Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation

BACKGROUND: X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1) repeats are relatively enriched on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes. RESULTS: Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could confer the capacity for relatively efficient chromosome-wide silencing. CONCLUSIONS: This study provides insight into the requirements for efficient Xist mediated silencing and specifically identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major influence on the ability of Xist-mediated silencing to be propagated in a continuous manner in cis

Educational nt is in space of the point-rating system

The educational technologies used in an educational process require permanent perfection. Setting of shell of the last operating system of computer resulted in shutting down of CAS of testing and use of Bank of test tasks. Changes in Norms of time toward the increase of composition of academic group (2530 persons) resulted in distortions of the point-rating system.Образовательные технологии, используемые в учебном процессе, требуют постоянного совершенствования. Установка оболочки последней операционной системы компьютера привела к прекращению работы Автоматизированной системы тестирования (АСТ) и использования Банка тестовых заданий (БТЗ). Изменения в последних Нормах времени в сторону увеличения состава академической группы (2530человек) привели к искажениям балльно-рейтинговой системы (БРС)

France, Italy and Diplomatic End of Italo-Ethiopian War in League of Nations (May—July 1936)

The article is devoted to the policy of France towards Italy and Ethiopia at the final stage of the Italo-Ethiopian war of 1935—1936 and the question of the elimination of anti-Italian sanctions in the League of Nations. It was revealed that the great powers were mainly interested in restoring normal relations with Italy, while the defense of Ethiopia’s independence was only a “moral duty” for them, and in the clash of moral factors and real politics, the real interests of states won undoubtedly. It is argued that, taking ad-vantage of France’s interest in restoring stable Franco-Italian relations, Italy actually destroyed the political agreements of early 1935 and moved on to political rapprochement with Germany, which significantly changed the entire international situation in Europe and actually opened the way for the outbreak of World War II. In addition, for France, a significant political loss was the drop in the authority of the League of Nations, due to the helplessness of this organization in the face of aggression against one of the members of the League. The study is based on publications of Soviet, French, Italian and German diplomatic documents, documents of the League of Nations, memoirs of political figures of that era, as well as un-published documents from the Archives of the German Information Bureau (Germany)

Dodecanese Islands in Diplomatic Struggle during the Period of Italian Neutrality in WWI (1914-1915)

The history of the Italian diplomatic struggle for recognition of the Italian control over the Dodecanese Islands during the period of Italian neutrality during the First world war is considered. The archipelago, captured by Italy during the Libyan war of 1911-1912, was of great strategic importance as a natural centre for establishing a sphere of influence in the Eastern Mediterranean. Italy de facto refused to implement the provisions of international treaties providing for the evacuation of Italian occupation forces from the archipelago. The article proves that during the First world war, especially during the period of Italian neutrality (1914-1915), each of the opposing sides - the Entente (France, Great Britain, Russia) and the Central powers (Germany and Austria-Hungary) - sought Italy’s entry into the war on their side, using the issue of the Dodecanese Islands to strengthen Italy’s interest in participating in the war. At the same time, Greece, which the great powers also sought to bring to participate in the war, also sought to establish its own control over the Islands of the archipelago. In a situation where Germany and Austria-Hungary could not oppose the interests of their ally - the Ottoman Empire, for France and Britain the decisive question was which country they were more interested in attracting to participate in the war - Italy or Greece. As a result, Italy chose to go to war on the side of the Entente, because the territorial concessions offered by the Entente countries to Italy were much more significant than the proposals of Germany and Austria-Hungary. The Dodecanese Islands remained a bargaining chip in the great diplomatic game

France and Attempt to Resolve the Italo-Ethiopian Conflict in Late 1935: the Hoare–Laval Plan

The article is devoted to the policy of France towards Italy and Ethiopia at the initial stage of the Italo-Ethiopian war of 1935—1936. It is shown that in the autumn of 1935, the French government took a position aimed at a peaceful settlement of the Italian-Ethiopian conflict at the expense of Ethiopia, since relations with Italy were much more important for France than relations with Ethiopia, and “real policy” required France to reach an agreement primarily with Italy. It is noted that a similar position was taken by the United Kingdom. It is indicated that this resulted in the formation of a plan for the settlement of the conflict, put forward in December 1935 by the head of the French government, Pierre Laval, and the British foreign Minister, Samuel Hoare. It is proved that the Hoare–Laval plan was an early form of the policy of “appeasement of the aggressor,” which became the leading direction of French and British foreign policy during the collapse of the Versailles system of international relations in 1938—1939. The research is based on publications of Soviet, French, Italian and Canadian diplomatic documents, League of Nations documents, memoirs of political figures of that era, as well as unpublished documents from the Archive of Publicistic Activity (Germany)

Ethiopia and Great Powers in Final Stage of Italo-Ethiopian War (March — May 1936)

This article examines the political situation that emerged in international relations after Germany’s remilitarization of the Rhineland on March 7, 1936, and the impact this event had on the development of the Italo-Ethiopian War in both political and military spheres. Published diplomatic documents from Italy, France, the Soviet Union, and the League of Nations are studied. It is argued that the introduction of German troops into the Rhineland significantly diminished the interest of major powers in the Italo-Ethiopian War and brought to the forefront their desire for “Italy’s return to Europe,” as both France and Britain were interested in involving Italy in countering Germany and protecting Austria’s independence. Based on the examined documents, it is concluded that France and Britain sought to resolve the conflict through concessions from Ethiopia, as a realistic approach to international relations led to the belief that Ethiopia could not achieve a military victory, especially after its attempt to strike at Italy’s armed forces resulted in defeat at the Battle of Maychew. The capture of Ethiopia’s capital Addis Ababa and the exile of Emperor Haile Selassie I effectively destroyed any prospects for a peaceful resolution of the conflict, despite Ethiopia’s attempts to act through the structures of the League of Nations

Italy, Greece, Entente and Problem of Dodecanese Islands in Diplomatic Struggle of 1915-1923

The history of Italy’s diplomatic struggle for recognition of Italian control over the Dodecanese Islands during the period of Italy’s participation in the World War I and in the period of post-war settlement of territorial problems at the Paris and Lausanne peace conferences is considered. The article proves that during the World War I and during the post-war peace conferences Italy, referring to the articles of the London Treaty of 1915, sought international recognition of its possession of the Dodecanese Islands. It is reported that Greece, which also participated in the war on the Entente side, sought to establish its own control over the Islands of the archipelago. It is noted that in the current situation, Italy had undoubted advantages over Greece, primarily because the Islands were really under Italian control. It is shown that the discussion of the issue was seriously affected by the defeat of Greece in the war of 1919-1922 with Turkey, after which Greece could no longer be a real rival of Italy in the struggle for the Dodecanese Islands. It is reported that the outcome of the Lausanne peace conference in 1923 was the legal recognition of the Islands as the possession of Italy, with which both Turkey and Greece were forced to reconcile

Italy and Problem of Control over Dodecanese Islands in 1912-1914

The history of diplomatic struggle of Italy for the recognition of Italian control over the Dodecanese Islands is examined. It is emphasized that the archipelago, captured by Italy during the Libyan war of 1911-1912, had strategic importance as a natural centre to establish spheres of influence in the Eastern Mediterranean. It is noted that Italy had not originally sought the inclusion of the archipelago in its own land, but quickly showed interest to establish its power over the Dodecanese Islands and refused to implement the international agreements providing the evacuation of the Italian occupying forces from the archipelago. The article proves that the difficult diplomatic struggle in which, along with Italy, Greece and Ottoman Empire, the great European powers - France, Britain, Germany, Austria-Hungary - took part, did not led to the return of the disputed Islands to the Ottoman Empire or to their transfer to Greece, demanding these Islands on the basis of ethnic principle. The author argues that the persistence, under various pretexts, the Italian occupation of the Islands was as a result of significant diplomatic victory of Italy and subsequently allowed them to be Italian possession

‘Tunisian Question’ in Franco-Italian Relations (1922—1928)

The article is devoted to the development of relations between France and Italy in the context of the status of the Italian population of Tunisia issue. Thanks to the agreements reached by the Italian states and the government of Tunisia, in the first half of the 19th century mass emigration of Italians began to Tunisia, as a result, by the end of the 19th century, a significant Italian diaspora had formed in Tunisia. The establishment of a French protectorate over Tunisia led to the question of the status of the Italian population of Tunisia, which was eventually settled by the Franco-Italian convention of 1896. After the First World War, France refused to comply with the decisions of 1896. The French government set itself the goal of naturalizing Italians in Tunisia. The Italian government strongly opposed such a policy. The negotiations did not lead to a settlement of the conflict. The place of the ‘Tunisian question’ in relations between Italy and France in the 1920s is analyzed, the numerous discussions of the problem of the status of Italians in Tunisia and Italy’s attempts at least to maintain the situation, that existed in accordance with the 1896 convention, are considered in the article. It is proved that Tunisia, with its large Italian diaspora, occupied a significant place in the African policy of Italy during the period of fascism. It is substantiated that the period of the 1920s was essentially the preparatory work for a more serious discussion of the colonial problems that arose between France and Italy, which resulted in the Laval-Mussolini agreement of 1935