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.

A solution concept for network games: The role of multilateral interactions

We propose an allocation rule that takes into account the importance of both players and their links and characterize it for a fixed network. Our characterization is along the lines of the characterization of the Position value for Network games by van den Nouweland and Slikker (2012). The allocation rule so defined admits multilateral interactions among the players through their links which distinguishes it from the other existing rules. Next, we extend our allocation rule to flexible networks à la Jackson (2005).

Preparation of Dess-Martin periodinane - The role of the morphology of 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide precursor

1-Hydroxy-1,2-benziodoxol-3(1H)-one I-oxide prepared by oxidation of o-iodobenzoic acid with potassium bromate forms either a microcrystalline powder, a macrocrystalline material, or a mixture of both forms. This difference in physical form is the source of the difficulty in reproducibly converting 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide to the corresponding I-triacetoxy derivative. A simple method is given for conversion of crystalline 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide to the more reactive powder form, The microcrystalline powder and macrocrystalline material are characterised by X-ray diffraction.

Evolving national park models: The emergence of an economic imperative and its effect on the contested nature of the 'national' park concept in Northern Ireland.

National park models have evolved in tandem with the emergence of a multifunctional countryside. Sustainable development has been added to the traditional twin aims of conservation and recreation. This is typified by recent national park designations, such as the Cairngorms National Park in Scotland. A proposed Mournes national park in Northern Ireland has evolved a stage further with a model of national park to deliver national economic goals envisaged by government. This seeks to commodify the natural landscape. This paper compares Cairngorm and Mourne stakeholders’ views on the principal features of both models: park aims, management structures and planning functions. While Cairngorm stakeholders were largely positive from the outset, the model of national park introduced is not without criticism. Conversely, Mourne stakeholders have adopted an anti-national park stance. Nevertheless, the model of national park proposed possessing a strong economic imperative, an absence of the Sandford Principle as a means to manage likely conflicts, and lacking any planning powers in its own right, may still be insufficient to bring about widespread support for a Mourne national park. Such a model is also likely to accelerate the degradation of the Mourne landscape. Competing national identities (British and Irish) provide an additional dimension to the national park debate in Northern Ireland. Deep ideological cleavages are capable of derailing the introduction of a national park irrespective of the model proposed. In Northern Ireland the national park debate is not only about reconciling environmental and economic interests but also political and ethno-national differences.

Translation as an Evaluative Concept

Testing the hypothesis that the concept of translation is evaluative rather than merely descriptive, Blumczyński analyses its increasingly popular use in three areas: political discourse, life writing and biomedical publications. He argues that translation as an evaluative concept is concerned with profound rather than superficial issues: to translate something is to assert its significance and value. At the same time, translation brings to the surface real and authentic things, producing its therapeutic value: it makes us more visible to ourselves, exposes pretences and thus brings relief. Finally, translation delivers on its own ethical imperative by breaking the spell of proverbial good intentions and bringing things to completion.

Generation, Release, and Uptake of the NAD Precursor Nicotinic Acid Riboside by Human Cells

NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5'-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5'-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors.