Genomic instability in human lymphocytes irradiated with individual charged particles: Involvement of tumor necrosis factor a in irradiated cells but not bystander cells

Exposure to ionizing radiation can increase the risk of cancer, which is often characterized by genomic instability. In environmental exposures to high-LET radiation (e.g. Ra-222), it is unlikely that many cells will be traversed or that any cell will be traversed by more than one alpha particle, resulting in an in vivo bystander situation, potentially involving inflammation. Here primary human lymphocytes were irradiated with precise numbers of He-3(2+) ions delivered to defined cell population fractions, to as low as a single cell being traversed, resembling in vivo conditions. Also, we assessed the contribution to genomic instability of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFA). Genomic instability was significantly elevated in irradiated groups ( greater than or equal totwofold over controls) and was comparable whether cells were traversed by one or two He-3(2+) ions. Interestingly, substantial heterogeneity in genomic instability between experiments was observed when only one cell was traversed. Genomic instability was significantly reduced (60%) in cultures in which all cells were irradiated in the presence of TNFA antibody, but not when fractions were irradiated under the same conditions, suggesting that TNFA may have a role in the initiation of genomic instability in irradiated cells but not bystander cells. These results have implications for low-dose exposure risks and cancer. (C) 2005 by Radiation Research Society.

‘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).

Accumulation, Subcellular Distribution and Toxicity of Copper in Earthworm (Eisenia fetida) in the Presence of Ciprofloxacin

Land application of wastes from concentrated animal feeding operations results in accumulation of copper (Cu) and antimicrobials in terrestrial systems. Interaction between Cu and antimicrobials may change Cu speciation in soil solution, and affect Cu bioavailability and toxicity. In this study, earthworms were exposed to quartz sand percolated with different concentrations of Cu and ciprofloxacin (CIP). Copper uptake by earthworms, its subcellular partition, and toxicity were studied. An increase in the applied CIP decreased the free Cu ion concentration in external solution and mortalities of earthworm, while Cu contents in earthworms increased. Copper and CIP in earthworms were fractionated into five fractions: a granular fraction (D), a fraction consisting of tissue fragments, cell membranes, and intact cells (E), a microsomal fraction (F), a denatured proteins fraction (G), and a heat-stable proteins fraction (H). Most of the CIP in earthworms was in fraction H. Copper was redistributed from the metal-sensitive fraction E to fractions D, F, G, and H with increasing CIP concentration. These results challenge the free ion activity model and suggested that Cu may be partly taken up as Cu-CIP complexes in earthworms, changing the bioavailability, subcellular distribution, and toxicity of Cu to earthworms.

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.

AcT-2: A Novel Myotropic and Antimicrobial Type 2 Tryptophyllin from the Skin Secretion of the Central American Red-Eyed Leaf Frog, Agalychnis callidryas

Tryptophyllins are a diverse family of amphibian peptides originally found in extracts of phyllomedusine frog skin by chemical means. Their biological activities remain obscure. Here we describe the isolation and preliminary pharmacological characterization of a novel type 2 tryptophyllin, named AcT-2, from the skin secretion of the red-eyed leaf frog, Agalychnis callidryas. The peptide was initially identified during smooth muscle pharmacological screening of skin secretion HPLC fractions and the unique primary structure—GMRPPWF-NH2—was established by both Edman degradation and electrospray MS/MS fragmentation sequencing. A. cDNA encoding the biosynthetic precursor of AcT-2 was successfully cloned from a skin secretion-derived cDNA library by means of RACE PCR and this contained an open-reading frame consisting of 62 amino acid residues with a single AcT-2 encoding sequence located towards the C-terminus. A synthetic replicate of AcT-2 was found to relax arterial smooth muscle (EC50 = 5.1 nM) and to contract rat urinary bladder smooth muscle (EC50 = 9.3 μM). The peptide could also inhibit the growth of the microorganisms, Staphylococcus aureus, (MIC = 256 mg/L) Escherichia coli (MIC = 512 mg/L), and Candida albicans (128 mg/L). AcT-2 is thus the first amphibian skin tryptophyllin found to possess both myotropic and antimicrobial activities.

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.

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.