Plasma polymers from oregano secondary metabolites: Antibacterial and biocompatible plant-based polymers

Bacterial infection of chronic wounds is a major healthcare problem that affects the quality of life of millions of patients worldwide and leads to a substantial healthcare cost burden. This project focused on the manufacture of a potential wound healing agent. Plasma polymers from oregano secondary metabolites (PP-OSMs) were fabricated by radiofrequency plasma-enhanced chemical vapor deposition (RF-PECVD) in continuous and pulse plasma modes at room temperature. The surface, biocompatibility, and antibacterial properties of the PP-OSMs were investigated. Polymers fabricated by RF-PECVD retained the functional groups of OSMs, promoted human dermal fibroblast adhesion, inhibited Staphylococcus aureus attachment, and eliminated Pseudomonas aeruginosa. The PP-OSM coatings are potential candidates for use in medical applications where cell biocompatibility and antibacterial properties are required

Spiked Nanostructures Disrupt Fungal Biofilm and Impart Increased Sensitivity to Antifungal Treatment

There is a globally increasing demand for medically implanted devices, partly spurred by an aging population. In parallel, there is a proportionate increase in implant associated infection. Much focus has been directed toward the development of techniques to fabricate nanostructured antimicrobial biomaterials to mitigate infection. The present study investigates the interaction of the fungal pathogen Candida albicans with an antimicrobial surface bearing nanoscale protrusions. C. albicans cells were observed to be affected by cell wall stress, which impeded its ability to switch to a hyphal phenotype. There are significant differences in the expression of C. albicans virulence-associated genes between the untreated and nanostructured surfaces. To determine whether the observed inhibition of C. albicans would also sensitize it to antifungal drugs, a culture is established for 3 days on the nanostructured surface before being treated with the antifungal drug amphotericin B. The drug was able to kill all cells on the nanostructured surface at sub-clinical concentrations, while remaining ineffective against cultures grown on a smooth control surface. These findings may eventually prove to be impactful in the clinic, as clinicians may be able to reduce antifungal drug dosages and minimize the effects of drug associated toxicity

Bio-Inspired Nanostructured Ti-6Al-4V Alloy: The Role of Two Alkaline Etchants and the Hydrothermal Processing Duration on Antibacterial Activity

Inspired by observations that the natural topography observed on cicada and dragonfly wings may be lethal to bacteria, researchers have sought to reproduce these nanostructures on biomaterials with the goal of reducing implant-associated infections. Titanium and its alloys are widely employed biomaterials with excellent properties but are susceptible to bacterial colonisation. Hydrothermal etching is a simple, cost-effective procedure which fabricates nanoscale protrusions of various dimensions upon titanium, depending on the etching parameters used. We investigated the role of etching time and the choice of cation (sodium and potassium) in the alkaline heat treatment on the topographical, physical, and bactericidal properties of the resulting modified titanium surfaces. Optimal etching times were 4 h for sodium hydroxide (NaOH) and 5 h for potassium hydroxide (KOH). NaOH etching for 4 h produced dense, but somewhat ordered, surface nanofeatures with 75 nanospikes per µm2. In comparison, KOH etching for 5 h resulted sparser but nonetheless disordered surface morphology with only 8 spikes per µm2. The NaOH surface was more effective at eliminating Gram-negative pathogens, while the KOH surface was more effective against the Gram-positive strains. These findings may guide further research and development of bactericidal titanium surfaces which are optimised for the predominant pathogens associated with the intended application

A better life through information technology? The techno-theological eschatology of posthuman speculative science

This is the pre-peer reviewed version of the article, published in Zygon 41(2) pp.267-288, which has been published in final form at http://www3.interscience.wiley.com/journal/118588124/issueThe depiction of human identity in the pop-science futurology of engineer/inventor Ray Kurzweil, the speculative-robotics of Carnegie Mellon roboticist Hans Moravec and the physics of Tulane University mathematics professor Frank Tipler elevate technology, especially information technology, to a point of ultimate significance. For these three figures, information technology offers the potential means by which the problem of human and cosmic finitude can be rectified. Although Moravec’s vision of intelligent robots, Kurzweil’s hope for immanent human immorality, and Tipler’s description of human-like von Neumann probe colonising the very material fabric of the universe, may all appear to be nothing more than science fictional musings, they raise genuine questions as to the relationship between science, technology, and religion as regards issues of personal and cosmic eschatology. In an attempt to correct what I see as the ‘cybernetic-totalism’ inherent in these ‘techno-theologies’, I will argue for a theology of technology, which seeks to interpret technology hermeneutically and grounds human creativity in the broader context of divine creative activity

Bionic bodies, posthuman violence and the disembodied criminal subject

This article examines how the so-called disembodied criminal subject is given structure and form through the law of homicide and assault. By analysing how the body is materialised through the criminal law’s enactment of death and injury, this article suggests that the biological positioning of these harms of violence as uncontroversial, natural, and universal conditions of being ‘human’ cannot fully appreciate what makes violence wrongful for us, as embodied entities. Absent a theory of the body, and a consideration of corporeality, the criminal law risks marginalising, or altogether eliding, experiences of violence that do not align with its paradigmatic vision of what bodies can and must do when suffering its effects. Here I consider how the bionic body disrupts the criminal law’s understanding of human violence by being a body that is both organic and inorganic, and capable of experiencing and performing violence in unexpected ways. I propose that a criminal law that is more receptive to the changing, technologically mediated conditions of human existence would be one that takes the corporeal dimensions of violence more seriously and, as an extension of this, adopts an embodied, embedded, and relational understanding of human vulnerability to violence

Cold-sensitive mutants of p34^cdc2 that suppress a mitotic catastrophe phenotype in fission yeast

The p34cdc2 protein kinase plays a central role in the regulation of the eukaryotic cell cycle, being required both in late G1 for the commitment to S-phase and in late G2 for the initiation of mitosis. p34cdc2 also determines the precise timing of entry into mitosis in fission yeast, where a number of gene products that regulate p34cdc2 activity have been identified and characterised. To investigate further the mitotic role of p34cdc2 in this organism we have isolated new cold-sensitive p34cdc2 mutants. These are defective only in their G2 function and are extragenic suppressors of the lethal premature entry into mitosis brought about by mutating the mitotic inhibitor p107wee1 and overproducing the mitotic activator p80cdc25. One of the mutant proteins p34cdc2-E8 is only functional in the absence of p107wee1, and all the mutant strains have reduced histone H1 kinase activity in vitro. Each mutant allele has been cloned and sequenced, and the lesions responsible for the cold-sensitive phenotypes identified. All the mutations were found to map to regions that are conserved between the fission yeast p34cdc2 and functional homologues from higher eukaryotes.</p

Lipase-Responsive Amphotericin B Loaded PCL Nanoparticles for Antifungal Therapies

Amphotericin B is an antifungal drug used for the treatment of invasive fungal infections. However, its clinical use is limited due to its serious side effects, such as renal and cardiovascular toxicity. Furthermore, amphotericin B is administered in high doses due to its poor water solubility. Hence, it is necessary to develop an on-demand release strategy for the delivery of amphotericin B to reduce cytotoxicity. The present report describes a novel encapsulation of amphotericin B into lipase-sensitive polycaprolactone to form a nanocomposite. Nanocomposites were produced by the oil-in-water method and their physicochemical properties such as size, hydrodynamic diameter, drug loading, and zeta potential were determined. The in vitro release of amphotericin B was characterized in the presence and absence of lipase. The antifungal activity of the nanocomposites was verified against lipase-secreting Candida albicans, and cytotoxicity was tested against primary human dermal fibroblasts. In the absence of lipase, the release of amphotericin B from the nanocomposites was minimal. However, in the presence of lipase, an enzyme that is abundant at infection sites, a fungicidal concentration of amphotericin B was released from the nanocomposites. The antifungal activity of the nanocomposites showed an enhanced effect against the lipase-secreting fungus, Candida albicans, in comparison to the free drug at the same concentration. Furthermore, nanoencapsulation significantly reduced amphotericin B-related cytotoxicity compared to the free drug. The synthesized nanocomposites can serve as a potent carrier for the responsive delivery of amphotericin B in antifungal applications

Cold-sensitive mutants of p34^cdc2 that suppress a mitotic catastrophe phenotype in fission yeast

The p34cdc2 protein kinase plays a central role in the regulation of the eukaryotic cell cycle, being required both in late G1 for the commitment to S-phase and in late G2 for the initiation of mitosis. p34cdc2 also determines the precise timing of entry into mitosis in fission yeast, where a number of gene products that regulate p34cdc2 activity have been identified and characterised. To investigate further the mitotic role of p34cdc2 in this organism we have isolated new cold-sensitive p34cdc2 mutants. These are defective only in their G2 function and are extragenic suppressors of the lethal premature entry into mitosis brought about by mutating the mitotic inhibitor p107wee1 and overproducing the mitotic activator p80cdc25. One of the mutant proteins p34cdc2-E8 is only functional in the absence of p107wee1, and all the mutant strains have reduced histone H1 kinase activity in vitro. Each mutant allele has been cloned and sequenced, and the lesions responsible for the cold-sensitive phenotypes identified. All the mutations were found to map to regions that are conserved between the fission yeast p34cdc2 and functional homologues from higher eukaryotes.</p

Molecular cloning and sequence-analysis of mutant alleles of the fission yeast <em>cdc2</em> protein kinase gene:implications for cdc2 protein-structure and function

The cdc2 + gene function plays a central role in the control of the mitotic cell cycle of the fission yeast Schizosaccharomyces pombe. Recessive temperature-sensitive mutations in the cdc2 gene cause cell cycle arrest when shifted to the restrictive temperature, while a second class of mutations within the cdc2 gene causes a premature advancement into mitosis. Previously the cdc2 + gene has been cloned and has been shown to encode a 34 kDa phosphoprotein with in vitro protein kinase activity. Here we describe the cloning of 11 mutant alleles of the cdc2 gene using two simple methods, one of which is presented here for the first time. We have sequenced these alleles and find a variety of single amino acid substitutions mapping throughtout the cdc2 protein. Analysis of these mutations has identified a number of regions within the cdc2 protein that are important for cdc2 + activity and regulation. These include regions which may be involved in the interaction of the cdc2 + gene product with the proteins encoded by the wee1 +, cdc13 + and suc1 + genes

Nanomechanical tribological characterisation of nanostructured titanium alloy surfaces using AFM: A friction vs velocity study

Medical-grade titanium alloys used for orthopaedic implants are at risk from infections and complications such as wear and tear. We have recently shown that hydrothermally etched (HTE) nanostructures (NS) formed on the Ti6AlV4 alloy surfaces impart enhanced anti-bacterial activity which results in inhibited formation of bacterial biofilm. Although these titanium alloy nanostructures may resist bacterial colonisation, their frictional properties are yet to be understood. Orthopaedic devices are encapsulated by bone and muscle tissue. Contact friction between orthopaedic implant surfaces and these host tissues may trigger inflammation, osteolysis and wear. To address these challenges, we performed simulation of the contact behaviour between a smooth control Ti6Al4V alloy and HTE surfaces against a hardwearing SiO2 sphere using Atomic Force Microscopy (AFM) in Lateral Force Microscopy mode. The friction study was evaluated in both air and liquid environments at high (5 Hz) and low (0.5 Hz) scan velocities. Lower scan velocities demonstrated opposing friction force changes between the two mediums, with friction stabilising at higher velocities. The friction measured on the NS alloy surfaces was reduced by ~20% in air and ~80% in phosphate buffered saline, in comparison to the smooth control surface, displaying a non-linear behaviour of the force applied by the AFM tip. Changes in friction values and cantilever scan velocities on different substrates are discussed with respect to the Stribeck curve. Reduced friction on nanostructured surfaces may improve wear resistance and aid osseointegration