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SPIKE Prime Hub 3.0
Quiz by Sarah Carlson-Lier
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The SPIKE Prime Light Matrix is ___ rows of lights wide, by ____ columns of lights tall.
5, 4
4, 4
5, 5
4, 5
A _______ is a series of commands that are completed in a specific order.
Sequence
Lego Stack
Program Flow
Parameter
The SPIKE Prime Light Matrix is ___ rows of lights wide, by ____ columns of lights tall.
A _______ is a series of commands that are completed in a specific order.
True or false: A robot completes tasks in a sequence in a random order.
Program Flow is referred to as...
According to the program, how long will the hub display yellow for?
طرق وصيل وحدة تحكم Spike Prime روبوت في جهاز الحاسوبWhen it was his turn to speak, Adam Malik, Presidium Minister for Political Affairs and Minister for Foreign Affairs of Indonesia, recalled that about a year before, in Bangkok, at the conclusion of the peace talks between Indonesia and Malaysia, he had explored the idea of an organization such as ASEAN with his Malaysian and Thai counterparts. One of the “angry young men” in his country’s struggle for independence two decades earlier, Adam Malik was then 50 years old and one of a Presidium of five led by then General Soeharto that was steering Indonesia from the verge of economic and political chaos. He was the Presidium’s point man in Indonesia’s efforts to mend fences with its neighbors in the wake of an unfortunate policy of confrontation. During the past year, he said, the Ministers had all worked together toward the realization of the ASEAN idea, “making haste slowly, in order to build a new association for regional cooperation.” Adam Malik went on to describe Indonesia’s vision of a Southeast Asia developing into “a region which can stand on its own feet, strong enough to defend itself against any negative influence from outside the region.” Such a vision, he stressed, was not wishful thinking, if the countries of the region effectively cooperated with each other, considering their combined natural resources and manpower. He referred to differences of outlook among the member countries, but those differences, he said, would be overcome through a maximum of goodwill and understanding, faith and realism. Hard work, patience and perseverance, he added, would also be necessary. The countries of Southeast Asia should also be willing to take responsibility for whatever happens to them, according to Tun Abdul Razak, the Deputy Prime Minister of Malaysia, who spoke next. In his speech, he conjured a vision of an ASEAN that would include all the countries of Southeast Asia. Tun Abdul Razak was then concurrently his country’s Minister of Defence and Minister of National Development. It was a time when national survival was the overriding thrust of Malaysia’s relations with other nations and so as Minister of Defence, he was in charge of his country’s foreign affairs. He stressed that the countries of the region should recognize that unless they assumed their common responsibility to shape their own destiny and to prevent external intervention and interference, Southeast Asia would remain fraught with danger and tension. And unless they took decisive and collective action to prevent the eruption of intra-regional conflicts, the nations of Southeast Asia would remain susceptible to manipulation, one against another. “We the nations and peoples of Southeast Asia,” Tun Abdul Razak said, “must get together and form by ourselves a new perspective and a new framework for our region. It is important that individually and jointly we should create a deep awareness that we cannot survive for long as independent but isolated peoples unless we also think and act together and unless we prove by deeds that we belong to a family of Southeast Asian nations bound together by ties of friendship and goodwill and imbued with our own ideals and aspirations and determined to shape our own destiny”. He added that, “with the establishment of ASEAN, we have taken a firm and a bold step on that road”. For his part, S. Rajaratnam, a former Minister of Culture of multi-cultural Singapore who, at that time, served as its first Foreign Minister, noted that two decades of nationalist fervor had not fulfilled the expectations of the people of Southeast Asia for better living standards. If ASEAN would succeed, he said, then its members would have to marry national thinking with regional thinking. “We must now think at two levels,” Rajaratnam said. “We must think not only of our national interests but posit them against regional interests: that is a new way of thinking about our problems. And these are two different things and sometimes they can conflict. Secondly, we must also accept the fact, if we are really serious about it, that regional existence means painful adjustments to those practices and thinking in our respective countries. We must make these painful and difficult adjustments. If we are not going to do that, then regionalism remains a utopia.” S. Rajaratnam expressed the fear, however, that ASEAN would be misunderstood. “We are not against anything”, he said, “not against anybody”. And here he used a term that would have an ominous ring even today: balkanization. In Southeast Asia, as in Europe and any part of the world, he said, outside powers had a vested interest in the balkanization of the region. “We want to ensure,” he said, “a stable Southeast Asia, not a balkanized Southeast Asia. And those countries who are interested, genuinely interested, in the stability of Southeast Asia, the prosperity of Southeast Asia, and better economic and social conditions, will welcome small countries getting together to pool their collective resources and their collective wisdom to contribute to the peace of the world.” The goal of ASEAN, then, is to create, not to destroy. This, the Foreign Minister of Thailand, Thanat Khoman, stressed when it was his turn to speak. At a time when the Vietnam conflict was raging and American forces seemed forever entrenched in Indochina, he had foreseen their eventual withdrawal from the area and had accordingly applied himself to adjusting Thailand’s foreign policy to a reality that would only become apparent more than half a decade later. He must have had that in mind when, on that occasion, he said that the countries of Southeast Asia had no choice but to adjust to the exigencies of the time, to move toward closer cooperation and even integration. Elaborating on ASEAN objectives, he spoke of “building a new society that will be responsive to the needs of our time and efficiently equipped to bring about, for the enjoyment and the material as well as spiritual advancement of our peoples, conditions of stability and progress. Particularly what millions of men and women in our part of the world want is to erase the old and obsolete concept of domination and subjection of the past and replace it with the new spirit of give and take, of equality and partnership. More than anything else, they want to be master of their own house and to enjoy the inherent right to decide their own destiny …” While the nations of Southeast Asia prevent attempts to deprive them of their freedom and sovereignty, he said, they must first free themselves from the material impediments of ignorance, disease and hunger. Each of these nations cannot accomplish that alone, but by joining together and cooperating with those who have the same aspirations, these objectives become easier to attain. Then Thanat Khoman concluded: “What we have decided today is only a small beginning of what we hope will be a long and continuous sequence of accomplishments of which we ourselves, those who will join us later and the generations to come, can be proud. Let it be for Southeast Asia, a potentially rich region, rich in history, in spiritual as well as material resources and indeed for the whole ancient continent of Asia, the light of happiness and well-being that will shine over the uncounted millions of our struggling peoples.” The Foreign Minister of Thailand closed the inaugural session of the Association of Southeast Asian Nations by presenting each of his colleagues with a memento. Inscribed on the memento presented to the Foreign Minister of Indonesia, was the citation, “In recognition of services rendered by His Excellency Adam Malik to the ASEAN organization, the name of which was suggested by him.” And that was how ASEAN was conceived, given a name, and born. It had been barely 14 months since Thanat Khoman brought up the ASEAN idea in his conversations with his Malaysian and Indonesian colleagues. In about three more weeks, Indonesia would fully restore diplomatic relations with Malaysia, and soon after that with Singapore. That was by no means the end to intra-ASEAN disputes, for soon the Philippines and Malaysia would have a falling out on the issue of sovereignty over Sabah. Many disputes between ASEAN countries persist to this day. But all Member Countries are deeply committed to resolving their differences through peaceful means and in the spirit of mutual accommodation. Every dispute would have its proper season but it would not be allowed to get in the way of the task at hand. And at that time, the essential task was to lay the framework of regional dialogue and cooperation. The two-page Bangkok Declaration not only contains the rationale for the establishment of ASEAN and its specific objectives. It represents the organization’s modus operandi of building on small steps, voluntary, and informal arrangements towards more binding and institutionalized agreements. All the founding member states and the newer members have stood fast to the spirit of the Bangkok Declaration. Over the years, ASEAN has progressively entered into several formal and legally-binding instruments, such as the 1976 Treaty of Amity and Cooperation in Southeast Asia and the 1995 Treaty on the Southeast Asia Nuclear Weapon-Free Zone. Against the backdrop of conflict in the then Indochina, the Founding Fathers had the foresight of building a community of and for all Southeast Asian states. Thus the Bangkok Declaration promulgated that “the Association is open for participation to all States in the Southeast Asian region subscribing to the aforementioned aims, principles and purposes.” ASEAN’s inclusive outlook has paved the way for community-building not only in Southeast Asia, but also in the broader Asia Pacific region where several other inter-governmental organizations now co-exist. The original ASEAN logo presented five brown sheaves of rice stalks, one for each founding member. Beneath the sheaves is the legend “ASEAN” in blue. These are set on a field of yellow encircled by a blue border. Brown stands for strength and stability, yellow for prosperity and blue for the spirit of cordiality in which ASEAN affairs are conducted. When ASEAN celebrated its 30th Anniversary in 1997, the sheaves on the logo had increased to ten – representing all ten countries of Southeast Asia and reflecting the colors of the flags of all of them. In a very real sense, ASEAN and Southeast Asia would then be one and the same, just as the Founding Fathers had envisioned. This article is based on the first chapter of ASEAN at 30, a publication of the Association of Southeast Asian Nations in commemoration of its 30th Anniversary on 8 August 1997, written by Jamil Maidan Flores and Jun Abad.The Revolt of the Northern Earls (1569) Most people in the North remained loyal to the Catholic noble families who controlled the north and their Catholic faith. When Elizabeth came to power, she promoted ‘new men’ (Protestants) from the gentry and the powerful Catholic nobles lost their power and influence. This led them to organise the most serious rebellion of Elizabeth’s reign in 1569. Why did the Northern Earl’s revolt? The Earls had lost their power when Elizabeth became Queen (and wanted it back). They wanted Catholicism restored in England (and felt that ordinary Catholics would support it). Elizabeth was refusing to marry or to name an heir, causing uncertainty about England’s future. Mary Queen of Scots (if freed from prison) could replace Elizabeth and solve all these problems Who were the key players in the Revolt? Earl of Northumberland • A Catholic who had held an important position under Mary I. • He lost a lot of influence under Elizabeth (as she favoured Protestant gentry) • Elizabeth also took the rights to a valuable copper mine found on his lands Earl of Westmorland • From a rich Catholic family in the north Also the Duke of Norfolk’s brother in law Duke of Norfolk • England’s most senior Protestant noble, but he had very close links to old northern Catholic families, & was sympathetic to them & greedy for power. • He hated William Cecil & Robert Dudley, Earl of Leicester (Elizabeth’s favourite) who were Protestant and from the gentry • He planned to marry Mary QS, but later backed down and urged the earls to call off the rebellion. Mary also supported the plan to marry him What role did religion play? (7/10 – but only because it was linked to power) • Most northerners held onto their Catholic beliefs & although Elizabeth didn’t persecute them, they knew that she wanted their religion to gradually die out, so they supported the revolt. • In 1561 Elizabeth hired a strict Protestant as archbishop of Durham to promote Protestantism in the north, but he was unpopular & turned many northerners against the Protestant religion. What role did politics/power play? (9/10 – this was the most important cause of the revolt) • The Northern Earls lost a lot of their power/influence (even jobs/money under Elizabeth) • Northumberland was jealous of new Protestant families being given top jobs in the North • William Cecil & Robert Dudley were not from ancient noble families, but were very close to the Queen, so the northern Earls resented them getting top jobs in her Government • Elizabeth also confiscated large areas of land & the profits from their copper mines • It is possible, that had Elizabeth allowed the Catholic Northern Earls to keep their jobs, money and influence at court, they may have ‘tolerated’ her as a Protestant Queen (greedy/selfish). What role did Mary Queen of Scots and the Succession play? • Elizabeth was refusing to name an heir and it was becoming clear that she would not marry • If Mary Queen of Scots married the Duke of Norfolk, England would have an heir and England would be Catholic again. The country would be stable without people competing for power. • However, some of Elizabeth’s courtiers got worried that it might not work and that it might lead to charges of treason (punishable by death) • So by September 1569, Robert Dudley (Earl of Leicester) decided to tell Elizabeth about the plot. By this time it was much more serious than simply marrying Norfolk to Mary. • Mary QS had secretly asked Spain to send troops to help the rebellion & overthrow Elizabeth Plan for the Revolt of the Northern Earls (1569) • The Earls of Northumberland & Westmorland will raise rebel troops from their lands in the north and take control of Durham. • The rebels will then march south towards London to join with the Duke of Norfolk • 1000s of Spanish troops will land in England to support the rebel forces • The Duke of Norfolk & rebel forces will seize control of Government & overthrow Elizabeth • Mary Queen of Scots is to be freed, ready to marry the Duke of Norfolk Key Events of the Revolt • Once Elizabeth knew of the plot, Norfolk was arrested and sent to the Tower of London • The Northern Earls were worried they would be executed for their involvement and in a desperate attempt to avoid punishment, pushed ahead with the revolt • They raised an army of ordinary Catholics and took control of Durham cathedral • Catholic mass was celebrated across the north for 2 weeks. • They then headed south, to try and free Mary • Mary QSs was moved south to Coventry on the orders of Elizabeth, so she couldn’t escape • The rebellion failed as Spanish troops never arrived • Elizabeth’s friend (Earl of Sussex) had raised an army of 7,000 men to defend her throne. Results: • The rebellion was a serious threat to Elizabeth • She executed 450 rebels in the north • Northumberland was executed in 1572 & his head was put on a spike on the city gate • The Privy Council called for the Duke of Norfolk’s execution too, but Elizabeth released him. • Mary Queen of Scots was kept in prison for the next 14 years. • The failed plot also led the Pope to take action against Elizabeth • In 1570 he excommunicated Elizabeth from the Catholic Church • He also issued a Papal Bull (order) calling on all loyal Catholics to overthrow her hoping it would encourage another rebellion. • In 1571 Elizabeth called parliament to pass an Act making it treason to claim that she was not the rightful Queen and to bring in/print papal bulls in England. The Significance of the Revolt of the Northern Earls • It was the first and most serious rebellion by English Catholics against Elizabeth • Treason laws were made much harsher • It ended the influence of the powerful Catholic Earls in the North • It led to harsher treatment of Catholics, e.g. 1572 Elizabeth sent the Earl of Huntingdon (strict Protestant) to the north to carry out laws against Catholics (and suppress Catholicism). • Although Elizabeth’s brutal revenge on the rebels show how serious a threat it was, most Catholics in the north stayed loyal, but the Pope’s Papal Bull now put their loyalty in doubt There was little support for the revolt among the rest of the Catholic nobility and ordinary people. When faced with a choice between Elizabeth and their religion, most Catholics chose to support the Queen. 1569, was the last time English Catholics tried to remove Elizabeth by force. The future plots against her were always uncovered by Cecil & Walsingham, before they had a chance to get any public support. Despite this, the Northern Revolt & Papal Bull changed Elizabeth’s attitude towards Catholics who were now seen as potential traitors. From 1570, Elizabeth became less tolerant of recusants (people refusing to attend her church) & took increasingly tough measures against Catholics. The Ridolfi, Throckmorton & Babington plots • In the 1870s-80s, there were 3 Catholic plots to assassinate Elizabeth & replace her with Mary. • The plots were supported by France, Spain, the Pope and some Catholic nobles. • They reinforced the form Mary & from Catholics at home and abroad. Also the threat from Spain. The Ridolfi Plot (1571) • Ridolfi was an Italian banker living in England and a spy for the Pope. • He organised a plot to murder Eliz, marry Mary QS to the Duke of Norfolk & make her Queen. • The Pope & King Philip supported the plot & Philip told the Duke of Alba in the Netherlands to prepare 10,000 troops (but to only invade AFTER the English had overthrown Elizabeth). • The plot failed because Sir William Cecil intercepted coded letters & Norfolk was executed. • Mary was kept under closer watch. • Ridolfi was abroad when the plot was discovered and never returned to England. 1574: Catholic Priests and Priest Holes • From 1574 Catholic priests were smuggled into England to keep the religion alive. • They stayed with rich Catholic families, so Catholic families were kept under surveillance. • Catholic homes were raided – to find ‘priest holes’ where Catholic priests were hiding. • Catholic priests who were found could be hung, drawn and quartered (although not all were) • In 1581, Parliament also passed 2 new tougher laws against Catholics: • Recusants would be fined £20 (which would bankrupt most families) • Trying to convert people to Catholicism was now treason (punishable by death) The Throckmorton Plot (1583) • It aimed to assassinate Elizabeth and replace her with Mary. The French Duke of Guise (Mary’s cousin) would invade England with an army, funded by King Philip (Pope also supported it). • An Englishman, Throckmorton carried messages between Mary & Catholic plotters abroad. • Sir Walsingham (Secretary of State) uncovered the plot after his agents found the plans for the plot in Throckmorton’s house. Throckmorton confessed under torture and was executed. Significance: • The plots showed that Mary’s presence in England posed a serious threat • It also showed that France & Spain were a serious threat (& could invade) • Throckmorton’s papers showed a list of Catholic supporters in England, so the threat from English Catholics was also real • 1,000s of Catholics were imprisoned or kept under surveillance/house arrest • In 1585 another Act was passed to make helping Catholic priests punishable by death. • The Bond of Association was signed by the English nobles & gentry & forced them to promise to execute anyone who tried to overthrow the Queen. Weaknesses of the Plots The plots lacked public support & were uncovered by informers & spies before they had the chance to work King Philip was reluctant to destroy his alliance with Elizabeth (France was still a bigger rival) so is support for the plots was half-hearted, he rarely followed through on his promises to help the plotters or send an army The Babington Plot (1586) In 1586, Walsingham used his spy network to PROVE that Mary supported the Babington plot. His evidence persuaded Elizabeth to put Mary on trial & execute her for treason. • This was a plot to murder Elizabeth and put Mary on the throne • France would invade England with 60,000 men and Spain would also send an army • Babington was passing coded letters between Mary & her supporters in England & Europe. • But all of her letters were being intercepted and read by Walsingham. • Walsingham used his spies to follow every stage of the plot & had the letters decoded • One of Mary’s letters approved plans to murder the Queen and free Mary from prison • They also contained the names of 6 Catholics who planned to kill Elizabeth • They were arrested, hung, drawn and quartered for treason. • Mary had been implicated in plots before, but Elizabeth was always reluctant to execute her • But the proof found by Walsingham finally persuaded her to put Mary on trial • In October 1586, Mary was found guilty & was sentenced to death • But Elizabeth still hesitated, and did not sign the death warrant until February 1587. Significance 1) This plot was very significant because by 1585 England was effectively at war with Spain since Elizabeth had sent her army to help the Dutch Protestants fight the Spanish 2) This meant that Elizabeth’ situation was more dangerous than during previous plots. 3) Elizabeth’s government also became more determined to crush Catholicism 4) 1000s of recusants were arrested & 31 priests were executed 5) Mary’s execution removed the Catholic threat at home 6) English Catholics had no one to rally around, & lost hope of overthrowing Elizabeth 7) But Mary’s death increased the threat of a foreign invasion as England was at war with Spain and King Philip had been preparing an attack on England since 1585 8) Mary’s death made Philip even more determined to invade, Mary had left her claim to the English throne to King Philip upon her death Why was Mary Queen of Scots finally executed? 1 • A new Act in 1585 stated that in the event of Elizabeth’s assassination, Mary could be executed as long as she had been proved guilty & Walsingham had provided hard proof. 2 • Another reason was that by 1587, it was clear that Philip was planning to invade England • There were rumours that Spanish ships had landed in Wales & that Mary had escaped. This convinced Elizabeth that Mary had to be executed if she wanted to keep her throne. Walsingham’s Spy Network: • Walsingham (Secretary of State from 1573) had a network of spies all over England & abroad. He had spies in every English town, some were normal people paid to spy on neighbours. • He also had agents and spies in Spain, France, Germany and Italy • He hired mathematicians to crack written codes and people to open/seal letters secretly • He also pressured captured Catholic priests to spy on others for him in return for a pardon. • He used double agents to infiltrate Catholic networks - to help him discover traitors • But he only used torture against Catholic priests caught in England in the most serious cases • But 130 priests and 60 of their supporters were still executed during Elizabeth’s reign. Why did Relations with Spain get worse (1569-1588) • England had tried to stay on good terms with Spain, because Eliz wanted to avoid an expensive war that could lead to her being overthrown (English Catholics could support it) • But by the 1570s, Elizabeth wanted to have an empire of her own. • She also needed to make more money to defend her country and throne (by improving trade) • This religious, political and economic rivalry led to growing tensions between England & Spain Political and Religious Rivalry 1) Land abroad, gave countries wealth/power. By the 1580s, Eliz wanted an empire to rival Spain’s (especially as Spain had supported the Catholic plots against Eliz – even if it was half-hearted) 2) Religion was another cause of conflict. Philip opposed Elizabeth’s religious settlement 1559 3) Luckily for Elizabeth, in the 1550s Spain & France were competing to be the greatest European power and both wanted England as an ally against the other. 4) But from 1567, Spanish ships were sailing to the Netherlands with money for the Alba’s army 5) This alarmed English Protestants and Elizabeth’s Privy Council who put more and more pressure on her to send an army to help the Dutch Protestant rebels (in the Netherlands). Economic (commercial) Rivalry: The New World, privateers and Sir Francis Drake • Under Elizabeth, English merchants wanted to make big profits in the New World (Americas). • However, trading in the New World was difficult because of Spain’s power 1) Spain controlled most of the New World where there were huge profits to be made and anyone who wanted to trade there needed a licence from Spain (which it would not give): 2) But the Americas had valuable crops like tobacco, sugar, and also silver and gold 3) Elizabeth secretly encouraged privateers to trade illegally & raid Spanish ports & ships 4) At first Elizabeth denied responsibility for their actions, which delaye war with Spain Sir Francis Drake: Elizabeth sends Drake to rob Spanish colonies and ships (which infuriates Spain) 1) Spain’s support for the Ridolfi plot (1571) made her more willing to support Drake • In 1572 Eliz hired Drake to sail to the New World & steal £40,000 of Spanish silver • In 1577 she sent Drake back again with a secret mission to rob Spain’s colonies/ships • Drake brought back £400,000 of Spanish treasure & claimed an area of California in Elizabeth’s name (New Albion). He gave a lot of this money to Elizabeth • He boosted England’s finances at a time of growing concern over Spain’s threat • He became famous as the first Englishman to circumnavigate the globe. • Eliz knighted Drake as a reward, which infuriated Philip (as he saw Drake as a pirate) • Drake’s actions & his claim to California made it clear that England did not accept Spain’s domination of the New World. Elizabeth’s Support for the Dutch Rebels led to War with Spain (1585-88) • By the 1580s, tension between England & Spain had reached boiling point • At first, Eliz refused to send her army to help the Dutch rebels, because she wanted to avoid a war with Spain. So she tried to get the Spanish to leave the Netherlands in other INDIRECT ways: 1) By allowing Drake (& other English privateers) to attack and rob Spanish ships and colonies 2) By encouraging others (the French heir/mercenaries) to fight the Spanish in the Netherlands • In the 1570s, Elizabeth promised to marry the heir to the French throne (the Duke of Alencon) so that he would take an army to fight the Spanish in the Netherlands The Spanish Fury (1576) and the Pacification of Ghent (1576) • By 1576, the Spanish Govt in the Netherlands was bankrupt (the war was expensive) • After months without pay, Spain’s soldiers violently robbed Dutch towns in the “Spanish Fury” Spanish troops rebelling and robbing cities in the Netherlands in 1576. This united the Dutch Protestants & Catholics against Spain. They drew up the ‘Pacification of Ghent’ (demanding that): • Spanish troops leave the Netherlands • Spain allows the Dutch to rule themselves • The persecution of Dutch Protestants stops What did Elizabeth do? • Elizabeth sent £100,000 to help the Dutch rebels • In 1577 King Philip’s brother, Don Juan agreed to the rebels demands (but this was a trick) as just 6 months later Philip sent an even bigger army to attack the Dutch. • Elizabeth then hired a mercenary army of 6000 English & Scottish volunteers to help the Dutch. • But her plan backfired because the mercenaries destroyed Dutch Catholic churches, which caused the Catholics to make peace with Spain. • In 1578, her Privy Council urged Eliz to send her official army to help the Dutch, but she refused. The Dutch were disappointed & turned to France for help. The French Duke of Alencon arrived with an army to fight the Spanish, but by 1579 Spain had taken control again. • In 1580 Spain got even stronger after Philip won control of Portugal & its empire. • So Elizabeth gave the Duke of Alencon £70,000 to help him fight the Spanish • In 1582, Alencon took his army the Netherlands but failed to defeat Spain. • Elizabeth’s foreign policy in the Netherlands had failed & she had only managed to annoy Spain 1585: Why did Eliz finally decide to send her army to the Netherlands? (she lost her 2 main allies) • 1584 the Duke of Alencon died (so he could no longer fight the Spanish in the Netherlands) • 1 month later, William of Orange, the leader of the Dutch Protestant rebels was assassinated. • In 1585, Spain signed the Treaty of Joinville with France, agreeing to stamp out Protestantism in France/Europe meaning France & Spain were now allies against Protestantism • Elizabeth now felt she had no choice but to send her official army to the Netherlands • She signed the Treaty of Nonsuch with the Dutch rebels which promised them military help 1585: Robert Dudley’s campaign in the Netherlands was unsuccessful She sent 7,400 man army to the Netherlands led by Dudley. But he accepted the title of ‘Governor General’. Eliz was angry as it suggested that she had deposed King Philip so she told Dudley to resign this position. His army was defeated by the bigger Spanish Army as Eliz had not provided him with enough money to win. In 1587 Dudley resigned and returned to England. At the same time, Eliz had sent Drake to raid Spanish colonies in the New World to disrupt King Philip’s flow of money. Philip was furious and told the Pope he planned to invade England at the end of 1585. Drake singes the King of Spain’s beard 1587 • In 1587 Elizabeth ordered Drake to attack Spain’s most important port Cadiz • He destroyed 30 ships in 3 days – known as the ‘Singeing of the King of Spain’s Beard’ • He also stole lots of wood, meaning the Armada did not have quality barrels for food/water • Drake’s disruption delayed the Armada by a year (& meant that its food rotted in 1588). • This bought England more time to prepare for war. The Spanish Armada (1588) The Plan • By 1588, the Spanish Armada was ready to invade England • It had 130 ships with 8000 sailors & 18,000 soldiers • The Duke of Medina Sidonia would lead the Armada, but he had little experience at sea and didn’t want the job • The Armada would collect Parma’s army from France & sail to England under the protection of the Armada’s warships • Parma would march to London to depose Elizabeth & impose a Catholic government in England. 1) The Armada reached the English Channel The Armada set out in May 1588, but was delayed for a few weeks by bad weather In July the Armada was near England & signal fires were lit to warn Elizabeth English ships set sail to meet the Armada The Armada sailed up the channel in a crescent (half moon) formation, to use the large armed galleons to protect the weaker supply and army ships The English navy carried out a few minor raids, but did not inflict much damage Only 2 Spanish ships were lost (by accident) 2) The English attack the Spanish at Calais (with fire ships) and at Gravelines The Armada sailed up the English channel & anchored at Calais to wait for Parma’s army But Parma’s men didn't reach the coast in time (news had reached them too late) At midnight, the English sent 8 fireships into the Spanish ships causing panic They cut their anchors, broke formation & headed for the open sea (without Parma) The Spanish ships sailed to Gravelines, but bad weather stopped them returning to Calais The English attacked and the battle lasted many hours (5 Spanish ships were sunk) The rest were forced to sail away from France towards Scotland The English ships followed them to make sure they didn’t come back to collect Parma’s army 3) The Armada’s Journey back to Spain around Ireland was a disaster The Spanish called off the attack and returned to Spain around Scotland & Ireland Bad storms sank many ships and wrecked more on the Irish coast Many sailors died from starvation & disease – less than half the men made it back to Spain How did England defeat the Spanish Armada? !) Faster Ships • Years before the battle, England had started building smaller, faster ships (galleons) that could fire canon balls quicker & further than Spanish ships • Spanish ships were huge and slow to change direction. 2) Bad Planning & Communication (Spanish) • Philip’s plan to join with the Duke of Parma’s army in France was risky. • Parma had lots of small ships which took 48 hours to load, man and set sail. • It took too long (a week) for word to reach Parma that Medina was in the English Channel, by which time Medina had set sail to Calais. • Parma was not ready to set sail & the English were already ready to attack (leaving Medina with very little back up when anchored in France). 2) English Tactics were more effective • Spanish ships aimed to come alongside the English ones, jump on board & fight the enemy. But the English ships were faster & kept a safe distance. • They chased the Armada down the Channel, with heavy cannon fire, which forced the Spanish to arrive in France before Parma’s army was ready • As the Armada was waiting, the English sent fireships into the Spanish fleet. • This caused the Armada to panic, cut their anchors & sail away to the north • When the Spanish ships regrouped, the English attacked them in the Battle of Gravelines & the Armada was forced to sail north, chased by faster ships. 5) Bad Weather • Strong winds made it impossible for the Armada to return & pick up Parma’s army and storms wrecked or sunk Spanish ships as they tried to return home along the Scottish-Irish coasts. 2) Spanish Supplies • The Armada was not well supplied with food/weapons. Drake’s attack on Cadiz port in 1587 had destroyed food barrels. Delays in setting sail meant that by the time the English attacked the Armada it had been at sea for 10 weeks and had rotting food. 1000s died from starvation/disease. The consequences of the English victory? • Victory over the Spanish Armada gave Elizabeth a great propaganda victory • A new portrait was made, and a medal was made to commemorate her victory, it said “God blew and they were scattered”. • Elizabeth claimed that God was on the side of Protestantism • This led to a feeling of English pride and encouraged the Dutch rebels to renew their fight against the Spanish • The defeat of the Armada showed the strength of the English navy and gave England the confidence to trade and explore more widely at sea • Although Philip did not give up and continued the war for the rest of Elizabeth’s reign, the defeat had cost Spain dearly, both financially and in terms of its power • The Armada marked the start of a long decline in Spain’s power and fortunes. • English ships were sent on voyages of discovery and set up valuable new trade routes • By the end of Elizabeth’s reign, the navy was also trying to set up a new colony in Virginia • The English victory boosted Elizabeth’s popularity & strengthened the Protestant cause “On this night, we share a roof protecting us from fleets of inequity. Our unification promises a better tomorrow. Those larger than myself, sitting on their marble thrones, sipping blood from cups composed of human skin and singing songs of so-called virtue, grow weaker each moment. Their caravans are revolting. There is hope yet. There is progress! Though tonight may mark a countdown, it is still a celebration. Look at all we have done, not just for Trials but for Palatium Infra as a whole. In four years, when I’m no longer Sovereignty, the Spoiled Purity and his people will continue to strive. So drink! Smoke! Crush up those exotic plants and snort them! We will not falter, weaken, or wane. Our influence is expanding, and somebody new opens their eyes every day. Even the Silbys of Aculeus have reached alarming potentials despite their embittered minds. So long as you relish in tonight, dance, and pray to your “dead” Gods, our revolution shall rise beyond the bounds of class, and when I’m only a commoner, we shall rise again beyond our brainwashed adversaries! Cheers, my people. Cheers!” Followers raised their cups. Some clinked theirs together. Others stood still and screamed breathlessly in agreement. I smiled with courtesy, then stepped off my platform. My voice still rang across the cellar. Speeches before were grander. Those displays were supposed to be emptying, and yet this one left me bloated, swollen tight. I watched as they popped the corks of their bottles and chanted in the name of Purity. Maybe the quality of my words wasn’t what mattered to them anyway, so long as I screamed loud enough. There’s no merit in attacking your people, a voice corrected me. “That’s right,” I said aloud. “Knox, my-my Sovereign!” squealed a nearby devotee, jittering as he stuffed his face with catered pastries. He was one I’d never seen before or had failed to remember. “Look what I’ve found! It’s wine, and not the shoddy Infran kind, either. Earth-made with good fruit! I don’t know how anyone managed to get their hands on this. Maybe some space travel mischief.” He giggled and held up a small glass bottle. “How neat.” “I want you to have it, Sir.” I nodded my head. “Yes, of course. Thank you.” Backing off into the midst of rowdy disciples, I clutched the bottle. What a waste of grapes. It could have been jam instead. Earthly food had a superior taste, ripe with delicate intricacies and nostalgia, but Palatium Infra had mastered the art of alcohol. Why waste your time with a drunkenness so sad and sickening? The booze of trash. Not many more followers approached me. The barren peroration must have upset them. My hands itched to submerge into my suit pockets, and my legs stood suddenly numb, wobbling. Four more years until I’m nothing. But tonight, you are nothing. “Shut up,” I told myself. Tightly packed together in the corner of the dwelling sat the Sibyls. A mound of writhing fabric and tones of skin made up their unified silhouette. I snapped the strap of the nearest gown, balancing on my hands and knees, waving the bottle before them. In their almost rodent nature, narrow noses prodded my way. Their dresses wrinkled and fell to their ankles. Knees dropped, and eyes widened. Many grumbled at me like hungry she-beasts. Those newer ones with faded curtains for hair, sunken eyes, and dirtied nails looked, hid their face, then sobbed. I imagined them in a pack together, fighting wildly against the Spoiled Purity in their rat decorum–biting down with square teeth laced with rabies. “I’ve got you all something,” I said. “Go back off to your pedestal and yap some more. We don’t want it.” A woman rose from the pile and spat. “You don’t even know what it is yet. It's Earth hooch, or more likely a near-flawless replica. I figured you girls would also like a chance to enjoy yourselves tonight.” “Your playmates have been harassing us since the moment you hung the banners and opened the cellar door.” The youngest, with a striking cyan mop upon her head, uncoiled from the mass. What was she now? 20, 21? We celebrated a birthday recently, I thought as she spun around me. “I remember something about a promise. Multiple promises, actually. Are you trying to bribe us into just shutting up and taking it? Because if another sticky, 40-year-old, Earth-born virgin gropes my shoulder, I’m going to have an aneurysm!” the girl continued. “Why not an Infran follower? Do you like it when they touch you?” I returned her accusing tone. “I’m sorry, sweet prophets, that you feel I’ve neglected my duties. I’ll keep a better eye out. Remember, you can always just holler if somebody is bothering you. And Anwen, friend, if I’ve ever tried to bribe you with anything, it was certainly the hair dye. I mean, look at you! Such handsomeness!” I exclaimed. The other Siblys began to encircle her, uttering compliments or even announcements of their envy. Anwen disappeared in a wink with flushed cheeks back into the mound. “I’ll just leave this here.” Smiling, I set down the bottle. ** “141, 143. . .” I counted each step as I trekked the staircase. There was no doubt I lost track somewhere. The ledges kept spawning under my feet, infinitely multiplying until I wasn’t moving at all–swallowing me up in a whirlpool of stone. My tie still hung around my neck, and my blazer remained tied around my hips as a skirt. Streaks of red dribbled off from the cavity in my chest. It was a gorgeous marking, sensual to my fingertips as I traced its edges. Purity, oh, Purity. Purity and his wings of burnt skin. Purity and his many faces. Purity the spoiled. Purity the mutilated. The Silbys did not bother waiting for me. On bare feet, they stormed up the stairs to their room. A trail of red, though in paint unlike mine, streamed after them. None looked remotely near me as they squeaked and gossiped intangibly. I saved them, those Infran broads, enlightened them. As much as they liked to deny it, spit at me, and bask in the thought of their victimhood, in this home, they stood empowered. You’ve done well, my thoughts affirmed, though in the manner of an insincere commentator rather than a hype man. Teeth grace in tile violin goes laundry paper when. It dissolved into an intruding drivel. I rubbed my head and sniveled. “Do you need help, Knox?” called a Silby. Fattened by my coddling, her shadow fell upon me from the doorway steps ahead. I attempted counting again. There must’ve been at least another hundred between me and her. “I’m hallucinating some,” I said, breathing deeply to suppress a burp as I struggled to recall her name. Two syllables. Typically Latin, though sometimes English. Drops of slobber leaked from my mouth. “I’m hallucinating some, Tybal. Do you like your name, Tybal? I would have named you something better. Ty-Tyballinia. No, we’d have to eliminate the ‘ball’ aspect. It sounds too crude.” “One foot in front of the other,” she said. So I walked. Mess greeted me at the doorway. Dirtied culinary obscured the dark wooden countertops, and the sink lay running. I approached the kitchen table, sat, and set my face down upon its cool wooden surface. Assaulting my nose was the smell of neglected flowers, like soil mixed with the kind of sweet cough medicine that would have left me gagging as a child. Open windows whispered songs of the twilight hour through the vessels of busy trolleys and shooting guns. My mouth strained to vomit, but there was nothing in my stomach to regurgitate except the petals of Stulto’s bloom, which came out effortlessly in little sputters. Teetering, I stood up and brushed disgorged plant parts off the tabletop. “Love,” I said as I slogged up yet another staircase. “Are you awake?” She said she’d wait. Somebody’s gotten her. No, she always misses movie night. That sleepyhead, I assured myself. There was a stirring amidst the manor’s cloak of dusk. Portraits of myself, my wife, and my daughter turned to face me as the hallway lights flickered, escaping their quartz frames to penetrate my ears with nonsense. The taxidermied heads of Infran creatures bared their teeth. I stopped to stare at my favorite, an adabactor with daunting spiked tusks poking out from its forehead. Its nose remained black and sharp, and its eyes wide with malice. “Where is my Spes, Adaba-boy? Is she sleepy?” There’s someone in the house. The sounds of the stirring rose along with my blood pressure. Footsteps orbited around me, drawing near and far and then near again, little dancers in the dark. The carpet immersed me in its mass of purples and blues, leaving my skin stained indigo and my vision abstracted. I toiled to reach the master bedroom across the aisle as it stretched out to me with bright lights and celestial howling, like a dove struggling in a pool of oil. Never again with Stulto’s bloom. Never again on what was already a bad night. My hand brushed the doorknob, and the high abruptly faded into only a persistent hum-buzz twirling around my brain. The portraits returned to their typical depression–Spes posing with her ax, Ari’s school photo, and myself in the cap I wore when addressing the military with the Verbis emblem embroidered in its center. All lifeless shots. Who were they for when they captured not the subject’s essence but only some fragment of their identity? They used to feel personal, not advertisements of some supposed characters. Servants, babysitters, and likewise civilian guests, I reminded myself, mustn’t forget whose home they’re in. Yet my body moved independently, taking Ari’s from its hook and laying it backward against the wall to hide her distant grin and tamed posture. It was time for new pictures. Sweet ones, real ones; time was ticking. I approached my own when the stirring began again. Groans and squeals erupted from the vents as if someone had set a pen of pigs loose in my crawlspace. No, not the crawlspace, my bedroom door. I turned the ruby knob. Underneath a blanket wrestled my two squealing piglets, their skins melting together beneath the layer of duvet. Fishnet leggings and manicured nails outstretched and scraped at the sheet beneath them. One raised its head, a salmon-colored man with sweat running down his forehead. Through the crack in the door, we met eyes, his Infran Dr. Sesuss nose flaring its narrow nostrils. No mark of the Spoiled Purity existed carved onto his naked body. My chest felt tight. I stepped back. I was suffocating. Spes emerged from the linens, her hair flowing down her back and her dark skin glistening in front of the bedroom window. She giggled and held the man, the blanket falling and revealing inches of her body I had not seen in months. “Darling,” whispered the rosy-faced man, “look.” He was unfathomably ugly and grotesquely young, with beady, lifeless pupils that dilated when he faced me. The excess flesh on his face sagged while he bit down on his thin lips. My wife faced me, gasped, and strained to cover herself. Suddenly, I was a stranger. A small child who had walked into his parents having sex. I unfurled the door completely. “Get out of my house,” I said. The man stayed in place. “Get out of my house,” I repeated. “Knox,” Spes began. Tears ran down her round cheeks. “Shut up!” I turned to the man, picking up a marble trophy from on top of my dresser. “Get out of my house! I’ll kill you!” “Knox!” Spes sobbed. “God damn it! I hate you! You barely look at me. Every day, there’s less passion. God, God, God, I don’t want to fuck a dead man!” she screamed, “You get out! Get! Get!” My hands wrapped tighter around the statue. That pig of a man was attached to her at the side, his face equipped with a scowl that challenged mine. He thought I was weak; frail like a decaying dementia-ridden senior. I imagined his skull bashed in, his scowl gone, and the feist and confidence in his face beaten into numbness. A new portrait was in order of such brutality, him as a splintered slab of wood, rashed and beaten, a carcass licking my boot. The churning in my brain had come back. Every wall shook. Clock faces came to life and rang in alarm. Indescribable noises caressed my eardrum before breaking into sorrowful weeps. Was it my own? I stared at Spes in motionless frenzy, clenched my teeth, and screamed like a siren. Passionless. What a lie! An excuse, more like. One that erased all my ventures, reducing me to a nobody. But I was not a nobody. I thought of my sect, my campaigns, my endurance through the political brutality of my empty hive-mind world–even my collection of literature, maps, and artifacts. I thought of daring nights alone with Spes when we were young, ravaging each other, two sardonic eggheads suddenly overcome with desire. The veins in my neck throbbed as I gasped for air. It was all I had. I threw the figurine at the man’s head. Eye shut, I heard the thud. A million singing voices of victory flooded out of the cracks in the floorboard. Proving myself a man to the woman I loved in a display of fervent violence was passion. I strained my ears for his cries, though I did not look yet. There had to be a pause, a moment of relief, where I stood tall as a skyscraper and seemingly fought to stay contained in front of my wife and her wounded, quivering paramour. Frantic footsteps rushed off the bed and past my side. I turned and grappled against myself to seize my wife’s shoulder. “Spes!” My eyelids lifted. Escaping was the man with that same numb expression in which I had imagined him. “You’re insane,” he said. I swiveled back towards the bed. With her curly locks flowing over her breasts and her limbs bent at her sides, Spes sat limp pressed against the headboard, her forehead bludgeoned and the statue resting on her stomach. Lips pursed and sweet, my Renaissance beauty reclined there in the guise of a squashed bug. But she was not dead. The desk ornament I flung was only the size of my shoe. Spes, that dramatist, may have been slightly hurt but was far from dead. She only wanted me to think she was to observe me at my most distraught, like a leech feeding on misery. “Get up.” Staggering toward the bed, I said. “You wanted passion? I showed you passion. ‘Shoved it right into your head. Of course, we both know who that gesture was meant for. . .” I fumbled to find my wit. Cold skin met my hands as I stroked her face, unable to resist checking her pulse, even though she was not dead. “I love you, Spes,” I said. Rain pelted against a nearby window. “Spes, please. Please.” No vibration answered my plea. I lifted my hand, sitting next to her now. Tears did not come. There was not any blood on the trophy, but when I picked it up, it felt to be now only a cruel instrument. It depicted a younger me in white marble, with my glasses and collared shirt being the only things painted. Both were in pink. It was a favorable color. I scrambled from the bed to vomit pure digestive bile on the rug. My stomach heaved. I ran my nails along every piece of myself I saw, a dog chasing my tail. As I slammed myself against walls and convulsed, my own heart grew ever louder in my chest. “Dad? I heard–” Ari’s slippered feet hammered across the floor. “Mom? Mom?” I kept my eyes on the storm. Silence fell. “She-She isn’t—your—.” Gasps interrupted every syllable she spoke. “You’re a murderer. Bad. Like they said,” she breathed, “ You beat her!” The words became mush, alphabet soup. Ari ran back down the hall. “My-My mom is dead. . . .Yes. . . Manor of the Trials Sovereignty. . .Ari Sorkin. . . I’m afraid he’s going to hurt me,” she said, presumably over the phone. It was all too fast. I crawled onto the windowsill, opened the glass, and let myself plummet into the alley below. Gusts of wind howled. The lack of motion or sensation informed me I had passed and again lived. Another Palatium Infra, another strange planet in which the celestial endowed rotting men with the opportunity to inhabit. Was this it? Was it all just an impossible limbo of galactic traveling? My surroundings were overwhelmingly gray, an abyss of clouds. Perhaps I had now met the real coming world, and my family and old friends lived here, ready to rush to my sides, lift me up, and jump for joy. Spes would be there. She would be enraged, but at least she’d be there. You are a bad man. You are a bad man. My eyelashes fluttered. There was a tugging sensation in my leg. The fog was wavering along with my ascendance. “No,” I yearned, trying to grip the clouds and stick them in place. “Stay with me.” But the peace was fleeting. I felt the cement under me and the moist garments clinging to my figure. My leg burned. Carefully, I craned my neck, only to observe the promenade as my surroundings. The most underwhelming of filth and danger, individually Infran. Forever my coming world. What a fool I was, having forgotten my blessing. Those idiot Gods could not tell the difference between assassination and self-infliction; a faulty insurance plan. The urge to cry at last set over me, and so I sat and wailed hot salvia into my palm, shielding my mouth to muffle the noise. Thunder echoed my hushed howling. Raindrops turned to pebbles. Under the ambiance of the stormy night, I could have sworn I heard troops stomping, guns cocking, and the chanting of my name. They had all been waiting for this. Billboards came to life, and I could only sit and spectate as the scenery flashed red. I inhaled fear and sobriety through runny nostrils. “Trials Sovereign Vsevolod “Knox” Sorkin is currently at large for the suspected homicide of Spes Sorkin, breaking the first term of the Sovereignty Charter. We now instruct you to report any sightings of the Earth-born, caucasian, roughly 195 centimeters tall, brown-haired, and brown-eyed man to your local Guard post. One can identify the suspected convict specifically by an occult tattoo of Purity’s Coronet on his lower back. No attempted execution or elongated punishment will take place until our Guards conduct an autopsy proving his guilt, per Life’s 1238 commandment. We cannot be sure when or if the Gods will revoke his blessing. Remember, when Gods frown upon strife, opt for a peaceful life. We permit all grieving festivities until Cagidus 4th. Good year!” towering buildings sang out in broadcast, repeating that same convoluted message quicker the instant it ended. Sometimes, the announcer spoke in Latin for the Infran children, other times in Chinese, Hindi, or Spanish to cater to those of irrelevant tongues. You aren’t a bad man. You are a stupid boy. Puddles sloshed. Somebody was approaching. I didn’t dare waste any remaining energy avoiding the Guards and their prodding blades. How did that phrase go? You dug your grave. Now lie in it. And so I embraced the cement. “Knox?” said the Guard. No, her tone was too sincere, and no authority would proceed in such a manner. There wasn’t confirmation on whether or not I was armed, and it wasn’t as if she could shoot me first. She was a partygoer, having just left from the cellar’s backdoor. I shooed her away with my hand. She hovered, and I discerned her shadow hesitating over my body. A man could not rot in peace. “Come on, get up! They’re after you!” Hands reached around my torso, struggling to handle my weight as they urged me onto my feet. That leg, the burning one, my right, trembled and bent unnaturally upon impact with the ground. The partygoer slung my arm over her shoulder, balancing me. My eyes caught a glimpse of a cyan mop. “Anwen?” I rasped, “hu-who let you out?” Keys jangled in her hands–my keys. “I escaped,” she said casually, coercing me to walk beside her. “Quicken your pace. I just heard somebody on your front porch. ‘You see that compost bin down the alley? We’re gonna burrow right down into the depth of that. If they open it and uncover us, I’ll be on top, and I can hide you and act like I’m just a homeless amica trying to take a nap.” With a tightening grip, she led me like livestock to the stinking crate. “I don’t understand, Anwen,” I said. “They’re going to torture and kill you, stupid. You know they’ve been wanting to, and you just handed the opportunity to them!” “I understand that.” It was becoming increasingly challenging to hide the fragility emerging in my voice. “You said you were escaping. Why stop and help your captor?” “What else could I do? Leave you there?” Attempts to shove my wounded body inside its mass of discarded fruits and vegetables began. She yanked down upon my head and submerged me in the fertilizer sea. The evidence grows indisputable, I thought as I stared at the abruptly humane Infran girl, diving in after me, that I belong here. “Damn me to hell! I’ve killed her! My love is dead!” an uncontrollable cry leaped from my mouth. “Shut up! Soon you’ll be, too, if you don’t quiet down.” The actual noise of the Guards darted past us: disorientated marching, guns clanking against each other, cluttered belts rattling, the Latin squawking. One paused to open the bin’s lid, though only rummaged through the surface layer of peat before carrying on. “What are they talking about? I struggle with my Latin,” I whispered. “The search, mainly.” Aggression remained firey in Anwen’s clenched jaw. Though she sat on top of me, there was a monumental distance between our rain-soaked forms. I curled up into a ball, ducked my head between my knees, and dreamt of Spes, ignoring the stench of spoiled food rising from every crevice of my dwelling. The next coming world was due to adopt me again as I forced sleep. I prayed for a canyon of fluffy haze, where I waltzed with pale memories but found nothing but the petrifying stillness of my mind. Killed and ran. Violent as a Guard just to prove a point and watch it backfire. Why would any heaven want to welcome me? I clung to the picture of Spes in my head like it was the last ember of an extinguished flame. “Did you mean to kill her?” Anwen interrogated. “Someone like you would immutably believe yes.” “And who is someone like me? You can’t even treat me like a person for a moment, can you?” grating drama decorated her words. “You know my opinions. I have not seen much of your or your breed’s faces besides that of cruelty and ignorance.” I retorted. “I just saved you! Does that make me cruel and ignorant?” “It makes you an idiot, which is another word for somebody ignorant.” “And why am I an idiot?” She asked. “Because you helping me does no good. Thank you anyhow. Now, do yourself a favor and scram.” As she bent her leg in anticipation, preparing to strike me on the forehead, I sensed an invisible withdrawal widening the gap between us. “You never answered my question,” Anwen took me by the end of my tattered tie suddenly and started her game of shepherd and sheep over again, pulling me back up to the crate’s exit. It appeared as a shining light at the end of a maze of rubbish and mold. “No. Of course not. Spes was my everything,” I sniffled. “I knew it. You couldn’t even bring yourself to hit us, let alone murder your wife. The girls and I always figured you were sensitive.” My heart rate quickened. Today was one of humbling and misery–one to pray a hail spike would fall from the sky as sharp as a needle, pierce into my eyelid, and lobotomize me. I wished I could have merely died or hit my head hard enough not to have to deal with it all. No, I wished I was Anwen with her snarky, careless glow and lack of depth in her eyes. As we emerged from the compost bin together, I fantasized about strangling her until her face turned purple, her weakening spirit no longer categorizing me as “sensitive”, but the thought could only remind me of wielding that trophy and the microscopic traces of my wife’s tender skin tainting it, which turned my guts inside out. “That’s why I think you could use a little help,” Anwen said, “It seems like you can’t walk, either. Your leg is all twisted up.” She undid one of her trim pigtails and handed me the band. “Take off your tie and put up your hair. ‘Will make you less recognizable. Then swallow your pride and stick with me.”Gr''ade 3 Questions based on this chapter: English Alexander was a king of the ancient Greek kingdom of Macedonia. By the age of thirty, he had created one of the largest empires in the world, stretching from Greece to northwestern India. When Alexander was young, a trader brought a horse which was difficult to mount. Let us read about how Alexander tames the horse. One day King Philip bought a fine horse. He was a strong animal and the king paid a high price for him. But he was wild and no man could mount him, or do anything at all with him. This horse is really wild. It cannot be tamed by the royal men. Many have tried and failed. We tried everything possible, your Majesty. We tried to whip him but that only made him worse. Glossary wild rough/harsh mount a horse to climb onto the back of a horse to tame to control whip to beat using a long rope King Philip asked his men to take the horse away. It is a pity to send such a fine horse away. I think the men do not know how to tame him. I can try taming this beautiful horse. Perhaps you can do better than them. But be careful, my son. You are still very young to mount this violent animal. Alexander wanted to (mount/feed/tame/ ride) the horse. If you would give me the order, I will try. I am sure I can manage this horse better than anyone else. Antonym(s) worse x better young x old fail x succeed If I fail, I will pay you the price of the horse, Father. The courtiers told Alexander that it might be dangerous for a young boy to try taming the wild horse. They laughed at him. Alexander went near the horse and turned his head towards the sun. He had noticed that the horse was afraid of his own shadow. I will name you Bucephalus. Stay calm and I will do no harm. The horse was afraid of his own (body/courtiers/King Philip/shadow). English He then spoke gently to the horse. Bucephalus means 'ox-head'— head of an ox, in Ancient Greek. When he had quietened him a little, he made a quick spring and leapt upon the horse's back. I thought the little prince would be killed by this dangerous animal. What a miracle! The horse has recognized the young prince as his master. Alexander let the horse run. When Bucephalus had become tired of running, Alexander reined him in and rode back to the place where his father was standing. Glossary noticed (here) to see afraid scared/frightened calm quiet gently softly quietened to become calmer and less noisy a miracle a wonder/unusual event to rein to check or guide a horse Look at the young prince! He is mounted well! But the horse is still wild! Antonym(s); laughed x cried afraid x brave. English When he reached the place where his father was standing, he leapt to the ground. His father ran and kissed him. Dear Father! I shall add My son! Macedonia is a small kingdom more territories and bring for you. You must seek a larger kingdom glory to our kingdom. that will be worthy of you. Fascinating Fact(s) Alexandria Bucephalus was a city founded by Alexander in memory of his loyal horse Bucephalus. During Alexander's invasion of India, he had fought against the Indian King, Porus, near the river Hydaspes (modern day river Jhelum, Pakistan). His horse Bucephalus died there and he honoured his horse by naming the city after it. Antonym(s) worthy x unworthy proud x ashamed You have carried me across countries and stood bravely beside me as I fought to win the numerous fierce battles. You have saved my life many times. I am truly proud of you, Bucephalus. (Mesopotamia/Minneapolis/ Macedonia/Minnesota) was a small kingdom for Alexander to rule. Glossary numerous many fierce strong and violent Alexander and Bucephalus were said to be always together, for when one of them was seen, the other was sure to be not far away. Bucephalus would never allow anyone to mount him, but his master. Alexander became the most famous king and warrior, and for that reason, he is called 'Alexander the Great!. Riassunto lezione precedente Caratteristiche generali degli epiteli: ● avascolarizzati ● innervati ● capacità rigenerativa Funzioni: ● Barriera ● Secrezione Specializzazioni del dominio apicale: ● Microvilli, orletto a spazzola ● Stereociglia ● Ciglia Specializzazioni del dominio laterale ● Giunzioni cellulari [Qui inizia la lezione di oggi] Classificazione morfo-funzionale degli epiteliali di rivestimento ⮚ Epiteli pavimentosi: se le cellule sono pavimentose ⮚ Epiteli cubici: se le cellule sono cubiche, quindi altezza e larghezza si equivalgono ⮚ Epiteli cilindrici: se le cellule hanno altezza maggiore della larghezza. Possono essere sia monostratificati quindi epiteli semplici, oppure pluristratificati Nell’ epitelio pluristratificato il nome dell’epitelio lo capiamo dall’ultimo strato, per esempio se l’ultimo strato ha cellule appiattite l’epitelio sarà pavimentoso, se l’ultimo strato ha cellule cubiche sarà cubico stratificato. Non importa la forma delle cellule degli strati inferiori. Possono inoltre essere pluristratificati o epiteli di transizione. Classificazione in base alle specializzazioni ⮚ Epiteli ciliati ⮚ Epiteli non ciliati La morfologia dell’epitelio riflette un po’ la sua funzione, per esempio l’epitelio semplice si trova dove non serve una grande protezione da stress meccanico. Per esempio: epitelio squamoso semplice: nel polmone, dove devono essere facilitati gli scambi gassosi di ossigeno e anidride carbonica. Epitelio cubico semplice: nei dotti delle ghiandole esocrine; nei tubuli renali dove abbiamo sempre assorbimento o secrezione Epitelio colonnare semplice: riveste l’intestino, anche qui con funzione di assorbimento. Pseudostratificato: già visto nella lezione precedente, lo troviamo ad esempio nella trachea, ed è un epitelio ciliato, dove le ciglia non servono a spostarsi. Gli epiteli semplici li troveremo in zone non sottoposte a grandi stress meccanici, ma dove c’è bisogno di facilitare la funzione di assorbimento e scambio. Mentre gli epiteli stratificati li troviamo per esempio dell’epidermide, cavità orale dell’esofago, vagina, ovvero sedi anatomiche solitamente esposte a stress meccnici. Epitelio di transizione: tipico della vescica, la cui caratteristica fondamentale è l’estensione. Esempio di epitelio pavimentoso semplice: Endotelio ovvero l’epitelio dei vasi sanguigni I vasi possono essere molto diversi fra loro ⮚ Capillare: epitelio associato alla lamina basale ⮚ Arterie: endotelio e lamina basale, e lamina elastica (formata da elastina, favorisce la dilatazione del vaso) che formano la tonaca intima; strato intermedio, tonaca media dove troviamo cellule muscolari lisce; tonaca avventizia di tessuto connettivo ⮚ Vene: stessa struttura, ma è più abbondante lo strato di tonaca avventizia (tessuto connettivale) rispetto alle arterie, dove la più abbondante è la tonaca media. Nell’immagine si vede come la dimensione di vene e arterie può cambiarne la morfologia. CAPILLARI La funzione dell’epitelio è di favorire gli scambi tra il torrente circolatorio e i tessuti. I capillari sono costituiti da una “barriera” formata dalle cellule dell’endotelio e la lamina sottostante. dall’immagine possiamo vedere all’interno del capillare un globulo rosso, quindi il diametro di un capillare è molto ridotto, può essere anche più piccolo di un globulo rosso, che per passare si deve deformare. Si vede il globulo rosso, la piastrina e la cellula endoteliale a formare la parete del capillare, dove c’è l’asterisco è una zona più elettrondensa che rappresenta la giunzione occludente. Le strutture più sottili sono capillari Le arteriole le riconosciamo dalle cellule muscolari lisce. Possiamo vedere le cellule endoteliali che costituiscono la parete di questi vasi. Classificazione dei capillari A seconda della zona anatomica dove ci troviamo cambia la morfologia dei capillari. ⮚ Capillari continui: cellule endoteliali giustapposte fra loro, giunzioni occludenti, lamina basale contigua, passaggio di sostanze è ampiamente regolato dalla cellula stessa. Possiamo trovare associati al capillare i periciti, che sono cellule staminali e vescicole che fanno pinocitosi (endocitosi di particelle liquide) ⮚ Capillari fenestrati: dove devono essere favoriti gli scambi. Si formano fenestrazioni tra le cellule della parete del capillare. Recenti studi pensano che queste fenestrazioni siano il risultato di un’abbondante pinocitosi. ⮚ Capillari discontinui/sinusoidi: le fenestrazioni sono ancora più grandi e la lamina basale è discontinua, quindi passaggio favorito. Esempio in microscopia elettronica del capillare continuo e fenestrato nella prima immagine il capillare è continuo, non ci sono interruzioni della lamina basale, non ci sono fenestrazioni, sono evidenti le giunzioni cellulari, si vedono le vescicole di pinocitosi. Nella seconda immagine ci sono interruzioni delle cellule endoteliali. In questa immagine invece vediamo un e sinusoide in cui le fenestrazioni sono più grandi, la lamina basale è discontinua, quindi passa anche il plasma. Associato alla cellula endoteliale possiamo trovare il Pericita, cellula staminale mesenchimale (cellula mesenchimale da origine a tessuto osseo, muscolare). Queste cellule hanno capacita di migrare e differenziarsi. Se per esempio rimuoviamo i periciti e induciamo una lesione per esempio a livello della spina dorsale dell'animale c’è impossibilità di rigenerazione del tessuto. CONDIZIONI PATOLOGICHE È importante mantenere la continuità di questo epitelio, infatti la lesione dell’endotelio è patologica, si chiama Arterosclerosi una delle maggiori cause di morte. la lesione parte dalla tonaca intima (endotelio, lamina basale), per esempio causata da alti livelli di colesterolo. Infiltrazione, i monociti si depositano tra lamina elastica ed endotelio, i monociti migrano in questa zona, assorbono lipidi intorno a queste cellule schiumose e si può formare questa lesione che può far sforzare di più il cuore, o provocare un embolo. Istologia di un vaso normale e un vaso con arterosclerosi. La colorazione è la Tricromica di Masson, che colora in viola i nuclei, in rosso il citoplasma e tessuto muscolare, in blu il collagene. Essendo il collagene il principale componente del tessuto connettivo nella seconda immagine notiamo deposizioni di tessuto connettivo in seguito alla lesione. [il professore nomina Histology guide, un sito consultabile online dove troviamo la maggior parte delle sezioni e immagini istologiche che lui spiega a lezione] MESOTELIO Altro esempio di epitelio pavimentoso semplice è il mesotelio, che riveste o le parti interne del corpo: mesotelio parietale; o gli organi: mesotelio viscerale. Per esempio la pleura viscerale riveste direttamente il polmone e la pleura parietale la parete del torace. Mesotelio che riveste il rene: singolo strato di cellule pavimentose. Mesotelio cardiaco: abbiamo una parete esterna: pericardio parietale; poi il liquido pericaridico che riduce l’attrito; e pericardio viscerale: diretto contatto col cuore. Nell’istologia del mesotelio vediamo uno strato di cellule e sotto la lamina basale le grosse cellule bianche sono di tessuto adiposo. Questo tipo di epitelio lo troviamo per esempio nell’intestino. Peritoneo parietale: parte esterna Dopo la parete muscolare c’è la sierosa, mesotelio Viscerale, composto da cellule pavimentose semplici, lamina basale. ALVEOLO POLMONARE Nell’alveolo Polmonare l’epitelio pavimentoso semplice svolge un ruolo fondamentale, perché deve facilitare gli scambi gassosi. Strato sottile: pneumocita dell’epitelio alveolare Capillare con globulo rosso Giunzioni occludenti tra pneumociti PATOLOGIA Rottura degli alveoli polmonari, per esempio inalando particolato, o col fumo di sigaretta, c’è il collasso dell’alveolo polmonare, quindi infiltrazione di particolato: Enfisema; oppure con un’infezione per esempio polmonite vediamo la presenza di essudato ricco di leucociti, quindi le cellule infiammatorie. EPITELIO CUBICO SEMPLICE Il nucleo della cellula è rotondo, non pù schiacciato come nelle cellule pavimentose. La cellula ha larghezza e altezza simili. Questo tipo di tessuto si trova nei dotti di alcune ghiandole, o le cellule secernenti dei follicoli tiroidei. Quindi con funzione di trasporto o secrezione. EPITELIO CILINDRICO SEMPLICE Nucleo solitamente posizionato nella parte più vicina alla lamina basale, la cellula è alta e stretta. Tra le cellule epiteliali troviamo le cellule mucipare caliciformi. Cripte intestinali Spesso troviamo una presenza abbondante di microvilli che formano l’orletto. Nelle immagini vediamo lo stesso tessuto trattato con due colorazioni diverse, nella Tricromica di Masson la struttura colorata di azzurro è la lamina basale. Nelle cripte intestinali abbiamo sia assorbimento e secrezione. ● Enterociti: dedicati all’assorbimento ● Enteroendocrine: disperse nell’epitelio, considerate i maggiori organi esocrini del nostro organismo, rilasciano Somatotossina e istamina ● Cellule di Paneth: secernono sostanze antimicrobiche, funzione di protezione ● Cellule staminali: soprattutto nella parte più basale della cripta ● Cellule caliciformi Quelle indicate dalla freccia sono giunzioni occludenti PATOLOGIA La morfologia egli epiteli è importante, alterazioni di questi tessuti sono associate a patologie. Per esempio perdita di continuità dell’epitelio dell’intestino che è rivelatore di una trasformazione neoplastica. Le cellule epiteliali assumono funzione mesenchimale e possono invadere la sottomucosa. È importante individuare la lesione prima che invada la sottomucosa perché mentre l’epitelio è avascolarizzato nella sottomucosa ci sono i vasi sanguigni, e il tumore può fare metastasi. EPITELIO CILINDRICO SEMPLICE CILIATO nelle tube uterine abbiamo sia cellule ciliate che non ciliate, che provengono dalla stessa cellula iniziale che poi differenzia. [legge la slide accanto] EPITELIO PSEUDOSTRATIFICATO Come si può riconoscere? A prima vista sembra pluristratificato perché i nuclei sono posti su nuclei differenti, ma non è così, perché tutte le cellule poggiano sulla lamina basale. Ma non tutte le cellule arrivano nello strato apicale. Quindi il nucleo è delocalizzato nella parte più grande della cellula. Possono essere ciliati o non ciliati. L’epididimo per esempio ha specializzazioni ma sono Stereociglia, quindi è epitelio pluristratificato non ciliato. Mentre un esempio di epitelio pseudostratificato ciliato è la trachea. Le ciglia sono un po’ più corte. (si riconosce la trachea perché sotto l’epitelio ci sono dischi di cartillagine) All’interno dell’epitelio della trachea possiamo trovare cellule mucipare caliciformi, che secernono muco, e non sono ciliate. Evidente nell’immagine con microscopio elettronico a scansione. TESSUTO EPITELIALE Epiteli pluristratificati Abbiamo visto gli epiteli semplici, quindi un unico strato di cellule e zero stratificazioni. Adesso vedremo alcune delle caratteristiche degli epiteli pluristratificati, che ovviamente presentano più strati di cellule; spesso la forma delle cellule cambia all’interno dei vari strati, e il nome viene dato dallo strato più superficiale. In questo caso abbiamo epitelio pluristratificato pavimentoso, anche se in effetti la cellula dello strato basale è cubica. Qual è il ruolo di questi epiteli? È quello di garantire maggiore protezione. Una delle caratteristiche di questi epiteli è che la rigenerazione, il turn-over che si fa, cioè il cambio del tessuto, è garantito dallo strato basale, perché nello strato profondo abbiamo le cellule staminali. Può essere non cheratinizzato, e lo troviamo nella bocca, nella faringe, nell’esofago, nella vagina e nel retto, oppure cheratinizzato, che è l’epitelio caratteristico dell’epidermide. Ad esempio in questo caso (foto sopra) che tipo di epitelio è? Pluristratificato pavimentoso, perché le cellule circondate di azzurro nell’ultimo strato, danno un epitelio pavimentoso. Nell’esofago abbiamo un epitelio pluristratificato non cheratinizzato. Come si può notare subito sotto l’ultimo strato abbiamo il tessuto connettivo, con la presenza di vasi sanguigni e con la mucosa muscolare. Qual è una delle caratteristiche istologiche che già si può apprezzare, come prima osservazione di questo epitelio? Cosa cambia tra questo strato (1) e questo altro strato (2) ? La densità dei nuclei. L’aspetto dello strato basale, normalmente, è appunto caratterizzato dalla maggior presenza dei nuclei, perché come accennato, sono presenti le cellule staminali, quindi le cellule sono ancora capaci di replicarsi, per rimpiazzare le cellule che sono presenti negli strati più superficiali, che sono sfaldate dallo stress meccanico. In alcuni animali anche l’esofago ha un epitelio cheratinizzato. Una delle tecniche che possiamo utilizzare per rivelare la presenza di cellule staminali, di cellule che stanno proliferando nello strato basale, è l’immunoistochimica, con la quale usiamo un anticorpo, in questo caso un anticorpo rivolto verso una proteina chiamata CD156, che è un marcatore, una proteina, presente solo nelle cellule staminali; quindi se noi coloriamo il tessuto, facciamo un’ibridazione con un anticorpo rivolto verso questa proteina, questo anticorpo è legato ad un enzima, che fa precipitare il substrato (in foto di colore marrone), e al microscopio ottico possiamo vedere dove sono presenti le cellule staminali. L’alternativa è invece coniugare l’anticorpo con il fluoroforo, e andare ad osservare con un microscopio a fluorescenza. La pelle: l’epidermide Spesso troviamo in questo tipo di epiteli, questi ripiegamenti degli strati basali, ma anche negli strati più superficiali, cosa che è evidente anche nell’epidermide. La cute è composta sia da un epitelio chiamato epidermide, sia dal derma sottostante che è un tessuto di natura connettivale. A seconda della sede anatomica che si sta analizzando, possiamo avere una cute sottile o una cute più spessa, quello che cambia è proprio lo spessore dell’epidermide, in particolare dell’ultimo strato. Questo è un esempio di cute sottile (sx), mentre questa è una cute spessa (dx). Si può apprezzare come, ad esempio, siano presenti dei ripiegamenti degli strati basali, ma in parte anche degli strati più superficiali. Dove sono più evidenti queste pieghe, ad esempio? Dove si formano le impronte digitali, viene accentuato il ripiegamento dello strato superficiale. Qui (sempre immagine sopra a dx) possiamo notare che nello strato superficiale, rispetto allo strato basale, non sono presenti i nuclei. A differenza dell’esofago in cui i nuclei sono presenti anche negli strati più superficiali, nell’epidermide le cellule proprie degli strati superficiali (i cheratinociti) perdono i nuclei. Infatti così facendo viene creato lo strato chiamato cheratina. Ovvero nello strato corneo, quello più superficiale, non abbiamo la presenza di nuclei. Quello che cambia all’interno dei vari strati è la presenza o meno di determinati tipi di giunzioni. Nello strato basale sicuramente troviamo una giunzione, che non è presente negli altri strati, ovvero gli emidesmosomi. Questo perché l’emidesmosoma è una giunzione che si trova tra la cellula epiteliale e la lamina basale, che ovviamente è a contatto solo con l’ultimo strato. Quindi l’emidesmosoma qui colorato di verde (immagine sopra), è presente solo nello strato basale. Mentre cominciamo a vedere la presenza di desmosomi tra una cellula e l’altra, che si mantengono nello strato basale ma anche nello strato spinoso. Lo strato granuloso è caratterizzato ad esempio dalla presenza di giunzioni occludenti e aderenti, che quindi rendono impermeabile l’epidermide e impediscono il passaggio di sostanze attraverso questo strato. Questi ultimi tipi di giunzioni le troviamo anche nello strato lucido, mentre i desmosomi corneificati o corneodesmosomi, li troviamo nello strato corneo. Anche il numero di cellule dei vari strati è pressoché costante. Strato basale Tramite questa sezione dell’epidermide andiamo ad ingrandire lo strato basale, a contatto con il tessuto connettivo sottostante, e possiamo vedere, come è rappresentato questo stato, ovvero la presenza massiva di nuclei, dovuti alla proliferazione delle cellule, che infatti sono positive a quest’altro marcatore, che è un importante regolatore del ciclo cellulare Ki67. Se facciamo l'immunoistochimica per questo fattore, le cellule degli strati basali lo respingono, perché sono in attiva proliferazione. Quindi se per esempio abbiamo una lesione dell’epidermide, sicuramente questo marcatore non reagirà. Quindi le cellule perdono la capacità di proliferare, nello strato spinoso e nello strato granuloso la perdono totalmente, e addirittura nello strato corneo perdono proprio il nucleo, quindi è impossibile che la cellula si replichi. E questa è l’importanza dello strato basale, che regola il turnover di questo tessuto che è di circa 30-40 giorni, cioè una cellula passa dallo strato basale a quello corneo in 30-40 giorni, e così facendo si rinnova totalmente l’epidermide. Se guardiamo lo strato basale o germinativo, abbiamo una cellula piuttosto piccola, tondeggiante, prolifera e sono presenti sia desmosomi, sia emidesmosomi. Strato spinoso Nello strato spinoso, è presente uno spazio intercellulare tra una cellula e l’altra. Si possono osservare delle spine, questi sono dei processi citoplasmatici, che servono poi a connettere un cheratinocita e l’altro. Ovvero in queste spine sono presenti i desmosomi. In questo strato inizia il differenziamento cellulare, il cheratinocita inizia ad esprimere le cheratine, quindi perde la capacità di proliferare. Strato granuloso Lo strato granuloso è chiamato così, proprio per il suo aspetto istologico, per la presenza di granuli all’interno del citoplasma in ambiente cellulare. Normalmente dovrebbe riportare 3 file di cellule in questo strato, visualizzando la presenza dei granuli in ogni cellula. Questi granuli contengono proteine come cheratoialina, filegrina e loricrina, sostanze che serviranno, poi, a rendere l’epidermide resistente. Le giunzioni tra una cellula ed un’altra sono desmosomi e giunzioni occludenti, infatti, se noi facciamo l’immunofluorescenza per proteine come la claudina, che colora le giunzioni più immature, possiamo colorare anche cellule degli strati limitrofi; se invece utilizziamo l’immunofluorescenza per l’occludina, che è una giunzione più matura, si può vedere com’è proprio più localizzata e ristretta allo strato granuloso. Inoltre si può notare (foto sotto) anche la microscopia elettronica con le giunzioni occludenti. Qui (sotto) possiamo vedere una bellissima immunoistochimica proprio con la claudina, dove possiamo vedere la sezione dell’epidermide con l’immunoistochimica. E qui già possiamo vedere alcune cellule, che perdono il nucleo negli strati più superiori dello strato granuloso, e la cosa risulta poi evidente nello strato corneo, dove i nuclei sono assenti, che è la caratteristica fondamentale, con la quale si riconosce questo strato. Strato corneo La cellula quindi forma queste lamine, prive di nucleo, il citoplasma è farcito di cheratina aggregata, le giunzioni sono dei desmosomi modificati e sono rivestiti da un involucro cellulare corneificato, ovvero: involucrina, loricrina, filamenti di cheratina e molecole lipidiche, che rendono lo strato impermeabile. La cheratina va classificata tra i filamenti intermedi importanti nel citoscheletro. Infatti si ricordi la presenza dei filamenti sottili di actina, di tubulina e poi a seconda del tessuto possiamo avere dei determinati filamenti intermedi. In particolare, la cheratina forma il filamento intermedio nell'epitelio. I desmosomi, ovvero la giunzione tra un cheratinocita e l’altro, è regolata dal pH. Per questo è importante mantenere il pH della cellula, perché via via che aumentiamo l’acidità del pH, promuoviamo lo sfaldamento dei cheratinociti e quindi il ricambio dello strato più superficiale. In alcune sedi come, ad esempio, il palmo della mano e dei piedi, è presente un ulteriore strato, che è definito lucido, proprio per il suo aspetto istologico, ed è presente tra lo stato corneo e lo strato granuloso. Qui (sotto) abbiamo una microscopia elettronica a trasmissione di una sezione di tessuto di epidermide sottile, dove si possono vedere i cheratinociti nei vari strati. Questa la si può sempre colorare artificialmente e si può così riconoscere la struttura dei vari strati. Quindi sostanzialmente salendo dallo strato basale allo strato corneo, abbiamo il differenziamento dei cheratinociti dalle cellule staminali che sono in grado di replicarsi. Si ricordi infatti che per cellula staminale non si intende solo una cellula che è in grado di differenziarsi ma è anche in grado di autoregolarsi. Dunque da una parte formerà una nuova progenie di cellule staminali in grado di differenziarsi, dall’altra i cheratinociti iniziano il processo di differenziamento passando allo strato spinoso. Iniziano quindi ad esprimere le cheratine, cambiano la forma, cambiano il tipo di giunzione, fino a produrre l’involucro di cheratina nello strato corneo e questo ha un timing ben preciso a seconda della zona. Per capire l’importanza dell’aspetto molecolare di questo differenziamento (non verrà richiesto all’esame) si faccia presente che tutti i geni del differenziamento dell’epidermide sono presenti nei cluster presenti nel cromosoma umano. Ovvero sono presenti tutti i geni necessari per il progredire del differenziamento dei cheratinociti all’interno dell’epidermide. All’interno degli epiteli non abbiamo solo i cheratinociti, ma abbiamo quattro tipi cellulari: -i cheratinociti -i melanociti - le cellule di Langerhans - le cellule di Merkel I melanociti Sono i responsabili della produzione della melanina, che è un pigmento, che viene formato dalla ossidazione della tirosina, ad opera della tirosinasi, viene accumulata all’interno dei melanosomi, di queste vescicole, e poi vengono rilasciate dal melanocita e vanno a fondere con le cellule dei cheratinociti dello strato spinoso, e formano una sorta di barriera, al di sopra del nucleo delle cellule dello strato spinoso. La funzione importante della melanina è (oltre a “renderci più attraenti d’estate”) proteggere il nucleo delle cellule dell’epidermide dai raggi ultravioletti, per impedire l’insorgere di mutazioni. I melanociti si possono identificare nello strato basale, e infatti possiamo mettere in evidenza la presenza dei melanociti con dei marcatori (come, per esempio, le tirosinasi che formano la melanina), che sono localizzati nello strato basale. In questo caso possiamo vedere, nell’epitelio della cornea, la presenza dell’immunofluorescenza, dei melanociti marcati con questo marcatore specifico del melanocita (e che quindi sono proprio nello strato basale). Quest’ultimo in particolare è positivo alla p-caderina che è quindi un marcatore del melanocita della cellula nello strato basale. Mentre la cheratina/la pan cheratina marca gli strati superiori. Cosa succede se abbiamo una iperplasia del melanocita? A cosa ci si sta predisponendo? Al melanoma. Quindi sotto un punto di vista medico istologico, prima di avere la trasformazione tumorale, i melanociti diventano più abbondanti e di dimensioni più irregolari. In particolare li troviamo anche negli strati superiori e non solo nello strato basale quando viene effettuato l’esame istologico. Cellule di Langerhans Le cellule di Langerhans sono delle cellule del sistema immunitario, che derivano dalla famiglia dell’ovocita dei macrofagi, troviamo cellule derivate da questa famiglia in diversi tessuti, e nell’epidermide si differenziano nelle cellule di Langerhans. Per esempio nell’osso differenziano nell’osteoclasto, oppure nel connettivo in macrofagi. Quindi sono tutte cellule che derivano dall’ovocita (da questa famiglia), e che hanno delle caratteristiche comuni, come la capacità di fagocitare, o di presentare l’antigene. Sono marcate ad esempio dall’antigene Cd1, e sono la prima sentinella dell’epidermide per i noxa patogena. Ovvero possono fagocitare e possono attivare la risposta immunitaria in caso di patogeni. Qui possiamo vedere una cellula di Langerhans, all’interno di uno strato spinoso, con questi lunghi processi citoplasmatici, che caratterizzano la cellula di Langerhans, ma anche le altre cellule della stessa famiglia. Cellula di Merkel Infine abbiamo la cellula di Merkel, che è responsabile della percezione sensitiva, quindi tramite il tatto, è più abbondante in alcune zone anatomiche, come ad esempio i polpastrelli e le labbra. In questa microscopia elettronica a trasmissione, possiamo vedere, la cellula di Merkel sopra al nucleo, è presente nello strato basale, perché subito sotto dal tessuto connettivo arrivano le terminazioni nervose, che prendono contatto diretto con la cellula di Merkel. Quindi la cellula di Merkel funziona da meccanorecettore, che trasmette direttamente al sistema nervoso la percezione meccanica. E qui possiamo vedere la giunzione con una cellula nervosa e la presenza delle cellule di Schwann, che sono delle cellule di sostegno associate al neurone, che stabilizzano le giunzioni con le sinapsi dei neuroni, e hanno poi la funzione di formare la guaina mielinica lungo l’assone. Non esistono solo le cellule di Merkel come recettori del tatto associati alla cute (lo vedremo poi con anatomia), esistono terminazioni nervose libere, corpuscoli dei bacilli e altre strutture. Abbiamo poi gli epiteli pluristratificati pavimentosi. Ma abbiamo la distribuzione limitata anche degli epiteli pluristratificati cubici (in foto a dx), che sono presenti in alcuni solchi maggiori e in alcune ghiandole esocrine (la funzione è sempre quella di trasporto). Lo stratificato colonnare, che è molto raro nei mammiferi (in foto a sx), presenta sempre alcuni dotti di alcune ghiandole esocrine. È caratterizzato di solito da due strati: uno di cellule cubiche e uno superiore di cellule cilindriche o colonnari. Infine abbiamo l’epitelio di transizione, che a seconda dello stato rilassato o disteso dell’organo, ha una conformazione differente. Quando la vescica è rilassata, abbiamo un maggior numero di strati, le cellule superficiali hanno questa forma a cupola; quando, invece, la vescica è piena l’epitelio/il tessuto si distende, e questo anche grazie alla presenza delle giunzioni tra una cellula epiteliale e l’altra, le cellule cambiano di forma e ci appaiono più schiacciate, ad esempio negli strati più superficiali (quindi diminuisce il numero di strati). Questa caratteristica permette una grande capacità di distensione. Cosa intendiamo con Metaplasia? Intendiamo un processo che è ancora reversibile, dove la cellula epiteliale passa da un tipo di epitelio a un altro, perché sottoposta, ad esempio a stress, o costante infiammazione o infezione virale. Quindi la metaplasia è il primo passo della trasformazione carcinogenica a cellule squamose o ad adenocarcinoma. Per esempio in foto è presente la cervice uterina, dove l’epitelio colonnare semplice converte, quando abbiamo metaplasia, in epitelio squamoso stratificato, che è ovviamente disfunzionale. Per esempio se si prendesse la trachea di ratto, esposta o meno al fumo di sigaretta (ovvero un fattore stressogeno), le cellule sono sottoposte continuamente a sostanze infiammatorie, che possono causare la mutazione dell’epitelio della trachea, che è pseudostratificato ciliato, ad un epitelio che invece è stratificato. Quindi ovviamente, in questo caso si ha una perdita di funzione dell’epitelio della trachea. Lego spike Crea un quiz per docenti sui vari robot per la didattica. i robot presentati al corso sono doc clementoni, ozobot, lego wedo, mindotorm, spike, clementoni bubble, clementoni mind , bluebot e beebot