Enhanced antimicrobial activities of 1-alkyl-3-methyl imidazolium ionic liquids based on silver or copper containing anions

We have developed a series of 1-alkyl-3-methylimidazolium tetrachlorocuprate(II) and dibromoargentate(I) ionic liquids with enhanced antimicrobial activity when compared with 1-alkyl-3-methylimidazolium chloride ionic liquids. These new ionic liquids proved to be effective against a range of pathogenic bacteria and fungi.

‘5 ways to say your prayers’:The Art and Architecture of Curating People, Place and Creativity in a Post-Conflict Context. The Shed, Galway, Ireland 18th June – 23rd July 2013 Includes: 1. Co-Curation of Exhibition with Peter Mutschler, Director of PS² and 2. Morrow’s individual work as part of the exhibition, entitled ‘Departures & Arrivals: Academic Interactions with the Activities, Artists and Archive of PS² ’

This exhibition profiles the curatorial approach of PS² and the work of creative practitioners who have practiced alongside and with the organisation. PS² is a Belfast-based, voluntary arts organisation that initiates projects inside and outside its project space. It seeks to develop a socio-spatial practice that responds to the post-conflict context of Northern Ireland, with particular focus on active intervention and social interaction between local people, creative practitioners, multidisciplinary groups and theorists.
Morrow has collaborated with PS² since its inception in 2005, acting as curatorial advisor specifically on the projects that occur outside PS² . She regards her involvement as a parallel action to her pedagogical explorations within architectural education.

Morrow's personal contribution to the Exhibition aimed to:
-interrogate PS² spatial projects
-contextualise PS² curatorial practice
-open up the analytical framework and extend to similar local practices

The Shed, Galway, Ireland is a joint Galway City Arts and Harbour Company venture. The exhibition subsequently travelled to DarcSpace Gallery, Dublin (Sept 2013).

Spatial autocorrelation in the response of soft-bottom marine benthos to gas extraction activities: The case of amphipods in the Ionian Sea

The spatial distributions of marine fauna and of pollution are both highly structured, and thus the resulting high levels of autocorrelation may invalidate conclusions based on classical statistical approaches. Here we analyse the close correlation observed between proxies for the disturbance associated with gas extraction activities and amphipod distribution patterns around four hydrocarbon platforms. We quantified the amount of variation independently accounted for by natural environmental variables, proxies for the disturbance caused by platforms, and spatial autocorrelation. This allowed us to demonstrate how each of these three factors significantly affects the community structure of amphipods. Sophisticated statistical techniques are required when taking into account spatial autocorrelation: nevertheless our data demonstrate that this approach not only enables the formulation of robust statistical inferences but also provides a much deeper understanding of the subtle interactions between human disturbance and natural factors affecting the structure of marine invertebrates communities. (C) 2012 Elsevier Ltd. All rights reserved.

Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities

Here we report two novel 17-mer amidated linear peptides (TsAP-1 and TsAP-2) whose structures were deduced from cDNAs cloned from a venom-derived cDNA library of the Brazilian yellow scorpion, Tityus serrulatus. Both mature peptides were structurally-characterised following their location in chromatographic fractions of venom and synthetic replicates of each were subjected to a range of biological assays. The peptides were each active against model test micro-organisms but with different potencies. TsAP-1 was of low potency against all three test organisms (MICs 120-160µM), whereas TsAP-2 was of high potency against the Gram-positive bacterium, Staphylococcus aureus (MIC 5µM) and the yeast, Candida albicans (10µM). Haemolytic activity of TsAP-1 was low (4% at 160µM) and in contrast, that of TsAP-2 was considerably higher (18% at 20µM). Substitution of four neutral amino acid residues with Lys residues in each peptide had dramatic effects on their antimicrobial potencies and haemolytic activities, particularly those of TsAP-1. The MICs of the enhanced cationic analogue (TsAP-S1) were 2.5µM for S.aureus/C.albicans and 5µM for E.coli but with an associated large increase in haemolytic activity (30% at 5µM). The same Lys residue substitutions in TsAP-2 produced a dramatic effect on its MIC for E.coli lowering this from >320µM to 5µM. TsAP-1 was ineffective against three of the five human cancer cell lines tested while TsAP-2 inhibited the growth of all five. Lys residue substitution of both peptides enhanced their potency against all five cell lines with TsAp-S2 being the most potent with IC50 values ranging between 0.83 and 2.0 µM. TsAP-1 and TsAP-2 are novel scorpion venom peptides with broad spectrum antimicrobial and anticancer cell activities the potencies of which can be significantly enhanced by increasing their cationicity.

Cathelicidin-like Helminth Defence Molecules (HDMs):Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects.

Partial purification of lymphokine activities by iso-electric focusing

A continuous cell-line has been shown to be adaptable to preparation of supernatants containing lymphokine activities. Separation and partial purification of migration inhibiting, colony stimulating and interferon activities from such preparations has been achieved by the use of density gradient iso-electric focusing.

Distribution of arsenic and risk assessment of activities on a golf course fertilised with arsenic-containing Ascophyllum nodosum seaweed

The use of seaweed fertilisers in sports green maintenance has become a common practice across the globe due to its image as an “eco-friendly” alternative to chemical fertilisers. The aim of this study was to characterise the risk of human exposure to arsenic (As), via dermal absorption, from golfing activities on a private golf course in the UK, where As contaminated seaweed fertiliser (~ 100 mg/kg d.wt.) is applied. This was fulfilled by, 1) determining As concentrations in shallow soils with GIS geo-statistical analysis, 2) measuring As concentrations from an on-site borehole groundwater well, and (3) developing a risk assessment calculation for golfing activities based on field and questionnaire data. Total As concentrations in shallow soils were less than the UK threshold for domestic soils, however, frequent and sustained dermal contact between site-users and surface soil attributed to a maximum carcinogenic risk value of 2.75 × 10− 4, which is in the upper limit of the acceptable risk range. Arsenic concentrations in underlying groundwater exceeded the WHO's permissible drinking water standard, demonstrating the risk of groundwater contamination following the application of seaweed fertiliser to golf course soils. This is the first risk study on dermal As absorption via the application of a seaweed fertiliser.

Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation

Objective: Enhanced oxidative stress is involved in mediating the endothelial dysfunction associated with hypertension. The aim of this study was to investigate the relative contributions of pro-oxidant and anti-oxidant enzymes to the pathogenesis of endothelial dysfunction in genetic hypertension. Methods: Dilator responses to endothelium-dependent and endothelium-independent agents such as acetylcholine (ACh) and sodium nitroprusside were measured in the thoracic aortas of 28-week-old spontaneously hypertensive rats (SHR) and their matched normotensive counterparts, Wistar Kyoto rats (WKY). The activity and expression (mRNA and protein levels) of endothelial nitric oxide synthase (eNOS), p22-phox, a membrane-bound component of NAD(P)H oxidase, and antioxidant enzymes, namely, superoxide dismutases (CuZn- and Mn-SOD), catalase and glutathione peroxidase (GPx), were also investigated in aortic rings. Results: Relaxant responses to ACh were attenuated in phenylephrine-precontracted SHR aortic rings, despite a 2-fold increase in eNOS expression and activity. Although the activity and/or expression of SODs, NAD(P)H oxidase (p22-phox) and GPx were elevated in SHR aorta, catalase activity and expression remained unchanged compared to WKY. Pretreatment of SHR aortic rings with the inhibitor of xanthine oxidase, allopurinol, and the inhibitor of cyclooxygenase, indomethacin, significantly potentiated ACh-induced relaxation. Pretreatment of SHR rings with catalase and Tiron, a superoxide anion (O) scavenger, increased the relaxant responses to the levels observed in WKY rings whereas pyrogallol, a O -generator, abolished relaxant responses to ACh. Conclusion: These data demonstrate that dysregulation of several enzymes, resulting in oxidative stress, contributes to the pathogenesis of endothelial dysfunction in SHR and indicate that the antioxidant enzyme catalase is of particular importance in the reversal of this defect. © 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

A randomised controlled trial of increasing fruit and vegetable intake and how this influences the carotenoid concentration and activities of PON-1 and LCAT in HDL from subjects with type 2 diabetes

Background

High density lipoproteins (HDL) have many cardioprotective roles; however, in subjects with type 2 diabetes (T2D) these cardioprotective properties are diminished. Conversely, increased fruit and vegetable (F&V) intake may reduce cardiovascular disease risk, although direct trial evidence of a mechanism by which this occurs in subjects with T2D is lacking. Therefore, the aim of this study was to examine if increased F&V consumption influenced the carotenoid content and enzymes associated with the antioxidant properties of HDL in subjects with T2D.

Eighty obese subjects with T2D were randomised to a 1- or ≥6-portion/day F&V diet for 8-weeks. Fasting serum was collected pre- and post-intervention. HDL was subfractionated into HDL₂ and HDL₃ by rapid ultracentrifugation. Carotenoids were measured in serum, HDL₂ and HDL₃ by high performance liquid chromatography. The activity of paraoxonase-1 (PON-1) was measured in serum, HDL₂ and HDL₃ by a spectrophotometric assay, while the activity of lecithin cholesterol acyltransferase (LCAT) was measured in serum, HDL₂ and HDL₃ by a fluorometric assay.

In the ≥6- vs. 1-portion post-intervention comparisons, carotenoids increased in serum, HDL₂ and particularly HDL₃, (α-carotene, p = 0.008; β-cryptoxanthin, p = 0.042; lutein, p = 0.012; lycopene, p = 0.016), as did the activities of PON-1 and LCAT in HDL₃ (p = 0.006 and 0.044, respectively).

To our knowledge, this is the first study in subjects with T2D to demonstrate that increased F&V intake augmented the carotenoid content and influenced enzymes associated with the antioxidant properties of HDL. We suggest that these changes would enhance the cardioprotective properties of this lipoprotein.

METAMORPHOSE VI – the Virtual Institute for artificial electromagnetic materials and metamaterials: Origin, mission, and activities

In this paper, we outline the background, mission, and activities of the Virtual Institute for Artificial Electromagnetic Materials and Metamaterials (METAMORPHOSE VI). This international association, founded in the framework of the FP-6 Network of Excellence METAMORPHOSE, aims at promoting and developing research, training, and dissemination activities in the emerging and highly dynamic field of advanced electromagnetic materials and metamaterials at both European and International levels. More than 300 researchers are currently associated with the METAMORPHOSE VI which networks them together in a learnt society. After a brief description of the association and its mission, we present an overview of the activities developed by the METAMORPHOSE VI, with a particular emphasis on the coordination of the European Doctoral Program on Metamaterials (EUPROMETA) and the organization of the International Congress on Advanced Electromagnetic Materials in Microwaves and Optics – metamaterials congress.

AaeAP1 and AaeAP2: Novel Antimicrobial Peptides from the Venom of the Scorpion, Androctonus aeneas: Structural Characterisation, Molecular Cloning of Biosynthetic Precursor-Encoding cDNAs and Engineering of Analogues with Enhanced Antimicrobial and Anticancer Activities

The main functions of the abundant polypeptide toxins present in scorpion venoms are the debilitation of arthropod prey or defence against predators. These effects are achieved mainly through the blocking of an array of ion channel types within the membranes of excitable cells. However, while these ion channel-blocking toxins are tightly-folded by multiple disulphide bridges between cysteine residues, there are additional groups of peptides in the venoms that are devoid of cysteine residues. These non-disulphide bridged peptides are the subject of much research interest, and among these are peptides that exhibit antimicrobial activity. Here, we describe two novel non-disulphide-bridged antimicrobial peptides that are present in the venom of the North African scorpion, Androctonus aeneas. The cDNAs encoding the biosynthetic precursors of both peptides were cloned from a venom-derived cDNA library using 3'- and 5'-RACE strategies. Both translated precursors contained open-reading frames of 74 amino acid residues, each encoding one copy of a putative novel nonadecapeptide, whose primary structures were FLFSLIPSVIAGLVSAIRN and FLFSLIPSAIAGLVSAIRN, respectively. Both peptides were C-terminally amidated. Synthetic versions of each natural peptide displayed broad-spectrum antimicrobial activities, but were devoid of antiproliferative activity against human cancer cell lines. However, synthetic analogues of each peptide, engineered for enhanced cationicity and amphipathicity, exhibited increases in antimicrobial potency and acquired antiproliferative activity against a range of human cancer cell lines. These data clearly illustrate the potential that natural peptide templates provide towards the design of synthetic analogues for therapeutic exploitation.

Direct and indirect antimicrobial activities of neuropeptides and their therapeutic potential

As global resistance to conventional antibiotics rises we need to develop new strategies to develop future novel therapeutics. In our quest to design novel anti-infectives and antimicrobials it is of interest to investigate host-pathogen interactions and learn from the complexity of host defense strategies that have evolved over millennia. A myriad of host defense molecules are now known to play a role in protection against human infection. However, the interaction between host and pathogen is recognized to be a multifaceted one, involving countless host proteins, including several families of peptides. The regulation of infection and inflammation by multiple peptide families may represent an evolutionary failsafe in terms of functional degeneracy and emphasizes the significance of host defense in survival. One such family is the neuropeptides (NPs), which are conventionally defined as peptide neurotransmitters but have recently been shown to be pleiotropic molecules that are integral components of the nervous and immune systems. In this review we address the antimicrobial and anti-infective effects of NPs both in vitro and in vivo and discuss their potential therapeutic usefulness in overcoming infectious diseases. With improved understanding of the efficacy of NPs, these molecules could become an important part of our arsenal of weapons in the treatment of infection and inflammation. It is envisaged that targeted therapy approaches that selectively exploit the anti-infective, antimicrobial and immunomodulatory properties of NPs could become useful adjuncts to our current therapeutic modalities. © 2012 Bentham Science Publishers.