Molecular characterization of a possible progenitor sodium channel toxin from the Old World scorpion Mesobuthus martensii

AbstractToxins affecting sodium channels widely exist in the venoms of scorpions throughout the world. These molecules comprise an evolutionarily related peptide family with three shared features including conserved three-dimensional structure and gene organization, and similar function. Based on different pharmacological profiles and binding properties, scorpion sodium channel toxins are divided into α- and β-groups. However, their evolutionary relationship is not yet established. Here, we report a gene isolated from the venom gland of scorpion Mesobuthus martensii which encodes a novel sodium channel toxin-like peptide of 64 amino acids, named Mesotoxin. The Mesotoxin gene is organized into three exons and two introns with the second intron location conserved across the family. This peptide is unusual in that it has only three disulfides and a long cysteine-free tail with loop size and structural characteristics close to β-toxins. Evolutionary analysis favors its basal position in the origin of scorpion sodium channel toxins as a progenitor. The discovery of Mesotoxin will assist investigations into the key issue regarding the origin and evolution of scorpion toxins

St Peter-On-The-Wall: Landscape and heritage on the Essex coast

The Chapel of St Peter-on-the-Wall, built on the ruins of a Roman fort, dates from the mid-seventh century and is one of the oldest largely intact churches in England. It stands in splendid isolation on the shoreline at the mouth of the Blackwater Estuary in Essex, where the land meets and interpenetrates with the sea and the sky. This book brings together contributors from across the arts, humanities and social sciences to uncover the pre-modern contexts and modern resonances of this medieval building and its landscape setting. The impetus for this collection was the recently published designs for a new nuclear power station at Bradwell on Sea, which, if built, would have a significant impact on the chapel and its landscape setting. St Peter-on-the-Wall highlights the multiple ways in which the chapel and landscape are historically and archaeologically significant, while also drawing attention to the modern importance of Bradwell as a place of Christian worship, of sanctuary and of cultural production. In analysing the significance of the chapel and surrounding landscape over more than a thousand years, this collection additionally contributes to wider debates about the relationship between space and place, and particularly the interfaces between both medieval and modern cultures and also heritage and the natural environment

The effect of single nucleotide polymorphisms and metabolic substrates on the cellular distribution of mammalian BK channels.

Humans are approximately 99% similar with inter-individual differences caused in part by single-nucleotide polymorphisms (SNPs), which poses a challenge for the effective treatment of disease. Bioinformatics resources can help to store and analyse gene and protein information to address this challenge, however these resources have limitations, so the collation and biocuration of gene and protein information is required. Using the large conductance calcium- and voltage-activated potassium channel, also known as the Big Potassium (BK) channel as an example, due to its ubiquitous expression and widespread varied role in human physiology, this study aimed to prioritise SNPs with the potential to affect the function of the channel. Using a BK channel resource created with bioinformatics tools and published literature, mSlo SNPs H55Q and G57A, located in the S0-S1 linker, were prioritised and selected for lab-based verification. These SNPs flank three cysteine residues proven to modulate channel cellular distribution via palmitoylation, a reversible process shown to increase protein association with the cell membrane. The SNPs alter the predicted palmitoylation status of C56, one of the cysteine residues located in the S0-S1 linker. The cellular distribution of BK channels incorporating the SNPs was assessed using confocal microscopy and revealed that the direction and magnitude of SNP mimetic cell membrane expression was closely related to the C56 predicted palmitoylation score; a 'C56 palmitoylation pattern' was observed. It was shown that exposure to metabolic substrates glucose, palmitate and oleate modulated SNP-mimetic cellular distribution and could invert the 'C56 palmitoylation pattern', indicating that there is interplay between the metabolic status of the cell and the amino-acid composition of the channel via palmitoylation. The creation of a novel BK channel resource in this thesis highlighted the limitations, and inter-dependency of bioinformatics and lab based experimentation, whilst SNP verification experiments solidified the link between S0-S1 cysteine residues and BK cellular distribution. BK channel function is linked with a number of physiological processes; thus, the potential clinical consequences of the SNPs prioritised in this thesis require further research

Multi-species and multi-interest management: An ecosystem approach to market squid (Loligo opalescens) harvest in California

Market squid (Loligo opalescens) plays a vital role in the California ecosystem and serves as a major link in the food chain as both a predator and prey species. For over a century, market squid has also been harvested off the California coast from Monterey to San Pedro. Expanding global markets, coupled with a decline in squid product from other parts of the world, in recent years has fueled rapid expansion of the virtually unregulated California fishery. Lack of regulatory management, in combination with dramatic increases in fishing effort and landings, has raised numerous concerns from the scientific, fishing, and regulatory communities. In an effort to address these concerns, the National Oceanic and Atmospheric Administration’s (NOAA) Channel Islands National Marine Sanctuary (CINMS) hosted a panel discussion at the October 1997 California Cooperative Oceanic and Fisheries Investigations (CalCOFI) Conference; it focused on ecosystem management implications for the burgeoning market squid fishery. Both panel and audience members addressed issues such as: the direct and indirect effects of commercial harvesting upon squid biomass; the effects of harvest and the role of squid in the broader marine community; the effects of environmental variation on squid population dynamics; the sustainability of the fishery from the point of view of both scientists and the fishers themselves; and the conservation management options for what is currently an open access and unregulated fishery. Herein are the key points of the ecosystem management panel discussion in the form of a preface, an executive summary, and transcript. (PDF contains 33 pages.

The Recent History of Platelets in Thrombosis and Other Disorders

The transcript of a Witness Seminar held by the Wellcome Trust Centre for the History of Medicine at UCL, London, on 25 November 2003. Introduction by Professor Tom Meade, London School of Hygiene and Tropical Medicine.First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2005. ©The Trustee of the Wellcome Trust, London, 2005. All volumes freely available following the links to publications and Wellcome Witnesses at www.ucl.ac.uk/histmed.Annotated and edited transcript of a Witness Seminar held on 25 November 2003. Introduction by Professor Tom Meade, London School of Hygiene and Tropical Medicine.Annotated and edited transcript of a Witness Seminar held on 25 November 2003. Introduction by Professor Tom Meade, London School of Hygiene and Tropical Medicine.Annotated and edited transcript of a Witness Seminar held on 25 November 2003. Introduction by Professor Tom Meade, London School of Hygiene and Tropical Medicine.Annotated and edited transcript of a Witness Seminar held on 25 November 2003. Introduction by Professor Tom Meade, London School of Hygiene and Tropical Medicine.Annotated and edited transcript of a Witness Seminar held on 25 November 2003. Introduction by Professor Tom Meade, London School of Hygiene and Tropical Medicine.Annotated and edited transcript of a Witness Seminar held on 25 November 2003. Introduction by Professor Tom Meade, London School of Hygiene and Tropical Medicine.The recent history of research on platelets and its applications in medicine started with the introduction of ex vivo methods for studying platelet behaviour. The Witness Seminar held on 25 November 2003, chaired by Professor Tom Meade, considered the detailed study of platelets starting with the recognition of their role in haemostasis, both in thrombotic and bleeding disorders . Professor Gustav Born described his research and the invention and development of the optical aggregometer that bears his name. Other topics included the biochemistry and function of platelets ; the platelet release reaction and the effect of aspirin on it ; the Nobel Prize-winning discovery by Sir John Vane of how aspirin inhibits the natural production of prostaglandins; and results of randomized controlled trials of aspirin and other thrombolytic drugs for the prevention of thrombotic conditions. An appendix includes a discussion of the streptokinase trials, 1986-96, from the unpublished Witness Seminar meeting on Thrombolysis held on 28 January 2003, chaired by Professor Brian Pentecost. Participants : Dr Y S [Mick] Bakhle, Sir Christopher Booth, Professor Donald Chambers, Professor John Dickinson, Professor Peter Elwood, Professor Rod Flower, Professor Alison Goodall, Professor John Hampton, Professor Michael Harrison, Professor Stan Heptinstall, Dr Peter Hunter, Dr Peter MacCallum, Dr Marty Mahaut-Smith, Professor Salvador Moncada, Professor Michael Oliver, Professor Clive Page, Professor Sir Stanley Peart, Professor Colin Prentice, Professor Peter Richardson, Dr Stewart Sage, and Dr Duncan Thomas; and from Thrombolysis, Dr Hewan Dewar, the late Sir Richard Doll, Professor John Hampton, Dr Arthur Hollman, Professor Desmond Julian, Dr Robin Norris, Professor Tom Quinn, Dr Roger Smith, and Professor Andrew Stevens. Reynolds L A, Tansey E M. (eds) (2005) The Recent history of platelets in thrombosis and other disorders, Wellcome Witnesses to Twentieth Century Medicine, vol. 23. London: The Wellcome Trust Centre for the History of Medicine at UCL.The Wellcome Trust Centre for the History of Medicine at UCL is funded by the Wellcome Trust,which is a registered charity, no. 210183

Cholesterol, Atherosclerosis and Coronary Disease in the UK, 1950–2000.

Annotated and edited transcript of a Witness Seminar held on 8 March 2005. Introduction by Dr Nick Myant, Hammersmith Hospital, London.First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2006. ©The Trustee of the Wellcome Trust, London, 2006. All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/Annotated and edited transcript of a Witness Seminar held on 8 March 2005. Introduction by Dr Nick Myant, Hammersmith Hospital, London.Annotated and edited transcript of a Witness Seminar held on 8 March 2005. Introduction by Dr Nick Myant, Hammersmith Hospital, London.Annotated and edited transcript of a Witness Seminar held on 8 March 2005. Introduction by Dr Nick Myant, Hammersmith Hospital, London.Annotated and edited transcript of a Witness Seminar held on 8 March 2005. Introduction by Dr Nick Myant, Hammersmith Hospital, London.Annotated and edited transcript of a Witness Seminar held on 8 March 2005. Introduction by Dr Nick Myant, Hammersmith Hospital, London.Annotated and edited transcript of a Witness Seminar held on 8 March 2005. Introduction by Dr Nick Myant, Hammersmith Hospital, London.Cholesterol began to be accepted after the Second World War as a significant cause of atherosclerosis and associated conditions such as coronary heart disease (CHD). This Witness Seminar, chaired by Professor Michael Oliver, included a discussion of the basic research on cholesterol. Early epidemiological studies demonstrated the relationship between excess saturated fat consumption and elevated levels of cholesterol, although cholesterol alone did not explain all population differences. Work on lipoprotein metabolism pointed to hypercholesterolaemia as one of, if not the major, risk factors for CHD, culminating in the development of cholesterol-lowering drugs, particularly the successful statins, available in the UK from the 1980s, and confirmed by randomized controlled trials. The role of diet in heart disease had always been controversial in the UK, and although extreme diets could reduce cholesterol, patient conformity remains difficult. Later, recommended limits on the composition of dietary fat were agreed, assisted by the food industry's introduction of functional foods such as cholesterol-lowering margarine. An introduction by Dr Nick Myant and appendices, on the diet-heart hypothesis by Professor Gerry Shaper and the development of lovastatin by Dr Jonathan Tobert, compliment the transcript. Contributors include Professor David Barker, Professor John Betteridge, Professor Gustav Born, Professor Richard Bruckdorfer, Professor George Davey Smith, Professor Paul Durrington, Professor David Galton, Dr Arthur Hollman, Professor Steve Humphries Professor Gordon Lowe, Professor Vincent Marks, Dr Paul Miller, Professor Jerry Morris, Professor Chris Packard, Professor Stuart Pocock, Professor Kalevi Pyörälä, Professor Thomas Sanders, Professor James Scott, Dr Elspeth Smith, Professor Anne Soutar, Professor Gilbert Thompson, Professor Hugh Tunstall-Pedoe, Professor Neville Woolf and Professor John S Yudkin. Reynolds L A, Tansey E M. (eds) (2006) Cholesterol, atherosclerosis and coronary disease in the UK, 1950–2000, Wellcome Witnesses to Twentieth Century Medicine, vol. 27. London: The Wellcome Trust Centre for the History of Medicine at UCL.The Wellcome Trust Centre for the History of Medicine at UCL is funded by the Wellcome Trust, which is a registered charity, no. 210183

GABA is an inhibitory neurotransmitter in the neural circuit regulating metamorphosis in Ilyanassa obsoleta

The marine mud snail, Ilyanassa obsoleta, displays a biphasic life cycle. The initial phase consists of weakly swimming larval animals with ciliated feeding structures on the head, the velar lobes. The second phase consists of adult animals residing on intertidal mudflats as obligate omnivores. Metamorphosis, the event that links these life history stages, is initiated by external stimuli but coordinated by internal signaling molecules. Internally, molluscan metamorphosis includes neurotransmitters that modify the behavior of cells in neural circuits. For several species of molluscs, including abalone and scallops, larval metamorphosis can be induced by the external application of the neurotransmitter, gamma-aminobutyric acid (GABA). In this situation, GABA is presumed to mimic the actions of food-related ligands that bind to external sensory receptors. GABA is the only neurotransmitter known to act in such a fashion. In contrast, results of our preliminary experiments with I. obsoleta strongly support the hypothesis that GABA works internally in this species as a neurotransmitter in the larval central nervous system (CNS) to inhibit metamorphosis. External application of GABA to metamorphically competent larvae of I. obsoleta does not elicit metamorphosis, but does repress metamorphic induction. I utilized a battery of GABAergic reagents to modify internal GABAergic activity to address the hypothesis that GABA inhibits metamorphosis due to its actions within the larval CNS. My results strongly suggest that GABA inhibits metamorphosis in this molluscan model organism. My results indicate that GABA acts downstream from or directly on serotonergic neurons to decrease the metamorphosis-inducing effects of serotonin

The Courier, Volume 6, Issue 30, May 31, 1973

Stories: Students Tour Building, Coin Word ‘Sodbusters’ Woman Politician Says Get Involved Experimental College Still ‘Daring’ After 3rd Year Faculty Deplores 2.7% Raise Selected Colleges That May Interest Transferees “Promises, Promises”, ‘Darned’ Exuberant Play “Worlds” Reflects Our Hidden Selves Editorial Views on Watergate People: Joan Anderson Narin Bowde