Textual analysis Essay Example | Topics and Well Written Essays - 1000 words - 4

Printed examination - Essay Example In this article, portrayal is a significant strategy to present and describe fundamental characters and settings. It assists perusers with envisioning how these individuals look and where these occurrences occurred. The youngster was terrified of Staples, not just in light of the fact that Staples is a â€Å"youngish dark man†, yet in addition since his garments and his conduct made him look like â€Å"a mugger† or â€Å"a rapist†. Brent Staples portrayed himself as â€Å"the youngish dark manâ€a expansive six feet two crawls with a facial hair and surging hair, two hands pushed into the pocket of a cumbersome military coat â€Å"(40) in his mid twenties. He utilizes â€Å"broad†, â€Å"billowing† and â€Å"bulky† to make individuals consider him to be enormous and forcing. Staples additionally utilizes the word â€Å"shove† over the word â€Å"put†, which recommends brutality and causes Staples to show up progressively gro und-breaking. Thusly, Staples effectively depicts how he appears to be alarming to others. After Staples â€Å"felt [sadness] at so regularly being taken for a criminal† (42), he had to focus on his garments and his conduct. Brent Staples says, â€Å"I give a wide compartment to anxious individuals on metro stages during the extremely early times, especially when I have trade business garments for pants. On the off chance that I happen to enter a structure behind certain individuals who seem sketchy, I may stroll by, letting them clear the anteroom before I return, so as not to appear to be following them† (42). Staples portrays a few views that normally occur in people’s day by day lives. He places perusers into the stages and structures as though they are looking as things occur. In the last section of the article, Staples says, â€Å"I whistle tunes from Beethoven and Vivaldi and the more famous traditional writers. Indeed, even steely New Yorkers slouching toward evening time goals appear to unwind, and once in a while they even join in the tuneâ €  (42). In this depiction, Staples puts perusers onto the road where outsiders whistle tunes to welcome one another.

Ethics Leadership and Decision-Making Management

Question: Examine about the Ethics Leadership and Decision-Making Management. Answer: Presentation: The arrangement of comprehension and the convictions that an organization need to follow are known as Business morals (Noddings, 2013). All driving business organizations and the establishments follow a few morals. The practices center for the most part around the genuineness, trust and the reasoning methodology that is considered over the benefit lines. Moral practices once in a while hamper the benefit of the organization in a present moment yet in a drawn out business strategy, moral is rehearses are considered as a productive ones. This expositions examinations the significance of moral practices, difficulty and the connection between the morals, administration and the dynamic approaches of Apples Inc. The business bunch consistently positively affects the general morals that is actualized by the association (Carroll Buchholtz, 2014). Business morals consistently set the particular standard for a specific organization that follows the strategy by which the business can be led. Moral elements have huge impact on that specific association or the foundations A significant angle on moral business is a moral speculation as the enormous scope venture center around the market powers that considers incredibly the popular feeling (Dewey, 2016). The current idea of moral practices centers around the social obligation of the corporate, globalization, maintainability on social venture and shared cooperatives of the representatives. In present days, associations gets preferences on acting morally, in view of empathy, mankind with the particular thought all through the world (Peters, 2015)(Ford Richardson, Ethical dynamic: An audit of the observational writing, 2013).Ethics can be connected with the issues that any association faces while playing out the morals that they itself has recorded on their organization plans. One of the serious issues that an organization comes up short while acting in the promoting stream is the moral issues. Each organization records their own advertising exchanges that draw out the desire set dependent on the status of the relationship on the business that will exist and the conduction of the exchanges must be recorded. The attack in the showcasing dependent on the approach and the generalizing, serious issues in statistical surveying. Nonetheless, whenever performed carelessly, the consequence of the generalizing can prompt the moral peril. Specific showcasing debilitates the principle request from the undesirable advertising divisions or smothers them in an agreed way. Another issue that centers identifies with these helpless crowds in developing markets in the rising nations, as general society don't know about the rising promoting territories and the plots (Dinnie, 2015) One of the most disputable promoting channels centers around the spontaneous methodologies. For instance, TV ads and the immediate sends are the most widely recognized models. Selling and the electronic spam push the outskirts of legitimateness and morals all the more emphatically. A specific sort of showcasing that isn't explicit to a specific objective market and anybody can go for open elements. There are a few laws that can be introduced for the buyers. Cleverness is one of the technique for the fruition that demonstrations a departure or gives help from different sort of human impediment and some consultant takes the advantages by this kind of unrepresentatively uncovering the items that can appropriately mitigate the bit of leeway towards the confinements through entertaining ways. A strategy utilized for structuring an item with a constrained valuable material in life is known to be arranged oldness. It turns out to be peaceful unfashionable or out of date after a specific timeframe and commandingly put the client in strain to buy a specific thing once more. The training for selling a specific item or administrations at a low value, intended to drive out of different contenders from the market or making obstructions for the new contenders. The significant startling issue harms their picture that is related with the press declaration of exploitative practices. Hardly any advertisers center around the shoppers taste as preferences to the showcasing morals. The compelling and morally endeavors are important to get together the great advertising procedures. Fortune magazine granted Apple as the Worlds Most Admired Companies. The home office is situated in California. Apple is procuring the principal position throughout the previous four years. As per, a huge number Apple represents the quality, advancement and eminence (Apple, 2017) Many organizations came into thought for duplicating its item however nothing could stand and battle with it. The purpose for the Apple for being its uniqueness is as yet obscure. Individuals accept the achievement of Apple originates from the blend of the administration abilities by Steve Jobs and the working environment culture where development stirs up with the eagerness. These consolidating characteristics made Apple as a progressive task of the innovation (Apple, 2017) In the Apples history, the main item propelled was Apple I, was altogether different from todays items. Steve Wozniak, prime supporter of Apple, built the primary high quality PC unit. The items, Mac I and the Newton were not effective. Steve Jobs came back to the organization as CEO and made a decent attempt to spare the organization by battling hard to endure (Apple, 2017). The rebound of Jobs, presented another stage for Apple and began changing the corporate condition. His came back to the organization and presented an arrangement, called shut entryway approach (Apple, 2017). Apple had a place with one of the mindful and securing innovation by guaranteeing its security issues. Occupations additionally made an alternate hierarchical structure by not by layering the administrators to deal with the representatives, rather he tended to them straightforwardly. An extension occurred from telephones to the Ipod-music player, that is convenient which changed the music business perpetually (Apple, 2017). They likewise present iTunes, a kind of programming, which permits the transferring of music from CDs into the Mac gadgets for sorting out and customizing the tune libraries in the year 2001. Following two years, they presented ITunes store, from where various music can be downloaded. In the year 2007, Jobs presented an Apple counter and named as Apple Inc. This connotes Apple as a hotspot for buyer electronic drivers, similar to Apple TV, iPad, iPhone, iTunes and iPods from moving ceaselessly from the Mac PCs (Apple, 2017). Macintosh has become a hotspot for rehashing PCs. On presenting tablet PCs, it increased top significant rivalry in the electronic business and ideally it will develop with an extremely high rate (Apple, 2017). Despite the fact that Apple has taken off high to arrive at the apex, it experiences a few moral quandaries upsetting its respectability in the business associations. The main edge brand watches some specific standards so as to keep up an appropriate business direct. The standards being genuineness, consistence, privacy and regard structure an unshakable establishment for corporate administration. Notwithstanding, in spite of having made sure about the highest most situation as Worlds Most Admired Company there have been sure moral issues that are endeavoring to disrupt its transcending reputation(Clarke Boersma, 2015). The causes behind apples trap are as per the following: Item Quality: Behind Apples remarkable worship and prominence among the shoppers lies the top notch quality highlights gives in the handsets. The iPhone arrangement is exceptionally acclaimed distinctly for its novel and new-formed highlights that one can scarcely discover in some other contenders of it. Normally, the iPhones are valued at a much-expanded level, which would do equity just if the clients are guaranteed of its quality. Lamentably, Apple bombed setting this standard to their clients subsequent to presenting iPhone4 in the market(Chan, Pun, Selden, 2013). Buyers confronted issues with gathering of system due to recieving wire obstruction when the telephone was held with a specific goal in mind. Therefore, Consumer Reports prevented any further support from securing this item and it appeared to pale the notoriety of the organization(Page, 2013). Consequently, Apple needed to give its clients cases and free guards for a specific timeframe. Protection: In 2011, Apple was again grieved for an area security issue, which as indicated by Google and Apple was probably going to unveil and follow the clients areas through some applications. In spite of the fact that Google had reported to cause the shoppers to feel sure that the clients can without much of a stretch recognize those applications and in this way deactivate them it was viewed as an encroachment on privacy(De Montjoye, Hidalgo, Verleysen, Blondel, 2013). In any case, this was not so much relevant to the iPhone sets as they despite everything keep on social event area data with no earlier information. Supportability: Apples items and their activities are answerable for discharging 9.6 million metric huge amounts of metric gases as conceded by Apple specialists. Consequently, Apple has stepped forward for a greener creation and endeavors to make its items with materials recyclable. It has vowed to expel cathode-beam tubes in its merchandise and lessen harmful materials while fabricating. Protected innovation: To defend its licensed innovation Apple can go to any degree and it really has been seen policing them forcefully. This has included Apple in a few claims against driving associations like Microsoft. In any case, the claims asserting an area name from Ben Cohen and with Cisco Systems(2007) included major moral issues with respect to Apple. In the claim against Ben Cohen, Apple won with the judgment that Ben Cohen had appreciated some one-sided bit of leeway of Apple and that he had damaged the enrollment rights(Berger, 2013). In any case, this triumph is viewed as the triumph of a monster in front to the detriment of a minor. IN another claim with Cisco Apple was blamed for copyright infringement encroaching its iPhone trademark. Representative Abuse: Due to lesser work and producti

Development of motion picture. Do not plagiarism please instructor Essay

Improvement of film. Don't literary theft please teacher checks Thanks - Essay Example The article gives a background marked by Chaney’s acting vocation in the period of oddity show epitome in motion pictures, and his evident enjoying o playing dreary and strange characters in the films. Chaney is delineated as having gained a religious after from his motion pictures, particularly among the male sexual orientation. Be that as it may, ladies and youngsters are uncommon fanatics of the actor’s works. From the article, I am of the feeling that the writer best brings out Chaney’s character and history. Regardless of a portion of the analysis depicted, I feel that Chaney was supported in depicting the unusual characters in the motion pictures, incompletely on account of the present enthusiasm for crack demonstrates and in light of the fact that entertainers must be one of a kind to succeed. It is clear that Chaney pulled in a ton of enthusiasm from the male populace in view of the bizarreness of his films and terrified away ladies and kids on account of the revulsions he delineated in the

Essay on Week 1 Assignment

Article on Week 1 Assignment Article on Week 1 Assignment EMG4412 August 29, 2014 Commander Honor’s conduct doesn't completely accommodate my pattern of a compelling pioneer. In the wake of exploring more data about the episode, I accept that Captain Honors believed that he was giving satire and giggling to an in any case unbending condition. He demonstrated a shortcoming in his administration by acting as such. I accept that he utilized misguided thinking by indicating the video. I don’t accept that he understood the observation that he was depicting to his team. I am certain that he was attempting to utilize this video as a way to communicate his point about permitting gay individuals into the military, yet going about it along these lines was an immature method to do it. He had incredible impact on the men on his boat. How could he realize that one of the men on his group wasn’t gay or that they had gay companions or family? What sort of view of him would they at that point have? He was their pioneer and ought to be showing others how its d one. Great pioneers consider the view of the entirety of their representatives and how they see the world through their social recognitions. Commander Honors likewise showed a generalization of gay individuals. His announcement was that ALL gay individuals acted in the manner he depicted them in the video. He likewise accepted that nobody would be affronted by the foul language and sexual presentations. I viewed the video and in spite of the fact that I thought that it was diverting, I would have been completely humiliated to watch it with individuals I work with, particularly in the event that they had been in it. As indicated by news reports, he had a decent affinity with his team and they sponsored him 100 percent and recognized it on the web. This shows that he was so compelling to his group. He ought to have considered the repercussions that would follow from doing this and the view of how his representatives would take a gander at him later on just as his commanders’ im pression of him. Skipper Honors settled on a terrible decision and when the video surfaced, lost his activity and afterward his validity with the Navy. References: BUMILLER, E. (2011, January 4). The New York Times. Recovered from Aircraft Carrier Captain Is Removed Over His Role in Coarse Videos: nytimes.com/2011/01/05/us/05military.html?_r=0 Kinicki, An., and Fugate, M. (2012). Hierarchical Behavior, Key Concepts, Skills and Best Practices. New York: McGraw-Hill. YouTube Video. (2011, January 4). Recovered from Captain Owen P. Praises Jr. ( The Greatest Comedy Sketch Ever) : https://www.youtube.com/watch?v=CU8Yp2h_RVs EMG4412 Educator Curtis Curry August 30, 2014 As indicated by the part opening case, characteristics that are intrinsic to significant level administrators, for example, Mark Zuckerberg are in accordance with the Big Five Personality Dimensions, including extraversion, pleasantness, good faith, passionate security, and receptiveness to encounter. In the second sentence of the case, Zuckerberg’s father portrayed him as â€Å"strong-minded† and â€Å"persistent† (Kinicki and Fugate, 2012). For an amazing duration, my folks named me as â€Å"strong-willed† and â€Å"stubborn†. I generally had a â€Å"I can do that† mentality. I hated that somebody would reveal to me I couldn’t accomplish something. When contrasting myself with the depiction of Zuckerberg for the situation story, I find numerous likenesses, for example, being socially unbalanced or unengaged. It isn't that I am it is possible that, I simply have

Cultural Diversity and Its Effect on Mnc’s Essay

Nowadays social decent variety assumes a noteworthy job in an organization. The rules segregating these gatherings incorporate race, geographic premise, human progress, sex, age, utilitarian or instructive foundation, physical and psychological skill, language, ways of life, convictions, social foundation, monetary classification, inhabitance with the association and sexual inclination. As a MNC works in a worldwide market it must be prepared to identify every single imaginable change in the worldwide condition and it must have the option to convey and adjust the character of the organization to them. For instance in India women’s won't work for night so they possess to oversee energy for their benefit. The organization can’t offer quality items or administrations to the clients on the off chance that it doesn’t comprehend and consider the effect that the way of life has in all the procedures. Laborers as a rule believe that their conduct hasn’t got any im pact on the last item or administration, however to be successful, each part should have an away from of the organization and a reasonable crucial it. The social, political and venture structure relies upon everybody in the organization, so the interior region and the HR, one of the most significant territories of an organization, must be created with the remainder of the organization to accomplish their objectives. The misconception and disregarding of various societies, language and verifiable foundation lead to debacles in the field of setting up worldwide business. To maintain a strategic distance from this, a general information on another nation’s culture and history is basic. So broad social information, whenever combined with bias and prejudgment, is an obstruction to successful worldwide administration. 2.1 Communication and language boundaries One primary test under culture is language obstructions. Correspondence is fundamental for the board. However correspondence depends upon a typical language, a condition that doesn't exist in numerous worldwide business circumstances and that is the point at which the issues start. The most articulated indication of the language obstruction at work can be found in the connection between a worldwide parent organization and its system of worldwide auxiliaries. A few components add to the trouble of accomplishing and supporting powerful interchanges and a profitable, collective relationship. Regardless of whether a representative is moderately able in the language of the other party, loss of explanatory aptitudes is constantly present as the utilization of silliness, imagery, affectability, exchange, influence and inspiration requires an elevated level of familiarity. 2.2 Attitudes towards Appointments and Deadlines In America, Americans were give severe acquiescence to time duties and it was a fundamental standard of demonstrable skill and considerate conduct. Since everything will in general be carefully booked, delays in a single arrangement or cutoff time can have a genuine gradually expanding influence on a colleague or customer’s other work responsibilities. In any case, for instance: The more adaptable and open-finished way to deal with time of Indian and Sri Lankan organizations culture can make pressures and unfavorable impacts on American partners 3. MNC Workforce Diversity Global Companies (MNC) needed to confront various new difficulties in their day by day business over the recent years. Globalization changed different things for worldwide players. When all is said in done MNC structure shows an emphasis on their principle assets and divisions like money, innovation, advertising, deals and creation, since they need to have an enormous number of clients and to win benefit. A tremendous test MNC need to oversee is their workforce decent variety. The achievement explore by Hofstede with 116,000 volunteers of IBM, a mammoth MNC in 50 nations and 3 districts perceived four social qualities in the work environment: Individualism-cooperation, Power contrast, Uncertainty evasion and manliness gentility. For instance: the United States was the best and Guatemala was most minimal in independence. Malaysia was the most noteworthy and Austria was the least in the force separation esteems. Greece was the most noteworthy and Singapore was the least in the vulnerab ility shirking esteems. Japan was the most noteworthy and Sweden was the least in the manliness esteems. There have been critical measure of intercultural and multifaceted examinations with these social qualities, and a few investigations showed the connection between correspondence styles with a portion of these qualities. As a result of this assorted variety one of the key achievement components of MNC is the enlistment and determination of HR who offer significant uniqueness. These people are shaping the qualities and convictions of a business. There are two key difficulties inside worldwide HRM explicitly constructing worldwide corporate societies and creating worldwide pioneers that must be aced so as to oversee decent variety and be effective in the worldwide business environmental factors. Overseeing decent variety in MNC during HRM To oversee workforce decent variety in MNC it’s a test for the human asset the board to set up a worldwide corporate culture. To perceive with the corporate culture of the organization is the most noteworthy thing for the workforce. That is the reason constructing a worldwide corporate culture is one of the most significant difficulties for Multinational Companies. Representative conduct is perhaps the most basic test that global associations need to manage. In Multinational Companies there is a colossal capability of contentions, on account of its various characters. Because of this tensions will emerge among representatives. People attempt to adjust their practices to fit the requests of a specific domain. So as to adjust to the earth, people penance their independences to fit in with their new cooperatives. People become joined into the way of life of an association when they are effectively comprehended into the work environment. Effective social adjustment lessens members ’ tension, job struggle, and aims to leave. Furthermore, effective adjustment increments hierarchical commitment, work fulfillment, certainty, and employment commonality just as fruitful cultural assimilation and foundation of relationship. 4. Difficulties of Working across Culture 4.1Stereotyping They are typically distortions and mistakes fixed in bogus estimates and flawed investigation. Typically this valuation is found in a negative viewpoint. The difficulties to associations are to recognize contrasts in positive terms. Force battles and can be the aftereffect of generalizing in associations. For instance, putting ladies, who characteristically have had lower status than men in the public arena; in senior administration positions make status incongruence in the brains of a considerable lot of the individuals. This can establish complexities in the pioneer/subordinate relationship and can establish power contrasts in a business. This is done so that subsidiaries of minority gatherings may think that its difficult to utilize impact over choice procedures in the association. 4.2 Ethnocentrism Ethnocentrism results when directors distinguish the distinctions in societies †in any case, have an affinity to feel that their way of life and their method for doing things is the correct way, their method for doing things is the main way and the most ideal way. Any distinction from their way of life or from their method for doing things is viewed as â€Å"distortion† or as a â€Å"mistake† or as â€Å"Wrong way†. A great many people have the inclination to seek after ethnocentrism. Americans, Japanese, Chinese, Germans, French, Scandinavians, and Russians are more inclined to ethnocentrism than different societies †when contrasted with different Asians, Latin Americans, British, Australians, Africans and Indians. 4.3Informal Integration Casual gatherings assume a huge job in any business. They impact both the achievement of the business and the vocation accomplishment of people. Absolute quality plans rely vigorously upon representative commitment and casual systems can extraordinarily affect this procedure. Casual gatherings are impacted by variables, for example, normal language, saw social similitude, and ethnocentrism. These aggregate systems are basic for correspondence in associations. It has been discovered that race majorly affects aggregate systems administration. This isn't bewildering as you would anticipate that individuals should have an inclination for cooperation with individuals from one’s own way of life gathering, particularly in a casual setting. 4.4 Parochial Attitude Parochial demeanor alludes to a person’s inability to see social assorted variety. This is actually the converse of ethnocentrism. Chiefs who are sent abroad every now and again meet individuals who are additionally wearing suits and communicate in their language †this prompts them to dismiss all other social contrasts and cause them to feel that all others are â€Å"just like us†. In today’s business globe, a great many people are adept to dress comparatively †in suits or different equations and talk in English, however this doesn't demonstrate that all individuals have a similar culture †yet individuals regularly just observe the surface and feel that the other individual offers the equivalent social qualities. Administrators from US/UK frequently will in general presentation a solid parochial disposition †essentially in light of the fact that the individuals with whom they relate on ordinary premise can communicate in English and are dresse d comparably in suits or western dresses.

De schakelaars van de celcyclus exit - Free Essay Example

Hoofdstuk 1: Inleiding Om als organisme te kunnen groeien is er celdeling nodig. Deze celdeling wordt gereguleerd door middel van de celcyclus en zal hier kort uitlegd worden. De celcyclus is in twee delen opgedeeld. De interfase en de M-fase. Tijdens de interfase groeit de cel en verdubbelt het zijn chromosomen. De interfase is ook weer opgedeeld in 3 delen, Gap fase 1 (G1), Synthese (S) en Gap fase 2 (G2) (zie figuur 1). In de G1 groeit de cel en bereidt het zich voor op de S-fase. In de S-fase wordt het genoom verdubbeld waarna het naar de G2 fase gaat waar de cel verder gaat met groeien tot het klaar is om te delen. Na de interfase komt de mitose of M-fase waar de cel uiteindelijk een nucleaire deling en en cytoplasmatische deling ondergaat. Wanneer de M-fase is afgerond zijn er twee cellen ontstaan die weer de celcyclus kunnen ingaan vanaf de G1 fase. Afhankelijk van de omgevings- en ontwikkelingssignalen kunnen cellen in G1 tijdelijk of permanent de celcyclus verlaten. De cellen komen dan in een rust fase van de celcyclus waar de cellen niet delen. Deze fase wordt ook wel de G0 genoemd. De meeste cellen in het lichaam van een volwassen vertebraat delen weinig en bevinden zich het grootste deel van de tijd in de G0 fase. Wanneer een cel uit de celcyclus gaat naar de G0 fase wordt dit meestal cel cyclus exit genoemd. Er zijn drie soorten van tijdelijke of definitieve rust fase na cel cyclus exit te onderscheiden. De eerste is quiescence, een niet delende conditie waarin de cel terug kan keren naar de celcyclus. Quiescence komt vaak voor bij cellen met DNA schade of cellen die niet de juiste benodigdheden voor proliferatie hebben. Wanneer DNA uit de cel beschadigd is maar niet te repareren is zal deze vaak in apoptose, celdood, gaan. Een tweede is terminale differentiatie, waarin de cel zich blijvend in een postmitotische staat bevind. De derde vorm van G0 fase is proliferatieve senescence, een andere vorm van permanente posmitotische staat. De beslissing van een cel om te delen wordt gemaakt in de G1-fase. Deze beslissing wordt gemaakt na afwezigheid van verwarring, schade, of stres in de cel, volgens een zeer gecoÃÆ' ¶rdineerd maar automatisch proces. [sherr 99] Het punt waarop deze beslissing wordt gemaakt is een checkpoint die hier restrictiepunt wordt genoemd. Intracellulaire en extracellulaire signalen kunnen de celcyclus op deze checkpoints blokkeren. Wanneer er daarna weer goede condities aanwezig zijn, zoals voldoende nutriÃÆ' «nten en groeifactoren en er geen inhibitie factoren zijn, zal een cel in quiescente staat terug de celcyclus in gaan. Er zijn meerdere checkpoints in de celcyclus aanwezig. Zo is er aan het einde van de G2 fase een checkpoint voor controle of de omgevings condities nog steeds voordelig zijn en al het DNA verdubbeld is en is er een checkpoint aan het einde van de M fase of alle chromosomen wel aan de spoel gehecht zijn voordat de cel gaat delen. Wanneer een cel gaat delen moeten beid e van de chromatide van een chromosoom namelijk eerst aan de spoelen aan weerzijden van de cel gehecht zijn. De chromosomen kunnen hierdoor gelijk gesplitst worden doordat ze uit elkaar worden getrokken richting beide polen. Dit levert twee gelijkwaardige cellen op. In dit essay zijn de laatste twee checkpoints verder niet van belang. De gehele celcyclus wordt gereguleerd door de activatie of inactivatie van verschillende cycline-afhankelijke kinasen (Cyclin-Dependent Kinases, CDKs). CDKs zijn kleine eiwit kinasen die associatie met een cycline subunit nodig hebben voor activatie [vd Heuvel 05]. Bij elke fase van de celcyclus zijn verschillende cycline/CDK complexen actief en de regulatie van de activiteit wordt geregeld via de cyclines. Tijdens elke cel cyclus ondergaan cyclines een cyclus van synthese waarna de CDKs complexen vormen met passende cyclines om vervolgens afgebroken te worden. De CDK-cycline complexen katalyseren de aanhechting van een fosfaat groep aan specifieke serine of threonine aminozuren in een doel eiwit. De fosfaat groepen veranderen eigenschappen van de doel eiwitten, zoals de interactie met andere eiwitten. CDKs worden daarom ook wel serine/threonine kinasen genoemd. De G1 wordt gereguleerd door meerdere cyclines waaronder Cycline D1, D2, D3 en E. De belangrijkste G1 CDKs zijn CDK4 en CDK6, die aan de D-type cyclines binden, en CDK2, die voornamelijk aan cycline E en cycline A bind [Sherr 04]. In figuur 2 wordt een overzicht gegeven van de cyclines en CDKs die tijdens de celcyclus een rol spelen. Omdat er in dit essay vooral wordt gekeken naar de exit van de celcyclus tijdens de G1 en S fase worden de andere cyclines en CDKs niet besproken. Ontregeling van de celcyclus speelt een grote rol in de ontwikkeling van kankercellen. Overexpressie van eiwitten die de celcyclus progressie regelen zoals CDKs en cyclines, en remming van eiwitten die de celcyclus stoppen kan leiden tot ongecontroleerde cel proliferatie. In menselijke tumoren zijn vooral de genen die coderen voor eiwitten die de overgang van G1 naar de S fase regelen veranderd. Het begrijpen van de gehele celcyclus en daarmee ook vooral het gedeelte van de celcyclus exit is daarom erg belangrijk. Organismen moeten genoeg cellen kunnen vormen door deling maar wanneer ze niet bijtijds stoppen met delen kan dit leiden tot kankercellen. Kanker onderzoek richt zich dan ook vaak op het uitschakelen van de celcyclus regulatie. Dit proces is eveneens belangrijk in de regeneratie van cellen voor onderzoek naar degeneratie ziektes, waarbij bepaalde type cellen hun functie verliezen of verloren gaan. In regeneratie onderzoek wordt er op twee manieren geprobeerd de weefsels weer functionele cellen te geven. Zo wordt er onderzoek gedaan om de cellen terug te brengen naar de staat waarin ze nog niet ge-dedifferentieerd zijn maar wel weer delen. Een tweede onderzoek is gebaseerd op cel herprogrammering waarbij de cellen volledig worden ge-dedifferentieerd. Het probleem hierbij is dat ze wel tijdig moeten stoppen met delen om geen kankervorming te krijgen. Het begrijpen ho e een cel de celcyclus uitgaat is dus voor veel onderzoeken van belang. Om de celcyclus exit verder te begrijpen staat daarom in dit essay de vraag wat zijn de regulatie mechanismen van de celcyclus exit? centraal. Deze vraag zal worden uitgelicht door gebruik te maken van eerder gepubliceerde artikelen en zal om nader uitgelegde redenen vooral bekeken worden in het modelorganisme Drosophila melanogaster. Hoofdstuk 2: de celcyclus exit bepalende componenten modelorganisme Om een duidelijk beeld van de regulatie mechanismen van de celcyclus exit te krijgen is er hier gekozen om dit te bekijken in het modelorganisme Drosophila melanogaster. Dit omdat D. melanogaster een veel voorkomend modelorganisme in de genetica is. Het genoom is bekend en veel van de genen zijn al beschreven. Het heeft een snelle reproductie tijd waardoor er snel nakomelingen geproduceerd kunnen worden en er snel over veel organismen te beschikken is. Hiernaast is D. melanogaster erg klein en heeft het weinig voedingsstoffen en geen ingewikkelde leefomstandigheden nodig om te overleven. Dit maakt D. melanogaster een handig dier om in het laboratorium mee te werken. Naast deze voordelen is dit modeldier ook gemakkelijk in in vivo systemen te gebruiken. De meest belangrijke reden waarom D. melanogaster hier gebruikt wordt als model organisme is dat het dezelfde componenten in de celcyclus exit heeft als zoogdieren maar minder varianten van deze componenten heeft waardoor het systeem g emakkelijker te bestuderen is. Aan het einde van dit hoofdstuk zal er een vergelijking met andere modelorganismen gemaakt worden. Retinoblastoma eiwit familie Een van de belangrijkste componenten in de celcyclus exit wordt gecodeerd door het retinoblastoma gen. Het retinoblastoma gen is het eerste tumor onderdrukkende gen dat is geÃÆ' ¯dentificeerd en werd gevonden in 1986. Het gen was eerder gekloneerd als resultaat van een zeldzame oog tumor bij kinderen, retinoblastoma kanker. Waarom deze oog tumor ontstaat door een gen die zich in het hele lichaam bevind is niet bekend. Het retinoblastoma gen codeert voor een aminozuur fosfoproteÃÆ' ¯ne, het Rb eiwit. Het Rb eiwit is een tumor onderdrukkend eiwit en is defect in de meeste vormen van kanker. Rb remt cellen in de G1 fase naar de S fase te gaan tot dat de cel klaar is om te delen[Harbour 00] (zie figuur 3). Buitensporige cel groei wordt hierdoor tegen gegaan. Er kan hierdoor gezegd worden dat Rb een negatieve regulatie op de cel cyclus heeft en daardoor de cel cyclus exit stimuleert. Rb heeft meerdere functionele delen die samen de centrale pocket van het eiwit vormen. Rb behoort daarom tot de pocket eiwitten. Het bestaat uit twee geconserveerde delen, een A en B domein (zie figuur 4), die verantwoordelijk zijn voor de meeste eiwit-eiwit interacties. D. melanogaster bevat twee RB familie leden, RBF en RBF2. RBF2 is echter niet een essentieel gen. Rbf2 mutant vliegen vertonen namelijk geen duidelijk fenotypen [Stevaux 05]. Hier in tegen, voldoet RBF aan alle cel cyclus gerelateerde functies van een Rb eiwit familie in Drosophila. De regulatie van RBF op een cel om te stoppen in G1 of door te gaan naar de S fase wordt gereguleerd door cycline/cdk complexen. Een van de belangrijkste taken van deze complexen is het fosforyleren en defosforyleren van RBF tijdens de celcyclus. De RBF eiwit familie bevat hiervoor meerdere fosforylatie punten die gefosforyleerd kunnen worden. Bij de G1 fase zijn het de cyclineD/cdk4 complexen en bij de G1/S fase zijn het de cyclineE/cdk2 en cyclineA/cdk2 complexen die RBF fosforyleren. De hyper-gefosforyleerde vorm, wat de inactieve vorm is, is dominant in prolifererende cellen. De hypogefosryleerde vorm, wat de actieve vorm is, komt meestal voor in quiescente cellen of differentiÃÆ' «rende cellen. [Du 06] E2F transcriptie factoren De biologische functie van RBF bestaat uit tumor onderdrukking, regulatie van de cel cyclus, differentiatie en apoptose. Deze functies van RBF worden allemaal gereguleerd in combinatie met een heleboel cellulaire eiwitten. Een van die eiwitten die interactie met RBF aangaat is E2F. In de begin dagen stond E2F bekend als DRTF1/E2F. E2F was ontdekt als een cellulaire factor nodig voor de vroege regio 1A (E1A)-transformatie eiwit van het adenovirus om de transcriptie activatie van een viraal E2A promoter te reguleren [Nevins 92]. DRTF1 was eerder geÃÆ' ¯dentificeerd als een transcriptie factor waarvan de DNA bindings activiteit verlaagd werd tijdens de differentiatie van F9 embryonale carcinoma stam cellen [la Thangue 87]. De consensus DNA bindings site voor DRTF1 en E2F waren gelijk net als andere observaties. Dit suggereerde dat DRTF1 en E2F verwant waren. Interesse in E2F nam toe doordat, door studies van cellulaire targets van virale oncoproteÃÆ' ¯nes, het ontdekt was dat E2F belangrijk was voor de functie van RBF [Nevins 92]. E2F behoort tot de E2F familie van DNA-bindende transcriptie factoren. De meeste E2F eiwitten worden geassocieerd met een dimerisatie partner (DP) eiwit en vormen een heterodimeer complex dat aan DNA bind in een sequentie specifieke manier. Beide E2Fs en dDP hebben hiervoor een DNA-bindings domein (DBD) en een dimerisatie domein (Dim) (zie figuur 5). De D. melanogaster E2F familie leden kunnen in tweeÃÆ' «n worden gesplitst. dE2F1 functioneert voornamelijk als een transcriptie activator en dE2F2 functioneert voornamelijk als een actieve onderdrukker van transcriptie. Cel cyclus exit door onderdrukking van transcriptie De cel kan door meerdere modellen van RBF-E2F in cel cyclus exit gaan. Een hiervan is het mechanismen waarbij E2F geregelde transcriptie door retinoblastoma familie leden wordt onderdrukt. Dit kan op drie manieren gebeuren. Bij de eerste manier bind RBF aan de E2F transcriptie factoren en blokkeert hiermee hun mogelijkheid tot het activeren van gentranscriptie. Cycline-cdk complexen kunnen RBF fosforyleren, zoals eerder beschreven, waardoor het E2F-DP complex vrij komt te liggen en er weer transcriptie plaats kan vinden en een cel de cel cyclus weer kan vervolgen (zie figuur 6). Bij een tweede manier blokkeert RBF het vormen van pre-initiatie complexen waardoor aangrenzende transcriptie factoren worden onderdrukt. Bij een derde manier gebruikt RBF een eiwit interactie domein die afgescheiden is van zijn E2F-bindings plaats om geassocieerd te worden met complexen die chromatine structuren veranderen [Frolov 04]. Over deze manieren zal in het volgende hoofdstuk meer volgen. Cdk remming Cdk activiteit is gereguleerd door cycline afhankelijke kinase onderdrukkers (Cyclin dependent kinase inhibitors, CKIs). De Cip/Kip familie behoort tot deze CKIs. De Cip/Kip onderdrukker in D. melanogaster is Dacapo, die homoloog is aan p21/p27 van het zoogdier. De Cip/Kip moleculen zijn in staat tot het binden van alle soorten cyclines en cdks en ze daardoor inactiveren. In figuur 7 is te zien dat Dacapo eiwit, dap, cycline-cdk complexen in vitro kan remmen. Om dit te testen zijn wild-type en mutant eiwitten vergeleken in de mogelijkheid tot inhibitie van kinase activiteit van gezuiverde eiwit complexen. Bacterieel tot expressie gekomen Dacapo kon histon H1 kinase activiteit van het humaan cyclineE-cdk2 remmen. De twee mutant eiwitten met onderbrekingen in de bindings regio van cycline konden dit niet.Ook is er in ditzelfde onderzoek aangetoond dat overexpressie van dap celcyclus progressie in vivo kan remmen en dat expressie van dap gecorreleerd is met de exit van de cel cyclus [de Nooij 96]. CKIs kunnen de cyclines en cdks apart binden maar hebben meer affiniteit voor de heterodimere complexen. Hierdoor kunnen ze een regulerende functie hebben in alle fasen van de cel cyclus. Omdat cycline-cdk complexen een remmende werking op RBF hebben en CKIs een remmende werking op cycline-cdks stimuleren CKIs RBF als het ware via een negatief-negatieve pathway (zie figuur 3). CKIs zijn daarom naast RBF remmers van de cel cyclus en daarmee stimulansen van de cel cyclus exit. APC/C Zoals eerder besproken is cdk activiteit een belangrijke factor voor de progressie van de cel cyclus. Cdk speelt hier echter maar een rol tot de metafase. Voortgang in de anafase wordt namelijk door een ander regulatie component gereguleerd. Een ubiquitine-eiwit ligase die anafase-promoting complex (APC) of cyclosoom wordt genoemd speelt hier deze rol. Het ubiquitineert verschillende regulatie eiwitten en richt deze daarbij naar het proteasoom voor afbraak. De APC/C activiteit schommelt in reactie op veranderingen in de samenkomst van het APC met de activerende subunits Cdc20 of Cdh1 [Sullivan 07] (zie figuur 8). Associatie van het APC met Cdc20 in het middelste deel van de mitose lijdt tot de initiatie van de anafase. Associatie van het APC met Cdh1 in het late deel van de mitose onderhoudt het APC activiteit door de G1 fase. Een belangrijk doelwit van het APC is securine. Securine is normaal gehecht aan separase wat het inactief maakt. Wanneer securine wordt afgebroken komt separas e vrij en initieert het chromosoom splitsing. Het APC ubiquitineert ook mitotische cycline. De afbraak van deze cyclines inactiveert de cdks en staat fosfatases toe om de cdk substraten in de cel te defosforyleren. Defosforylatie van cdk substraten is nodig voor normale chromosoom en spoel beweging in de anafase zoals in eerder beschreven. Het is ook belangrijk voor de gebeurtenissen die hierop volgen in de telofase waarin de spoel uiteen valt, de kern opnieuw wordt gevormd en het chromatine wordt gedecondenseert [Sullivan 07]. De laatste delen van de mitose worden dus gereguleerd door defosforylatie van cdk substraten en ubiquitinatie van APC substraten. APC/C heeft hiernaast ook een rol in de cel cyclus blokkades die lijden tot quiescence. Ook Skp-Cullin-F-box (SCF) ubiquitine ligase complexen spelen hier een rol in [Buttita 07]. Naast de eerder genoemde degradaties van substraten in de mitose heeft APC/C ook een degraderende rol voor Skp2. De degradatie van de degradatie machine is gekoppeld aan de cel cyclus exit pathway. Hypogefosforyleert RBF kan namelijk worden geassocieerd met het APC/C, voornamelijk wanneer het geactiveerd wordt door Cdh1 [Binne 07]. Dit stimuleert degradatie van Skp2, een component van het SCFskp2 complex die verantwoordelijk is voor degradatie van p27 en p21. De RBF/APC/C interactie resulteert dus in de tot stand houding van p27 en p21. RBF kan hierdoor in een tweede, E2F onafhankelijke manier, de cel cyclus tegen houden (zie figuur 3) [Buttita 07]. Wanneer een gemuteerd RBF wordt genomen, die niet aan Cdh1 kan binden, kan gedemonstreerd worden dat de RBF/APC/C interactie nodig is voor RBF om de cel cyclus in prolifererende cellen tegen te houden [Binne 07]. Uit verschillende APC/C en SCF mutant studies in vivo is echter gebleken dat de cel cyclus maar tijdelijk wordt vertraagd. Dit wijst erop dat de eiwit degradatie machine en rol speelt in de cel cyclus exit maar dat er meerdere mechanismen nodig zijn om uiteindelijk een cel cyclus exit te krijgen [Buttita 07]. Prospero Het laatste component die een rol speelt in de cel cyclus exit is prospero (Pros) (zie figuur 3). Pros is een homeobox transcriptie factor die naast cel cyclus exit ook terminale differentiatie coÃÆ' ¶rdineert. In neuroblasten is Pros asymmetrisch gelokaliseerd op het cytoplasmisch membraan. Tijdens het delen van de cel wordt Pros geÃÆ' «rfd door ÃÆ' ©ÃƒÆ' ©n dochter cel, de ganglion moeder cel (GMC). Hier zal Pros de nucleus ingaan en terminale differentiatie aansporen. In meerdere studies van Pros in het Drosophila embryo werd er aangetoond dat Pros de transcriptie van cycline E en String tegenhield [Li 00]. Het bleef echter onduidelijk of dit een indirect effect van Pros was op differentiatie of een meer direct effect op deze cel cyclus genen [Buttita 07]. Uit later onderzoek waarin de genoom-wijde binding van Pros op chromatine werd onderzocht bleek dat Pros een directe rol had in het transcriptioneel tegen houden van meerdere sleutel cel cyclus genen waaronder, naast cycline E en string, ook e2f1. Pros heeft hiernaast ook een directe rol in het activeren van een aantal terminale differentiatie genen in neuronen wat het een dubbel functioneel signaal maakt [Choksi 06]. Pros expressie wordt in bepaalde type cellen erg onderdrukt. Hierdoor is het niet waarschijnlijk dat Pros een universele rol in de cel cyclus exit speelt. Uit onderzoek in de darmen van Drosophila is een stam cel differentiatie pathway gevonden waarin eenzelfde asymmetrisch delings patroon is gevonden gevolgd door differentiatie zonder tussen komst van mitose. Pros komt precies tot uiting in een van de resulterende postmitotische cel types waar het waarschijnlijk de terminale differentiatie van de celcyclus exit coÃÆ' ¶rdineert. Andere Homeobox eiwitten zouden eenzelfde rol kunnen spelen in andere cel types. Er blijft daarom nog veel onderzoek naar dubbel-functionele transcriptie factoren [Buttita 07]. Celcyclus regulatie van C. elegans en zoogdieren Twee andere model organismen waarin er veel onderzoek is gedaan naar de celcyclus exit zijn Caenorhabditis elegans en zoogdieren. Het voornaamste verschil tussen deze model organismen is het verschil in Rb en E2F-familie leden (zie tabel 1). Het zoogdier heeft namelijk acht E2F familie leden (E2f1-E2F8) en drie Rb familie leden (pRb, p107 en p130) waar D. melanogaster er van beide families maar twee heeft en C. elegans er drie E2F familie leden (Efl-1, Efl-2 en F49E12.6) en slechts ÃÆ' ©ÃƒÆ' ©n Rb familie lid (Lin-35) heeft. In het zoogdier is de verdeling van de E2F familie leden hetzelfde als in D. melanogaste (zie figuur 9). De E2F familie is opgedeeld in activatoren (E2F1-E2F3a) en onderdrukkers (E2F3b-E2F8). E2F1-E2F6 bevatten net als dE2F-1 en dE2F-2 van D. melanogaster dimerisatie domeinen en vormen DNA-bindings heterodimeren met eiwitten van de differentiatie-regulatie transcriptie factor-1 polypeptide (DP) familie. E2F6 vormt complexen met polycomb-groep (PcG) eiwitten. E2F7 en E2F8 hebben deze DP-bindings domeinen niet maar bevatten tandem repeats van een E2F DNA-bindings domein. E2F1-E2F5 bevatten C-terminale domeinden waarmee ze interactie aangaan met de pocket domeinen van de Rb familie leden. De drie familie leden associÃÆ' «ren met verschillende E2F eiwitten. Zo heeft pRB de voorkeur voor E2F1-E2F3a en E2F3b-E2F5 en hebben p107 en p130 de voorkeur voor associatie met E2F3b-E2F5. De pRB familie leden van zoogdieren worden net als die van D. melanogaster gereguleerd door fosforylatie van cycline-cdk complexen. [vd Heuvel 08] Het C. elegans eiwit product van het Rb gen gerelateerde gen cell lineage-abnormal-35 (lin-35) vertoont de meeste homologie met p107 en p130. Het C. elegans gen bevat ÃÆ' ©ÃƒÆ' ©n DP-achtig gen, dpl-1. Van de drie potentiÃÆ' «le homologen aan de zoogdier E2F transcriptie factoren (E2F-like-1 (efl-1), efl-2 en F49E12.6) is efl-1 het enige E2F gerelateerde gen met een duidelijk loss-of-function fenotype. De fenotypes van efl-1, dpl-1 en lin-35 mutanten hebben veel overeenkomsten en hun producten functioneren waarschijnlijk in een co-onderdrukkings complex. [vd Heuvel 08] Naast de verschillen in Rb en E2F familie leden zijn er ook verschillen in cycline afhankelijke kinase remmers, CKIs (zie tabel 1). Zoogdieren hebben net als D. melanogaster Cip/Kip type CKIs. Ze hebben drie verschillende eiwitten van deze familie, p21Cip1, p27Kip1 en p57Kip2. Naast de Cip/Kip type CKIs hebben zoogdieren ook nog Ink4 type CKIs. Deze Ink4 type CKIs familie bevat vier leden, p15, p16, p18 en p19, vernoemd naar hun moleculaire omvang. Ink4 remmers binden, in tegen stelling tot Cip/Kip type CKIs die aan alle cdks en cyclines binden, alleen aan cdk4 en cdk6 waardoor ze associatie met D cyclines voorkomen [Pajalunga 07]. C. elegans heeft twee CKI familie leden, CKI-1 en CKI-2. Beide eiwitten lijken erg op de Cip/Kip types p21 en p27 in de aminozuur sequentie maar alleen CKI-1 functioneert op dezelfde wijze in de celcyclus.[vd Heuvel 05] In deze vergelijkingen is te zien dat D. melanogaster meer op het zoogdier lijkt op het niveau van regulatie van de celcyclus dan C. elegans. Ook is op te merken dat het zoogdier door zijn vele leden van de Rb, E2F transcriptie factor en CKI families veel complexer is dan D. melanogaster wat deze vlieg tot een geschikt model organisme maakt in onderzoek naar de celcyclus exit. Hoofdstuk 3: regulatie van de celcyclus exit componenten Welke componenten de cel cyclus exit bepalen is grotendeels bekend (weergegeven in figuur 3). Waar nog een heleboel vraagtekens liggen is hoe deze componenten op hun beurt weer worden gereguleerd. In dit hoofdstuk zal zover er tot nu toe bekend is hier een antwoord op worden gegeven. Er zal worden gekeken welke signalen er aangrijpen op de celcyclus remmende componenten RBF en CKI. Hiernaast zal er verder ingegaan worden op dE2F target genen en de regulatie hiervan. Retinoblastoma regulatie Zoals eerder beschreven wordt de activatie en inactivatie van RBF gereguleerd door fosforylatie. Het fosforyleren van RBF door CDKs wordt geÃÆ' ¯nhibeerd door CKIs wat zorgt voor celcyclus exit. Dit lijdt tot gehypofosforyleerde RBF die een complex vormen met dE2F en zo celcyclus gen expressie blokkeert. Een volgende vraag is dan hoe gehypofosforyleerde RBF ontstaan wanneer CKIs afwezig zijn of wanneer cycline-cdk activiteit niet daalt. Om dit uit te zoeken wordt er onderzoek gedaan naar fosfatases die werken op RBF. Uit eerder onderzoek werd Protein Phosphatase 1 (PP1) als een potentiÃÆ' «le fosfatase geÃÆ' ¯dentificeerd. Een RBF-specifieke fosfatase, gevoelig voor concentraties van fosfatase remmer, is namelijk gevonden in mitotische extracten van cellen [Nelson 97]. Hiernaast is ook een PP1 katalytisch subunit geÃÆ' ¯soleerd door zijn mogelijkheid om interactie aan te gaan met pRb, homoloog van RBF (zie figuur 10) [Vietri 06]. Uit latere studies in D. melanogaster bleek echter dat PP1 niet nodig is voor de regulatie van RBF [Swanhart 07]. Hoe RBF fosforylatie gereguleerd zou kunnen worden door differentiatie signalen is ook nog niet duidelijk [Buttita 07]. Deze connectie zal in de toekomst verder onderzocht moeten worden. Chromatine remodellering Naast de fosforylatie van RBF voor het reguleren van de celcyclus exit speelt RBF zelf een rol in chromatine remodellering wat een rol speelt bij dE2F afhankelijke gen repressie. De basis van chromatine is een nucleosoom die bestaat uit DNA gewikkeld om een histon octameer. Elke histon bevat een bolvormige regio, een histon-vouw domein en een minder gestructureerde N-terminale staart die naar buiten steekt. Deze staarten zijn het doelwit van meerdere post-translationele modificaties zoals acetylatie, ubiquitylatie, fosforylatie, methylatie en meer. Deze veranderingen spelen een rol in regulatie van gen expressie. Histonen zijn in het algemeen gehyperacetyleerd bij de promoter van actief afgeschreven genen en gehypoacetyleerd bij momenteel inactieve genen. Veel transcriptie regulators gebruiken histon acetyltransferase (HAT) en histon deacetylase (HDAC) activiteiten (zie figuur 11). Acetylatie van histon staarten maakt de DNA histon contacten losser waardoor chromatine minder compact wordt. Hierdoor kan een SWI/SNF ATP afhankelijke chromatine remodellerings complex binden en transcriptie gestimuleerd worden. Bij gedeacetyleerde chromatine is het DNA histon contact strakker en is het minder toegankelijk voor transcriptie factoren en daarmee transcriptie. Methylatie van de histonen door histon methyltransferase (HMT) complexen in combinatie met deacetylatie zorgt voor structuren waar geen transcriptie plaats vind zoals in heterochromatine. Dit zou op een mechanisme waarbij E2F afhankelijke celcyclus genen onderdrukt kunnen worden door de Rb familie in celcyclus exit kunnen duiden. Het is echter nog niet duidelijk welke associaties er functioneel relevant zijn voor onderdrukking van celcyclus genen in terminale differentiatie [Buttita 07]. dE2F kan door RBF geremd worden door gebruik van chromatine remodellerings enzymen zoals HDAC en HAT (zie figuur 12). HDAC geassocieerd met RBF-dE2F stimuleert nucleosoom vorming aan de promoter. Hierdoor wordt de toegang van het transcriptie mechanisme geblokkeerd. dE2F activiteit kan ook worden geremd door deacetylatie van het eiwit waardoor het niet meer aan het DNA kan binden. HAT activiteit geassocieerd met dE2F kan binding van dE2F aan de promoter stimuleren en het kan nucleosoom formatie juist remmen waardoor er wel transcriptie van het E2F target gen plaats zou kunnen vinden. [Harbour 00] E2F target genen E2F target genen werden als eerste gevonden bij onderzoek naar promoters van genen die bekend stonden om aangeschakeld te worden bij de G1/S fase overgang voor E2F bindingsplaatsen. Deze studies identificeerde E2F target genen die of celcyclus regulatoren (zoals cyclines E, A en B) of DNA replicatie factoren (zoals PCNA, dihydrofolate reductase (DHFR) en thymidine kinase) waren [Du 06]. Later zijn er meerdere evolutionair behouden complexen betrokken in de regulatie van E2F target genen gevonden. Deze complexen worden dREAM (Drosophila RBF, E2F en Myb-interacterende eiwitten) of Myb/MuvB genoemd en bevatten Rb/E2F complexen, Myb en Myb interacterende eiwitten. dREAM-Myb/MuvB is betrokken in transcriptionele onderdrukking maar bevat geen chromatine modificerende enzymen. Uit onderzoek [Korenjak 04] is gebleken dat het dREAM complex alleen bindt aan gedeacetyleerde histon H4 staarten en niet aan geacetyleerd histon H4 staarten (zie figuur 13). Dit duidt waarschijnlijk op een mechanisme waarbij dREAM acetylatie van target gen promoters voorkomt en ze in een onderdrukte staat houdt. Uit het onderzoek van Korenjak kwamen ook resultaten dat het dREAM complex nodig is om de genen arp53D, CG17142 enCG3505 (groep E genen) in S2 cellen stil te leggen. Deze genen zijn permanent onderdrukt in S2 cellen en geven een seks- of weefsel-specifiek expressie patroon. Hiernaast werd er in dit onderzoek aangetoond dat de dREAM subunits dE2F2 en Mip130/TWIT, in vivo, fysiek geassocieerd kunnen worden met deze groep E genen. Dit wijst erop dat dREAM complexen assembleren bij de genen arp53D, CG17142 enCG3505 en effect hebben op hun permanente onderdrukking in prolifererende cellen. Dit onderdrukkende effect blijkt echter specifiek te zijn voor genen die betrokken zijn in ontwikkelings- of seks-specifieke expressie patronen. Mogelijk is er een nog ander dE2F-RBF complex nodig voor de onderdrukking van celcyclus genen of onderdrukt het dREAM-Myb/MuvB complex de celcyclus controle targets onder andere condities. [Blais 07]. Regulatie van CKI In D. melanogaster embryos wordt de celcyclus exit gekarakteriseerd door een abrupte downregulatie van Cycline E en een korte piek van Dacapo expressie. In dap mutant embryos falen de meeste cellen in de epidermis en het perifere zenuwstelsel om op het juiste moment uit de mitotische cyclus te gaan en ondergaan een extra mitotische deling. Tijdens deze extra cyclus gaan de mutant cellen wel in mitotische rust wat erop wijst dat er meerdere mechanismen betrokken zijn in de exit van de mitotische cyclus. Waarschijnlijk functioneert downregulatie van de positieve cel cyclus regulator Cycline E in combinatie met de activatie van dap expressie voor celcyclus exit [de Nooij 00]. In figuur 14 is te zien dat in Cycline E mutant embryos een verlaging van Dacapo is. Cycline E is dus nodig voor Dacapo expressie. Uit eerdere onderzoeken was echter gebleken dat dap expressie geÃÆ' ¯nitieerd werd wanneer Cycline E niveaus daalde. Er waren ook resultaten dat er juist erg hoge Cycline E niveaus waren maar dat Dacapo niet geÃÆ' ¯nduceerd werd. Deze resultaten hebben tot het regulatie model in figuur 15 geleidt. Voordat de cel naar de celcyclus exit gaat en er precursor cellen worden ontwikkeld voorkomen ontwikkelings signalen de expressie van Dacapo ondanks de aanwezigheid van Cycline E. De remming van Dap expressie komt mogelijk door het gebrek aan essentiÃÆ' «le transcriptie activatoren of door de activiteit van transcriptie onderdrukkers. Vlak voordat de cellen klaar zijn met delen en differentiÃÆ' «ren worden ontwikkelingsremmers vrijgelaten en is Cycline E in staat tot het induceren van dap expressie. Dap translatie wordt gepromoot waardoor een snelle accumulatie van Dap ontstaat. Een hoge Cycline E activiteit promoot hiernaast de degradatie van Dap. Dit zorgt ervoor dat het Dap n iveau snel mee daalt wanneer het Cycline E niveau weer zal gaan dalen volgens het golvende model. Dap expressie zal na het volledig dalen ven het Cycline E niveau niet meer geÃÆ' ¯nduceerd worden. Uit de data van het onderzoek van de Nooij et al. blijkt dat Cycline E dap reguleert op transcriptioneel en post-transcriptioneel niveau. Ook blijkt uit de gegevens dat dap ook door andere signalen dan Cycline E wordt gereguleerd. Differentiatie signalen kunnen CKIs ook transcriptioneel reguleren zodat ze cellen aanzetten om in celcyclus exit te gaan. De Cip/Kip type CKIs worden onder andere gereguleerd door basic Helix Loop Helix (bHLH) transcriptie factoren. Hiernaast zetten groei-inhibitie signalen Kip type CKI aan tot accumulatie of activatie. Deze groei-remmende cytokines zoals morfogenen van de TGF-ÃŽÂ ² superfamilie en interferonen, en cel-cel contact induceren de synthese van de Cip/Kip CKIs [Mittnacht 98]. Ook condities van cellulaire stress zoals DNA schade of replicatie remming kunnen CKI synthese stimuleren. Er zijn dus meerdere factoren die de componenten van de celcyclus exit reguleren en veel hierover moet nog verder onderzocht worden. Hoofdstuk 4: conclusie In de laatste twintig jaar is er veel ontdekt over het mechanisme achter de celcyclus exit. Dit begon allemaal met de ontdekking van het eerste tumoronderdrukkende gen Rb. Ook E2F speelt een centrale rol in het coÃÆ' ¶rdineren van celcyclus progressie bij de G1 naar S fase of G0 overgang. De regulatie van specifieke target genen door Rb/E2F hangt echter niet alleen af van de aanwezigheid van specifieke Rb en E2F familie leden. Hun post-translationele modificaties en andere inter-acterende factoren spelen ook een belangrijke rol. Cyclines, cycline afhankelijke kinases en CDK inhibitoren spelen eveneens een belangrijke rol bij de celcyclus regulatie. Ondanks dat er al veel bekend is, blijven er ook een heleboel vraagtekens over de fysiologische rollen van Rb en E2F en het specifieke actie mechanisme dat deze rollen weer aanstuurt. Modelorganismen helpen bij het onderzoeken, van deze rollen en van gen functies, in verschillende fysiologische contexten. Vragen die overblijven en meer onderzoek nodig hebben zijn bijvoorbeeld: Hoe is de RB-familie en CKI activiteit gecoÃÆ' ¶rdineerd in het proces van terminale differentiatie? Zijn RBs en CKIs de enige cel cyclus remmers? En hoe grijpen de signalen aan op deze en mogelijk andere cel cyclus remmers? Een vraag die naar een ander pad van de celcyclus exit leidt is hoe de celcyclus exit behouden blijft in gedifferentieerde weefsel en niet weer gaat delen? Alleen quiescente cellen kunnen van nature de celcyclus exit verlaten en weer aan de celcyclus mee doen. Ze doen dit in de aanwezigheid van proliferatie-inducerende condities. Quiescente cellen kunnen in afwezigheid van groeifactoren geÃÆ' ¯nduceerd worden tot proliferatie door het weghalen van CKIs [Pajalunga 08]. Groeifactoren zijn dus waarschijnlijk voornamelijk nodig om de balans van positieve tegen negatieve celcyclus regulatoren te veranderen. Terminale differentiatie en senescente cellen kunnen niet van nature terug de celcyclus in gaan. Ze kunnen hier echter wel toe gestimuleerd worden. Verschillende soorten terminale differentiatie cellen kunnen door expressie van DNA-tumor-virus oncogenen, zoals SV40 LT of adenovirus E1A, gedwongen worden de celcyclus weer in te gaan [Pajalunga 08]. De verschillende groeiremmende mech anismen en moleculen hierachter zijn nog niet helemaal bekend en begrepen en er zal hier dus ook meer onderzoek naar gedaan moeten worden. Terminale differentiatie cellen kunnen ook door reactivatie van cdk4/6 kinase door overexpressie van cdk4/6 en cycline D1 weer terug de celcyclus ingaan. Ze kunnen hierbij weer skelet spier myotubes, adipocyten, enkele neuronen en cardiomyocyten vormen. Dit laat zien dat de voornaamste reden waarom terminale differentiatie cellen nooit spontaan de cel cyclus weer ingaan de negatieve controle van de cdk4/6 kinase is [Pajalunga 08]. Ook senescente cellen kunnen van nature niet terug de celcyclus in gaan. Ze kunnen wel weer geactiveerd worden en prolifereren door het weghalen van de CKIs p21 of p16 [Pajalunga 08]. In senescente cellen komt een hoog niveau van CKI complexen voor. De senescente cellen worden dus net als terminale differentiatie cellen in de celcyclus exit gehouden door hoge niveaus van remmers. De wetenschap dat de celcyclus weer geactiveerd kan worden door het weg halen van CKIs kan een belangrijke rol spelen voor omstandigheden waar de proliferatie zwak is zoals bij weefsel repair, cel vervangingstherapie, en regeneratie. De ontdekkingen in celcyclus regulatie helpen bij het beter begrijpen van kwaadaardige cel transformatie en bij de ontwikkeling van nieuwe therapieÃÆ' «n tegen kanker. Het is verder moeilijk om te beantwoorden welke componenten in het mechanisme van de celcyclus er nog missen. Een compleet antwoord op de vraag wat de regulatie mechanismen van de celcyclus exit zijn is er dus nog niet. Hopelijk leidt meer onderzoek uiteindelijk tot het volledig begrijpen van dit mechanisme. Referenties: Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, P. Molecular biology of the cell. Vierde editie. New York: Garland Science, Taylor and Francis group, 2002.p. 985. Fig 17-3. Bardin, A. J. Amon, A.Men and sin: whats the difference?Nat. Rev. Mol. Cell Biol.2, 815-826 (2001) Binne, U. K.et al. Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit.Nat. Cell Biol.9, 225-232 (2007). Blais, A. Dynlacht, B. D.E2F-associated chromatin modifiers and cell cycle control.Curr. Opin. Cell Biol.19, 658-662 (2007). Buttitta, L. A. Edgar, B. A.Mechanisms controlling cell cycle exit upon terminal differentiation.Curr. Opin. Cell Biol.19, 697-704 (2007). Choksi, S. P.et al. Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells.Dev. Cell.11, 775-789 (2006). de Nooij, J. C., Graber, K. H. Hariharan, I. K.Expression of the cyclin-dependent kinase inhibitor Dacapo is regulated by cyclin E.Mech. Dev.97, 73-83 (2000). de Nooij, J. C., Letendre, M. A. Hariharan, I. K.A Cyclin-Dependent Kinase Inhibitor, Dacapo, Is Necessary for Timely Exit from the Cell Cycle during Drosophila Embryogenesis.Cell87, 1237-1247 (1996). Du, W. Pogoriler, J.Retinoblastoma family genes.Oncogene25, 5190-5200 (2006). Frolov, M. V. Dyson, N. J.Molecular mechanisms of E2F-dependent activation and pRB-mediated repression.J. Cell. Sci.117, 2173-2181 (2004). Harbour, J. W. Dean, D. C.The Rb/E2F pathway: expanding roles and emerging paradigms.Genes Dev.14, 2393-2409 (2000). Korenjak, M.et al. Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes.Cell119, 181-193 (2004). La Thangue, N. B. Rigby, P. W.An adenovirus E1A-like transcription factor is regulated during the differentiation of murine embryonal carcinoma stem cells.Cell49, 507-513 (1987). Li, L. Vaessin, H.Pan-neural Prospero terminates cell proliferation during Drosophila neurogenesis.Genes Dev.14, 147-151 (2000). Mittnacht, S.Control of pRB phosphorylation.Curr. Opin. Genet. Dev.8, 21-27 (1998). Nelson, D. A., Krucher, N. A. Ludlow, J. W.High molecular weight protein phosphatase type 1 dephosphorylates the retinoblastoma protein.J. Biol. Chem.272, 4528-4535 (1997). Nevins, J. R.E2F: a link between the Rb tumor suppressor protein and viral oncoproteins.Science258, 424-429 (1992). Pajalunga, D., Mazzola, A., Franchitto, A., Puggioni, E. Crescenzi, M.The logic and regulation of cell cycle exit and reentry.Cell Mol. Life Sci.65, 8-15 (2008). Sherr, C. J. Roberts, J. M.Living with or without cyclins and cyclin-dependent kinases.Genes Dev.18, 2699-2711 (2004). Sherr, C. J. Roberts, J. M.CDK inhibitors: positive and negative regulators of G1-phase progression.Genes Dev.13, 1501-1512 (1999). Stevaux, O.et al. Retinoblastoma family 2 is required in vivo for the tissue-specific repression of dE2F2 target genes.Cell. Cycle4, 1272-1280 (2005). Sullivan, M. Morgan, D. O.Finishing mitosis, one step at a time.Nature Reviews Molecular Cell Biology8, 894-903 (2007). Swanhart, L. M., Sanders, A. N. Duronio, R. J.Normal regulation of Rbf1/E2f1 target genes in Drosophila type 1 protein phosphatase mutants.Developmental Dynamics236, 2567-2577 (2007). Trimarchi, J. M. Lees, J. A.Sibling rivalry in the E2F family.Nat. Rev. Mol. Cell Biol.3, 11-20 (2002). van den Heuvel, S.Cell-cycle regulation.WormBook, 1-16 (2005). van den Heuvel, S. Dyson, N. J.Conserved functions of the pRB and E2F families.Nat. Rev. Mol. Cell Biol.9, 713-724 (2008). Vietri, M., Bianchi, M., Ludlow, J. W., Mittnacht, S. Villa-Moruzzi, E.Direct interaction between the catalytic subunit of Protein Phosphatase 1 and pRb.Cancer. Cell. Int.6, 3 (2006).

The Inexplicable Mystery Into Comparing and Contrasting Essay Samples

The Inexplicable Mystery Into Comparing and Contrasting Essay Samples There are similarities no matter location, like the company chosen to observe the movie, and the movie itself. It is probable that you could pick out more dissimilarities than similarities. You should have your reasons, and our principal concern is that you wind up getting a great grade. For instance, if you need to write about two different historical figures, it makes sense to select two great artists as opposed to an artist and a politician. The Basics of Comparing and Contrasting Essay Samples Express that will the people contrast in a variety of approach. It started in North America and was produced by the Native Americans. In addition, in the summertime, vacation destinations are often overcrowded and costly, while those very same places may be much easier to enjoy during the winter. Artworks of Yolanda and Barbara for the very first site appear to be this distinct. Characteristics of Comparing a nd Contrasting Essay Samples A decent compare-and-contrast essay goes beyond a very simple listing of similarities and differences to earn a meaningful statement about a bigger topic. Kafka strengthens the notion of the gap between that which we are and what we wish to be, which is quite often hard to escape. When you have the title and aspects to compare but without a definite number of criteria to cover similarities and differences, you've got to brainstorm. When you begin brainstorming and researching the subject, the odds are high you'll locate a wide collection of differences and similarities. Besides family, there are different elements that help determine the evolution of mental illness in these short stories. The context will be different depending on the character of the essay. Some essays may just speak about similarities, though others might just speak about differences. Students learn how to analyze info about two subjects. In the span of obtaining an education, they have to deal with different tasks and overcome various challenges of different complexity. Conclusions ought to be short just enjoy the introduction as it comprises the gist of the essay. You might also understand the evaluation essay templates. Evaluation The next step is a very simple analysis of everything that you've written down. Your capability to make a great paper is dependent on structuring an ideal outline. This focus is dependent upon the length and range of the essay. There are good methods to begin a compare and contrast essay in this informative article. There are additionally some lessons that you will need to always keep in mind before you get started writing your essay. Keep in mind, ensure you do your research, and go at your own pace writing. It might not be a slice of cake, but if you like writing, it is going to grow in you to write more. The most frequently encountered paper writing service that the majority of our clients require is essay writing. When writing any form of academic paper, an individual needs to be able to get familiar with the basics of writing. Every student was assigned a compare and contrast essay at least one time in a lifetime. To start with, in the same way as any other bit of academic writing, a comparative essay ought to have an objective. Finding the Best Comparing and Contrasting Essay Samples After the essay demands a large number of approaches to explore, it's important to understand how to organize it correctly in an effort to guarantee easy reading. On this phase of the writing process you must have a good idea of the objective of this essay. If you are thinking about how to begin a compare and contrast essay or merely wish to know how to write one well, first you have to comprehend its goal. Write your conclusion depending on the general flow of the essay. There's, obviously, a limit on the variety of pages even our finest writers can produce with a pressing deadline, but usually, we can satisfy all the clients seeking urgent assistance. To begin with, you can include as many paragraphs as possible based on the ideas which you have. The very first draft isn't always the perfect. With the samples that we've got within this post, it is going to be faster for you to recognize the points of discussion that you should provide.

Anxiety Disorder And Anxiety Disorders - 2598 Words

For a huge amount of people, anxiety is a normal response to everyday stress. It’s a normal emotion that everyone goes through at a certain points in their lives. Many people feel anxious or nervous when facing problems at work, school, etc. Anxiety disorders however, are super different. They can cause such distress that interferes with a person’s ability to live a normal life. Anxiety disorders are the most common psychological disorders in the United States. About 27.6 million people in the U.S. are suffering from different types of anxiety disorder. There are four different types of anxiety disorders: phobia, generalized anxiety disorder, panic disorder and obsessive-compulsive disorder also know an OCD. Extreme levels of worry and tension are a way of living for people who suffer with anxiety disorder. Anxiety is an uncomfortable feeling of fearful thoughts about what might happen in the near future. It can be a serious mental illness for people that suffer this disorder. What is an anxiety disorder? If you were to ask people around your classroom or work area for example, if they felt anxious from time to time, they would most likely say they do. But for people who struggle with a server state of anxiety, basically an anxiety that occurs more than often. The definition of anxiety can mean something way different to them. These individuals anxiety is nothing compared to the anxiety you get over a big exam or a small concern. We all know what anxiety feels like before aShow MoreRelatedAnxiety Disorder And Anxiety Disorders1224 Words   |  5 PagesAnxiety is defined as a persistent fear that occurs in the absence of a threat. Anxiety and fear are typical human reactions that can be exaggerated. When an individual’s anxiety interferes with their everyday life, it is then refe rred to as an anxiety disorder. There are five classes of anxiety disorder, which include: generalized anxiety disorder, phobic anxiety disorder, panic disorders, obsessive-compulsive disorders, and posttraumatic stress disorder. There is not a specific cause to anxietyRead MoreThe Anxiety Disorder ( Anxiety )1126 Words   |  5 Pages A Psychology disorder known as anxiety disorder, is the most common in the United States. In a result of, 18% of 40 million people suffers from anxiety. However, there are six different types of anxiety disorders in the results of stress, depression, social interaction, obsessive compulsive, and phobia. Which characteristic functions as a natural part of life, that can be treated thought several methods. Anxiety is a feeling of numerous of things, whether its danger or a sense of threat andRead MoreAnxiety Disorder And Anxiety Disorders1868 Words   |  8 Pagesof both physical and mental development. Mood disorders are often overlooked during this time for the brain becoming more developed; however among children, anxiety disorders seem to be the most common disorders to be experienced (Nelson; Israel, pg 112). Barlow (2002) defines anxiety as a future-oriented emotion that is characterized by the inability to be in control and predict future events that can be potentially dangerous to the individual. Anxiety shares commonalities with fear, but the differenceRead MoreAnxiety Disorder And Anxiety Disorders1075 Words   |  5 Pagesdefinition for anxiety from a text book stand point. Someone that has or has experienced anxiety would describe it differently. An anxiety problem can be developed through genetics, past life events, and personality. Anxiety can be broken down into six different branches: generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, phobia, post-traumatic stress disorder, and social anxiety disorder. People with generalized anxiety disorder (GAD) often have increased anxiety over somethingRead MoreThe Anxiety Disorders : Social Anxiety Disorder2032 Words   |  9 PagesClient Goal There are many adolescences that suffer from anxiety that interferes with them performing in the school setting, and often affects their behavior and grades. One of these anxiety disorders is social anxiety disorder, which is â€Å"characterized by significant discomfort and avoidance of social or performance situations† (Ryan Warner, 2012, p. 105). Studies have found that â€Å"recent estimates indicate that 6% of children and 12.1% of adolescents meet criteria for this diagnosis† (Ryan Read MoreAnxiety Disorder3897 Words   |  16 Pageson Anxiety Disorder Jeffrey S. Fletcher, M.A. Kathleen B. Stinger Psychopathology and Counseling, Coun 656 4, May 2014 Author Note Jeffrey S. Fletcher, Student, Liberty University. Correspondence concerning this paper should be addressed to Jeffrey S. 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Among that population, Social Pho bia or Social Anxiety Disorder (SAD) is the second most common disorder, affecting 6.8% adults (ADAA, 2015). The onset of SAD generally happens around ages 13 up to 18, when people are more susceptible to the disorder. According to the American Psychological Association (2012), a Phobia is an anxiety disorder involving a persistent fear of an object, place orRead MoreThe And Social Anxiety Disorder1087 Words   |  5 PagesRunning head: DERMATILLOMANA AND SOCIAL ANXIETY DISORER 1 Dermatillomana and Social Anxiety disorder Brittany J Duncan Antelope Valley College Instructor Richard Manley Abnormal Psychology 234 DERMATILLOMANA AND SOCIAL ANXIETY DISORER 2 Impulsive control disorders consist of many different mental illnesses but one caught my attention which was skin picking also known as Dermatillomana. Dermatillomana is an impulsive disorder where one might find him or herselfRead MoreSeparation Anxiety Disorders1401 Words   |  6 PagesThere are several treatment options for separation anxiety disorder in children. The golden standard treatment of separation anxiety and other anxiety disorders is cognitive behavioral therapy, also known as CBT (Ehrenreich, Santucci, Weiner, 2008). There are a couple of goals for this approach that involve both the child and parent (James, James, Cowdrey, Soler, Choke, 2015). These researchers state that one of the goals is for the child to be able to recognize their own anxious feelings and

Antigone And Ismene Analysis - 925 Words

Antigone, a play by Sophocles, contain the events that occur after the death of Oedipus. Oedipus’ death marked the ending of the preceding book, Oedipus at Colonus. Antigone, as reflected in the title, focuses on the life of Antigone, one of Oedipus’ daughters. Within the play, Antigone is faced with a major disagreement with her sister regarding the proper burial of their brother, Polyneices. Antigone and Ismene are characters that hold contrasting ideals and opinions in reference to the law of the gods v. the law of the state, family, loyalty, and the role of women in society; however, these characters come from the same background, so there are certain things that shape their reputation in the same ways. There was a clear divide†¦show more content†¦In the text, she speaks about how their family has been through a lot of reputational damage already and claims that doing this would only further harm their reputations. On page 193, Ismene says, â€Å"Sister, please, please! Remember how our father died hated, in disgrace†¦ and now, we two are left.† Lastly, the sisters have very different views on the role of women in society and the boundaries placed on women in society. In the time the play is set in, there is a clear patriarchy set in place. Burials are to be done by men; therefore, Antigone’s plan to give her brother a proper burial herself is an outrageous act that has a serious legal consequence. Though her plan went against the accepted social paradigm of the time, she stayed true to her promise and went ahead with the burial. In the beginning of the play, when Antigone asks Ismene to accompany her in paying homage to their brother, Ismene uses their role in society as a reason not to do so. â€Å"Remind ourselves that we are women and as such are not made to fight with men.† (Roche 193.) In many ways, Antigone was assuming the role of a man in society, rather than a woman for women had little independenc e in their community. Antigone and Ismene are represented with totally different personalities. Antigone is a headstrong, relentless, independent woman who would do anything for her family. This is made evident in both her success in giving her brother a proper burial and in her loyalty to her father in Oedipus atShow MoreRelatedAntigone, The Daughter Of Oedipus And Clytemnestra839 Words   |  4 PagesIn this Greacan tragedy, Antigone, the daughter of Oedipus and Clytemnestra seeks to bury her brother Polyneices much against the wishes and orders of her uncle and the king, Creon. Her parents and her brothers are both dead and she wishes to leave behind her beautiful sister Ismene and join her family in the underworld. Polyneices, her brother died fighting for the throne against his brother Eteocles. Polyneices fought against Eteocles for the throne and died fighting. He was from Thebes and inRead MoreGender Roles In Antigone1547 Words   |  7 PagesIn Sophocles’ Antigone, gender roles are a maj or conflicting theme throughout the entire play. The setting of the play was written during the Greek mythological days, around 442 B.C. During these days, men were dominant and held all of the power, so women were automatically treated as less. Antigone and Creon portray the conflicting sides between male and female, and Ismene and Haemon portray opposing sides to Antigone and Creon’s actions. Antigone, Ismene, Creon, and Haemon each show differencesRead MoreAntigone Feminist Analysis1622 Words   |  7 PagesAntigone, a Greek tragedy pertaining to the events following the deaths of Eteocles and Polynices, Oedipus’ sons, due to a conflict over power. Upon the death of both children their uncle Creon takes the throne of Thebes for himself and declares Polynices a traitor to the state and withheld his burial rights from him. Antigone choose to disobey Creon’s decree and bury her bother. Sophocles’ play has been a long treasure piece of literature througho ut the ages; sparking many papers and debates fromRead MoreAnalysis of Antigone862 Words   |  4 PagesAnalysis of Antigone Today the United States is controlled by three branches, but the executive branch is the branch that is commonly referred to when mentioning the United States; the President. Who was once just a loyal friend of Oedipus, now the ruler of Thebes, Creon can be considered Thebes’s president. A ruler who believes and insists that his word is final when it deals with anything under his jurisdiction, meets a match in Antigone, the daughter of the former ruler of Thebes before heRead MoreThe Feminist Criticism Of Antigone Essay1703 Words   |  7 PagesStudent’s Name Tutor’s Name Course Code Date Sophocles Antigone The feminist criticism approach evaluates how sexual identity impacts the creation and perception of literary pieces of art. It was originally an offshoot of the feminist movements but has currently employed certain approaches, such as the Masculinity approach, which is advocated by Robert Bly. Feminist criticism takes a primary role in articulating the patriarchal perceptions that have dominated the Western thought. The perceptionsRead MoreAnalysis Of Oedipus The King And Antigone1170 Words   |  5 Pagesworld. In civilizations such as Athens, women were looked down upon and this battle to leave behind tradition proved to be almost if not fatal. Sophocles Oedipus the King and Antigone exemplify three distinct female Athenian characters who approach this battle with different fronts. Through analysis of Ismene, Antigone and Jocasta’s distinct characters, the reader better understands how Sophocles uses a feminine voice to break away from the tradition discerned in Athenian life to advocate for theRead MoreAn Interpretive Analysis On Conflicting Self Reassurance1337 Words   |  6 Pages Antigone: An Interpretive Analysis on Conflicting Self-Reassurance Antigone is a complex, yet debatable play, written by Sophocles somewhere around 442 BC. Chronologically, it is the third of the three Theban plays, but was the first to be written. In addition, Antigone was also one of the most famous tragedies ever to be written. The setting of the play is set in front of the Palace, Thebes, and Ancient Greece. Though most Greek playwrights were from Athens, their plays areRead MoreEssay on Antigone1426 Words   |  6 Pagesimprudent judgments will ultimately suffer from the consequences of their actions. In Sophocles Antigone, these prejudices notably surface in the form of paternalism as demonstrated through Creons government, highlighting the importance of gender roles throughout the play. Therefore, analyzing the motif of gender roles and its effect on the definition of justice through the perspectives of Ismene, Antigone, and Creon enables the audience to understand how Sophocles macroscopic analogy to humanitysRead MoreAntigone Character Analysis1468 Words   |  6 PagesIn the play of Antigone, Sophicles creates a plot that I believe playfully would make viewers sympathetic of the protagonist Antigone. At the beginning of the play, viewers obviously were very sympathetic to Antigone. All she wanted to do was bury her dead brother, and Kreon made it illegal to do such a deed. However, as the play went on, I gained more and more insight on Kreon and my opinion changed. Although Antigone sacrificed her life for what she believed was right, I sympathize more with KreonRead MoreAnalysis And Comparison Of Ophelia And Antigone1485 Words   |  6 PagesAnalysis and Comparison of Ophelia and Antigone Analysis of Antigone Antigone s story begins in the middle of things as the audience is expected to be aware of her background. Antigone firmly believed that she and her sister were the final victims of a curse that was placed upon their family long ago. The rest of her family members had already paid the price of the evil, and it was, therefore, their destiny to die as well. As a result of the curse, Antigone, and her sister Ismene are destined to

Theme Of Duality In Jekyll And Hyde - 976 Words

Many have heard the story of Jekyll and Hyde, but not many have had the thought to look for the deeper meaning in this story. In the beginning of the Book, it addresses four main characters Mr. Enfield, as well as as Mr. Utterson, and Dr jekyll and Mr. Hyde. The story gives all four characters a specific personality. The book specifies Mr Enfield as quiet and conservative but extremely popular. Mr. Utterson on the other hand is more outgoing and more social as well as Enfield and Hyde are cousins. As we com across Mr Jekyll this man is outgoing, smart, kind, and popular. Hyde is complete different from all of these people probably a different species as well. Hyde is a man with no morals and no heart, he is greedy and pure evil. Jekyll†¦show more content†¦Making This evil him gets angry angrier for hiding it away like that. The duality of humans is everywhere they seem to be way more than one personality in many people today. This is not a problem just a conflict that has t o be reviewed and checked then dealt with. This book is clearly the weapon the author uses to identify the problem to the public if someone does not deal with their problem and just hide it away. Robert uses his book to demonstrate the consequences of not finding a way to help lower your evil side. The author obviously argues his argument with Jekyll and Hyde the star of his book. But in the beginning it does state how Mr Enfield would kill his brother. With the philosophy of Cain ofcourse the brother jealous of the other. Robert Louis Stevenson also shows in the beginning how Everyone thought Jekyll was crazy for letting Hyde have the access of the house, of course they did not know it was him yet. Towards the End it also states how the way your dark pleasures may be it is not defining who you are just merely stating that not everyone is perfect. The author has probably have dealt with this before and warning everyone else who will soon come across this as well. But the problem her e is that not everyone knows how to control it and it may go out of hand sometimes. It probably is difficult to control and maybe that is why this world has murders and all kinds of people who commits crime. PeopleShow MoreRelatedJekyll And Hyde Character Analysis968 Words   |  4 PagesStrange Case of Dr. Jekyll and Mr. Hyde, explores the duality of human nature. He writes this novel to show us that humans have split personalities, and that there are two sides to human’s personality: good and evil. In the late-Victorian literature, duality appears to be a common theme; serving as a way for modern readers to analyze late-Victorian literature and culture. Stevenson weaves throughout the novel a theme of duality + which appears in the characters of both Jekyll and Hyde as well as in Stevenson’sRead MoreStevenson and Conrad: The Duality of Human Nature 778 Words   |  3 Pagescontroversial issue of the duality of human nature has been found at the heart of many Victor ian works. The theme of the duality of man can be found in the works of two famous English authors, Robert Louis Stevenson and Joseph Conrad. Stevenson and Conrad both incorporate the theme of the duality of human nature within their own novellas. Stevenson employs this theme throughout his novella The Strange Case of Dr. Jekyll and Mr. Hyde and similarly Conrad employs this theme throughout his novella HeartRead MoreThe Strange Case Of Dr. Jekyll And Mr. Hyde : Literary Review1515 Words   |  7 PagesThe Strange Case of Dr. Jekyll and Mr. Hyde: Literary Review The Romantic era was plagued with class conflict, poverty, and labor issues. The Victorian novel allows those who had access to them discover and focus on moral issues with society. Among the novel that were created during the era, the genre of a gothic novella emerged. Well knowns gothic novellas included Frankenstein, The Picture of Dorian Gray, and The Strange Case of Dr. Jekyll and Mr. Hyde. Robert Stevenson’s gothic novella The StrangeRead MoreDuality In Literature1347 Words   |  6 PagesDuality in Literature One of the main hobbies enjoyed by society today is reading. Classic works of literature and new pop culture novels are the basis of much of the discussion used in everyday life, and man is delving deeper into the novels known and loved. Dedicated readers are contemplating the purpose of this phrase in this chapter, why this word is used here, and what theme best expresses the author’s main idea. Probably the most popular theme in literature today is the use of duality. DualityRead MoreTheme Of Dualism In Dr. Jekyll And Mr. Hyde972 Words   |  4 Pagesselling novel, Dr. Jekyll and Mr. Hyde. It told the terrifying story of the power of addiction and the monsters that lurk within all of humanity. In this story many readers are intrigued by the psychological depth that Stevenson puts into the duo of Dr. Jekyll and his alternate personality Mr. Hyde, and even today the names of this alternating couple have become a kind of parable for any â€Å"devil in disguise†. The t heme of dualisms main role is proven in this story as the theme when Jekyll undergoes radicalRead MoreThe Strange Case Of Dr. Jekyll And Mr. Hyde Essay1069 Words   |  5 Pages Nia Givens The Strange Case of Dr. Jekyll Mr. Hyde Christianity was very important in Victorian London. The concept of the duality of good and evil that was taught in the story of the Garden of Eden was widely used in Victorian literature. â€Å"Duality, humorously and simply stated, is the split of one into two, while still existing as one.† (Lopez). Duality is a theme found throughout Robert Louis Stevenson’s ‘The Strange Case of Dr. Jekyll Mr. Hyde’. Most of the story is related in the thirdRead MoreStevensons Representation of Evil in Dr Jekyll and Mr Hyde Essay1424 Words   |  6 PagesStevensons Representation of Evil in Dr Jekyll and Mr Hyde Dr Jekyll and Mr Hyde is a classic novel telling the story of the struggle between good and evil. The good being shown in the form of a well-respected Doctor Henry Jekyll and the evil being released from a lengthy repression in the form of Mr Edward Hyde. In my essay I will be concentrating on the influences of the Victorian age and how Stevenson involved aspects of his own life into the writing of the bookRead MoreStevenson and Conrad: The Duality of Human Nature 949 Words   |  4 PagesConrad also employs the literary device of symbolism to further display the theme, the duality of human nature in his novella Heart of Darkness. Three major examples of symbolism are evident in this novella. These examples include, light and dark, the Congo River, and ivory. Similar to Stevenson, Conrad uses light and dark symbolism throughout his novella. Yet curiously in Heart of Darkness, light does not symbolize genuine goodness nor does dark symbolize pure calamity. Marlow proves this when heRead MoreDuality Of Human Nature949 Words   |  4 Pagespredominant themes in literature is the duality of human nature. According to the Merriam Webster Dictionary, dualism is a view of human beings as constituted of two irreducible elements. 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Mirroring Characters In Wuthering Heights - 1895 Words

Throughout life there will be times when someone would feel betrayed that would cause them to seek for revenge. That way they would feel they are taking matters in their own hands, and giving them a feeling of satisfaction. However, satisfaction would only be temporary, after harming people they love, it ends up causing them and whoever relates to the problem, pain. In Wuthering Heights by Emily Bronte, the protagonist, Heathcliff was abused throughout his life and was betrayed by his love. That is what caused him to seek revenge to whoever had done him wrong. He thought there he would get stratification, but that just end up bring pain to him and whoever that was was part of the problem and to the future generation as well. Bronte†¦show more content†¦For Heathcliff, even though he was the one that plot the revenge he was the one also in pain because he was creating pain to the person he loved. Since his lover betrayed him. In chapter 3, it shows the present when Heathclif f is in pain, calling for the person he loved. ‘â€Å"Come in! Come in!†. he sobbed. â€Å"Cathy, do come. Oh. Do once more! Oh! My heart’s darling! hear me this time, Catherine, at last!† (p.30). Heathcliff already did his revenge towards Catherine, and thinking it would satisfy him, but it didn t. Instead throughout the years, he had been thinking of Catherine and hope he could see her. The revenge that Heathcliff plotted, it also affected Hareton. Since Hindley was abused Heathcliff which caused Heathcliff to cause his son to become a servant like what Hindley did to him. Since Hareton became a servant it caused him to lack in education. Since he is in the bottom of the social class it caused him to be vulnerable to be verbally abused by Linton. In chapter 17, it explains how Hareton was suppose to be the one inherit Wuthering Heights, but he wasn t since Heathcliff revenge toward Hindley was to get all his money which allows him to become the owner of Wuthering Heights. â€Å"In that manner Hareton, who should now be the first gentleman in the neighborhood†¦ dependence on his father’s inveterate enemy, and lives in his own house as a servant, deprived of the advantage of wages and quiteShow MoreRelatedThe Sinusoidal Nature Of Generations1310 Words   |  6 PagesThe Sinusoidal Nature of Generations Emily Bronte’s melodramatic sensational novel, Wuthering Heights, is a heart-rending love story illustrated by a spectator narration. The story consumes the life of two romantic â€Å"soul mates† predestined to never ultimately be together and the impact of their lives on those who surround them. Each novel follows an undefined different story of a sole family. Gabriel Marquez’s One Hundred Years of Solitude explores comparable themes as those in Bronte’s novel unravelingRead MoreStructure and Narrative Technique in Wurthering Heights and Return of the Native1154 Words   |  5 Pagesserious revision, `Wuthering Heights would have ultimately appeared as more baffling to Victorian readership. Here most of the action has passed before the novel begins, which causes a string of narrators to be used for various effect. We are rarely given differing viewpoints on the same event, and, combined with the almost anti-chronological nature of `Wuthering Heights, the story is often seen as difficult to interpret. The fact that Bronte does not comment directly upon her characters allows us toRead MoreAn Analysis Of Wuthering Heights 1432 Words   |  6 PagesLifelong Immaturity Wuthering Heights’s Catherine Earnshaw is infamous for her complex character, some arguing that she is egocentric and manipulative, others sympathizing with the difficult choices she is faced with. However, there is no doubt that she is innately childish. As Catherine grows older, her character is not changed; she remains juvenile and selfish, making everything a game that revolves around her and not empathizing with other characters and their needs - subconsciously orRead MoreThe Everlasting Child : Wuthering Heights1832 Words   |  8 PagesThe Everlasting Child Wuthering Heights’s Catherine Earnshaw is infamous for her complex character, some arguing that she is manipulative, others sympathizing with the difficult choices she is faced with. However, there is no doubt that she is innately childish. As Catherine grows older, her character is not changed; she remains juvenile and selfish, making everything a game that revolves around her. In a sense, her mindset never progresses past one of a child. As Sigmund Freud wrote inRead MoreThe Everlasting Child : Wuthering Heights1832 Words   |  8 PagesThe Everlasting Child Wuthering Heights’s Catherine Earnshaw is infamous for her complex character, some arguing that she is manipulative, others sympathizing with the difficult choices she is faced with. However, there is no doubt that she is innately childish. As Catherine grows older, her character is not changed; she remains juvenile and selfish, making everything a game that revolves around her. In a sense, her mindset never progresses past one of a child. As Sigmund Freud wrote inRead MoreFeminism, Narrative And Psychoanalysis1991 Words   |  8 Pagessecond modus operandi is the ‘translation of narrative plot into psychoanalytic life history’ (Maggie Humm). I intend to contextualize Mitchell’s reading of the trajectory of Catherine’s life, as a psychoanalytic attempt at textual metaphor in Wuthering Heights – a novel with complex constructions of gender identity and repression. Mitchell begins by establishing an inextricable link between two seemingly-disjoint fields–literary narratives and psychoanalysis. She observes that psychoanalysisRead MoreAbuse of Power in Heart of Darkness and in Frankenstein1614 Words   |  7 Pagesthat he is distancing himself from his work to avoid racist claims that comments like this are inevitably going to provoke, however during the period that Conrad wrote the book (the late 1890s) framed narratives were very popular, -for example wuthering heights- and one could argue that he is simply writing in accordance with the fashions at the time of the book’s conception. However one can conclude that the use of the framed narrative shows that Conrad is abusing his power as the novelist, particularlyRead MoreEssay on Creating and Maintaining Suspense in Great Expectations2943 Words   |  12 Pagesmade the Dickens family fall down the social class ladder and become very poor. While Charless father was in prison, he died this meant that Charles had a very traumatic childhood. This childhood has featured in many of Dickenss books through characters, for example, Great Expectations involves crime, class, London and bad family life, Charles experienced all of these things as a child. Also as a child Dickenss experienced both classes - rich and poor, as Pip does in Great Expectations.