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Events/Ideas that Changed the World Notes Day 1 What is a dictatorship? Origins: Dictatura, ancient Roman term, wasn’t originally negative, it was just a title, Caesar went by it. What it meant was that the republican senate in rome determined there was a threat to the social order, they would elect a dictator. We need to give someone total power for six months to protect the country from whatever threat. They would choose two guys, and then choose a dictator from them. That dictator would establish order, then step down. The dictator was given extralegal powers, they couldn’t change laws, but they didn’t have to, because they could do whatever they wanted for six months. It did work for awhile, but what happens if someone decides not to leave? Caesar was elected dictator, but never left, until he was murdered. After that, they started to rethink the whole system. Tyrant and Despot also used to be neutral terms. They were just court titles. It was a term for someone that had power in a local area, but gained that power in an unusual way, usually through buying it. Later, they become synonymous with illegitimate rule. Day 2 Notes Dictatorship wasn’t originally considered a negative term. You were called a Despot, which was also a neutral term. Hobbes was a believer in dictatorship, using the countries around them as evidence that they needed a monarch; they couldn’t do whatever they wanted, although they basically could, because removing them was near impossible. The logic with electing a dictator temporarily was that they assumed the public would turn against them once it was time to leave, and they would fold under public pressure. Once Caesar came in, he pretended the emergency was still going on, and he swayed the public vote in favour of him. In the 18th/19th century, tyranny and despotism started to be synonymous with power being exercised illegitimately. French Revolution, revolutionary dictatorship to achieve the social equality you need. We will force you to be free. Napoleon makes himself dictator of France, temporarily, and then makes himself emperor of France. Switch definition of what public support means, such as making nonaggress the enemy. Karl Marx wanted to overthrow the capitalist system by overthrowing the dictatorship. Vladimir Lenin took power of Russia in 1917 through a violent revolution against a long standing monarchy. They openly refer to themselves as dictators at first, saying that they need to eliminate enemies, or it will allow the enemies to come back. Post WW1: positive use of dictatorship declines, even in the Soviet Union. Mussolini seized power in 1922, establishing a Fascist state. Dictatorship starts to become a negative term. Mussolini used the term Totalitarianism, he adopted the term as positive. He wanted to neutralize the masses to preserve power and social order. Day 3 Notes Cult of Personality Non necessary element of dictatorships. Legitimize the leader. Legitimize an ideology by identifying it with said leader. Establish the leader as both above normal human concerns and as the fatherly protector of the people. Manipulation of mass media. They establish the leader as above normal human concerns, but also the fatherly protector of the people. Triumph of the Will, 1935 documentary, an account of the Nazi party. It’s an example of propaganda from the nazi party. Day 4 Notes Italy was divided into various city states, kingdoms, and other empires, for centuries. Italy was mostly unified as one country by 1861. The pope was basically the head of the country at this point. They especially welded power over Rome. The vast majority of Italians then and now are Catholics. They didn’t believe the people were ready to govern themselves, or vote, they believed in a monarchy, just not a dictatorship. The Ethiopian Army destroyed the Italians in their war, which destroyed the narrative that the black people needed help to be governed, given that they destroyed the Italians. A narrative develops that the liberals were at fault for Italy losing, creating a desire for a new leader. Enter Mussolini, he was a militant socialist advocating violence (propaganda of the deed). Was arrested many times, he was influenced by Nietzsche, Filppo Marinetti. He believed violence was useful and necessary, that it purified people. Ironically, he referred to the military a lot, yet was arrested for avoiding being drafted. He said he would only fight for the working class, not the country. WW1 breaks out, he did serve there. He started a newspaper during this time, and Italy entered the war in 1915, turning on allies Germany, and joining France, Britain, and Russia. Originally, he didn’t support Italy entering the war, but eventually decided he agreed with it. He was a socialist, and socialists didn’t support capitalist centered wars, Mussolini disagreed and expected that they would finally get all the territory Italy deserves back. He’s kicked out of the socialist party for these beliefs. In his newspaper, he starts promoting pro-intervention views. He denounces socialism entirely, and says he was kicked out for promoting violence. Day 5 Notes Fascism in a couple words is fighting in action, that’s what it’s about. It’s difficult to turn into a government. The Fascists originally didn't get as many votes as the National Fascist Party in Italy. Speech in October, march on Rome, if Fascists were not given power, they would take it by force. Day 6 Notes Mussolini's goal was to reestablish the Roman Empire, and wants to go back to a Roman Empire. It’s about obliterating earlier society, replacing corrupt liberal democracy. Mussolini's party murdered a political opponent, named Giacomo Matteotti, who was a socialist and a vocal opposition. He went missing in June, found dead in August. Vatican City, which is the smallest country in the world, smaller than the university. Italy and Mussolini recognized the Pope as a sovereign of an independent nation, which is now Vatican City, it will now be a separate country from Italy, the Pope will control it. Italy will live there, if the Pope agrees to stay out of Italian politics, and be neutral on international affairs unless asked, and all bishops in Italy have to pledge loyalty to the Fascist movement. Italy also paid this new country a big sum of money, they also agreed to teach Catholicism in schools, along with Fascists. This was viewed at the time as a win for Mussolini. Most Catholics saw it as a decent win for the church as well. Mussolini gained popularity as a result. Mussolini is even painted alongside Jesus in some churches in Italy. The Pacificiation of Libya, has since been labelled a genocide. It was meant to crush local resistance to Italian ruling. They used mustard gas on civilians and rebels. Innocent LIbyan citizens died during this. They eventually arrested the resistance leader. By the end of it, the Italians labelled Libya as pacified. Italy still deals with this in today's politics, with the fallout of committing this act to Libya. It seems like there might have been a racial motivation for it. The racial motivation was viewed as Mussolini simply seeing Italians as better than everyone else, Libyans were inferior to Italians, and in their deserved territory. One of the major problems with dictatorships is that you can never get the truth, nobody is going to tell you if there is a problem, out of fear for their lives. He didn’t know how popular Fascism was, and there wasn’t a reliable way to find out. He tries to do things to earn the popular vote, like war, like conquering things. Ethiopia was very symbolic, they had lost to Ethiopia in a previous war, that embarrassed them. So, he decides to get some getback. Mussolini has to be careful, their army can’t take Britain or France, so he has to take Ethiopia without provoking the Europeans, so he bluffs. He lies and says that his troops were attacked by Ethiopian troops, unprovoked. He threatened force to measure the reactions of the other count Day 7 Notes Mussolini was concerned about the lack of enthusiasm about fascism in Italy, He even created an encyclopedia of Fascism. Now that Mussolini has indicated they have relatively similar views with Germany, they form an alliance, there is economic dependence on each other, this is not a popular move, as Italians don’t like Germany. In 1939, they signed the Pact of Steel, this is a military agreement, they agree to attack anyone that attacks them. They continued to invade other countries, for no real reason, it was cheered, but now we were seeing the natural end of Fascism. How can you stick with an ideology that is centered around violence, if you’ve won, what do you do then? Mussolini introduced racially motivated laws called the Defense of the Race in 1938, which was very similar to the laws introduced by the Nazis. It frustrated Italians that he was just doing what Hitler was doing, it’s possible he was trying to center out specific people to explain why things aren’t perfect yet, to distract from his incompetent leadership. In 1940, Italy declared war on Britain and France. Mussolini didn't join the war early on. Poland is getting destroyed by Germany, but on the Western front, it’s quiet for a while. Mussolini changes that, by swooping in to take advantage of Hitlers chaos, who quickly destroys most of Western Europe. Hitler now owns France, Mussolini thinks things look good for Hitler. So, he declares war. His justification was that the Italians were trapped, they needed living space. Sounds very similar to Hitler there. It works, at first. Mussolini tries to expand his African empire. The Italian army was not ready for this, even his war commanders who supported him told him they would lose the war. Mussolini ignored them, insisting Fascism would always win. They start to lose the war, they don’t have the military capable of doing this. It embarrassed Mussolini greatly. His only idea is to continue to expand, but that doesn’t work either. By 1943, the Italians collapsed, and Germany had to come save them. The problem is that Germany is now fighting wars on several fronts, and that proves too much. Hitler is now really angry with Mussolini that he had to come save him. The Allies were counting on Southern Italy not being as supportive of Mussolini, so they invaded there, and the Southern Italians didn’t fight the Allies, simply because they didn’t like Mussolini. That year, Mussolini was voted out by his own Fascist Grand Council as leader. They voted him out on the basis that he was no longer promoting true Fascism, most of the council were his relatives, they still voted him out. Mainland Italy is invaded, and they surrender. This leads to a civil war. Germany is still fighting the Allies in Italy, plus Northern Italy still believes in Fascism, while Southern Italy no longer does. Hitler, while angry with Mussolini, still believes he could be useful, so he decides to liberate him from a castletop prison. THey break in with a helicopter and hand gliders, they kill all the guards, and they get Mussolini. Hitler installed Mussolini as a puppet leader of the Italian Social Republic. Hitler sees him as a useful figurehead so they can claim that Italy is still independent. The Italian Social Republic is not a well run country, and is nothing but revenge plots, Mussolini gets his son in law who voted him out, and executes him in front of his daughter. That’s what Mussolini does for the last years of his life, is take revenge. Day 8 Notes Mussolini was captured in 1945, he and numerous other Fascists were executed right after being captured. Adolf Hitler The Habsburg family led Germany for many years, they controlled various German states. Around when Hitler was born, some of the other German states were controlled by other people, eventually they were unified, the differences were religious in nature. Germany is eventually unified, Austria is left out of the proceedings. In 1867, the conflict was settled, the Hungarians took over the nation, although the other nation states were not happy about this. Hitler was born into a dysfunctional family, his parents died at a young age. Hitler had two siblings, but five siblings died as infants. He was born sick, but he survived. His mother did not work. Even Hitlers name is confusing, his father was born out of wedlock, and the gossip is that Hitler might've actually been jewish. We don’t know who his grandfather was. His step siblings ditched the abuse after their parents died, so he has to raise his sister. He did not get into the Academy of Graphic Arts. He then just works odd jobs in Vienna, sells some paintings, he’s living off the little bit that his father left him, he is often homeless. Vienna is home to many different ideologies. He’s attracted to Pan Germanism, Volkisch nationalism, and antisemitism. Pan Germanism is that the Germans needed all the German states to give them living space so that they could thrive. He sees the Hasbergs as a problem. He hated Catholicism. He blamed them for Austria being left out, and he begins to identify with Germany a lot more than Austria, despite not yet being a German citizen. Day 9 Notes Hitler existed in the military in 1914, he initially refused to serve, but eventually changed his mind. He was blinded by gas in 1918. As he was recovering from this, Germany surrendered. He did have to get special permission, as he was not a citizen. Losing this war, much like with Italy, was a shock to German nationalism. He never drank, and stopped eating meat. He fights a lot, and wins awards for bravery. He really starts to internalize social Darwinism. They believed that the European countries that were winning wars was because nature had determined they were the strongest. The destiny of Germany was to win, but they didn't, they lost. The media was telling the citizens that they had been winning, so it was a shock that they lost. The king, a monarch, abdicates, so monarchy is now gone too. A myth that Germany was stabbed in the back by internal traitors starts, communists, jews, socialists, that’s why Germany lost the war. Hitler becomes a regular in what’s known as beer hall politics. Nobody knows what to do with a lot of the vets that survived the war. So, one thing they do is hire them as military intelligence, as with Hitler. They decide they need to stop political violence. Hitler gets hired to spy on a party, called the German Worker’s Party, but it’s actually a far right party, they call themselves that so they can appeal to the working class. Their goal is to get rid of the Jews so that they can fix capitalism. Hitler joins it, to spy on it. While doing it though, he looks around, and likes some of their ideas, but it’s not extreme enough, they need more. So, Hitler starts speaking on the events, and stops spying on them. Within a couple of years, he is the leader of the group, and they rebrand themselves as the Nazi party. The Nazis are far more willing to commit violence, and are more far right than other groups of that time. He believes it’s about saving not just Germany, but the world. Ernst Rohm led the Storm Troopers. His job was to beat up political rivals, and Hitler eventually got his eye. This political violence works, it scares people into voting for the Nazis. Hitler is also able to say that he is separated from the violence because someone else runs the violent part of things. Hitler is able to stop the violence, he is able to stop Rohm. Day 10 Notes The people in charge of Hitlers trial were Nazi sympathizers, and gave Hitler and Nazis light sentences, while also allowing him to speak at his trial, which gave him ample time to gain fame, it made national news. Hitler is convicted anyway, for five years, but only serves nine months, in a min security prison, and is allowed visitors, where he converts most of the prison to his worldview, and also writes Mein Kempf. Hitler now learns that he can’t use force to win the government, he needs to win them over. Paul von Hindenburg uses the emergency act to be a dictator temporarily after the depression, but uses it several times. He does not believe in democracy. His plan is to stop the left from forming a party and organizing. There are about five elections in 1931, because the left keeps getting elected, but the emergency act is being used to overrule it, though it annoys the German population. However, it was being used as an example of the fact that democracy doesn’t work. The Nazis continued to grow, there were several elections in 1932, where the Nazis got 37 % of the popular vote, the largest single party. This is one of the worst points of depression. After less than a year, Hitler became dictator. Franz von Papen convinced Hindenburg to appoint Hitle chancellor in 1933. Their popularity starts to decline, the only way to get around that is for Hindenburg to hire Hitler, they count on him being a peasant that will be too stupid to do much. Papen will be co chancellor, to watch things, we’ll be able to control him. A fire happened in 1933, historians still don’t know who started it, but it was blamed on a communist conspiracy at the time. The Nazis use this to get more power, they pass the Enabling Act, which gives Hitler a dictatorship. A couple of months later, all non Nazi political parties were removed. In 1934, Hindenburg died, he didn't replace him, he just merged his position with his own, so he gained more power. A significant amount of violence and intimidation happens in his early years. The Night of the Long Knives happens during this time, that is when Hitler killed rivals of the Nazi party, sending out goons later known as the SS, and brutally hundreds of people he believes are challenging him for power. He killed Rohm for being gay, though he had known this since he had met him. In 1939, they opened their first concentration camp. From the first party, it’s usually enemies of the Nazis, communists, the left, starts to include more Jews as it goes. This is justified by saying these people are threats to the government. Day 11 Notes You had to get a racial card, if you had more than 3 jewish relatives, you would not be considered a german citizen. If it was less than that, you would temporarily be a German citizen. This would get restricted even more as time goes on. These regulations consider who you can marry, who can drive cars, everything is regulated. Property is taken away from Jews. If you were gay, or religious, you would be regulated. They also sterilized thousands of people as well. THey gas brought 500 000 people in three years. Hundreds of jews were shot in public merely for being Jews, then the Germans blamed them for property damage, justification for restricting the jews even more. He took Germany out of the League of Nations. That’s what Nazis do, they create conditions that then they can point to and say see, you need us, we need war, it’s being forced upon us. Hitler invades Czechia, but claims he only wants the part that has mostly german speaking people, people on the Allies side don’t believe him, others say that they don’t want to fight a war. So they hammer out an agreement to give him this land, guess who they get to negotiate? Mussolini. Hitler then immediately betrays everybody, takes the land he was given, but then also invades the rest of Czechia. So Hitler is told, if he does anything else, they will go to war. Hitler then invades Poland, Britain and France soon declare war, and WW2 begins. The West is pretty quiet at this time, a different story in the East. We’re at war, even with the total destruction of Poland, the Allies do nothing, they seem to be holding out hope that maybe things can be resolved. The Germans through the 40s took Denmark, Norway, Sweden, Netherlands, France, Belgium. France was one of the strongest empires in the world at the time, and they fell in six weeks, now the Nazis have a monopoly. The Allies are losing by a lot at this point. Nobody seems to be able to stand up to Germany, Hitler is the most powerful man in the world. Some of this was revenge for WW1. Hitler has more power than anybody on earth pretty much, and portrays himself as a Messiah, but he’s not actually very good at this, it’s mostly the military taking advantage. Hitler starts to believe his own hype, and believes that he’s infallible. He starts to execute military leaders that contradict him, creating a bunch of yes-men. Hitler even allowed the Allies to escape at one point when they had him on the run because of a decision made by Hitler. This is causing the empire to crack. Hitler decided in 1941 to invade the Soviet Union. His racial version of the world centers around this, and he’s convinced that they have enough to stop the Russians. They bet it all on one giant hit on the SU, really fast, it’ll take them all out, and then they will own Russia. This was briefly successful at first, but then it’s not. The top reason is that Russia is really big, and it’s cold, the Soviets don’t just collapse, 27 million Soviets die in this war. However, they don’t fold, they retreat, burn everything so the Nazis can’t get supplies, but unlike Hitler, Stalin goes the other direction, he listens to military leaders. Htiler is doubling down on making his own decisions. To the point all the decisions are made by Hitler, which leads to inaction in several areas, they stretch out the Germans supplies and people, and then winter hits. The Germans weren’t prepared for the cold, and they slowed down significantly. The Soviets then join the Allies. So the Soviets get supplies from the Allies, and it helps them as the Germans are now isolated in Russia. America then entered the war in 1941. Japan attacks the States, and so the States have to enter the war, they are a powerhouse. They help the Allies, but the States also give supplies to the Russians against the Nazis. All of a sudden, the advantage in the war has moved to the allies. Day 12 Notes In just two days in 1941, the Nazis shot 33 thousand Jews, in another two day span, 28 thousand, in a couple weeks, 70 thousand. However, the Nazis realize that they are using too much resources, and it comes to light that some of the soldiers are showing signs of guilt, and that needs to be minimized, so they need to come up with a better way. Hitler had permission to come up with a plan, so they went back to what they had been doing to disabled: gas them. They determine they will build extermination camps, the whole point being to kill as many people as possible. They did this by putting gas in showers. It’s estimated roughly 1.1 million people that were deported into Germany were killed. The Germans couldn’t function, they were terribly disorganized. D Day, the Allies decided to attack the Nazis where they were at their strongest. They believed that they had reallocated so many resources to the Eastern front, that the area was weak enough in the West that the Allies could break through, while it was difficult, they were correct. Hitler refused to believe that the Allies could break through the West, so even though he was warned, he ignored the warnings. From this point, everyone knows the Nazis will lose eventually. In 1944, there was an assanation attempt on Hitler. A group of military elites and citizens were banded together to try and kill Hitler, a pretty diverse group of people that had different motivations for why they wanted Hitler dead. Some for moral reasons, for most of them, were afraid of what Hitler was going to do to the country, thinking he was a madman. If they got rid of them, they could surrender and get peace. Some had been active members in getting rid of Jews, they agreed with his mindset, but believe he specifically is a madman. Their plan involves a meeting that is approaching for military leaders, one of them was going to bring two bombs, and place them next to Hitler, who would blow up. They would then claim someone inside of the Nazi government had killed him, they would arrest everybody, and establish a new government. One of the bombs doesn’t work, he can only arm one. He places it next to Hitler, someone by chance moves it a little bit, and when it explodes, it explodes a table. Anyone involved, and their families, are executed. Several thousand are killed in the next few days, as he believes the hype that he’s a god even more. Hitler then orders the Battle of the Bulge, against advice, and it fails. He believed he could hit the Allies once, and they would get defeated, which of course doesn’t happen. The Western front has collapsed. The Red Army has pushed the Nazis back to Poland. They keep getting to the areas quicker and quicker, for the first time, the Russians find the concentration camps, and share the information with the world, they didn’t know this. Some believe the Russians even made it up. Hitler keeps demanding more deaths, starves thousands in the Netherlands, orders half a million deaths in Hungary, and he starts realizing that the walls are closing in on him. He’s about to lose. The Allies had debated whether they should invade Berlin, in 45, they decided that they needed to kill him, otherwise the war would never end, so they decided to go all out on Berlin, which they did. They destroy Berlin. Hitler lived the rest of his days in an underground bunker, Hitler had said that if he died, he would take the Germans with him. So, Hitler stayed in Berlin. Day 13 Notes Germany is slowly encircled, Hitler is all powerful, but he has no counter strategy. Berlin is under attack, and Hitler refuses all concessions. he then commits suicide, with a will and a last dictate left behind him. Germany surrenders a week after he dies. He appointed a heir to his dictatorship, and Hitler also married his girlfriend a few hours before they both commited suicide. The war still is going on, because Japan does not surrender. Hitler did try to make a deal to get away from the Allies, they of course refused. Joseph Stalin Under the Tsarist government, the Russian Empire was one of the major powers of Europe for centuries. The majority of the country were serfs. The dictator of the nation was called a Tsar, this idea was taken from what Caesar was called. Serfs were not technically considered slaves, though they had a similar role to one. They had no personhood, and were legally considered property. They were technically considered people, they had some rights, but very few. They were peasants, tied to the land forever. They owed their allegiance to the local princes, usually a rich family in the area that reported to the tsar. Almost none of the population went to high school, especially peasants. Stalin was a peasant, but he did go to hs for about a year. Most of the population was completely illiterate. Things started to change in the 19th century, new ideas started to come into Europe, and Alexander the second freed the serfs, technically, with a lot of qualifications. Stalin was raised poor, but in the school he was able to attend, he thrived. He rather suddenly converted to socialism in 1896. He became a professional revolutionary, one that got arrested frequently. Once he converts to socialism, he is kicked out of the seminary he was a part of, and eventually joins a Socialist Party. Day 14 Notes Stalin was arrested for trying to organize a strike in a factory in Georgia. Marxism is a pretty complicated set of ideas. Marxists believe history has a beginning, middle, and end, these stages are defined by the economic stages of the time. Marxists believe these are the laws of history, these ideas are widely criticized, especially for the idea history is predictable, it’s scientific. History will evolve until we reach the final class conflict, the ones that own the means of production, and then everyone else. Marxist believe work is essential to who we are as people, class consciousness is when people are tricked into believing that they have to work and not knowing that work should define who they are. Religion dulls the senses and makes you easier to control. The Su was a little bit different from the Nazis in that they claimed that they accidentally persecuted the Jews, not for their race specifically. Whereas the Jews were specifically targeted and that was made obvious by the Nazis. First, a Social Democratic Workers Party was started, in 1898. Russia needed to develop to be ready for revolution. Then, three years later, the Socialist Revolutionary Party was started, they needed land reform. It was labelled at the time as a party split, as the Social Democratic party was split on how to handle the situation. Russia lost the Russo-Japan war just four years later, Russia lost. This is a disaster, for obvious reasons, but it was also an embarrassment. There’s also racism involved, how could Russia lose to a non-European country? It signaled to many that Russia was collapsing. Workers started going on strike, over 100,000 workers, a couple of years later, which grinds the country's production to a halt. Then a bread march led to a czar's house, demanding food, the Russian soldiers came out, killing hundreds and wounding thousands. The czar started to break, allowing a very restricted vote, which temporarily kept people at bay. However, he reverted those policies a couple of years later. The socialist parties, all of them, pulled out of working with the czar entirely. This emboldened radicals, including Stalin. In 1912, Stalin was part of the two parties officially splitting. He was arrested for sedition in 1913, and this time, the authorities sentenced him to exile in the Arctic, this is his first real punishment. He’s stuck there when WW1 breaks out a year later. His party publicly advocates for Russia to lose the war, because that party believes it’s the inevitable result of capitalism, so if you destroy them, it would lead to communism being enforced. So, the party sabotages their own country. Russia, for more than one reason, handles the war really poorly. The Tsar says that they are getting involved to protect the Slavs peoples, which was a race. They lost the Battle of Tannenberg to the Germans badly. In 1917, the Tsar was overthrown, the family had run Russia for three centuries, but Russia is getting dominated by Germany. In his place, a provisional government takes over, there is no vote. So, a coalition of the two parties and several others are all formed to form a government in Russia. At the same time, in the major cities, groups called Soviets, or a Workers Council, are rising, and organizing the cities. They become strong locations of authority that counters the provisional government. Day 15 Notes The new party promised peace immediately, and delivered, this made them popular. They promised war would end. They threw the only real election in Russian history at this time. They lost the election really badly. They believe the election was tainted somehow. After this party signs a peace treaty with Germany, it pulls them out of the war, but they seize a significant amount of land. Giving up the land was not popular. Russia then breaks into a civil war, with three sides, the communist, the red side, very well organized. The whites, they are a loose grouping of anti communists. The greens were really effective, they were the socialist revolutionaries, the reds are afraid of the greens, they are powerful, but the whites kill them because they don’t like communists, then the reads finished them off. Russia becomes a Communist state, with Stalin being a background member of the party. They hold farce elections at this point, where there are several communist from the same party to choose from, but you pick the same party no matter what. Stalin was named General Secretary by Lenin in 1922. He parlays this position to gain further power. The leadership of the party notices that Stalin is growing more power. Vlad Lenin releases a document on his death called the Testament where he warns his party of the threat Stalin presents. He asked the party to think of a way to get rid of Stalin. His testament is debated, but Stalin stays in power. Against the wishes of Lenin and his widow, they embalm his body to hold it for display to the party. Stalin survives the vote, and decides he can outmanuever everybody. He does this by continuing a cycle of forming alliances, breaking them with another alliance, breaking that one, and so on. Stalin is part of a trio that is leading the Socialist party. They align themselves against Trotsky's ideas of permanent revolution to save the world. He was outed by the trio. The trio's idea is to let the Western powers weaken themselves, it’s inevitable with a capitalist system, in the meantime, make sure socialism is strong here in Russia first. By outing Trotsky, Stalin gains even more power and influence. Stalin then betrays his two partners of the trio right after. Stalin changes his mind on whether some members of his party, including his partners, aren’t really spies, or not dedicated enough, to what is now known as Marxism-Lenism. He fosters distrust in those members of the party. Despite it being counterintuitive, Stalin makes friends with the capitalists of the party, and uses that alliance to vote out the two members of the trio, even having them killed and/or expelled from the country. He’s now the only one left from the last era, and the undisputed leader. Day 16 Notes Stalin plans now to abolish private property. Everything is owned by the state. This is being done to provide food to other cities, and the SU starts building industrial cities. Stalin is building, or rearming Russia. They had gone through a lot, and he was getting fresh war material. They are planning on going to war with the capitalist countries eventually. They call it the five year plan. Stalin blames most of the problems on peasants who had been successful during this dark time for Russia. A key part of this period was to remove the peasants as a problem, by murdering them all. So, there are mass killings of anybody that identifies with that system. Stalin, by 1929, was a full dictator, he got rid of all challengers. It’s widely debated on whether this actually worked, within a decade, they had collectivised almost everything. Production, however, went down. This caused a massive famine that spread across the whole US, leading to millions of deaths. It’s debated over whether Stalin targeted specific people groups with the famine. Stalin's wife kills herself because of her husband being responsible for this. Stalin blames the failures of the system on the industrial production people in charge, killing them. Stalin also imprisoned millions of people in labour camps. One of the consequences of purging the people is that Stalin can make the people more dependent on him, so he appoints puppet leaders. They introduced a new Constitution in 1936, however, it made little change. All of the culture was still very traditional, criminalizing abortion, limiting divorce rights. This was called the Depression. Stalin knew SU was not ready for a WW in the 30’s. He attempted to ally with the Western powers, but that didn’t work, he tried again with Germany, but that also didn’t work. Enter the Spanish Civil War. Stalin thinks that if he waits for the capitalist countries to go to war, he can wait and then come in and wipe them all out. The Nazis offered the SU good terms for an alliance. However, they didn’ count on the Nazis trying to promote racial conquest. SU fought Finland in the Winter War in 1939, the SU didn't start off very well, despite outnumbering the Fins. The Fins start off well because they have a good strategy. Stalin actually took Finland to defend against Germany, even though they were allies. Eventually, SU overwhelmed Finland. Day 17 Notes Nazis invaded the USSR in 1941. Early disaster for the SU, German forces are halted outside of Moscow. Stalin goes into hiding, for weeks on end after the Nazis invade. Both sides wipe out whole populations, with nobody being safe. Stalin rallies, as he creates more positions for himself to fill. The difference between Stalin and Hitler was charisma, with the exception being a famous speech in 1941 to motivate his soldiers. Women fight in the Soviet Union, unique for those times. The Germans make it all the way to Moscow, then are stopped. In the West of the Soviet Union, it’s a blood bath, and the Final Solution begins. Everybody is wiped out. When territory would be invaded, you would have to decide whether you would ally with the Nazis or with the Soviet Union. The SU refuses to retreat from Moscow, and it works. stalin from this point starts to delegate and not just do all of it himself. He allows the military experts to do what they do. Gregory Zhukov leads the military effort against the Nazis and turns the tables. They also get a significant amount of money, before America gets in the war, they don’t want to get involved in the war. The Soviets, unlike the Allies, are willing to sacrifice their people to win. Stalin starts to relent on things like religion, as well as delegating. However, Stalin, due to believed disloyality, orders his daughter in law arrested and murdered, killed his brother in law, and their wife, and Stalin's son was captured as a POW, and he allowed his son to die. From this, Stalin became a world leader in the big state. They were willing to ally with the Soviets despite disagreeing with him because of the threat the Nazis faced. The Soviets held the Nazis off long enough that the other countries realized the threat the Nazis faced, and they acted. Poland is stuck between Germany and Russia. So, they are sacrificed. Stalin goes to the Allies, and says that he needs help, he’s been fighting the Nazis by himself. He believes the Allies should attack the West so weaken Germany, which eventually happens and he is correct. This adds to Stalin's credibility. Because they are capitalists, Stalin believes that the Allies will negotiate with Hitler as soon as they can sell out the Soviets. So, he pushed the Red Army to aggressively pursue Hither, the Allies were also racing there for a different reason, they didn’t want to give a lot of the land to the Russians. Stalin encouraged his soldiers to rape Germans, and to kill as many citizens as possible. It didn't matter if they were Nazis or not. They also start to liberate concentration camps. The war ends, the Soviets are now a superpower. The reason for the Cold War starting is heavily debated, who started it? Was it Americans, or Russians? Could it have been stopped? The Soviet Union was scared of being invaded again, given recent history. However, the SU are now more powerful than after WW1, they are now in the Security Council and the United Nations. Stalin says that he wants Poland to be free, but friendly to the SU. That’s not what happens. The elections that do happen are not free or fair. Stalin does not trust former allies. In 1947, the United States agreed to the Marshall Plan, this is a generous infusion of American dollars, billions, into Europe, to help it recover from the war, with almost no strings attached. Stalin doesn’t trust it. He’s suspicious of those that participated in the war coming back to the Soviet Union, he worries his people have been Westernized. Stalin is angry at the donations, he believes Communism is being destroyed. He refuses the marshall plan, and forces various countries in the East to refuse it too. He threatens invasion. Day 18 Notes The Marshall Plan was made in part to stop eastern countries from becoming communist. The tensions in the Cold war ramp up. The Soviets stop food from going into Berlin if it’s not given to them by the West. The West ignored the demands, flew over the blockade that the Soviets had set up, and delivered food. The Soviets are still somewhat in a position of weakness, not as strong as the US, so they back down. Stalin is at his most powerful, but is more suspicious than ever. He was scared of the different military leaders, as some of them were executed. He believes some of his people that had been in the war had been exposed to the western version of living. He starts having his own family members executed, his daughter escapes, and actually advocates against him Stalin's anti-semitism became stronger during this time as well. Stalin died in March 1953, they had not attended a meeting, so had been scared that he would kill them, so it took several days for anyone to realize he was dead. He had tens of millions of people killed during his reign, de stalinization began almost immediately, although the dictatorship was maintained for decades. Mao Zedong Qing Dynasty Was a Manchu family, a small minority within the massive country of China. However, they are the royal family. This was not well received by most of the country, since Manchus were considered outsiders. Most of China are peasants, Mao comes from a royal family, but his father had been a peasant, and had worked his way up to being a successful farmer, where he hired people. He was rural, but being a land owner at the time was a big deal in China. Mao is outspoken and rebellious, that doesn’t fit into society. His mother is a devout Buddhist, and is illiterate. She had bound her feet for most of her life, which was a tradition that deformed the feet of those that did it. Mao wants to be more than the farmer that his dad is. Day 19 Notes Sino Japanese war is a war that the Japanese won soundly over the Chinese, where the Chinese called it the Century of Darkness. The Chinese were unable to protect land, and were unable to modernize their military. This is when America gets involved, takes over Spain, and wages war against the Filipino population. This was seen as a good step towards China, America has interest in China for economic possibilities. However, America is late in the game, compared to the European powers. They try to negotiate, this doesn’t go well, the negotiation, rather unconvincingly saying that they should negotiate together against the Chinese, without taking them, but we’re not taking them over, just control the whole economy. The Chinese Revolution is next, moderate reforms at first, such as local elected assemblies. Don’t have much power, but the idea is you can give them a place to vent anger. Dr. Sun Yat sen founded the Revolutionary Alliance, he believed in nationalism. He founded a political party as well. Dedicated to overthrowing the monarchy. The Qing dynasty was overthrown, though Mao is not a part of the Revolution. Shikai names himself emperor, and only lasts three days. China started to enter world politics, called Warlordism. China is disintegrated into regional warlords and competing authorities. Remnants of Shikais Beiyang government. Sun Yat-sen returned from exile to the south, re-established the Guomindang, and tried to organize a rival power. May 4th Movement, student led protest against Treaty of Versailles. Left wing radicalism gained in popularity. The treaty was an agreement they had to get stuff back that had been taken from them from Germany, however, it was given to Japan. It was around here when Mao started reading Marx, anything he can get translated. So, the Chinese Communist Party came into play in 1921. To this day, they rule the government in China. Mao was converted to Communism in two years, and was a founding participant. He organizes labour and students. He is concerned about the anti-nationalism parts of it however. Is looked at as a voice of the people because he was well educated while also being a peasant at the same time. It was Guomindang and the CCP worked together to oust the Beiyang government and the warlords. Chiang Kai shek Sun Yat sen died in 1925, succeeded by Kai shek. He was a military leader in the Guomindang, leader of the right wing faction of the party. Keep the United Front, but only for convenience. Mao began to theorize more about the centrality of the peasantry for the achievement of true Chinese Communism. Mobilization of mass peasantry, radical transformation from spontaneous mass action. Day 20 Notes In 1926-28, warlordism was broken, Chiang established a government in Nanjing. Started to purge Communists and leftists in 26. Mao was unsure at this point about supporting the United Front, but stayed the course. The People would decide the revolution, not the United Front. So, the White Terror starts in 1927, Chiang betrays the Communists, slaughtering thousands. Mao and roughly 1000 communists organize the Chinese Red army. Shiang is trying to wipe out the Communist party in one fell swoop. Mao leads his faction to killing thousands of political opponents. Chiang becomes obsessed with wiping out communists, they lose a whole region of China under his rule, and they are forced to negotiate with the Japanese. Only Mao's stronghold was left, and they had to abandon it. So, what do they do? Why don’t we just leave, and walk somewhere else? We need to pick a time period where Chiang is busy, then we can try and escape. The Long March 1934-35, a 6000 mile walk, 18 mountain ranges. Roughly 70,000 people died, one of the reasons for that is that soldiers were following them, any mistakes, they die. Mao consolidated support by acting against Soviet advice. Portrayed the March as moving against Japanese imperialism. Guomindang was weak in face of foreign influence. They can’t fully wipe them out though. There are only 20,000 communists left, yet they are able to rebuild. Mao almost dies on the march. Japan invaded 1937, resulting in GMD-CCP United Front, CCP and Mao proved to be more capable at reaching out to the peasantry, crushing internal opposition and enforcing ruthless discipline centred in Mao's interpretations of Marxism. Red Army forces were often on the frontlines against Japan. Shiang is forced to constantly give concessions to the Japanese, he can’t do anything else, CCP calls him a cronie, he complains that it’s only because he has to deal with the Communists. Shiang is now told he can’t work with the Japanese anymore, they just signed a deal with the Nazis and Fascist Italy. They get tired of Shiang, so his own military kidnaps him. Shiang concedes, and says they will focus on Japan as well now. Day 21 Notes Another new wife for Mao, named Jiang Qing. For WW2, Guonmindang and CCP forces forced a stalemate on Japan. The Red Army cultivated grassroots support in occupied China. Guomindang is not in occupied China and continues in corruption and even sometimes its anti CCP actions. Mao Zedong Thought: Became the official ideology of the CCP, Rectification Movement, and self criticism to save people from error. Mao used the fact that Sheng needed help to take over. One of the reasons Japan lost is due to the violence they were inflicting, they were unable to gain allies. Part of it too is Shiang tries to force people into joining his army, his government is also super corrupt. IN this period, the SU is dealing with something else, which helps Mao. Japan and Germany had terrible communication with each other, in part because Hitler didn’t want to communicate with them, because he thought they were lesser. For Pearl Harbour, for example, Germany didn’t advise Japan on that. China was viewed as the fourth of the big three, and was underestimated. Not consulted on the plan to bomb Japan by the Allies, the Allies also didn’t trust Sheng's government. They didn’t understand the GMD CCP hatred, didn’t understand the appeal of the CCp in China, and didn’t see China as an issue in the postwar era. Mao agreed to American backed negotiations for a coalition government. Mao and Sheng are actively trying to backstab each other at this time. The United Nations were formed in October 1945, General Assembly, one nation, one vote, where most of the big stuff happens. Security Council: 5 permanent, 6 rotating members, China was one of the 5 permanent members, Chiang's Republic of China would hold this seat until 1971. Another Civil War breaks out between CCP and GMD forces. Mao ordered strategic retreat into the countryside and abandonment, which had been going on for almost 40 years at this point. Mao knew the longer the war went, it would be worse for GMD. GMD corruption, reliance on conscription, reliance on foreign money. They rely on the people's support, and have far more discipline. They outsmart Shiang's army. CCP now occupied Beijing, Nanjing, and Shanghai. Chiang fled to Taiwan, with men, civilians, and money. They are still the Republic of China. Mao declared the People's Republic of China, there are now technically two Chinas. Day 22 Notes Korean War Communist North Korea invaded Western allied South Korea, prompting a United Nations backed, US led force. Mao was pressured into involvement by North Korean weakness and US strength. China lost 500k troops, stood against the USs, who now was committed to permanently protect Taiwan. The economy was militarized. Eventually, China gets pulled in, North Korea gets pretty far, but the US forces push the North Koreans back. The US forces were told not to cross a border line so as to not provoke the Chinese, the men didn’t listen, and the Chinese entered the war. War ends in a stalemate, with little to no territory changing hands. Mao commits to building a massive bomb, and announces a five year plan. To collectivize agriculture to support the military and industrialization. Thousands were executed in a two year span. America decides that Taiwan needs to be defended, which sends a massive fleet to protect them from China, the forces are still there. Taiwan at this time was run by Shiang's government. China and Taiwan are often still considered the same, much to the chagrin of people from Taiwan. They launch the Hundred Flowers Campaign. The Chinese people are too afraid to criticize Mao because he was in power, so he’s willing to criticize himself, then they are willing to criticize him. He encourages this feedback. A few months later, he kills them all. He was trying to make the enemies of the people clear. It led to the greatest famine in human history, killing at least 34 million people. Any suffering was covered up. Mao fails to take responsibility for this famine. Mao is so determined to prove himself right he exports grain to the Soviet Union to impress them, leading to more deaths. The alternative to Stalin's communism is Mao's, which isn’t anything better. Maos has a book on how to fight imperialists, which enables people around the world to model themselves after Mao. Soviets don’t like this. The two of them finally realize that the two countries need to learn how to live together, Mao looks down upon the Soviets for backing off of Stalin's approach. Mao also believes they are trying to isolate China. They broke diplomatic relations in 1961, that was the case for about 25 years, almost going to war multiple times. Mao retreated from the public eye, and focused on developing a cult of personality. He realizes that his rule has been a disaster, but he needs a scapegoat. So, he allows two other people to clean up the mess, to enact some reforms to help the people recover. They were similar to Stalin, allowed some private property, didn't take their food, etc. He allows this so that he can blame them later for China being poorly run. A key part of this cult of personality is the little red book. It’s been printed hundreds of millions of times, it’s actually known as Quotations of Mao, literally just quotes of wisdom from Mao that spread his cult of personality. In 1964, China tested its first bomb. This changes how the West sees China, gaining them respect out of fear. Day 23 Notes Mao is being convinced that the Revolution is being corrupted from within. Starting in 1966, Chinese society was purified of bourgeois intellectualism. Empowered youth to murder authority figures. Mao thought the SU had lost its way and condemned Stalin's legacy, he believed the Communist Party didn’t care about the Revolution anymore, just staying in power. He didn’t want this to happen in China. The Chinese had really struggled, but Mao blaming himself wasn’t an option, so he advertised that the Revolution was being corrupted. May 16th, Mao announced that some people in authority were capitalists, he said that they would try to seize power. Striking fear among the people by bringing up the Soviet Union as an example. The Gang of Four stands out in Mao's camp as being especially violent and aggressive, one of them being Mao's wife, despite not having a great relationship. Young people should attack their parents, professors, and unleash a tidal wave. There was no significant challenge to him at this time. China is now in social and economic chaos. Mao disbanded the Red Guards, ordered them to be labour for peasants. The People's Liberation Army is now tasked with protecting the Revolution. In the 70’s, Mao was almost dead. He continues to purge the parties. He is concerned with what will happen when he dies. SU and China are still bickering about who the Communist Party truly is. Mao then decides to meet with the West, specifically Richard Nixon. Nixon is a strong capitalist, why is he meeting with Mao in China? The talks aren’t extensive, more symbolic, but there are some trade talks, and it ends up increasing trade between the two of them. China opens its markets up to the world eventually. He likely had Parkinsons, maybe ALS. Addicted to drugs, poor hearing, likely was blind. Multiple heart attacks as well. Died in 1976. Day 25 Notes Idi Amin is our African dictator. Uganda is divided significantly regionally, tribally, ethnically. Buganda was viewed by the British as civilized by Africans. The Bugandans were propped up by the British as sort of being trusted and capable. The Northerners were viewed as backwards and primitive. It was claimed they had no government, which wasn’t true, though it wasn’t very capable. They were called Muslims, maybe even Arabic, however, they were good fighters, it was all based on racist assumptions. Britain used these divisions to their advantage by convincing the population that they will need to oversee them. Idi Amin was a Muslim convert, his father was a police officer and in the King's Army Rifles, and his mother was a traditional healer, or witch according to the British. The British claimed they wanted to remove slavery, they just changed it to indebted servitude, which they viewed as the same thing by raising taxes to such an extent that most would have to do it. Idi was one of many that joined the military to avoid this. He enlisted in 1946, and gained a reputation as an effective soldier. He is very violent, and helps quash Black African resistance to British rule in Uganda. Through the 50’s, he helped quash the Mau Mau uprising in Kenya. He was seen as a stooge of the British, this was because he was a part of the British forces that took down African resistance, he betrayed his people. Critics of that would say that assuming that is racist in and of itself, he may not have identified with black people necessarily, he was also following orders. British forces viewed Amin as an ideal candidate if armed forces were to be Africanized, although that is not the plan that they favour. Gets to a point where he is one of two black supervisors. Amin rose quickly, Ugandan independence came in 1962 under PM Milton Obote. Amin was very important during this time under Obote, he helped to calm down mutinies and present grievances to Obote, who made concessions. He was seen as defending Ugandan rights, while also proving himself to the British. There are significant revolts during this time, where the Africans recognize and believe that the British are still running the show. Amin uses the fact he is one of them to appeal to them. Amin takes demands from the people to Obote, which show to be reasonable. It doesn’t last, but helps to prove Amin. Obote, worried for his powers, goes on the offensive, suspending the constitution. Amin is appointed head of the armed forces. He is united Uganda, whether anyone likes it or not. This created a rift between Amin and Obotoe after a while. They negotiated with the British during the Cold War, threatening to not help them if they didn't give in. Amin is promoted to commander of the army during this time as well. Amin knows at this point Obotoe will try to kill him, but nonetheless Obotoe gets convinced to go to an important meeting in Singapore. Amin overthrows his government while Obotoe is at the meeting. Amin is named temporary leader. Immediately, Amin purges the military, which is the only thing he seems to know how to do. He relies on an army from his hometown, which he gives special privileges to. Obote allied forces attacked Uganda in 1972 of people that didn't like Amin. Repression increases significantly during this time. Amin orders the expulsion of all Asians, he calls himself the Black Hitler. Thousands of people have to leave during this time. The West condemns this, but most Ugandans support it. But it devastated the Ugandan economy. Day 28 Notes The Vietnam war went poorly for the States because they weren’t willing to sacrifice their own people. Bombs were dropped on Cambodia, an innocent party, in 1973, by the Americans. It kills a lot of Vietnamese, but the Vietnamese don’t care about losing people, eventually, they realize the Americans won’t keep killing citizens like that. They reach a treaty, but the treaty is quickly broken. So the Democratic Republic of Kampuchea takes over. They are unknowns, they were not known as the people that had taken over Cambodia. In fact, the citizens think they defeated the Americans, and the war was going to stop. They had been in the rural areas through most of this area. Within weeks, the Kampuchea over evacuated everyone in the cities, everyone was an enemy of the people that needed to be eradicated or removed. Leads to significant deaths as the Kampuchea starts to purge, if they aren’t helpful to the revolution, they are killed. Sick people, old people, children. They abolish money, and all forms of religion. Money is no longer worth anything. Poi Pot is the general secretary of the Democratic party, but no one knows he’s the leader, as he lies in the background. The head of state tries to rein them in, ends up getting kidnapped and becomes a puppet leader. To the detriment of the Cambodian people, they continue to rule for years. Collectivize agriculture to gather money, even though they had gotten rid of money. They would be able to stand on their own against their enemies, primarily Vietnam. They wanted the country to be self-sufficient. Pot was very convinced it only didn’t work because people didn’t try hard enough, so he executed people as his system didn’t work. Pot arrests all the people he’s been allied with for years. Pot also abolishes education, turning high school into an interrogation complex, which is now a genocide museum. One example is over 5000 people were in the place, only 6 survived. The people from April 17th were turned into slaves, many of which died. They went to war with Vietnam in 1977. A series of border raids are carried out by the Cambodians, which in response leads to attacks. He resented Vietnam for believing that they didn’ t respect Cambodia. Su supported Vietnam, China supported Cambodia, became a proxy war between two communist nations, and supported by communist parents. It doesn’t go well with Cambodia, who had killed all of the people that could have served in the army. When Vietnam is able to liberate prisoners, Pot kills the soldiers, this method obviously has consequences. Most of the fighting takes place in Cambodia. In 1978, Vietnam invaded Cambodia fully, which they won easily and quickly. Vietnam then creates their own Communist government. They kick out Poi Pot. They publicize Poi Pot's crimes. Vietnam gives the government the same name as the previous one, basically a puppet government for Vietnam. Poi Pot and some others are able to flee to Thailand. By 1980, everyone knows what Poi Pot did, in less than four years, they had killed about 25% of the Cambodian population. However, because of Vietnam's reputation, Thailand agrees to protect Poi Pot and his people, in exchange for China not funding Vietnam. So, China sends supplies and pays for Poi Pot, and so does America, they reject the new government in Cambodia because they lost in Vietnam. America supports Poi Pot being protected and funded by Thailand and China. Pot carries out raids in Cambodia from Thailand trying to retake it. Also means they keep their seats in the United Nations for 14 years after his crimes were made public. The justification made by the US is that Pot isn’t running the party anymore, which he claims, but he’s lying. In the mid 90’s, Cambodia had an election under the supervision of the UN, which didn't last very long. This ends all the international support for Poi Pot. In 1997, he ordered the murder of his closest ally and their family. Finally, his party has enough, and they consider Poi Pot a traitor, Pot dies while on trial by heart attack. Some repetition from previous tests. Need to know authors' last names and who they wrote about. Will focus on major events, themes, people, and organizations. Won’t be testing on specific dates or stats. Guest lectures can be included. Most questions will be about a specific dictator, although some might be on themes. What were the themes or the focus of specific readings? List of Authors of Readings + Subheadings Non-Specific Dictators: Dictatorship: Modern Tyranny Between Leviathan and Behemoth by Jan C Behrends Benito Mussolini: Mussolini by Peter Neville Chapters 2,5,6,9 Sub Headings: Chapter 2: The Achievement of Power The Genesis Fascism The Red Two Years The Death of Liberal Italy The Taking of Power The March on Rome Fascism: revolution or counter-revolution? Mussolini and Parliament The Fascist Grand Council The Voluntary Militia for National Security The 1924 Elections Chapter 5: Italian society under Mussolini, 1931–39 Winning Over Italy's Youth Women Under Fascism The Media Corporativism and the Great Depression The Dopolavoro Opposition in Fascist Italy Anti-Semitism Was there a Fascist consensus? Chapter 6: The Ethiopian War, 1935–36 The end of the old diplomacy, 1932–35 The Austrian crisis Fascism in Africa The Ethiopian Question The invasion of Ethiopia’ The Hoare–Laval Pact The consequences of the war Chapter 9: The last phase, 1943–45 The foundation of the Italian Social Republic A dictator's twilight The Congress of Verona The last days Conclusion Mussolini in retrospect Adolf Hitler Hitler by Ian Kershaw Eva Braun: Life With Hitler by Heike Gortenmaker War and Genocide: A Concise History of the Holocaust by Doris Bergen Kershaw Chapter 1: Power of the Idea No subheadings Braun Chapter 9: Isolation of War The Outbreak of War The Berghof of Fuhrer Headquarters The Beginning of the End Bergen Death Throes and Killing Frenzies Attacks on the Nazi Regime The Soviet Advance Allied Bombing and Conditions in Germany D Day - Allied Invasion from the West The Plot of 20 July, 1944 The Volkssturm The Warsaw Uprising Germany's Allies and the Jews of Hungary Auschwitz and the end of war The Death Marches Final Collapse Joseph Stalin Popular Opinion in Stalin’s Russia: Terror, Propaganda, and Dissent, 1934- 1941 by Sarah Davis Stalin by Hiroaki Kuromiya Davis Chapter 9: The leader cult in official discourse The evolution of the cult The cult as official culture Chapter 10: Affirmative representations of the leader and the leader cult The leader as benefactor The traditional defender of the people The Charismatic Leader Kuromiya Chapter 7: Twilight of the god Victory Cold War Death Also, supposed to read Conclusion ig Mao Zedong From Urban Radical to Rural Revolutionary: Mao from the 1920s to 1937 by Brantly Womack War, Cosmopolitanism, and Authority: Mao from 1937-1956 by Han J
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Regulation of Gene Expression Lecture Outline Overview: Differential Expression of Genes • Both prokaryotes and eukaryotes alter their patterns of gene expression in response to changes in environmental conditions. • Multicellular eukaryotes also develop and maintain multiple cell types. ○ Each cell type contains the same genome but expresses a different subset of genes. ○ During development, gene expression must be carefully regulated to ensure that the right genes are expressed only at the correct time and in the correct place. • Gene expression in eukaryotes and bacteria is often regulated at the transcription stage. ○ Control of other levels of gene expression is also important. • RNA molecules play many roles in regulating eukaryotic gene expressions. • Disruptions in gene regulation may lead to cancer. Concept 18.1 Bacteria often respond to environmental change by regulating transcription • Natural selection favors bacteria that express only those genes whose products are needed by the cell. ○ A bacterium in a tryptophan-rich environment that stops producing tryptophan conserves its resources. • Metabolic control occurs on two levels. • First, cells can adjust the activity of enzymes already present. ○ This may happen by feedback inhibition, in which the activity of the first enzyme in a pathway is inhibited by the pathway’s end product. ○ Feedback inhibition, typical of anabolic (biosynthetic) pathways, allows a cell to adapt to short-term fluctuations in the supply of a needed substance. • Second, cells can vary the number of specific enzyme molecules they make by regulating gene expression. ○ The control of enzyme production occurs at the level of transcription, the synthesis of messenger RNA coding for these enzymes. ○ Genes of the bacterial genome may be switched on or off by changes in the metabolic status of the cell. • The basic mechanism for the control of gene expression in bacteria, known as the operon model, was described by Francois Jacob and Jacques Monod in 1961. The operon model controls tryptophan synthesis. • Escherichia coli synthesizes tryptophan from a precursor molecule in a series of steps, with each reaction catalyzed by a specific enzyme. • The five genes coding for the subunits of these enzymes are clustered together on the bacterial chromosome as a transcription unit, served by a single promoter. • Transcription gives rise to one long mRNA molecule that codes for all five polypeptides in the tryptophan pathway. • The mRNA is punctuated with start and stop codons that signal where the coding sequence for each polypeptide begins and ends. • A key advantage of grouping genes with related functions into one transcription unit is that a single on-off switch can control a cluster of functionally related genes. ○ In other words, these genes are coordinately controlled. • When an E. coli cell must make tryptophan for itself, all the enzymes are synthesized at one time. • The switch is a segment of DNA called an operator. • The operator, located within the promoter or between the promoter and the enzyme-coding genes, controls the access of RNA polymerase to the genes. • The operator, the promoter, and the genes they control constitute an operon. ○ The trp operon (trp for tryptophan) is one of many operons in the E. coli genome. • By itself, an operon is turned on: RNA polymerase can bind to the promoter and transcribe the genes of the operon. • The operon can be switched off by a protein called the trp repressor. ○ The repressor binds to the operator, blocks attachment of RNA polymerase to the promoter, and prevents transcription of the operon’s genes. • Each repressor protein recognizes and binds only to the operator of a particular operon. • The trp repressor is the protein product of a regulatory gene called trpR, which is located at some distance from the operon it controls and has its own promoter. • Regulatory genes are transcribed continuously at slow rates, and a few trp repressor molecules are always present in an E. coli cell. • Why is the trp operon not switched off permanently? • First, binding by the repressor to the operator is reversible. ○ An operator vacillates between two states, with and without a repressor bound to it. ○ The relative duration of each state depends on the number of active repressor molecules around. • Second, repressors contain allosteric sites that change shape depending on the binding of other molecules. ○ The trp repressor has two shapes: active and inactive. ○ The trp repressor is synthesized in an inactive form with little affinity for the trp operator. ○ Only if tryptophan binds to the trp repressor at an allosteric site does the repressor protein change to the active form that can attach to the operator, turning the operon off. • Tryptophan functions in the trp operon as a corepressor, a small molecule that cooperates with a repressor protein to switch an operon off. • When concentrations of tryptophan in the cell are high, more tryptophan molecules bind with trp repressor molecules, activating them. ○ The active repressors bind to the trp operator and turn the operon off. • At low levels of tryptophan, most of the repressors are inactive, and transcription of the operon’s genes resumes. There are two types of operons: repressible and inducible. • The trp operon is an example of a repressible operon, one that is inhibited when a specific small molecule (tryptophan) binds allosterically to a regulatory protein. • In contrast, an inducible operon is stimulated (induced) when a specific small molecule interacts with a regulatory protein. • The classic example of an inducible operon is the lac operon (lac for lactose). • Lactose (milk sugar) is available to E. coli in the human colon if the host drinks milk. ○ Lactose metabolism begins with hydrolysis of lactose into its component monosaccharides, glucose and galactose. ○ This reaction is catalyzed by the enzyme ß-galactosidase. • Only a few molecules of b-galactosidase are present in an E. coli cell grown in the absence of lactose. ○ If lactose is added to the bacterium’s environment, the number of ß-galactosidase molecules increases by a thousandfold within 15 minutes. • The gene for ß-galactosidase is part of the lac operon, which includes two other genes coding for enzymes that function in lactose metabolism. • The regulatory gene, lacI, located outside the operon, codes for an allosteric repressor protein that can switch off the lac operon by binding to the operator. • Unlike the trp operon, the lac repressor is active all by itself, binding to the operator and switching the lac operon off. ○ An inducer inactivates the repressor. ○ When lactose is present in the cell, allolactose, an isomer of lactose, binds to the repressor. ○ This inactivates the repressor, and the lac operon can be transcribed. • Repressible enzymes generally function in anabolic pathways, synthesizing end products from raw materials. ○ When the end product is present in sufficient quantities, the cell can allocate its resources to other uses. • Inducible enzymes usually function in catabolic pathways, digesting nutrients to simpler molecules. ○ By producing the appropriate enzymes only when the nutrient is available, the cell avoids making proteins that are not needed. • Both repressible and inducible operons demonstrate negative control of genes because active repressors switch off the active form of the repressor protein. ○ It may be easier to see this for the trp operon, but it is also true for the lac operon. ○ Allolactose induces enzyme synthesis not by acting directly on the genome, but by freeing the lac operon from the negative effect of the repressor. Some gene regulation is positive. • Positive gene control occurs when a protein molecule interacts directly with the genome to switch transcription on. • The lac operon is an example of positive gene regulation. • When glucose and lactose are both present, E. coli preferentially uses glucose. ○ The enzymes for glucose breakdown in glycolysis are always present in the cell. • Only when lactose is present and glucose is in short supply does E. coli use lactose as an energy source and synthesize the enzymes for lactose breakdown. • When glucose levels are low, cyclic AMP (cAMP) accumulates in the cell. • The regulatory protein catabolite activator protein (CAP) is an activator of transcription. • When cAMP is abundant, it binds to CAP, and the regulatory protein assumes its active shape and can bind to a specific site at the upstream end of the lac promoter. ○ The attachment of CAP to the promoter increases the affinity of RNA polymerase for the promoter, directly increasing the rate of transcription. ○ Thus, this mechanism qualifies as positive regulation. • If glucose levels in the cell rise, cAMP levels fall. ○ Without cAMP, CAP detaches from the operon and lac operon is transcribed only at a low level. • The lac operon is under dual control: negative control by the lac repressor and positive control by CAP. ○ The state of the lac repressor (with or without bound allolactose) determines whether or not the lac operon’s genes are transcribed. ○ The state of CAP (with or without bound cAMP) controls the rate of transcription if the operon is repressor-free. ○ The operon has both an on-off switch and a volume control. • CAP works on several operons that encode enzymes used in catabolic pathways. It affects the expression of more than 100 E. coli genes. ○ If glucose is present and CAP is inactive, then the synthesis of enzymes that catabolize other compounds is slowed. ○ If glucose levels are low and CAP is active, then the genes that produce enzymes that catabolize whichever other fuel is present are transcribed at high levels. Concept 18.2 Eukaryotic gene expression is regulated at many stages • Like unicellular organisms, the tens of thousands of genes in the cells of multicellular eukaryotes turn on and off in response to signals from their internal and external environments. • Gene expression must be controlled on a long-term basis during cellular differentiation. Differential gene expression is the expression of different genes by cells with the same genome. • A typical human cell probably expresses about 20% of its genes at any given time. ○ Highly specialized cells, such as nerves or muscles, express a tiny fraction of their genes. ○ Although all the cells in an organism contain an identical genome, the subset of genes expressed in the cells of each type is unique. • The differences between cell types are due to differential gene expression, the expression of different genes by cells with the same genome. • The function of any cell, whether a single-celled eukaryote or a particular cell type in a multicellular organism, depends on the appropriate set of genes being expressed. ○ Problems with gene expression and control can lead to imbalance and disease, including cancer. • Our understanding of the mechanisms that control gene expression in eukaryotes has been enhanced by new research methods, including advances in DNA technology. • In all organisms, a common control point for gene expression is at transcription, often in response to signals coming from outside the cell. ○ For this reason, the term gene expression is often equated with transcription. • With their greater complexity, eukaryotes have opportunities for controlling gene expression at additional stages. Chromatin modifications affect the availability of genes for transcription. • The DNA of eukaryotic cells is packaged with proteins in a complex called chromatin. ○ The basic unit of chromatin is the nucleosome. • The location of a gene’s promoter relative to nucleosomes and to the sites where the DNA attaches to the chromosome scaffold or nuclear lamina affect whether the gene is transcribed. • Genes of densely condensed heterochromatin are usually not expressed. • Chemical modifications of the histone proteins and DNA of chromatin play a key role in chromatin structure and gene expression. • The N-terminus of each histone molecule in a nucleosome protrudes outward from the nucleosome. ○ These histone tails are accessible to various modifying enzymes, which catalyze the addition or removal of specific chemical groups. • Histone acetylation (addition of an acetyl group, —COCH3) and deacetylation of lysines in histone tails appear to play a direct role in the regulation of gene transcription. • Acetylation of lysines neutralizes their positive charges and reduces the binding of histone tails to neighboring nucleosomes, easing access for transcription proteins. ○ Some of the enzymes responsible for acetylation or deacetylation are associated with or are components of transcription factors that bind to promoters. • Thus, histone acetylation enzymes may promote the initiation of transcription not only by modifying chromatin structure but also by binding to and recruiting components of the transcription machinery. • Other chemical groups, such as methyl and phosphate groups, can be reversibly attached to amino acids in histone tails. ○ The attachment of methyl groups (—CH3) to histone tails leads to condensation of chromatin. ○ The addition of a phosphate group (phosphorylation) to an amino acid next to a methylated amino acid has the opposite effect. • The recent discovery that modifications to histone tails can affect chromatin structure and gene expression has led to the histone code hypothesis. ○ This hypothesis proposes that specific combinations of modifications, as well as the order in which they have occurred, determine chromatin configuration. ○ Chromatin configuration in turn influences transcription. DNA methylation reduces gene expression. • While some enzymes methylate the tails of histone proteins, other enzymes methylate certain bases in DNA itself, usually cytosine. ○ DNA methylation occurs in most plants, animals, and fungi. • Inactive DNA is generally more highly methylated than actively transcribed regions. ○ For example, the inactivated mammalian X chromosome is heavily methylated. ○ Individual genes are usually more heavily methylated in cells where they are not expressed. Removal of extra methyl groups can turn on some of these genes. • In some species, DNA methylation is responsible for the long-term inactivation of genes during cellular differentiation. ○ Deficient DNA methylation leads to abnormal embryonic development in organisms as different as mice and the plant Arabidopsis. • Once methylated, genes usually stay that way through successive cell divisions in a given individual. • Methylation enzymes recognize sites on one strand that are already methylated and correctly methylate the daughter strand after each round of DNA replication. • This methylation pattern accounts for genomic imprinting, in which methylation turns off either the maternal or paternal alleles of certain mammalian genes at the start of development. • The chromatin modifications just discussed do not alter the DNA sequence, and yet they may be passed along to future generations of cells. • Inheritance of traits by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance. • The molecular systems for chromatin modification may well interact with each other in a regulated way. ○ In Drosophila, experiments suggest that a particular histone-modifying enzyme recruits a DNA methylation enzyme to one region and that the two enzymes collaborate to silence a particular set of genes. ○ Working in the opposite order, proteins have also been found that bind to methylated DNA and then recruit histone deacetylation enzymes. ○ Thus, a dual mechanism, involving both DNA methylation and histone deacetylation, can repress transcription. • Researchers are amassing more and more evidence for the importance of epigenetic information in the regulation of gene expression. ○ Epigenetic variations may explain why one identical twin acquires a genetically based disease, such as schizophrenia, while another does not, despite their identical genomes. ○ Alterations in normal patterns of DNA methylation are seen in some cancers, where they are associated with inappropriate gene expression. • Enzymes that modify chromatin structure are integral parts of the cell’s machinery for regulating transcription. Transcription initiation is controlled by proteins that interact with DNA and with each other. • Chromatin-modifying enzymes provide initial control of gene expression by making a region of DNA more available or less available for transcription. • A cluster of proteins called a transcription initiation complex assembles on the promoter sequence at the upstream end of the gene. ○ One component, RNA polymerase II, transcribes the gene, synthesizing a primary RNA transcript or pre-mRNA. ○ RNA processing includes enzymatic addition of a 5¢ cap and a poly-A tail, as well as splicing out of introns to yield a mature mRNA. • Multiple control elements are associated with most eukaryotic genes. ○ Control elements are noncoding DNA segments that serve as binding sites for protein transcription factors. ○ Control elements and the transcription factors they bind are critical to the precise regulation of gene expression in different cell types. • To initiate transcription, eukaryotic RNA polymerase requires the assistance of proteins called transcription factors. • General transcription factors are essential for the transcription of all protein-coding genes. ○ Only a few general transcription factors independently bind a DNA sequence such as the TATA box within the promoter. ○ Others are involved in protein-protein interactions, binding each other and RNA polymerase II. • Only when the complete initiation complex has been assembled can the polymerase begin to move along the DNA template strand to produce a complementary strand of RNA. • The interaction of general transcription factors and RNA polymerase II with a promoter usually leads to only a slow rate of initiation and the production of few RNA transcripts. • In eukaryotes, high levels of transcription of particular genes depend on the interaction of control elements with specific transcription factors. • Some control elements, named proximal control elements, are located close to the promoter. • Distal control elements, grouped as enhancers, may be thousands of nucleotides away from the promoter or even downstream of the gene or within an intron. • A given gene may have multiple enhancers, each active at a different time or in a different cell type or location in the organism. ○ Eukaryotic gene expression can be altered by the binding of specific transcription factors, either activators or repressors, to the control elements of enhancers. • Two structural elements are common to many activator proteins: a DNA-binding domain and one or more activation domains. ○ Activation domains bind other regulatory proteins or components of the transcription machinery to facilitate transcription. • Protein-mediated bending of DNA brings bound activators in contact with a group of mediator proteins that interact with proteins at the promoter. ○ These interactions help assemble and position the initiation complex on the promoter. • Eukaryotic repressors can inhibit gene expression by blocking the binding of activators to their control elements or to components of the transcription machinery. ○ Other repressors bind directly to control-element DNA, turning off transcription even in the presence of activators. • Some activators and repressors act indirectly to influence chromatin structure. ○ Some activators recruit proteins that acetylate histones near the promoters of specific genes, promoting transcription. ○ Some repressors recruit proteins that deacetylate histones, reducing transcription or silencing the gene. • Recruitment of chromatin-modifying proteins seems to be the most common mechanism of repression in eukaryotes. The control of transcription in eukaryotes depends on the binding of activators to DNA control elements. • The number of different nucleotide sequences found in control elements is surprisingly small: about a dozen. • On average, each enhancer is composed of about ten control elements, each of which can bind to only one or two specific transcription factors. ○ The particular combination of control elements in an enhancer may be more important than the presence of a unique control element in regulating transcription of the gene. • Even with only a dozen control element sequences, a large number of combinations are possible. • A particular combination of control elements is able to activate transcription only when the appropriate activator proteins are present, at a precise time during development or in a particular cell type. • The use of different combinations of control elements allows fine regulation of transcription with a small set of control elements. • In prokaryotes, coordinately controlled genes are often clustered into an operon with a single promoter and other control elements upstream. ○ The genes of the operon are transcribed into a single mRNA and translated together. • In contrast, very few eukaryotic genes are organized this way. • More commonly, co-expressed genes coding for the enzymes of a metabolic pathway are scattered over different chromosomes. ○ Coordinate gene expression depends on the association of a specific control element or combination of control elements with every gene of a dispersed group. ○ A common group of transcription factors binds to all the genes in the group, promoting simultaneous gene transcription. • For example, a steroid hormone enters a cell and binds to a specific receptor protein in the cytoplasm or nucleus, forming a hormone–receptor complex that serves as a transcription activator. ○ Every gene whose transcription is stimulated by that steroid hormone has a control element recognized by that hormone–receptor complex. • Other signal molecules control gene expression indirectly by triggering signal-transduction pathways that lead to activation of transcription. ○ The principle of coordinate regulation is the same: Genes with the same control elements are activated by the same chemical signals. • Systems for coordinating gene regulation probably arose early in evolutionary history. • The nucleus has a defined architecture and regulated movements of chromatin. • Recent techniques allow researchers to cross-link and identify regions of chromosomes that associate with each other during interphase. • Loops of chromatin extend from individual chromosomal territories into specific sites in the nucleus. ○ Different loops from the same chromosome and loops from other chromosomes congregate in such sites, some of which are rich in RNA polymerases and other transcription-associated proteins. ○ These sites are likely areas specialized for a common function or transcription factories. Post-transcriptional mechanisms play supporting roles in the control of gene expression. • Regulatory mechanisms that operate after transcription allow a cell to rapidly fine-tune gene expression in response to environmental changes, without altering its transcriptional patterns. ○ RNA processing in the nucleus and the export of mRNA to the cytoplasm provide opportunities for gene regulation that are not available in prokaryotes. • In alternative RNA splicing, different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns. ○ Regulatory proteins specific to a cell type control intron-exon choices by binding to regulatory sequences within the primary transcript. • Alternative RNA splicing significantly expands the repertoire of a set of genes. ○ It may explain the surprisingly low number of human genes: similar to those of a soil worm, a mustard plant, or a sea anemone. ○ Between 75% and 100% of human genes that have multiple exons probably undergo alternative splicing. ○ The extent of alternative splicing increases the number of possible human proteins, likely correlated with complexity of form. • The life span of an mRNA molecule is an important factor in determining the pattern of protein synthesis. ○ Prokaryotic mRNA molecules are typically degraded after only a few minutes, while eukaryotic mRNAs typically last for hours, days, or weeks. ○ In red blood cells, mRNAs for hemoglobin polypeptides are unusually stable and are translated repeatedly. • Nucleotide sequences in the untranslated trailer region (UTR) at the 3¢ end affect mRNA stability. ○ Transferring such a sequence from a short-lived mRNA to a normally stable mRNA results in quick mRNA degradation. Translation presents an opportunity for the regulation of gene expression. • The initiation of translation of an mRNA can be blocked by regulatory proteins that bind to specific sequences within the 5¢ or 3¢ UTR of the mRNA, preventing ribosome attachment. • The mRNAs present in the eggs of many organisms lack poly-A tails of sufficient length to allow initiation of translation. ○ During embryonic development, a cytoplasmic enzyme adds more adenine nucleotides so that translation can begin at the appropriate time. • Translation of all the mRNAs in a eukaryotic cell may be regulated simultaneously by the activation or inactivation of the protein factors required to initiate translation. ○ This mechanism starts the translation of mRNAs that are stored in eggs. ○ Just after fertilization, translation is triggered by the sudden activation of translation initiation factors, resulting in a burst of protein synthesis. • Some plants and algae store mRNAs during periods of darkness. Light triggers the reactivation of the translational apparatus. The final opportunities for controlling gene expression occur after translation. • Often, eukaryotic polypeptides are processed to yield functional proteins. ○ For example, cleavage of pro-insulin forms the active hormone. • Many proteins must undergo chemical modifications before they are functional. ○ Regulatory proteins may be activated or inactivated by the reversible addition of phosphate groups. ○ Proteins destined for the surface of animal cells acquire sugars. • Regulation may occur at any of the steps involved in modifying or transporting a protein. • The length of time a protein functions before it is degraded is strictly regulated. ○ Proteins such as the cyclins that regulate the cell cycle must be relatively short-lived. • To mark a protein for destruction, the cell attaches a small protein called ubiquitin to it. ○ Giant protein complexes called proteasomes recognize and degrade the tagged proteins. • Mutations making specific cell cycle proteins impervious to proteasome degradation can lead to cancer. • The scientists worked out the regulated process of protein degradation won the 2004 Nobel Prize in Chemistry. Concept 18.3 Noncoding RNAs play multiple roles in controlling gene expression • Only 1.5% of the human genome codes for proteins. Of the remainder, only a very small fraction consists of genes for ribosomal RNA and transfer RNA. • Until recently, it was assumed that most of the rest of the DNA was untranscribed. Recent data have challenged that assumption, however. ○ Study of a region comprising 1% of the human genome found that over 90% of the region was transcribed. ○ Introns accounted for only a fraction of this transcribed, nontranslated RNA. • A significant amount of the genome may be transcribed into non–protein-coding RNAs (or noncoding RNAs or ncRNAs), including a variety of small RNAs. • A large, diverse population of RNA molecules may play crucial roles in regulating gene expression in the cell. MicroRNAs can bind to complementary sequences in mRNA molecules. • In the past few years, researchers have found small, single-stranded RNA molecules called microRNAs (miRNAs) that bind to complementary sequences in mRNA molecules. • miRNAs are formed from longer RNA precursors that fold back on themselves to form one or more short, double-stranded hairpin structures stabilized by hydrogen bonding. • An enzyme called Dicer cuts each hairpin into a short, double-stranded fragment of about 22 nucleotide pairs. • One of the two strands is degraded. The other strand (miRNA) associates with a protein complex and directs the complex to any mRNA molecules that have a complementary sequence of 7-8 nucleotides. • The miRNA–protein complex either degrades the target mRNA or blocks its translation. • Expression of up to one-half of all human genes may be regulated by miRNAs. • The phenomenon of inhibition of gene expression by RNA molecules is called RNA interference (RNAi). • Injecting double-stranded RNA molecules into a cell somehow turns off expression of a gene with the same sequence as the RNA. ○ This RNA interference is due to small interfering RNAs (siRNAs), similar in size and function to miRNAs and are generated by similar mechanisms in eukaryotic cells. • Both miRNAs and siRNAs can associate with the same proteins, with similar results. ○ The distinction between these molecules is the nature of the precursor molecules from which they are formed. ○ Each miRNA forms from a single hairpin in the precursor RNA, while multiple siRNAs form from a longer, double-stranded RNA molecule. • Cellular RNAi pathways lead to the destruction of RNAs and may have originated as a natural defense against infection by double-stranded RNA viruses. ○ The fact that the RNAi pathway can also affect the expression of nonviral cellular genes may reflect a different evolutionary origin for the RNAi pathway. • Many species, including mammals, possess long, double-stranded precursors to small RNAs that interfere with various steps in gene expression. Small RNAs can remodel chromatin and silence transcription. • Small RNAs can cause remodeling of chromatin structure. ○ In yeast, siRNAs are necessary for the formation of heterochromatin at the centromeres of chromosomes. • An RNA transcript produced from DNA in the centromeric region of the chromosome is copied into double-stranded RNA by a yeast enzyme and then processed into siRNAs. ○ The siRNAs associate with a protein complex, targeting the complex back to the RNA sequences made from the centromeric sequences of DNA. ○ The proteins in the complex recruit enzymes to modify the chromatin, turning it into the highly condensed centromeric heterochromatin. • A newly discovered class of small ncRNAs, called piwi-associated RNAs (piRNAs) also induce formation of heterochromatin, blocking expression of parasitic DNA elements in the genome known as transposons. ○ piRNAs, 24–31 nucleotides in length, are processed from single-stranded RNA precursors. ○ In germ cells of many animal species, piRNAs help re-establish appropriate methylation patterns in the genome during gamete formation. • Chromatin remodeling not only blocks expression of large regions of the chromosome; RNA-based mechanisms may also block the transcription of specific genes. ○ Some plant miRNAs have sequences that bind to gene promoters and can repress transcription; piRNAs can also block expression of specific genes. ○ In some cases, miRNAs and piRNAs activate gene expression. • Small ncRNAs regulate gene expression at multiple steps and in many ways. ○ Extra levels of gene regulation may allow evolution of a higher degree of complexity of form. ○ An increase in the number of miRNAs encoded in the genomes of species may have allowed morphological complexity to increase over evolutionary time. • A survey of species suggests that siRNAs evolved first, followed by miRNAs and later piRNAs, which are found only in animals. ○ While there are hundreds of types of miRNA, there appear to be many thousands of types of piRNAs, allowing the potential for very sophisticated gene regulation by piRNAs. • Many ncRNAs play important roles in embryonic development, the ultimate example of an elaborate program of regulated gene expression. Concept 18.4 A program of differential gene expression leads to the different cell types in a multicellular organism • In the development of most multicellular organisms, a single-celled zygote gives rise to cells of many different types. ○ Each type has a different structure and corresponding function. ○ Cells of different types are organized into tissues, tissues into organs, organs into organ systems, and organ systems into the whole organism. • Thus, the process of embryonic development must give rise not only to cells of different types but also to higher-level structures arranged in a particular way in three dimensions. A genetic program is expressed during embryonic development. • As a zygote develops into an adult organism, its transformation results from three interrelated processes: cell division, cell differentiation, and morphogenesis. • Through a succession of mitotic cell divisions, the zygote gives rise to many cells. ○ Cell division alone would produce only a great ball of identical cells. • During development, cells become specialized in structure and function, undergoing cell differentiation. • Different kinds of cells are organized into tissues and organs. • The physical processes that give an organism its shape constitute morphogenesis, the “creation of form.” • Cell division, cell differentiation, and morphogenesis have their basis in cellular behavior. ○ Morphogenesis can be traced back to changes in the shape and motility of cells in the various embryonic regions. ○ The activities of a cell depend on the genes it expresses and the proteins it produces. ○ Because almost all cells in an organism have the same genome, differential gene expression results from differential gene regulation in different cell types. • Why are different sets of activators present in different cell types? • One important source of information early in development is the egg’s cytoplasm, which contains both RNA and proteins encoded by the mother’s DNA, distributed unevenly in the unfertilized egg. • Maternal substances that influence the course of early development are called cytoplasmic determinants. ○ These substances regulate the expression of genes that affect the developmental fate of the cell. ○ After fertilization, the cell nuclei resulting from mitotic division of the zygote are exposed to different cytoplasmic environments. ○ The set of cytoplasmic determinants a particular cell receives helps determine its developmental fate by regulating expression of the cell’s genes during cell differentiation. • The other important source of developmental information is the environment around the cell, especially signals impinging on an embryonic cell from nearby cells. ○ In animals, these signals include contact with cell-surface molecules on neighboring cells and the binding of growth factors secreted by neighboring cells. • These signals cause changes in the target cells, a process called induction. ○ The molecules conveying these signals within the target cells are cell-surface receptors and other proteins expressed by the embryo’s own genes. ○ The signal molecules send a cell down a specific developmental path by causing a change in its gene expression that eventually results in observable cellular changes. Cell differentiation is due to the sequential regulation of gene expression. • During embryonic development, cells become visibly different in structure and function as they differentiate. • The earliest changes that set a cell on a path to specialization show up only at the molecular level. ○ Molecular changes in the embryo drive the process, called determination, which leads to the observable differentiation of a cell. • Once it has undergone determination, an embryonic cell is irreversibly committed to its final fate. ○ If a determined cell is experimentally placed in another location in the embryo, it will differentiate as if it were in its original position. • The outcome of determination—observable cell differentiation—is caused by the expression of genes that encode tissue-specific proteins. ○ These proteins give a cell its characteristic structure and function. • Differentiation begins with the appearance of cell-specific mRNAs and is eventually observable in the microscope as changes in cellular structure. • In most cases, the pattern of gene expression in a differentiated cell is controlled at the level of transcription. • Cells produce the proteins that allow them to carry out their specialized roles in the organism. ○ For example, liver cells specialize in making albumin, while lens cells specialize in making crystalline. ○ Skeletal muscle cells have high concentrations of proteins specific to muscle tissues, such as a muscle-specific version of the contractile proteins myosin and actin, as well as membrane receptor proteins that detect signals from nerve cells. • Muscle cells develop from embryonic precursors that have the potential to develop into a number of alternative cell types. ○ Although the committed cells are unchanged, they are now myoblasts. ○ Eventually, myoblasts begin to synthesize muscle-specific proteins and fuse to form mature, elongated, multinucleate skeletal muscle cells. • Researchers have worked out the events at the molecular level that lead to muscle cell determination by growing myoblasts in culture and analyzing them with molecular biology techniques. ○ Researchers isolated different genes, caused each to be expressed in a separate embryonic precursor cell, and looked for differentiation into myoblasts and muscle cells. ○ They identified several “master regulatory genes” that, when transcribed and translated, commit the cells to become skeletal muscle. • One of these master regulatory genes is called myoD. ○ myoD encodes MyoD protein, a transcription factor that binds to specific control elements in the enhancers of various target genes and stimulates their expression. ○ Some target genes for MyoD encode for other muscle-specific transcription factors. ○ MyoD also stimulates expression of the myoD gene itself, helping to maintain the cell’s differentiated state. • All the genes activated by MyoD have enhancer control elements recognized by MyoD and are thus coordinately controlled. • The secondary transcription factors activate the genes for proteins such as myosin and actin to confer the unique properties of skeletal muscle cells. • The MyoD protein is capable of changing fully differentiated fat and liver cells into muscle cells. • Not all cells can be transformed by MyoD, however. ○ Nontransforming cells may lack a combination of regulatory proteins in addition to MyoD. Pattern formation sets up the embryo’s body plan. • Cytoplasmic determinants and inductive signals contribute to pattern formation, the development of spatial organization in which the tissues and organs of an organism are all in their characteristic places. • Pattern formation begins in the early embryo, when the major axes of an animal are established. • Before specialized tissues and organs form, the relative positions of a bilaterally symmetrical animal’s three major body axes (anterior-posterior, dorsal-ventral, right-left) are established. • The molecular cues that control pattern formation, positional information, are provided by cytoplasmic determinants and inductive signals. ○ These signals tell a cell its location relative to the body axes and to neighboring cells and determine how the cell and its progeny will respond to future molecular signals. • Studies of pattern formation in Drosophila melanogaster have established that genes control development and have identified the key roles of specific molecules in defining position and directing differentiation. • Combining anatomical, genetic, and biochemical approaches in the study of Drosophila development, researchers have discovered developmental principles common to many other species, including humans. • Fruit flies and other arthropods have a modular construction. ○ An ordered series of segments make up the three major body parts: the head, thorax (with wings and legs), and abdomen. • Cytoplasmic determinants in the unfertilized egg provide positional information for two developmental axes (anterior-posterior and dorsal-ventral axis) before fertilization. • The Drosophila egg develops in the female’s ovary, surrounded by ovarian cells called nurse cells and follicle cells that supply the egg cell with nutrients, mRNAs, and other substances. • During fruit fly development, the egg forms a segmented larva, which goes through three larval stages. ○ The fly larva forms a pupal cocoon within which it metamorphoses into an adult fly. • In the 1940s, Edward B. Lewis used mutants to investigate Drosophila development. ○ Bizarre developmental mutations were on the fly’s genetic map, providing the first concrete evidence that genes somehow direct the developmental process. ○ These homeotic genes control pattern formation in the late embryo, larva, and adult. • In the late 1970s, Christiane Nüsslein-Volhard and Eric Weischaus set out to identify all the genes that affect segmentation in Drosophila. They faced three problems. • First, because Drosophila has about 13,700 genes, there could be either only a few genes affecting segmentation or so many that the pattern would be impossible to discern. • Second, mutations that affect segmentation are likely to be embryonic lethals, leading to death at the embryonic or larval stage. ○ Flies with embryonic lethal mutations never reproduce, and cannot be bred for study. ○ Nüsslein-Volhard and Wieschaus focused on recessive mutations that could be propagated in heterozygous flies. • Third, because of maternal effects on axis formation in the egg, the researchers also needed to study maternal genes. • After exposing flies to mutagenic chemicals, Nüsslein-Volhard and Wieschaus looked for dead embryos and larvae with abnormal segmentation. ○ Through appropriate crosses, they found heterozygotes carrying embryonic lethal mutations. • Nüsslein-Volhard and Wieschaus identified 1,200 genes essential for embryonic development. ○ About 120 of these were essential for normal segmentation. • The researchers grouped the genes by general function, mapped them, and cloned many of them. • In 1995, Nüsslein-Volhard, Wieschaus, and Lewis were awarded a Nobel Prize. Gradients of maternal molecules in the early Drosophila embryo control axis formation. • Cytoplasmic determinants produced under the direction of maternal effect genes are deposited in the unfertilized egg. • A maternal effect gene is a gene that, when mutant in the mother, results in a mutant phenotype in the offspring, regardless of the offspring’s own genotype. ○ In fruit fly development, maternal effect genes encode proteins or mRNA that are placed in the egg while it is still in the ovary. ○ When the mother has a mutation in a maternal effect gene, she makes a defective gene product (or none at all) and her eggs will not develop properly when fertilized. • Maternal effect genes are also called egg-polarity genes because they control the orientation of the egg and consequently the fly. ○ One group of genes sets up the anterior-posterior axis, while a second group establishes the dorsal-ventral axis. • One gene called bicoid affects the front half of the body. • An embryo whose mother has a mutant bicoid gene lacks the front half of its body and has duplicate posterior structures at both ends. ○ This suggests that the product of the mother’s bicoid gene is essential for setting up the anterior end of the fly and might be concentrated at the future anterior end. • This is a specific version of the morphogen gradient hypothesis, in which gradients of morphogens establish an embryo’s axes and other features. • Using DNA technology and biochemical methods, researchers were able to clone the bicoid gene and use it as a probe for bicoid mRNA in the egg. ○ As predicted, the bicoid mRNA is concentrated at the extreme anterior end of the egg cell. • After the egg is fertilized, bicoid mRNA is transcribed into protein, which diffuses from the anterior end toward the posterior, resulting in a gradient of proteins in the early embryo. ○ Injections of pure bicoid mRNA into various regions of early embryos resulted in the formation of anterior structures at the injection sites. • The bicoid research is important for three reasons. 1. It identified a specific protein required for some of the earliest steps in pattern formation. 2. It increased our understanding of the mother’s role in the development of an embryo. 3. It demonstrated a key developmental principle: a gradient of molecules can determine polarity and position in the embryo. • Maternal mRNAs are crucial during development of many species. ○ In Drosophila, gradients of specific proteins encoded by maternal mRNAs determine the posterior and anterior ends and establish the dorsal-ventral axis. • Later, positional information encoded by the embryo’s genes establishes a specific number of correctly oriented segments and triggers the formation of each segment’s characteristic structures. Concept 18.5 Cancer results from genetic changes that affect cell cycle control • Cancer is a set of diseases in which cells escape the control mechanisms that normally regulate cell growth and division. ○ The gene regulation systems that go wrong during cancer are the systems that play important roles in embryonic development and immune response. • The genes that normally regulate cell growth and division during the cell cycle include genes for growth factors, their receptors, and the intracellular molecules of signaling pathways. ○ Mutations altering any of these genes in somatic cells can lead to cancer. ○ The agent of such changes can be random spontaneous mutations or environmental influences such as chemical carcinogens, X-rays, and some viruses. Proto-oncogenes can become oncogenes, contributing to the development of cancer. • Cancer-causing genes, oncogenes, were initially discovered in viruses. ○ Close counterparts have been found in the genomes of humans and other animals.å • Normal versions of cellular genes, called proto-oncogenes, code for proteins that stimulate normal cell growth and division. • A proto-oncogene becomes an oncogene following genetic changes that lead to an increase in the proto-oncogene’s protein production or in the intrinsic activity of each protein molecule. ○ These genetic changes include movement of DNA within the genome, amplification of the proto-oncogene, and point mutations in a control element or the proto-oncogene itself. • Cancer cells frequently have chromosomes that have been broken and rejoined incorrectly. ○ A fragment may be moved to a location near an active promoter or other control element. • Amplification increases the number of copies of the proto-oncogene in the cell. • A point mutation in the promoter or enhancer of a proto-oncogene may increase its expression. • A point mutation in the coding sequence may lead to translation of a protein that is more active or longer-lived. • All of these mechanisms can lead to abnormal stimulation of the cell cycle, putting the cell on the path to malignancy. Mutations to tumor-suppressor genes may contribute to cancer. • The normal products of tumor-suppressor genes inhibit cell division. • Some tumor-suppressor proteins normally repair damaged DNA, preventing the accumulation of cancer-causing mutations. • Other tumor-suppressor proteins control the adhesion of cells to each other or to an extracellular matrix, which is crucial for normal tissues and often absent in cancers. • Still others are components of cell-signaling pathways that inhibit the cell cycle. ○ Decreases in the normal activity of a tumor-suppressor protein may contribute to cancer. • The proteins encoded by many proto-oncogenes and tumor-suppressor genes are components of cell-signaling pathways. • Mutations in the products of two key genes, the ras proto-oncogene and the p53 tumor-suppressor gene, occur in 30% and over 50% of human cancers, respectively. • The Ras protein, the product of the ras gene, is a G protein that relays a growth signal from a growth factor receptor on the plasma membrane to a cascade of protein kinases. ○ At the end of the pathway is the synthesis of a protein that stimulates the cell cycle. • Many ras oncogenes have a point mutation that leads to a hyperactive version of the Ras protein that trigger the kinase cascade in the absence of growth factor, resulting in excessive cell division. • The p53 gene, named for its 53,000-dalton protein product, is a tumor-suppressor gene. ○ The p53 protein is a specific transcription factor for the synthesis of several cell cycle-inhibiting proteins. ○ The p53 gene has been called the “guardian angel of the genome.” • Once activated by DNA damage, the p53 protein functions as an activator for several genes. ○ The p53 protein can activate the p21 gene, whose product halts the cell cycle by binding to cyclin-dependent kinases, allowing time for DNA repair. ○ p53 also activates expression of a group of miRNAs, which inhibit the cell cycle. ○ The p53 protein can also turn on genes directly involved in DNA repair. ○ When DNA damage is irreparable, the p53 protein can activate “suicide genes” whose protein products cause cell death by apoptosis. • A mutation that knocks out the p53 gene can lead to excessive cell growth and cancer. Multiple mutations underlie the development of cancer. • More than one somatic mutation is generally needed to produce the changes characteristic of a full-fledged cancer cell. • If cancer results from an accumulation of mutations, and if mutations occur throughout life, then the longer we live, the more likely we are to develop cancer. • Colorectal cancer, with 140,000 new cases and 50,000 deaths in the United States each year, illustrates a multistep cancer path. ○ The first sign is often a polyp, a small benign growth in the colon lining. ○ The cells of the polyp look normal but divide unusually frequently. ○ Through gradual accumulation of mutations that activate oncogenes and knock out tumor-suppressor genes, the polyp can develop into a malignant tumor. ○ A ras oncogene and a mutated p53 tumor-suppressor gene are usually involved. • About a half dozen DNA changes must occur for a cell to become fully cancerous. • These changes usually include the appearance of at least one active oncogene and the mutation or loss of several tumor-suppressor genes. ○ Because mutant tumor-suppressor alleles are usually recessive, mutations must knock out both alleles. ○ Most oncogenes behave like dominant alleles and require only one mutation. Cancer can run in families. • The fact that multiple genetic changes are required to produce a cancer cell helps explain the predispositions to cancer that run in families. ○ An individual inheriting an oncogene or a mutant allele of a tumor-suppressor gene is one step closer to accumulating the necessary mutations for cancer to develop. • Geneticists are devoting much effort to finding inherited cancer alleles so that a predisposition to certain cancers can be detected early in life. • About 15% of colorectal cancers involve inherited mutations. • Many of these mutations affect the tumor-suppressor gene adenomatous polyposis coli or APC. ○ Normal functions of the APC gene include regulation of cell migration and adhesion. ○ Even in patients with no family history of the disease, APC is mutated in about 60% of colorectal cancers. • Between 5% and 10% of breast cancer cases show an inherited predisposition. ○ Breast cancer is the second most common type of cancer in the United States, annually striking more than 180,000 women and leading to 40,000 deaths. • Mutations in one gene, BRCA1, increase the risk of breast and ovarian cancer. ○ Mutations in BRCA1 and the related gene BRCA2 are found in at least half of inherited breast cancers. • A woman who inherits one mutant BRCA1 allele has a 60% probability of developing breast cancer before age 50 (versus a 2% probability in an individual with two normal alleles). ○ Both BRCA1 and BRCA2 are considered tumor-suppressor genes because their wild-type alleles protect against breast cancer and their mutant alleles are recessive. • BRCA1 and BRCA2 proteins function in the cell’s DNA damage repair pathway. ○ BRCA2, in association with another protein, helps repair breaks that occur in both strands of DNA. • Because DNA breakage can contribute to cancer, the risk of cancer can be lowered by minimizing exposure to DNA-damaging agents, such as ultraviolet radiation in sunlight and the chemicals found in cigarette smoke. • In addition to mutations and other genetic alterations, a number of tumor viruses can cause cancer in various animals, including humans. ○ In 1911, Peyton Rous, an American pathologist, discovered a virus that causes cancer in chickens. ○ The Epstein-Barr virus, which causes infectious mononucleosis, has been linked to several types of cancer in humans, notably Burkitt’s lymphoma. ○ Papillomaviruses are associated with cancer of the cervix, and a virus called HTLV-1 causes a type of adult leukemia. • Worldwide, viruses seem to play a role in about 15% of the cases of human cancer. • Viruses can interfere with gene regulation in several ways if they integrate their genetic material into a cell’s DNA. ○ Viral integration may donate an oncogene to the cell, disrupt a tumor-suppressor gene, or convert a proto-oncogene to an oncogene. ○ Some viruses produce proteins that inactivate p53 and other tumor-suppressor proteins, making the cell more likely to become cancerous. Lecture Outline for Reece et al., Campbell Biology, 10th Edition, Copyright © 2014 Pearson Education, Inc
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Week 12 - Impossibility
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