Domoic acid is a kainic acid-type neurotoxin that causes amnesic shellfish poisoning. It is produced by algae and accumulates in shellfish and anchovies; when sea lions, cetaceans and other predators eat contaminated animals, poisoning may result. Exposure to this compound affects the brain, causing seizures, death. There has been little use of domoic acid throughout history except for in Japan, where it has been used as an anthelmintic for centuries. Domoic acid was first isolated in 1959 from a species of Chondria armata, in Japan. Poisonings in history undocumented. In 2015, the North American pacific coast was impacted by an algal bloom, consisting predominantly of the domoic acid producing pennate diatom, Pseudo-nitzschia. Elevated levels of domoic acid were measured in stranded marine mammals, prompting the closure of beaches and damaging razor clam, rock crab and Dungeness crab fisheries. In 1961, seabirds attacked the Capitola area in California, though it was never confirmed, they were thought to be under the influence of domoic acid.
In 1987, on Prince Edward Island, there was a shellfish poisoning resulting in 3 deaths. Blue mussels contaminated with domoic acid were blamed. Domoic acid has been suggested to have been involved in incident in which took place on June 22, 2006, when a California brown pelican flew through the windshield of a car on the Pacific Coast Highway. On Friday, June 14, 2019, a teenager was attacked and injured by a sea lion, alleged to be under the influence of domoic acid in Pismo Beach on the Central California coast Domoic acid is a structural analog of kainic acid and endogenous excitatory neurotransmitter glutamate. Ohfune and Tomita, who wanted to investigate its absolute stereochemistry, were the first and only to synthesize domoic acid in 1982. In 1999, using 13C- and 14C-labelled precursors, the biosynthesis of domoic acid in the diatom genus Pseudo-nitzschia was examined. After addition of -acetate, NMR spectroscopy showed enrichment of every carbon in domoic acid, indicating incorporation of the carbon isotopes.
This enrichment was consistent with two biosynthetic pathways. The labeling pattern determined that domoic acid can be biosynthesized by an isoprenoid intermediate in combination with a tricarboxylic acid cycle intermediate. In 2018, using growth conditions known to induce domoic acid production in Pseudo-nitzschia multiseries, transcriptome sequencing identified candidate domoic acid biosynthesis genes responsible for the pyrrolidine core; these domoic acid biosynthesis genes, or ‘Dab’ enzymes were heterologously expressed and annotated as dabA, dabB, dabC, dabD. Domoic acid biosynthesis begins with the DabA-catalyzed geranylation of L-glutamic acid with geranyl pyrophosphate to form N-geranyl-L-glutamic acid. DabD performs three successive oxidation reactions at the 7′-methyl of L-NGG to produce 7′-carboxy-L-NGG, cyclized by DabC to generate the occurring isodomoic acid A. Finally, an uncharacterized isomerase could convert isodomoic acid A to domoic acid. Further investigation is needed to resolve the final isomerization reaction to complete the pathway to Domoic acid.
Using intermediates 5 and 6, a Diels-Alder reaction produced a bicyclic compound. 7 underwent ozonolysis to open the six-membered ring leading to selenide. 8 was deselenated to form 9, lastly leading to the formation of domoic acid. The effects of domoic acid have been attributed to several mechanisms, but the one of concern is through glutamate receptors. Domoic acid is an excitatory amino acid analogue of glutamate. Domoic acid has a strong affinity for these receptors, which results in excitotoxicity initiated by an integrative action on ionotropic glutamate receptors at both sides of the synapse, coupled with the effect of blocking the channel from rapid desensitization. In addition there is a synergistic effect with endogenous glutamate and N-Methyl-D-aspartate receptor agonists that contribute to the excitotoxicity. In the brain, domoic acid damages the hippocampus and amygdaloid nucleus, it damages the neurons by activating kainate receptors, causing an influx of calcium. Although calcium flowing into cells is normal, the uncontrolled increase of calcium causes the cells to degenerate.
Because the hippocampus may be damaged, short-term memory loss occurs. It may cause kidney damage – at levels considered safe for human consumption, a new study in mice has revealed; the kidney is affected at a hundred times lower than the concentration allowed under FDA regulations. Domoic acid producing algal blooms are associated with the phenomenon of amnesic shellfish poisoning. Domoic acid can bioaccumulate in marine organisms such as shellfish and sardines that feed on the phytoplankton known to produce this toxin, it can accumulate in high concentrations in the tissues of these plankton feeders when the toxic phytoplankton are high in concentration in the surrounding waters. Domoic acid is a neurotoxin that inhibits neurochemical processes, causing short-term memory loss, brain damage, and, in severe cases, death in humans. In marine mammals, domoic acid causes seizures and tremors. Studies have shown that there are no symptomatic
The Diplomatic Academy of the United Kingdom is part of the Foreign and Commonwealth Office. The creation of a new Diplomatic Academy was announced in a speech by William Hague, Secretary of State for Foreign and Commonwealth Affairs, on 19 September 2013 on the occasion of the opening of the FCO's new Language Centre; the Academy began operating in 2014 and was opened by Foreign Secretary Philip Hammond on 10 February 2015. The Academy is a Directorate of the FCO; the initial Director of the Academy was Jon Davies. His successor as Director is Jon Benjamin; the Academy was structured into 11 thematic areas, or "Faculties": These were: International Policy, Diplomatic Practice and Societies, Understanding the UK, Consular and Crisis Management and Prosperity, Multilateral, Security Defence and Intelligence and Languages. A twelfth Faculty - Trade Policy and Negotiations - was added in 2016 after the UK vote to leave the European Union. In 2017 the Academy absorbed further internal responsibilities for management and leadership training and for the FCO's overseas network of Regional Learning & Development Teams, which were renamed as the Diplomatic Academy Regional Teams.
The Diplomatic Academy is now the principal learning and development organisation of the FCO. The administrative offices and training rooms of the Diplomatic Academy are located in the main building of the FCO in King Charles Street, London. A new learning facility named the Mayhew Theatre was opened on 4 March 2019 by Prince William, Duke of Cambridge; the theatre was given this name following a vote of FCO staff. The Academy's face-to-face and online programmes are aimed at FCO employees and employees of other UK government departments and agencies who are working in international roles, it does not offer external enrolment on face-to-face courses, but it did pilot a Massive Open Online Course entitled Diplomacy in the 21st Century, developed with the Open University and ran on the FutureLearn platform in January–March and May-July 2019 with over 13,500 registrations in total. A second online course entitled Introduction to British Diplomacy is set to launch on 17 February 2020
David Barron is a British film producer, best known for his involvement in the Harry Potter film series. Barron has worked in the entertainment industry for more than 25 years, beginning his career in commercials before moving into television and film production, he has held a wide range of posts, including location manager, assistant director, production manager and production supervisor, working on such films as The French Lieutenant's Woman, The Killing Fields, Legend, The Princess Bride and Franco Zeffirelli's Hamlet. In 1991, Barron was appointed executive in charge of production on George Lucas' ambitious television project The Young Indiana Jones Chronicles; the following year, he served as the line producer on the feature The Muppet Christmas Carol. In 1993, Barron joined Kenneth Branagh's production team as associate producer and unit production manager on Mary Shelley's Frankenstein; that film began an association with Branagh, with Barron going on to produce the director's films A Midwinter's Tale and Love's Labour's Lost.
Barron produced Oliver Parker's Othello, in which Branagh starred with Laurence Fishburne. In spring 1999, he formed Contagious Films, with British director Paul Weiland. Barron more launched Runaway Fridge Films and Beagle Pug Films, he worked as a producer on Harry Potter and the Deathly Hallows – Part 1 and Part 2. He served as a producer on Harry Potter and the Half-Blood Prince and Harry Potter and the Order of the Phoenix, he was an executive producer on both Harry Potter and the Chamber of Secrets and Harry Potter and the Goblet of Fire. Escape from Pretoria — Producer Mowgli: Legend of the Jungle – Producer Terminal – Producer Breathe – Producer The Legend of Tarzan – Producer Cinderella – Producer Frank – Producer Jack Ryan: Shadow Recruit – Producer Harry Potter and the Deathly Hallows – Part 2 – Producer Page Eight – Producer Harry Potter and the Deathly Hallows – Part 1 – Producer Harry Potter and the Half-Blood Prince – Producer Harry Potter and the Order of the Phoenix – Producer Harry Potter and the Goblet of Fire – Executive Producer Sahara – Co-Producer Harry Potter and the Chamber of Secrets – Executive Producer Possession – Executive Producer It Was an Accident – Executive Producer Love's Labours Lost – Producer Hamlet – Producer In the Bleak Midwinter – Producer Othello – Producer Mary Shelly's Frankenstein – Associate Producer, Unit Production Manager The Muppet Christmas Carol – Line Producer Nightbreed – Production Supervisor Strapless – Production Supervisor The Lonely Passion of Judith Hearne – Production Supervisor The Princess Bride – Production Manager Revolution – Production Manager Legend – Unit Manager The Killing Fields – 2nd Assistant Director The French Lieutenant's Woman – Location Manager David Barron on IMDb