due largely to reduced food intake, but MIC-1/GDF15-treated high-fat-fed mice also displayed increased energy expenditure that may be due to increased thermogenesis. MIC-1/GDF15-treated high-fat-fed mice also had higher circulating level of adiponectin and lower tissue expression, and circulating levels of leptin and inflammatory mediators associated with insulin resistance. Peripheral insulin and glucose intolerance were improved in both MIC-1/GDF15-treated high-fat-fed and chow-fed mice compared to that of their vehicle-treated control mice. MIC-1/GDF15 is highly effective in reducing adiposity and correcting the metabolic dysfunction of mice with high-fat fed. These studies suggest that MIC-1/GDF15 may be a candidate anti-obesity therapeutic.
Mucin‐containing pancreatic lymphoepithelial cyst: a potential surgical pitfall
Publisher: Wiley
Date: 17-02-2020
DOI: 10.1111/ANS.15772
Amino acid metabolism during batch culture of a murine hybridoma, AFP-27
Publisher: Springer Science and Business Media LLC
Date: 06-1996
DOI: 10.1007/BF02215661
Nanosilver Targets the Bacterial Cell Envelope: The Link with Generation of Reactive Oxygen Radicals
Publisher: American Chemical Society (ACS)
Date: 13-01-2020
Abstract: The work describes the interactions of nanosilver (NAg) with bacterial cell envelope components at a molecular level and how this associates with the reactive oxygen species (ROS)-mediated toxicity of the nanoparticle. Major structural changes were detected in cell envelope biomolecules as a result of damages in functional moieties, such as the saccharides, amides, and phosphodiesters. NAg exposure disintegrates the glycan backbone in the major cell wall component peptidoglycan, causes complete breakdown of lipoteichoic acid, and disrupts the phosphate-amine and fatty acid groups in phosphatidylethanolamine, a membrane phospholipid. Consistent with the oxidative attacks, we propose that the observed cell envelope damages are inflicted, at least in part, by the reactive oxygen radicals being generated by the nanoparticle during its leaching process, abiotically, without cells. The cell envelope targeting, especially those on the inner membrane phospholipid, is likely to then trigger the rapid generation of lethal levels of cellular superoxide (O
Heterologous Production and Purification of a Functional Chloroform Reductive Dehalogenase
Publisher: American Chemical Society (ACS)
Date: 24-01-2018
DOI: 10.1021/ACSCHEMBIO.7B00846
Abstract: Reductive dehalogenases (RDases) are key enzymes involved in the respiratory process of anaerobic organohalide respiring bacteria (ORB). Heterologous expression of respiratory RDases is desirable for structural and functional studies however, there are few reports of successful expression of these enzymes. Dehalobacter sp. strain UNSWDHB is an ORB, whose preferred electron acceptor is chloroform. This study describes efforts to express recombinant reductive dehalogenase (TmrA), derived from UNSW DHB, using the heterologous hosts Escherichia coli and Bacillus megaterium. Here, we report the recombinant expression of soluble and functional TmrA, using B. megaterium as an expression host under a xylose-inducible promoter. Successful incorporation of iron-sulfur clusters and a corrinoid cofactor was demonstrated using UV-vis spectroscopic analyses. In vitro dehalogenation of chloroform using purified recombinant TmrA was demonstrated. This is the first known report of heterologous expression and purification of a respiratory reductive dehalogenase from an obligate organohalide respiring bacterium.
ANZHPBA Post-Fellowship Training in HPB Surgery: A Comprehensive Review from the First 10 Years
Publisher: Elsevier BV
Date: 2021
Macrophage inhibitory cytokine‐1/growth differentiation factor‐15 as a predictor of colonic neoplasia
Publisher: Wiley
Date: 06-2017
DOI: 10.1111/APT.14156
Abstract: Serum macrophage inhibitory cytokine-1 (MIC-1/GDF15) concentration has been associated with colonic adenomas and carcinoma. To determine whether circulating MIC-1/GDF15 serum concentrations are higher in the presence of adenomas and whether the level decreases after excision. Patients were recruited prospectively from a single centre and stratified into five groups: no polyps (NP) hyperplastic polyps (HP) sessile serrated ademona (SSA) adenomas (AP) and colorectal carcinoma (CRC). Blood s les were collected immediately before and 4 weeks after colonoscopy. MIC-1/GDF15 serum levels were quantified using ELISA. Participants (n=301) were stratified as: NP n=116 (52%), HP n=37 (12%), SSA n=19 (7%), AP n=68 (23%) and CRC n=3 (1%). Patients were excluded from the study due to nondiagnostic pathology (n=9, 3%) and exclusion criteria (n=20, 6%). In the 272 remaining subjects (M=149 F=123), age (P=.005), history of colonic polyps (P=.003) and family history of colonic polyps (P=.002) were associated with presence of adenomas. Baseline median MIC-1/GDF15 serum levels increased significantly from NP 609 (460-797) pg/mL, HP 582 (466-852) pg/mL, SSA 561 (446-837) pg/mL to AP 723 (602-1122) pg/mL and CRC 1107 (897-1107) pg/mL (P<.001). In the pre- and postpolypectomy paired adenoma s les median MIC-1/GDF15 reduced significantly from 722 (603-1164) pg/mL to 685 (561-944) pg/mL (P=.002). A ROC analysis for serum MIC-1/GDF15 to identify adenomatous polyps indicated an area under the curve of 0.71. Our data suggest that serum MIC-1/GDF15 has the diagnostic characteristics to increase the detection of colonic neoplasia and improve screening.
Organohalide respiring bacteria and reductive dehalogenases: Key tools in organohalide bioremediation
Publisher: Frontiers Media SA
Date: 03-2016
Production and characterisation of recombinant human chaperonin 10 for treatment of inflammatory disease
Publisher: Elsevier BV
Date: 10-2015
Surgical tetralogy: simultaneous perforated gastric ulcer and appendicular perforation with liver and cerebral abscesses
Publisher: Wiley
Date: 18-03-2020
DOI: 10.1111/ANS.15816
A Fluorescence-Based High-Throughput Screen to Identify Small Compound Inhibitors of the Genotype 3a Hepatitis C Virus RNA Polymerase
Publisher: Elsevier BV
Date: 10-2013
Abstract: The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) plays an essential role in the replication of HCV and is a key target for novel antiviral therapies. Several RdRp inhibitors are in clinical trials and have increased response rates when combined with current interferon-based therapies for genotype 1 (G1) HCV patients. These inhibitors, however, show poor efficacy against non-G1 genotypes, including G3a, which represents ~20% of HCV cases globally. Here, we used a commercially available fluorescent dye to characterize G3a HCV RdRp in vitro. RdRp activity was assessed via synthesis of double-stranded RNA from the single-stranded RNA poly(C) template. The assay was miniaturized to a 384-well microplate format and a pilot high-throughput screen was conducted using 10,208 "lead-like" compounds, randomly selected to identify inhibitors of HCV G3a RdRp. Of 150 compounds demonstrating greatest inhibition, 10 were confirmed using both fluorescent and radioactive assays. The top two inhibitors (HAC001 and HAC002) demonstrated specific activity, with an IC(50) of 12.7 µM and 1.0 µM, respectively. In conclusion, we describe simple, fluorescent-based high-throughput screening (HTS) for the identification of inhibitors of de novo RdRp activity, using HCV G3a RdRp as the target. The HTS system could be used against any positive-sense RNA virus that cannot be cultured.
Antimicrobial activity of T4 bacteriophage conjugated indium tin oxide surfaces
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JCIS.2017.12.029
Abstract: We report the antimicrobial activity of bare and surface functionalized indium tin oxide (ITO) conjugated with T4 bacteriophage towards E. coli. A ∼ 10
A Tunable Tumor Microenvironment through Recombinant Bacterial Collagen-Hyaluronic Acid Hydrogels
Publisher: American Chemical Society (ACS)
Date: 07-06-2022
Abstract: Laboratory models of the tumor microenvironment require control of mechanical and biochemical properties to ensure accurate mimicry of patient disease. In contrast to pure natural or synthetic materials, hybrid approaches that pair recombinant protein fragments with synthetic scaffolding show many advantages. Here we demonstrate production of a recombinant bacterial collagen-like protein (CLP) for thiol-ene pairing to norbornene functionalized hyaluronic acid (NorHA). The resultant hydrogel material shows an adjustable modulus with evidence for strain-stiffening behavior that resembles natural tumor matrices. Cysteine terminated peptide binding motifs are incorporated to adjust the cell-adhesion points. The modular hybrid gel shows good biocompatibility and was demonstrated to control cell adhesion, proliferation, and the invasive properties of MCF7 and MD-MBA-231 breast adenocarcinoma cells. The ease in which multiple structural and bioactive components can be integrated provides a robust framework to form models of the tumor microenvironment for fundamental studies and drug development.
Variable palatability of coral eggs to a planktivorous fish
Publisher: CSIRO Publishing
Date: 2001
DOI: 10.1071/MF00144
Abstract: Predation by fish is generally assumed to be an important source of mortality of coral propagules. Field observations have confirmed that fish feed within the slicks of gametes that form following the annual mass spawning of corals on the Great Barrier Reef. However, these studies cannot determine which species are being consumed. To test whether the eggs of coral species were equally palatable, the eggs of eight common broadcast spawning scleractinian corals were fed to a planktivorous fish. Pomacentrus moluccensis readily consumed the eggs of five acroporid species and two faviid species, but often rejected the eggs of the agariciid Pachyseris speciosa only 60% of the P. speciosa eggs were ingested compared with 90% of eggs of the other species. Assay testing for chemical defence showed that P. speciosa eggs were chemically distasteful to P. moluccensis.
Reversible Antimicrobial Photoswitching in Nanosilver
Publisher: Wiley
Date: 29-01-2009
A bacterial chloroform reductive dehalogenase: purification and biochemical characterization
Publisher: Wiley
Date: 20-06-2017
Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium Pseudoalteromonas tunicata
Publisher: MDPI AG
Date: 30-10-2021
DOI: 10.3390/BIOMEDICINES9111586
Abstract: Drug resistance among parasitic nematodes has resulted in an urgent need for the development of new therapies. However, the high re-discovery rate of anti-nematode compounds from terrestrial environments necessitates a new repository for future drug research. Marine epiphytes are hypothesised to produce nematicidal compounds as a defence against bacterivorous predators, thus representing a promising yet underexplored source for anti-nematode drug discovery. The marine epiphytic bacterium Pseudoalteromonas tunicata is known to produce several bioactive compounds. Screening heterologously expressed genomic libraries of P. tunicata against the nematode Caenorhabditis elegans, identified as an E. coli clone (HG8), shows fast-killing activity. Here we show that clone HG8 produces a novel nematode-killing protein-1 (Nkp-1) harbouring a predicted carbohydrate-binding domain with weak homology to known bacterial pore-forming toxins. We found bacteria expressing Nkp-1 were able to colonise the C. elegans intestine, with exposure to both live bacteria and protein extracts resulting in physical damage and necrosis, leading to nematode death within 24 h of exposure. Furthermore, this study revealed C. elegans dar (deformed anal region) and internal hatching may act as a nematode defence strategy against Nkp-1 toxicity. The characterisation of this novel protein and putative mode of action not only contributes to the development of novel anti-nematode applications in the future but reaffirms the potential of marine epiphytic bacteria as a new source of novel biomolecules.
Biological impacts of TiO2 on human lung cell lines A549 and H1299: Particle size distribution effects
Publisher: Springer Science and Business Media LLC
Date: 03-2011
An evaluation of the antimicrobial properties of the eggs of 11 species of scleractinian corals
Publisher: Springer Science and Business Media LLC
Date: 19-05-2005
Widespread and Indiscriminate Nanosilver Use: Genuine Potential for Microbial Resistance
Publisher: American Chemical Society (ACS)
Date: 24-03-2017
Abstract: In this era of increasing antibiotic resistance, the use of alternative antimicrobials such as silver has become more widespread. Superior antimicrobial activity has been provided through fabrication of silver nanoparticles or nanosilver (NAg), which imparts cytotoxic actions distinct from those of bulk silver. In the wake of the recent discoveries of bacterial resistance to NAg and its rising incorporation in medical and consumer goods such as wound dressings and dietary supplements, we argue that there is an urgent need to monitor the prevalence and spread of NAg microbial resistance. In this Perspective, we describe how the use of NAg in commercially available products facilitates prolonged microorganism exposure to bioavailable silver, which underpins the development of resistance. Furthermore, we advocate for a judicial approach toward NAg use in order to preserve its efficacy and to avoid environmental disruption.
Acid degradable and biocompatible polymeric nanoparticles for the potential codelivery of therapeutic agents
Publisher: American Chemical Society (ACS)
Date: 16-09-2011
DOI: 10.1021/MA201085Z
The Anorectic Actions of the TGFβ Cytokine MIC-1/GDF15 Require an Intact Brainstem Area Postrema and Nucleus of the Solitary Tract
Publisher: Public Library of Science (PLoS)
Date: 27-06-2014
Chromera velia is Endosymbiotic in Larvae of the Reef Corals Acropora digitifera and A. tenuis
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.PROTIS.2012.08.003
Abstract: Scleractinian corals occur in symbiosis with a range of organisms including the dinoflagellate alga, Symbiodinium, an association that is mutualistic. However, not all symbionts benefit the host. In particular, many organisms within the microbial mucus layer that covers the coral epithelium can cause disease and death. Other organisms in symbiosis with corals include the recently described Chromera velia, a photosynthetic relative of the apicomplexan parasites that shares a common ancestor with Symbiodinium. To explore the nature of the association between C. velia and corals we first isolated C. velia from the coral Montipora digitata and then exposed aposymbiotic Acropora digitifera and A. tenuis larvae to these cultures. Three C. velia cultures were isolated, and symbiosis was established in coral larvae of both these species exposed to all three clones. Histology verified that C. velia was located in the larval endoderm and ectoderm. These results indicate that C. velia has the potential to be endosymbiotic with coral larvae.
SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study
Publisher: Oxford University Press (OUP)
Date: 24-03-2021
DOI: 10.1093/BJS/ZNAB101
Abstract: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351 best case 196, worst case 816) or non-cancer surgery (733 best case 407, worst case 1664). Both exceeded the NNV in the general population (1840 best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.
Enzymatic conversion of coconut oil for biodiesel production
Publisher: Elsevier BV
Date: 02-2013
Particle movement and fluid behavior visualization using an optically transparent 3D-printed micro-hydrocyclone
Publisher: AIP Publishing
Date: 11-2020
DOI: 10.1063/5.0025391
An analysis of the changes in soluble hydrogenase and global gene expression in Cupriavidus necator (Ralstonia eutropha) H16 grown in heterotrophic diauxic batch culture
Publisher: Springer Science and Business Media LLC
Date: 25-03-2015
Loop and drain technique for prevention of surgical site infection in upper gastrointestinal surgery
Publisher: Wiley
Date: 29-07-2022
DOI: 10.1111/ANS.17923
Abstract: Hepatobiliary and pancreatic surgery is frequently complicated by surgical site infections (SSI) with significant postoperative morbidity and mortality rates contributing to the economic burden on healthcare. Advancements in operative techniques to prevent SSI are gaining traction in clinical practice. This study compares the effectiveness of the ‘loop and drain technique (LDT)’, a combination method utilizing a continuous subcutaneous vessel loop and subcuticular suture for surgical wound closure in patients undergoing upper gastrointestinal surgery at a Metropolitan Hospital in Sydney. A retrospective review of patients who underwent an upper gastrointestinal procedure was conducted at Bankstown‐Lidcombe hospital between 2017 and 2019. There were 77 patients in the LDT group and 123 patients included in the control group. The primary outcome assessed was the rate of SSI. Secondary outcomes included length of stay (LOS) and drainage of surgical site infections. Two hundred adult patients were treated for an upper gastrointestinal procedure. The most common operation was a Whipple procedure (35.0%). The rate of SSI was 12.5% with all these patients receiving intravenous antibiotics. The LDT cohort had a significantly lower rate of SSI compared to their counterparts (3.9% vs. 17.9%, P = 0.004). The LDT method is associated with a decreased incidence of SSI and should be considered as a cost‐effective operative technique to improve patient outcomes after upper gastrointestinal surgery.
Process development for a recombinant Chinese Hamster Ovary (CHO) cell line utilizing a metal induced and amplified metallothionein expression system
Publisher: Wiley
Date: 2004
DOI: 10.1002/BIT.20194
Abstract: The suspension Chinese Hamster Ovary cell line, 13-10-302, utilizing the metallothionein (MT) expression system producing recombinant human growth hormone (hGH) was studied in a serum-free and cadmium-free medium at different fermentation scales and modes of operation. Initial experiments were carried out to optimize the concentration of metal addition to induce the MT promoter. Subsequently, the cultivation of the 13-10-302 cell line was scaled up from spinner flasks into bioreactors, and the cultivation duration was extended with fed-batch and perfusion strategies utilizing 180 microM zinc to induce the promoter controlling expression of recombinant hGH. It was shown that a fed-batch process could increase the maximum cell numbers twofold, from 3.3 to 6.3 x 10(6) cell/mL, over those obtained in normal batch fermentations, and this coupled with extended fermentation times resulted in a fourfold increase in final hGH titer, from 135 +/- 15 to 670 +/- 70 mg/L at a specific productivity q(hGH) value of 12 pg cell(-1)d(-1). The addition of sodium butyrate increased the specific productivity of hGH in cells to a value of approximately 48 pg cell(-1)d(-1), resulting in a final hGH titer of over a gram per liter during fed-batch runs. A BioSep acoustic cell recycler was used to retain the cells in the bioreactor during perfusion operation. It was necessary to maintain the specific feeding rates (SFR) above a value of 0.2 vvd/(10(6) cell/mL) to maintain the viability and productivity of the 13-10-302 cells under these conditions the viable cell number increased to over 10(7) cell/mL and resulted in a volumetric productivity of over 120 mg(hGH) L(-1)d(-1). Process development described in this work demonstrates cultivation at various scales and sustained high levels of productivity under cadmium free condition in a CHO cell line utilizing an inducible metallothionein expression system.
Nanosilver and the microbiological activity of the particulate solids versus the leached soluble silver
Publisher: Informa UK Limited
Date: 15-02-2018
DOI: 10.1080/17435390.2018.1434910
Abstract: Nanosilver (Ag NPs) is currently one of the most commercialized antimicrobial nanoparticles with as yet, still unresolved cytotoxicity origins. To date, research efforts have mostly described the antimicrobial contribution from the leaching of soluble silver, while the undissolved solid Ag particulates are often considered as being microbiologically inert, serving only as source of the cytotoxic Ag ions. Here, we show the rapid stimulation of lethal cellular oxidative stress in bacteria by the presence of the undissolved Ag particulates. The cytotoxicity characteristics are distinct from those arising from the leached soluble Ag, the latter being locked in organic complexes. The work also highlights the unique oxidative stress-independent bacterial toxicity of silver salt. Taken together, the findings advocate that future enquiries on the antimicrobial potency and also importantly, the environmental and clinical impact of Ag NPs use, should pay attention to the potential bacterial toxicological responses to the undissolved Ag particulates, rather than just to the leaching of soluble silver. The findings also put into question the common use of silver salt as model material for evaluating bacterial toxicity of Ag NPs.
GDF15 mediates adiposity resistance through actions on GFRAL neurons in the hindbrain AP/NTS
Publisher: Springer Science and Business Media LLC
Date: 31-05-2019
DOI: 10.1038/S41366-019-0365-5
Abstract: Elevated circulating levels of the ergent transforming growth factor-beta (TGFb) family cytokine, growth differentiation factor 15 (GDF15), acting through its CNS receptor, glial-derived neurotrophic factor receptor alpha-like (GFRAL), can cause anorexia and weight loss leading to anorexia/cachexia syndrome of cancer and other diseases. Preclinical studies suggest that administration of drugs based on recombinant GDF15 might be used to treat severe obesity. However, the role of the GDF15-GFRAL pathway in the physiological regulation of body weight and metabolism is unclear. The critical site of action of GFRAL in the CNS has also not been proven beyond doubt. To investigate these two aspects, we have inhibited the actions of GDF15 in mice started on high-fat diet (HFD). The actions of GDF15 were inhibited using two methods: (1) Groups of 8 mice under HFD had their endogenous GDF15 neutralised by monoclonal antibody treatment, (2) Groups of 15 mice received AAV-shRNA to knockdown GFRAL at its hypothesised major sites of action, the hindbrain area postrema (AP) and the nucleus of the solitary tract (NTS). Metabolic measurements were determined during both experiments. Treating mice with monoclonal antibody to GDF15 shortly after commencing HFD results in more rapid gain of body weight, adiposity and hepatic lipid deposition than the control groups. This is accompanied by reduced glucose and insulin tolerance and greater expression of pro-inflammatory cytokines in adipose tissue. Localised AP and NTS shRNA-GFRAL knockdown in mice commencing HFD similarly caused an increase in body weight and adiposity. This effect was in proportion to the effectiveness of GFRAL knockdown, indicated by quantitative analysis of hindbrain GFRAL staining. We conclude that the GDF15-GFRAL axis plays an important role in resistance to obesity in HFD-fed mice and that the major site of action of GDF15 in the CNS is GFRAL-expressing neurons in the AP and NTS.
Fundamentals and electrochemical applications of [Ni-Fe]-uptake hydrogenases
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3RA22668A
An improved process for the production of highly purified recombinant thaumatin tagged-variants
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.FOODCHEM.2017.06.018
Abstract: The sweetest tasting molecule known is the protein thaumatin, first isolated from the katemfe fruit, Thaumatococcus daniellii. Thaumatin is used in the food and beverage industry as a low-calorie sugar substitute. Thaumatin interacts with taste receptors in the oral cavity eliciting a persistent sweet taste and a bitter, liquorice flavor. Recombinant thaumatin was expressed in Pichia pastoris and through a co-expression strategy with a molecular chaperone, yields of one engineered thaumatin variant increased by greater than two-fold. A detailed purification strategy for thaumatin is reported resulting in a homogenous s le recovered at a yield of 42%. The recombinant thaumatins were extensively characterised using size exclusion chromatography for homogeneity, reversed-phase HPLC for purity (99%), peptide digest LC-MS/MS for sequence determination, and circular dichroism and tryptophan fluorescence spectroscopies for conformational characterisation. These new thaumatin variants are amenable for bioconjugation, providing chemical biology tools for thaumatin:taste receptor interaction studies.
Cereulide, the emetic toxin of Bacillus cereus, is putatively a product of nonribosomal peptide synthesis
Publisher: Oxford University Press (OUP)
Date: 11-2004
DOI: 10.1111/J.1365-2672.2004.02381.X
Abstract: To determine if cereulide, the emetic toxin produced by Bacillus cereus, is produced by a nonribosomal peptide synthetase (NRPS). NC Y, an emetic strain of Bacillus cereus, was examined for a NRPS gene using PCR with primers recognizing a fragment of a NRPS gene from the cyanobacterium Microcystis. The licon was sequenced and compared with other gene sequences using BLAST analysis, which showed that the licon from strain NC Y was similar in sequence to peptide synthetase genes in other micro-organisms, including Bacillus subtilis and B. brevis, while no such sequence was found in the complete genome sequence of a nonemetic strain of B. cereus. Specific PCR primers were then designed and used to screen 40 B. cereus isolates previously implicated in outbreaks of foodborne illness. The isolates were also screened for toxin production using the MTT cell cytotoxicity assay. PCR and MTT assay screening of the B. cereus isolates revealed a high correlation between the presence of the NRPS gene and cereulide production. The results indicate that cereulide is produced by a NRPS complex. This is the first study to provide evidence identifying the mechanism of production of cereulide, the emetic toxin of B. cereus. The PCR primers developed in the study allow determination of the potential for cereulide production among isolates of B. cereus.
Perfluorodecalin nanocapsule as an oxygen carrier and contrast agent for ultrasound imaging
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3RA47595F
Reductive Dehalogenases Come of Age in Biological Destruction of Organohalides
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.TIBTECH.2015.07.004
Abstract: Halogenated organic compounds (organohalides) are globally prevalent, recalcitrant toxic, and carcinogenic environmental pollutants. Select microorganisms encode enzymes known as reductive dehalogenases (EC 1.97.1.8) that catalyze reductive dehalogenation reactions resulting in the generation of lesser-halogenated compounds that may be less toxic and more biodegradable. Recent breakthroughs in enzyme structure determination, elucidation of the mechanisms of reductive dehalogenation, and in heterologous expression of functional reductive dehalogenase enzymes have substantially increased our understanding of this fascinating class of enzymes. This knowledge has created opportunities for more versatile (in situ and ex situ) biologically-mediated organohalide destruction strategies.
Lanthanide-based β-Tricalcium Phosphate Upconversion Nanoparticles as an Effective Theranostic Nonviral Vectors for Image-Guided Gene Therapy
Publisher: Ivyspring International Publisher
Date: 2022
DOI: 10.7150/NTNO.68789
Bi-functional gold-coated magnetite composites with improved biocompatibility
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.JCIS.2010.10.061
Abstract: The effect of gold attachment on the physical characteristics, cellular uptake, gene expression efficiency, and biocompatibility of magnetic iron oxide (MNP) vector was investigated in vitro in BHK21 cells. The surface modification of magnetite with gold was shown to alter the morphology and surface charge of the vector. Nonetheless, despite the differences in the surface charge with and without gold attachment, the surface charge of all vectors were positive when conjugated with PEI/DNA complex, and switched from positive to negative when suspended in cell media containing serum, indicating the adsorption of serum components onto the composite. The cellular uptake of all MNP vectors under the influence of a magnetic field increased when the composite loadings increased, and was higher for the MNP vector that was modified with gold. Both bare magnetite and gold-coated magnetite vectors gave similar optimal gene expression efficiency, however, the gold-coated magnetite vector required a 25-fold higher overall loading to achieve a comparable efficiency as the attachment of gold increased the particle size, thus reducing the surface area for PEI/DNA complex conjugation. The MNP vector without gold showed optimal gene expression efficiency at a specific magnetite loading, however further increases beyond the optimum loading decreased the efficiency of gene expression. The drop in efficiency at high magnetite loadings was attributed to the significant reduction in cellular viability, indicating the bare magnetite became toxic at high intracellular levels. The gene expression efficiency of the gold-modified vector, on the other hand, did not diminish with increasing magnetite loadings. Intracellular examination of both bare magnetite and gold-coated magnetite vectors at 48h post-magnetofection using transmission electron microscopy provided evidence of the localization of both vectors in the cell nucleus for gene expression and elucidated the nuclear uptake mechanism of both vectors. The results of this work demonstrate the efficacy of gold-modified vectors to be used in cellular therapy research that can function both as a magnetically-driven gene delivery vehicle and an intracellular imaging agent with negligible impact on cell viability.
Assembly of polyethylenimine-based magnetic iron oxide vectors: Insights into gene delivery
Publisher: American Chemical Society (ACS)
Date: 29-01-2010
DOI: 10.1021/LA9041919
Abstract: The use of a nonviral magnetic vector, comprised of magnetic iron oxide nanoparticles (MNP), polyethylenimine (PEI), and plasmid DNA, for transfection of BHK21 cells under a magnetic field is presented. Four different vector configurations were studied by systematically varying the mixing order of MNP, PEI, and DNA. The assembly of the vector has significant effects on its vector size, surface charge, cellular uptake, and level of gene expression. Mixing MNP with PEI first improved MNP stability, giving a narrow aggregate size distribution and positive surface charge at physiological pH, which in turn facilitated DNA binding onto MNP. The presence of serum in culture media improves vector dispersion and alters the surface charge of all vectors to negative charge, indicating serum protein adsorption. Cellular uptake was greater for larger vectors than the smaller vectors due to enhanced gravitational and magnetic aided sedimentation onto the cells. High MNP uptake by the cells, however, does not inevitably lead to increase gene expression efficiency. It can be shown that besides vector uptake, gene expression is affected by extracellular factors such as premature DNA release from MNP and DNA degradation by serum as well as intracellular factors such as vector lysosomal degradation, inability of DNA to detach from MNP, and cytotoxic effects of MNP at high uptake. Some of these extra- and intracellular properties are shown to be mediated by the presence of PEI.
Erratum to “Practice variation in anastomotic leak after esophagectomy: Unravelling differences in failure to rescue” [Eur J Surg Oncol 49 (5) (May 2023) 974–982]
Publisher: Elsevier BV
Date: 09-2023
Practice variation in anastomotic leak after esophagectomy: Unravelling differences in failure to rescue
Publisher: Elsevier BV
Date: 05-2023
The TGF-β superfamily cytokine, MIC-1/GDF15: A pleotrophic cytokine with roles in inflammation, cancer and metabolism
Publisher: Informa UK Limited
Date: 11-08-2011
DOI: 10.3109/08977194.2011.607137
Abstract: Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is associated with cardiovascular disease, inflammation, body weight regulation and cancer. Its serum levels facilitate the diagnosis and prognosis of cancer and vascular disease. Furthermore, its serum levels are a powerful predictor of all-cause mortality, suggesting a fundamental role in biological processes associated with ageing. In cancer, the data available suggest that MIC-1/GDF15 is antitumorigenic, but this may not always be the case as disease progresses. Cancer promoting effects of MIC-1/GDF15 may be due, in part, to effects on antitumour immunity. This is suggested by the anti-inflammatory and immunosuppressive properties of MIC-1/GDF15 in animal models of atherosclerosis and rheumatoid arthritis. Furthermore, in late-stage cancer, large amounts of MIC-1/GDF15 in the circulation suppress appetite and mediate cancer anorexia/cachexia, which can be reversed by monoclonal antibodies in animals. Available data suggest MIC-1/GDF15 may be an important molecule mediating the interplay between cancer, obesity and chronic inflammation.
Induced adaptation of Bacillus sp. to antimicrobial nanosilver
Publisher: Wiley
Date: 29-04-2013
Abstract: The natural ability of Bacillus sp. to adapt to nanosilver cytotoxicity upon prolonged exposure is reported for the first time. The combined adaptive effects of nanosilver resistance and enhanced growth are induced under various intensities of nanosilver-stimulated cellular oxidative stress, ranging from only minimal cellular redox imbalance to the lethal levels of cellular ROS stimulation. An important implication of the present work is that such adaptive effects lead to the ultimate domination of nanosilver-resistant Bacillus sp. in the microbiota, to which nanosilver cytotoxicity is continuously applied.
T4 bacteriophage conjugated magnetic particles for E. coli capturing: Influence of bacteriophage loading, temperature and tryptone
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.COLSURFB.2016.12.009
Abstract: This work demonstrates the use of bacteriophage conjugated magnetic particles (Fe
A two-step microengineered system for high-density cell retention from bioreactors
Publisher: Elsevier BV
Date: 2021
Construction and use of aCupriavidus necatorH16 soluble hydrogenase promoter (PSH) fusion togfp(green fluorescent protein)
Publisher: PeerJ
Date: 26-07-2016
DOI: 10.7717/PEERJ.2269
Abstract: Hydrogenases are metalloenzymes that reversibly catalyse the oxidation or production of molecular hydrogen (H 2 ). Amongst a number of promising candidates for application in the oxidation of H 2 is a soluble [Ni–Fe] uptake hydrogenase (SH) produced by Cupriavidus necator H16. In the present study, molecular characterisation of the SH operon, responsible for functional SH synthesis, was investigated by developing a green fluorescent protein (GFP) reporter system to characterise P SH promoter activity using several gene cloning approaches. A P SH promoter-gfp fusion was successfully constructed and inducible GFP expression driven by the P SH promoter under de-repressing conditions in heterotrophic growth media was demonstrated in the recombinant C. necator H16 cells. Here we report the first successful fluorescent reporter system to study P SH promoter activity in C. necator H16. The fusion construct allowed for the design of a simple screening assay to evaluate P SH activity. Furthermore, the constructed reporter system can serve as a model to develop a rapid fluorescent based reporter for subsequent small-scale process optimisation experiments for SH expression.
Serum Levels of Human MIC-1/GDF15 Vary in a Diurnal Pattern, Do Not Display a Profile Suggestive of a Satiety Factor and Are Related to BMI
Publisher: Public Library of Science (PLoS)
Date: 24-07-2015
Laparoscopic diagnosis and management of peritonitis chronica fibrosa incapsulata
Publisher: Wiley
Date: 10-01-2020
DOI: 10.1111/ANS.15673
Submicron and nano formulations of titanium dioxide and zinc oxide stimulate unique cellular toxicological responses in the green microalga Chlamydomonas reinhardtii
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.JHAZMAT.2013.06.067
Abstract: The work investigates the eco-cytoxicity of submicron and nano TiO₂ and ZnO, arising from the unique interactions of freshwater microalga Chlamydomonas reinhardtii to soluble and undissolved components of the metal oxides. In a freshwater medium, submicron and nano TiO₂ exist as suspended aggregates with no-observable leaching. Submicron and nano ZnO undergo comparable concentration-dependent fractional leaching, and exist as dissolved zinc and aggregates of undissolved ZnO. Cellular internalisation of solid TiO₂ stimulates cellular ROS generation as an early stress response. The cellular redox imbalance was observed for both submicron and nano TiO₂ exposure, despite exhibiting benign effects on the alga proliferation (8-day EC50>100 mg TiO₂/L). Parallel exposure of C. reinhardtii to submicron and nano ZnO saw cellular uptake of both the leached zinc and solid ZnO and resulting in inhibition of the alga growth (8-day EC50≥0.01 mg ZnO/L). Despite the sensitivity, no zinc-induced cellular ROS generation was detected, even at 100 mg ZnO/L exposure. Taken together, the observations confront the generally accepted paradigm of cellular oxidative stress-mediated cytotoxicity of particles. The knowledge of speciation of particles and the corresponding stimulation of unique cellular responses and cytotoxicity is vital for assessment of the environmental implications of these materials.
Cloning and expression of human V-genes derived from phage display libraries as fully assembled human anti-TNFα monoclonal antibodies
Publisher: Elsevier BV
Date: 03-1997
DOI: 10.1016/S1380-2933(96)00058-9
Abstract: With the advent of phage antibody libraries, access to completely human antibody fragments is feasible, either by direct selection from human antibody libraries, or by guided selection. After selection, Fabs and scFvs may need to be expressed as complete antibodies in mammalian cells for further characterisation, or if effector functions are required. To rebuild and express the human anti-TNF alpha antibody Fab-P3A2 (isolated as a Fab fragment from phage display libraries by guided selection) as a fully assembled, functional human antibody (gamma-1, lambda) in Sp2/0 myeloma cells, and to perform preliminary characterisation studies of the secreted IgG1 molecule. A further objective was to investigate the kinetics of human antibody production and the stability of antibody secretion in transfectomas cultured in various media formulations. A tripartite strategy was employed for cloning heavy chain gene (VH)-P3 and light chain gene V lambda-A2-C lambda into mammalian cell expression vectors p alpha Lys-30 and p alpha Lys-17 respectively. The cell line P3A2.B5 was isolated after co-transfection of Sp2/0 mouse myelomas with the constructs, expanded and weaned into a protein free medium. Fully assembled Ig-P3A2 antibody was purified by Protein A affinity chromatography and characterised with respect to size of antibody chains, and affinity for human TNF alpha. Stability of secretion was investigated by extended serial sub-culture and analysis of P3A2.B5 sub-clones. Strategies of media enrichment were tested for any effect on antibody productivity by selected P3A2.B5 sub-clones. The cell line P3A2.B5 secreted an assembled, human antibody Ig-P3A2, with heavy and light chains of molecular weight 55 and 28 KD respectively. Equilibrium capture studies showed Ig-P3A2 to have a dissociation constant of approximately 1.5 x 10(-8) M. The mean specific productivity of the cell line increased from 1.2 pg/cell/day to 7.8 pg/cell/day by a combination of medium enrichment and serum reduction. Prolonged serial sub-culture of P3A2.B5 showed the cell line to be unstable with respect to antibody secretion. We have outlined a method for expression of human V genes as assembled antibodies in Sp2/0 myeloma cells. A cloning strategy for the stable expression of scFv or Fab genes isolated from phage display libraries as assembled human antibodies of the IgGl subclass in Sp2/0 myeloma cells has been described. For maximising specific productivity of antibody-producing cell lines, supplementation of culture media with glucose, glutamine and amino acids increases antibody yield significantly compared to that in conventional media, indicating the latter is stoichiometrically limiting for production purposes.
Production and purification of a soluble hydrogenase from Ralstonia eutropha H16 for potential hydrogen fuel cell applications
Publisher: Elsevier BV
Date: 2016
Development of a sensitive sandwich ELISA specific to 2S albumin (Ana o 3) as a stable protein marker for cashew nut residue detection in pre-packaged food products
Publisher: Elsevier BV
Date: 02-2019
How to perform transcystic stenting in the COVID ‐19 pandemic: an approach to biliary stenting without specialized endobiliary stenting equipment
Publisher: Wiley
Date: 15-03-2021
DOI: 10.1111/ANS.16727
Laparoscopic repair of Morgagni hernia: an interesting case and complication
Publisher: Wiley
Date: 09-2013
DOI: 10.1111/ANS.12219
Bactericidal effects of titanium dioxide-based photocatalysts
Publisher: Elsevier BV
Date: 10-2005
Scanning Electrochemical Microscopy of Cytochrome c Peroxidase through the Orientation‐Controlled Immobilisation of Cytochrome c
Publisher: Wiley
Date: 31-05-2016
Pancreatectomy for metastatic renal cell carcinoma: twenty years of experience at a tertiary centre
Publisher: Medip Academy
Date: 26-07-2022
DOI: 10.18203/2349-2902.ISJ20221901
Abstract: Renal Cell Carcinoma (RCC) accounts for approximately 90% of primary renal malignancies, of which the clear cell subtype is most common. While metastatic disease is common at the time of diagnosis and generally confers a poor prognosis, metastatic RCC may demonstrate relatively indolent behaviour and present many years after resection of the primary tumour, including to the pancreas. The available literature suggested that surgical resection was appropriate for select patients, including those with a solitary pancreatic metastasis, minimal comorbidities and uncomplicated progress from initial treatment of their primary renal malignancy. A retrospective case series of patients presenting with RCC metastases to the pancreas, managed via surgical resection at a tertiary teaching hospital was reviewed. Analysis of patient demographics, investigations, management and outcomes were performed, with a focus on post-operative morbidity and overall survival. Between 2000 and 2020, 7 patients underwent pancreatic resection of RCC metastases at our tertiary teaching hospital with curative intent. Median age at time of resection was 66 years. No post-operative mortality or major morbidity was experienced by the 7 patients, although 4 patients developed some degree of pancreatic insufficiency. Four patients experienced recurrent metastatic RCC, with median time to recurrence of 3.5 years. This was the largest local study to describe an Australian experience of the surgical management of RCC pancreatic metastases. These patients are frequently afforded prolonged survival following pancreatic resection, but often develop other distant sites of disease and second renal tumours.
Adsorption of T4 bacteriophages on planar indium tin oxide surface via controlled surface tailoring
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.JCIS.2016.01.052
Abstract: The work investigates the influence of surface physicochemical properties of planar indium tin oxide (ITO) as a model substrate on T4 bacteriophage adsorption. A comparative T4 bacteriophage adsorption study shows a significant difference in bacteriophage adsorption observed on chemically modified planar ITO when compared to similarly modified particulate ITO, which infers that trends observed in virus-particle interaction studies are not necessarily transferrable to predict virus-planar surface adsorption behaviour. We also found that ITO surfaces modified with methyl groups, (resulting in increased surface roughness and hydrophobicity) remained capable of adsorbing T4 bacteriophage. The adsorption of T4 onto bare, amine and carboxylic functionalised planar ITO suggests the presence of a unique binding behaviour involving specific functional groups on planar ITO surface beyond the non-specific electrostatic interactions that dominate phage to particle interactions. The paper demonstrates the significance of physicochemical properties of surfaces on bacteriophage-surface interactions.
Gastric cancer: A ustralian outcomes of multi‐modality treatment with curative intent
Publisher: Wiley
Date: 21-05-2014
DOI: 10.1111/ANS.12693
Abstract: Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Large Western trials have shown overall 5-year survival rates of 36-47%. Surgical resection remains the mainstay of curative treatment. We report the outcomes at a single Australian centre. We analysed a prospectively kept database of patients after gastric resection for adenocarcinoma at a tertiary Australian hospital. Disease-specific survival (DSS) was considered the primary end-point. One hundred and seventy-three patients underwent gastrectomy with curative intent. Average age at diagnosis was 68, with 72% being male patients. One hundred patients had a total gastrectomy and 73 had subtotal. The average number of lymph nodes examined was 23. All patients were discussed in a multidisciplinary setting. Perioperative morbidity rate was 31%, with 3.5% 30-day mortality. Five-year DSS was 67.4% with 91.2%, 76.7% and 39.3% for stage 1, 2 and 3 disease, respectively. Five-year overall survival considering death from any cause was 47.4%. This large Australian single centre study shows outcomes equivalent to other Western series and approaches that of Japanese data. High survival figures can be achieved when gastrectomy is performed by an experienced institution through a multi-modality approach with adequate staging, aggressive and appropriate resection and selective use of perioperative therapy.
Purification and characterization of Ara h1 and Ara h3 from four peanut market types revealed higher order oligomeric structures
Publisher: American Chemical Society (ACS)
Date: 09-10-2012
DOI: 10.1021/JF302800E
Abstract: This study aimed to purify and characterize the peanut allergens Ara h1 and Ara h3 from four cultivars that represent the four major market types to provide better understanding of the molecular organization of oligomers in different market types. The chromatographic profiles of Ara h1 and Ara h3 from the four cultivars obtained from anion exchange chromatography were similar. However, they differed in the distribution of trimeric and hexameric structures of Ara h3 isolated by size exclusion chromatography. The Menzies (Runner market type) and Walter (Spanish market type) cultivars, wherein Ara h3 proteins consist of two acidic subunits, exhibited trimeric and hexameric conformations proportionally. However, the Middleton (Virginia market type) and Kelinci (Valencia market type) cultivars, wherein Ara h3 proteins consist of three acidic subunits, showed predominantly a hexameric structure. The oligomeric structures of the purified Ara h1 demonstrated strong IgE binding properties, whereas the allergenic property of the oligomeric Ara h3 could not be performed due to lack of availability of specific IgE. In addition, the polyclonal antibodies raised against the purified Ara h1 and Ara h3 showed highly specific binding to their respective antigens.
Evidence of heterogeneity in the antibody response against the platelet antigen 3a; Recognition of an 11-mer peptide carrying the HPA-3a polymorphic determinant
Publisher: Wiley
Date: 08-03-2009
DOI: 10.1111/J.1423-0410.2008.01146.X
Abstract: The immune processes involved in the development of alloantibodies against the human platelet antigens in alloimmune disorders remain unclear. Antibody recognition of the platelet antigens on their respective platelet glycoproteins has been shown to be dependent on glycoprotein conformation. Furthermore, the post-translational modification of glycoproteins adds complexity to the alloantigenic determinants. Nine anti-HPA-3a sera along with several control sera were tested for reactivity to an 11-mer peptide straddling the HPA-3a/b polymorphism. Sera found to specifically recognize the 3a peptide were further assessed by platelet pre-exposure and immunoblotting. Three of the nine antisera were found to specifically recognize an 11-mer synthetic 3a peptide by ELISA. Further analysis of all anti-HPA-3a sera by Western blot showed that only those reactive to the 3a peptide were able to bind both reduced and non-reduced GPIIb. The results presented in this study provide the first known evidence for the identification of an antibody population capable of recognizing a linear and non-glycosylated form of the HPA-3a epitope.
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Publisher: Oxford University Press (OUP)
Date: 20-04-2023
DOI: 10.1093/BJS/ZNAD092
Abstract: Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling reducing use of anaesthetic gases and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices reducing use of consumables and reducing the use of general anaesthesia. This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries.
Macrophage inhibitory cytokine‐1 (MIC‐1/GDF15): a new marker of all‐cause mortality
Publisher: Wiley
Date: 21-10-2010
Design, Synthesis, and Evaluation of N- and C-Terminal Protein Bioconjugates as G Protein-Coupled Receptor Agonists
Publisher: American Chemical Society (ACS)
Date: 02-02-2018
DOI: 10.1021/ACS.BIOCONJCHEM.7B00716
Abstract: A G protein-coupled receptor (GPCR) agonist protein, thaumatin, was site-specifically conjugated at the N- or C-terminus with a fluorophore for visualization of GPCR:agonist interactions. The N-terminus was specifically conjugated using a synthetic 2-pyridinecarboxyaldehyde reagent. The interaction profiles observed for N- and C-terminal conjugates were varied N-terminal conjugates interacted very weakly with the GPCR of interest, whereas C-terminal conjugates bound to the receptor. These chemical biology tools allow interactions of therapeutic proteins:GPCR to be monitored and visualized. The methodology used for site-specific bioconjugation represents an advance in application of 2-pyridinecarboxyaldehydes for N-terminal specific bioconjugations.
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