document_title: Percy Jackson & the Olympians

question_text: what's the third percy jackson book called

question_tokens: what 's the third percy jackson book called

text: Percy Jackson & the Olympians

text: Origins[edit]

text: Development for both The Lightning Thief and the Percy Jackson series commenced when Rick Riordan began making stories for his son Haley Riordan, who had at the time been diagnosed with ADHD and dyslexia.[6] His son, Haley, had been studying Greek mythology in second grade and requested that his father tell him bedtime stories based on Greek myths. When Riordan ran out of myths, his son suggested that he make up new stories using existing mythological characters and new ones. This led Riordan to create the fictional character of Percy Jackson and create the story of how he travels across the United States to recover Zeus's lightning-bolt. Haley suggested that he should turn that story into a book, and Riordan wrote the book over the next year despite being busy at that time.[7]

text: Leaving his manuscript with his agent and editor for review, Riordan presented the book to a group of 6th, 7th, and 8th graders to read and critique. He gained their approval, and with their help, came up with the name of the book and created the way Percy's sword works.[8] In 2004, the book was sold to Miramax Books for enough money for Riordan to quit his job and focus on writing.[9] After it was released on 28 June 2005, it sold over 1.2 million copies. The book was released in multiple versions, including hardcover, paperback and audio editions.[10][11] It has been translated into multiple languages and published all over the world.[12]

text: Books[edit]

text: The Lightning Thief[edit]

text: The Lightning Thief is the first book in the series and was released on July 1, 2005.

text: After a harrowing experience at his school trip, Percy Jackson returns home for the summer vacation, wherein he and his mother Sally Jackson, travel to their cabin in Montauk to take their mind off things. However, the trip is cut short after a series of harrowing incidents, such as being attacked by the Minotaur. Percy finds himself at Camp Half-Blood, a training camp for demigods like him. He discovers that he is a demigod, son of Poseidon, the Greek god of the sea, earthquakes, and father of all horses, (which he made from sea foam). Percy also learns that his best friend, Grover Underwood, is actually a satyr, and that the Greek gods are accusing Percy of having stolen Zeus' master lightning bolt, the most powerful weapon in the world. To clear his name and save the world from another war between the Olympian gods, Percy sets out to retrieve the lightning bolt from Hades, who is suspected of being the real thief. Thus, Percy, Grover, and Annabeth Chase, a daughter of Athena, start on a journey to the underworld, facing numerous mythological monsters on the way. After confronting an innocent Hades, they learn that their friend Luke Castellan, son of Hermes, is the real thief who stole the bolt to allow Kronos, the defeated king of the Titans, a chance to rise again.

text: The book was adapted into a film by Chris Columbus and 20th Century Fox, under the title Percy Jackson & the Olympians: The Lightning Thief, and was released on February 12, 2010.

text: The Sea of Monsters[edit]

text: The Sea of Monsters is the second installment in the series, released on April 1, 2006.

text: Camp Half-Blood is under attack when Thalia's tree, which guards the borders of the camp, is poisoned and slowly begins to die. In order to save the tree and the camp, someone must recover the Golden Fleece, which is somewhere in the Sea of Monsters. At the same time, Percy finds out that Grover, who has left on a quest to find the missing god Pan, has been captured by the cyclops Polyphemus and that the Fleece is on Polyphemus' island. Together with Annabeth and his half-brother Tyson, a cyclops, Percy sets out to rescue Grover. Meanwhile, Clarisse La Rue, daughter of Ares, is sent on an official quest by Camp Half-Blood to retrieve the Fleece. The trip to the Sea of Monsters is long and hazardous and along the way the heroes encounter several dangers including Scylla and Charybdis, the sorceress Circe, the Sirens and their former friend Luke Castellan. Percy also learns about a prophecy from the Oracle about a child of one of the three most important gods (Zeus, Poseidon and Hades), playing a vital part in the success or failure of the resurrection of Kronos the Titan-King. The heroes eventually retrieve the Fleece and restore Thalia's tree but also unknowingly revive Thalia herself, daughter of Zeus, who had been turned into the tree by her father when she died.

text: The book was adapted into a film by Thor Freudenthal and 20th Century Fox, under the title Percy Jackson: Sea of Monsters, and was released on August 7, 2013.

text: The Titan's Curse[edit]

text: The Titan's Curse is the third installment in the series. It was released on May 11, 2007.[13]

text: On a mission to rescue half-bloods Bianca and Nico di Angelo; Percy, Annabeth, Thalia and Grover are attacked by a manticore and rescued by the goddess Artemis and her Hunters. However, Annabeth falls off a cliff whilst trying to fight the manticore and is said to be captured. Later, Artemis is captured by Luke's army while on the hunt for the Ophiotaurus, a cow-serpent monster that was foretold to bring the downfall of Olympus when its entrails are sacrificed to a fire. Her lieutenant Zoe Nightshade, daughter of Atlas, leads Bianca, Thalia and Grover on a quest to save her. Percy, who was not invited to join the party, follows them on behalf of Nico Di Angelo, promising that he will do his best to protect his sister, Bianca. The others eventually find Percy, and he joins their group. They become the prey of skeletons, who chase them across the country. Bianca is able to kill one, which leaves the others mystified. Bianca later dies as they make their way across a godly junkyard. They find Annabeth with Luke and Artemis, who is holding up the sky. Percy then takes it from Artemis and they trick Atlas into his original position under the sky. Thalia replaces Zoe, who dies, as Artemis' lieutenant. Thalia's induction as a lieutenant of Artemis ensures that she will become immortal, never aging to 16, thus escaping the Great Prophecy and leaving Percy to fulfill it. They return to camp and Percy informs Nico about Bianca's death during the journey. Nico blames Percy for failing to protect her and runs away, only after killing skeletons that invade the camp, so that Percy realizes that Hades is Nico's father.

text: The Battle of the Labyrinth[edit]

text: The Battle of the Labyrinth is the fourth installment in the series. It was released on May 6, 2008.

text: After being attacked by monsters, Percy returns to Camp Half-Blood and learns about the Labyrinth. Annabeth and Percy find an entrance into the Labyrinth in camp. Percy soon learns that Luke will use the entrance to lead his army through the Labyrinth straight into the heart of camp. Annabeth is chosen to lead a quest to prevent it, and chooses to bring Tyson, Percy, and Grover, even though it was traditional to bring only two companions on a quest, as explained by Chiron. While in the Labyrinth, Percy and Annabeth become separated from Grover and Tyson. They encounter Nico, who begins to forgive Percy. Percy and Annabeth arrive under Mount St. Helens. Percy accidentally causes St. Helens to erupt and washes ashore on Calypso's island, Ogygia. He returns to Camp Half-Blood, rather than staying with her, stating that "she would always be his biggest 'what-if'". Then he and Annabeth recruit a mortal girl, Rachel Dare to be a guide in the Labyrinth, using her sight through the Mist, the magical veil that separates the mythological world from the mortal world, and her knowledge for the quest. Daedalus is shown to be alive and to have given Ariadne's string to Luke. They find Grover and Tyson and discover Pan, and Grover tells him that he must return to the world. But Pan says that he cannot come and before dying tells Grover to tell those who will listen that he has died. Grover does what he is told. Percy also finds Luke's body in Kronos' coffin. A final demigod joins the Titans' cause, and Kronos fully rises, using Luke's body. They flee to camp, trying to stop the invasion. Kronos' forces attack the camp, but they are defeated. The book ends with Daedalus sacrificing himself after the battle to destroy the Labyrinth, as it is tied to his life force, and Nico Di Angelo fully forgiving Percy and proposing a dangerous plan for defeating the Titans.

text: The Last Olympian[edit]

text: The Last Olympian, the fifth and final book in the Percy Jackson series, was released on May 5, 2009.[14]

text: Percy Jackson learns that Kronos' forces are preparing to attack Olympus. Poseidon, Percy's father, decides that it is time for Percy to now fulfill the Great Prophecy. Seeking to defeat Kronos, like Achilles did, Percy bathes in the River Styx, making his body invulnerable except one small chosen part of his body (the small of his back). Kronos leads a siege of New York City and puts its citizens to sleep. Percy leads the campers, Hunters, nature spirits, and centaurs to protect Mount Olympus from Kronos and his forces. While they protect Olympus, the gods hold down the monster Typhon as he makes his way to New York. Kronos, possessing Luke's body, forces his way into Olympus and battles Percy in Olympus' throne room. Typhon reaches New York but is defeated after the arrival of Poseidon's forces, led by Tyson. Annabeth is able to make Luke come back to his senses, and Percy gives him Annabeth's knife. Luke stabs himself in his mortal spot (as he also was invulnerable from bathing in the River Styx) to destroy Kronos and save Mount Olympus, but Luke dies. The gods reward Percy and his friends, and offer him immortality. He rejects the offer, but instead requests the gods to claim all their children and to have cabins for all the gods, including the minor ones. Rachel Elizabeth Dare becomes the Oracle and recites the next Great Prophecy. The book finishes with Percy and Annabeth becoming a couple, and ominous clouds looming over Rachel's next Great Prophecy.

text: Supplementary works[edit]

text: The Demigod Files[edit]

text:
The Demigod Files, also written by Rick Riordan, is the first companion book to the series. It was released February 10, 2009, featuring three short stories, interviews with the campers, puzzles and pictures.[15] It is set between The Battle of the Labyrinth and The Last Olympian.[16] The book received mixed reviews, with some reviewers criticizing the lack of substantial material and others commenting on the writing of the short stories. The stories are Percy Jackson and the Stolen Chariot, Percy Jackson and the Bronze Dragon, The Camper Interviews, and Percy Jackson and the Sword of Hades. At the end of the book, there are portraits on the characters of the series.
[16]

text: The Ultimate Guide[edit]

text: The Ultimate Guide is a companion book, second to the series, released on January 19, 2010. This book has a magnetic cover and holographic character pictures that change into four different characters. Its 156 pages include trading cards, full-color diagrams and maps.[17] It also includes a dictionary of almost every monster Percy faces in the series, with pictures beside some, as well as various activities. The book tells of Percy Jackson's starting life as a half-blood, a tour of the Underworld by Nico di Angelo, the story of Sally Jackson's parents, and items used throughout the series. There is also a paperback version.

text: Graphic novels[edit]

text: A graphic novel based on The Lightning Thief was published on October 12, 2010. It follows a shortened version of Percy's adventures in The Lightning Thief with full color drawings. A graphic novel based on the second book in the series, The Sea of Monsters was released on July 2, 2013. Another graphic novel based on the third book, The Titan's Curse was released on October 8, 2013.[18]

text: Demigods and Monsters[edit]

text: Demigods and Monsters is an unofficial companion book and was released on February 11, 2009.[19] With an introduction by Riordan, it features essays written by various young adult authors that explore, discuss and provide further insight into the Percy Jackson series. At 196 pages, it also contains information on the places and characters of the series, as well as a glossary of Greek myths.[20]

text: The Demigod Diaries[edit]

text:
The Demigod Diaries contains four new stories with character interviews, illustrations of characters and more, puzzles, and a quiz. The four stories include the adventures of Thalia, Luke, and Annabeth, and others which precede the Percy Jackson and the Olympians series and a first-person narrative from Percy's viewpoint. Set a month after the events of The Last Olympian and before he goes missing in The Lost Hero, Percy and Annabeth retrieve Hermes' stolen staff.
One of the stories is written by Riordan's son, Haley, and revolves around one of the demigods who fought for Kronos during the Second Titan War and survived the battle in Manhattan.
As a part of the spin-off The Heroes of Olympus series, The Demigod Diaries contain a story involving Jason, Leo, and Piper that recounts their time spent at Camp Half-Blood between The Lost Hero and The Son of Neptune.

text: Characters[edit]

text: Reception[edit]

text: The Lightning Thief received mostly positive reviews and won awards including the School Library Journal Best Book of 2005.[21] The New York Times praised The Lightning Thief as “perfectly paced, with electrifying moments chasing each other like heartbeats”.[22] Author Rick Riordan said of the various awards:

text: "The ultimate compliment for a children's writer is when the kids like it."[23]

text: Like its predecessor, The Sea of Monsters won several prizes and received generally positive reviews as well.[24][25] It sold over 100,000 copies in hardcover by the time it was released in paperback[26] and reviewers have praised the storyline, themes and the author's style of writing.[27][28][29] Matt Berman, of Common Sense Media, praised the book, saying “The Percy Jackson series continues to be pure fun, with the author doing nearly everything right to produce a book that few kids will be able to resist.”[28] Kirkus reviewed The Battle of the Labyrinth as, “This volume can stand alone, but no one will be able to read just one […] look no further for the next Harry Potter, meet Percy Jackson as legions of fans already have.” As of February 13, 2016, it has been on the New York Times Children's Series Best Seller List for 379 weeks.

text: Some critics, especially Christian critics of Riordan have disapproved of the emphasis on pagan gods in his books. Riordan responds to these complaints by reminding his readers that first and foremost,[30] "The Lightning Thief explores Greek mythology in a modern setting, but it does so as a humorous work of fantasy. I’m certainly not interested in changing or contradicting anyone’s religious beliefs. Early in the book, the character Chiron makes a distinction between God, capital-G, the creator of the universe, and the Greek gods (lower-case g). Chiron says he doesn’t want to delve into the issue of God, but he has no qualms about discussing the Olympians because they are a "much smaller matter."

text: Critics such as The Calico Critic have also disagreed with the fusion of Greek mythology and modern American culture. They have stated that it is difficult to believe "the reality of the tale", claiming that "monsters in the St. Louis Arch" and "the entrance to Olympus in New York" were unimaginable, despite Riordan's explanations of why he chose these certain locations.[31]

text: However studies show that overall, readers appreciated the mundane language, witty tone and aesthetic plot of the novels, as well as how it introduced Greek mythology to them.[31]

text: In other media[edit]

text: Films[edit]

text: These films have been made from the books:

text:
Percy Jackson & the Olympians: The Lightning Thief
Percy Jackson: Sea of Monsters

text:
Chris Columbus directed and produced Percy Jackson & the Olympians: The Lightning Thief for 20th Century Fox through 1492 Pictures.[32][33] The film was released in 2010 in the United States, Canada and in the United Kingdom on February 12 and in Australia on February 11.[34]
Columbus has stated that he was drawn to directing the Percy Jackson movie because it gave him the "opportunity to do a movie that we haven't really seen before for this generation. When I was a kid, there were movies that dealt with Greek mythology, which in terms of visual effects was really primitive. So I thought this was an opportunity to deal with Greek mythology which children and adults all over the world are fascinated by and it was not a new genre but a new avenue, dealing with mythological creatures in a contemporary setting."

text: The second film in the series, Percy Jackson: Sea of Monsters,[35][36] was released on August 7, 2013.[5] Filming began in April 2012.

text: Chris Columbus stated that there will not be a third movie any time soon.[citation needed]

text: Video game[edit]

text: To accompany the film, a video game was produced. Michael Splechta gave it a 6/10, saying "Percy Jackson & the Olympians might not make a splash when it comes to movie tie-in games, but fans of turn-based combat might find some redeeming qualities in this otherwise bare-bones game."[37]

text: Musical[edit]

text: On January 12, 2017, A Series of Unfortunate Events story editor Joe Tracz wrote a new Off Broadway musical adaptation of Percy Jackson tale “The Lightning Thief.[38]

text: Legacy[edit]

text: Sequel series[edit]

text: The Heroes of Olympus[edit]

text: The Heroes of Olympus is a sequel series, also based on Camp Half-Blood and the Greek and Roman mythologies. The first book The Lost Hero was released on October 12, 2010. Like the first series, there are five books.[39] The official website requires a password, later revealed as newhero. On December 1, 2010, the site went live.[40]

text: The second book in The Heroes of Olympus, The Son of Neptune, was released in October 2011. The third book, The Mark of Athena, was released on October 2, 2012. The fourth book, The House of Hades, was released on October 8, 2013. The fifth and final book of The Heroes of Olympus series, The Blood of Olympus, was released on October 7, 2014.[41]

text: The Trials of Apollo[edit]

text: Riordan is currently at work on yet another follow-up series to The Heroes of Olympus book series titled The Trials of Apollo is a sequel series to both Percy Jackson & the Olympians and The Heroes of Olympus. The first installment titled, The Hidden Oracle (2016), features Apollo and his journey after being cast down from Olympus. The second book titled The Dark Prophecy was released in May 2017.The third book titled The Burning Maze was released on May 1, 2018.

text: Related series[edit]

text: The Kane Chronicles[edit]

text: The novels are set within the same fictional universe as the three previous book series, and is narrated alternately in first-person by the two protagonist-siblings Carter and Sadie Kane. The siblings are descended from the two pharaohs Narmer and Ramses the Great and are powerful magicians. They and their friends are forced to contend with Egyptian gods and goddesses who still interact with the real world. The series includes a trilogy consisting of The Red Pyramid (2010), The Throne of Fire (2011), and The Serpent's Shadow (2012), as well as three crossover books with the Percy Jackson & the Olympians series.

text: Magnus Chase and the Gods of Asgard[edit]

text: The main protagonist Magnus Chase, son of the Vanir god of fertility Frey, narrates the novel in first person. He is a cousin of Annabeth Chase, a main character of the Percy Jackson and the Olympians and The Heroes of Olympus series, who links the two series together.[42] The series consists of a trilogy of books, The Sword of Summer (2015), The Hammer of Thor (2016), and The Ship of the Dead (2017).


document_title: Cell nucleus

question_text: what is the outer layer of the nucleus called

root

text: Cell nucleus

text: History

text: The nucleus was the first organelle to be discovered. What is most likely the oldest preserved drawing dates back to the early microscopist Antonie van Leeuwenhoek (1632–1723). He observed a "lumen", the nucleus, in the red blood cells of salmon.[1] Unlike mammalian red blood cells, those of other vertebrates still contain nuclei.

tag: p

text: The nucleus was also described by Franz Bauer in 1804[2] and in more detail in 1831 by Scottish botanist Robert Brown in a talk at the Linnean Society of London. Brown was studying orchids under microscope when he observed an opaque area, which he called the "areola" or "nucleus", in the cells of the flower's outer layer.[3]

text: He did not suggest a potential function. In 1838, Matthias Schleiden proposed that the nucleus plays a role in generating cells, thus he introduced the name "cytoblast" (cell builder). He believed that he had observed new cells assembling around "cytoblasts". Franz Meyen was a strong opponent of this view, having already described cells multiplying by division and believing that many cells would have no nuclei. The idea that cells can be generated de novo, by the "cytoblast" or otherwise, contradicted work by Robert Remak (1852) and Rudolf Virchow (1855) who decisively propagated the new paradigm that cells are generated solely by cells ("Omnis cellula e cellula"). The function of the nucleus remained unclear.[4]

text: Between 1877 and 1878, Oscar Hertwig published several studies on the fertilization of sea urchin eggs, showing that the nucleus of the sperm enters the oocyte and fuses with its nucleus. This was the first time it was suggested that an individual develops from a (single) nucleated cell. This was in contradiction to Ernst Haeckel's theory that the complete phylogeny of a species would be repeated during embryonic development, including generation of the first nucleated cell from a "monerula", a structureless mass of primordial mucus ("Urschleim"). Therefore, the necessity of the sperm nucleus for fertilization was discussed for quite some time. However, Hertwig confirmed his observation in other animal groups, including amphibians and molluscs. Eduard Strasburger produced the same results for plants in 1884. This paved the way to assign the nucleus an important role in heredity. In 1873, August Weismann postulated the equivalence of the maternal and paternal germ cells for heredity. The function of the nucleus as carrier of genetic information became clear only later, after mitosis was discovered and the Mendelian rules were rediscovered at the beginning of the 20th century; the chromosome theory of heredity was therefore developed.[4]

text: Structures

text: The nucleus is the largest cellular organelle in animal cells.[5] In mammalian cells, the average diameter of the nucleus is approximately 6 micrometres (µm), which occupies about 10% of the total cell volume.[6] The viscous liquid within it is called nucleoplasm (or karyolymph), and is similar in composition to the cytosol found outside the nucleus.[7] It appears as a dense, roughly spherical or irregular organelle. The composition by dry weight of the nucleus is approximately: DNA 9%, RNA 1%, Histone Protein 11%, Residual Protein 14%, Acidic Proteins 65%.

text: Nuclear envelope and pores

text:
The eukaryotic cell nucleus. Visible in this diagram are the ribosome-studded double membranes of the nuclear envelope, the DNA (complexed as chromatin), and the nucleolus. Within the cell nucleus is a viscous liquid called nucleoplasm, similar to the cytoplasm found outside the nucleus.

A cross section of a nuclear pore on the surface of the nuclear envelope (1). Other diagram labels show (2) the outer ring, (3) spokes, (4) basket, and (5) filaments.

tag: table

text: The nuclear envelope, otherwise known as nuclear membrane, consists of two cellular membranes, an inner and an outer membrane, arranged parallel to one another and separated by 10 to 50 nanometres (nm). The nuclear envelope completely encloses the nucleus and separates the cell's genetic material from the surrounding cytoplasm, serving as a barrier to prevent macromolecules from diffusing freely between the nucleoplasm and the cytoplasm.[8] The outer nuclear membrane is continuous with the membrane of the rough endoplasmic reticulum (RER), and is similarly studded with ribosomes.[8] The space between the membranes is called the perinuclear space and is continuous with the RER lumen.

text: Nuclear pores, which provide aqueous channels through the envelope, are composed of multiple proteins, collectively referred to as nucleoporins. The pores are about 125 million daltons in molecular weight and consist of around 50 (in yeast) to several hundred proteins (in vertebrates).[5] The pores are 100 nm in total diameter; however, the gap through which molecules freely diffuse is only about 9 nm wide, due to the presence of regulatory systems within the center of the pore. This size selectively allows the passage of small water-soluble molecules while preventing larger molecules, such as nucleic acids and larger proteins, from inappropriately entering or exiting the nucleus. These large molecules must be actively transported into the nucleus instead. The nucleus of a typical mammalian cell will have about 3000 to 4000 pores throughout its envelope,[9] each of which contains an eightfold-symmetric ring-shaped structure at a position where the inner and outer membranes fuse.[10] Attached to the ring is a structure called the nuclear basket that extends into the nucleoplasm, and a series of filamentous extensions that reach into the cytoplasm. Both structures serve to mediate binding to nuclear transport proteins.[5]

text: Most proteins, ribosomal subunits, and some DNAs are transported through the pore complexes in a process mediated by a family of transport factors known as karyopherins. Those karyopherins that mediate movement into the nucleus are also called importins, whereas those that mediate movement out of the nucleus are called exportins. Most karyopherins interact directly with their cargo, although some use adaptor proteins.[11] Steroid hormones such as cortisol and aldosterone, as well as other small lipid-soluble molecules involved in intercellular signaling, can diffuse through the cell membrane and into the cytoplasm, where they bind nuclear receptor proteins that are trafficked into the nucleus. There they serve as transcription factors when bound to their ligand; in the absence of a ligand, many such receptors function as histone deacetylases that repress gene expression.[5]

text: Nuclear lamina

text: In animal cells, two networks of intermediate filaments provide the nucleus with mechanical support: The nuclear lamina forms an organized meshwork on the internal face of the envelope, while less organized support is provided on the cytosolic face of the envelope. Both systems provide structural support for the nuclear envelope and anchoring sites for chromosomes and nuclear pores.[6]

text: The nuclear lamina is composed mostly of lamin proteins. Like all proteins, lamins are synthesized in the cytoplasm and later transported to the nucleus interior, where they are assembled before being incorporated into the existing network of nuclear lamina.[12][13] Lamins found on the cytosolic face of the membrane, such as emerin and nesprin, bind to the cytoskeleton to provide structural support. Lamins are also found inside the nucleoplasm where they form another regular structure, known as the nucleoplasmic veil,[14] that is visible using fluorescence microscopy. The actual function of the veil is not clear, although it is excluded from the nucleolus and is present during interphase.[15] Lamin structures that make up the veil, such as LEM3, bind chromatin and disrupting their structure inhibits transcription of protein-coding genes.[16]

text: Like the components of other intermediate filaments, the lamin monomer contains an alpha-helical domain used by two monomers to coil around each other, forming a dimer structure called a coiled coil. Two of these dimer structures then join side by side, in an antiparallel arrangement, to form a tetramer called a protofilament. Eight of these protofilaments form a lateral arrangement that is twisted to form a ropelike filament. These filaments can be assembled or disassembled in a dynamic manner, meaning that changes in the length of the filament depend on the competing rates of filament addition and removal.[6]

text: Mutations in lamin genes leading to defects in filament assembly cause a group of rare genetic disorders known as laminopathies. The most notable laminopathy is the family of diseases known as progeria, which causes the appearance of premature aging in its sufferers. The exact mechanism by which the associated biochemical changes give rise to the aged phenotype is not well understood.[17]

text: Chromosomes

text: The cell nucleus contains the majority of the cell's genetic material in the form of multiple linear DNA molecules organized into structures called chromosomes. Each human cell contains roughly two meters of DNA. During most of the cell cycle these are organized in a DNA-protein complex known as chromatin, and during cell division the chromatin can be seen to form the well-defined chromosomes familiar from a karyotype. A small fraction of the cell's genes are located instead in the mitochondria.

text: There are two types of chromatin. Euchromatin is the less compact DNA form, and contains genes that are frequently expressed by the cell.[18] The other type, heterochromatin, is the more compact form, and contains DNA that is infrequently transcribed. This structure is further categorized into facultative heterochromatin, consisting of genes that are organized as heterochromatin only in certain cell types or at certain stages of development, and constitutive heterochromatin that consists of chromosome structural components such as telomeres and centromeres.[19] During interphase the chromatin organizes itself into discrete individual patches,[20] called chromosome territories.[21] Active genes, which are generally found in the euchromatic region of the chromosome, tend to be located towards the chromosome's territory boundary.[22]

text: Antibodies to certain types of chromatin organization, in particular, nucleosomes, have been associated with a number of autoimmune diseases, such as systemic lupus erythematosus.[23] These are known as anti-nuclear antibodies (ANA) and have also been observed in concert with multiple sclerosis as part of general immune system dysfunction.[24] As in the case of progeria, the role played by the antibodies in inducing the symptoms of autoimmune diseases is not obvious.

text: Nucleolus

text: The nucleolus is a discrete densely stained structure found in the nucleus. It is not surrounded by a membrane, and is sometimes called a suborganelle. It forms around tandem repeats of rDNA, DNA coding for ribosomal RNA (rRNA). These regions are called nucleolar organizer regions (NOR). The main roles of the nucleolus are to synthesize rRNA and assemble ribosomes. The structural cohesion of the nucleolus depends on its activity, as ribosomal assembly in the nucleolus results in the transient association of nucleolar components, facilitating further ribosomal assembly, and hence further association. This model is supported by observations that inactivation of rDNA results in intermingling of nucleolar structures.[25]

text: In the first step of ribosome assembly, a protein called RNA polymerase I transcribes rDNA, which forms a large pre-rRNA precursor. This is cleaved into the subunits 5.8S, 18S, and 28S rRNA.[26] The transcription, post-transcriptional processing, and assembly of rRNA occurs in the nucleolus, aided by small nucleolar RNA (snoRNA) molecules, some of which are derived from spliced introns from messenger RNAs encoding genes related to ribosomal function. The assembled ribosomal subunits are the largest structures passed through the nuclear pores.[5]

text: When observed under the electron microscope, the nucleolus can be seen to consist of three distinguishable regions: the innermost fibrillar centers (FCs), surrounded by the dense fibrillar component (DFC), which in turn is bordered by the granular component (GC). Transcription of the rDNA occurs either in the FC or at the FC-DFC boundary, and, therefore, when rDNA transcription in the cell is increased, more FCs are detected. Most of the cleavage and modification of rRNAs occurs in the DFC, while the latter steps involving protein assembly onto the ribosomal subunits occur in the GC.[26]

text: Other subnuclear bodies

text:
Subnuclear structure sizes

Structure name
Structure diameter

Cajal bodies
0.2–2.0 µm
[27]

Clastosomes
0.2-0.5 µm
[28]

PIKA
5 µm
[29]

PML bodies
0.2–1.0 µm
[30]

Paraspeckles
0.2–1.0 µm
[31]

Speckles
20–25 nm
[29]

text: Besides the nucleolus, the nucleus contains a number of other non-membrane-delineated bodies. These include Cajal bodies, Gemini of coiled bodies, polymorphic interphase karyosomal association (PIKA), promyelocytic leukaemia (PML) bodies, paraspeckles, and splicing speckles. Although little is known about a number of these domains, they are significant in that they show that the nucleoplasm is not a uniform mixture, but rather contains organized functional subdomains.[30]

text: Other subnuclear structures appear as part of abnormal disease processes. For example, the presence of small intranuclear rods has been reported in some cases of nemaline myopathy. This condition typically results from mutations in actin, and the rods themselves consist of mutant actin as well as other cytoskeletal proteins.[32]

text: Cajal bodies and gems

text: A nucleus typically contains between 1 and 10 compact structures called Cajal bodies or coiled bodies (CB), whose diameter measures between 0.2 µm and 2.0 µm depending on the cell type and species.[27] When seen under an electron microscope, they resemble balls of tangled thread[29] and are dense foci of distribution for the protein coilin.[33] CBs are involved in a number of different roles relating to RNA processing, specifically small nucleolar RNA (snoRNA) and small nuclear RNA (snRNA) maturation, and histone mRNA modification.[27]

text: Similar to Cajal bodies are Gemini of Cajal bodies, or gems, whose name is derived from the Gemini constellation in reference to their close "twin" relationship with CBs. Gems are similar in size and shape to CBs, and in fact are virtually indistinguishable under the microscope.[33] Unlike CBs, gems do not contain small nuclear ribonucleoproteins (snRNPs), but do contain a protein called survival of motor neuron (SMN) whose function relates to snRNP biogenesis. Gems are believed to assist CBs in snRNP biogenesis,[34] though it has also been suggested from microscopy evidence that CBs and gems are different manifestations of the same structure.[33] Later ultrastructural studies have shown gems to be twins of Cajal bodies with the difference being in the coilin component; Cajal bodies are SMN positive and coilin positive, and gems are SMN positive and coilin negative.[35]

text: RAFA and PTF domains

text: RAFA domains, or polymorphic interphase karyosomal associations, were first described in microscopy studies in 1991. Their function remains unclear, though they were not thought to be associated with active DNA replication, transcription, or RNA processing.[36] They have been found to often associate with discrete domains defined by dense localization of the transcription factor PTF, which promotes transcription of small nuclear RNA (snRNA).[37]

text: PML bodies

text: Promyelocytic leukaemia bodies (PML bodies) are spherical bodies found scattered throughout the nucleoplasm, measuring around 0.1–1.0 µm. They are known by a number of other names, including nuclear domain 10 (ND10), Kremer bodies, and PML oncogenic domains. PML bodies are named after one of their major components, the promyelocytic leukemia protein (PML). They are often seen in the nucleus in association with Cajal bodies and cleavage bodies.[30] PML bodies belong to the nuclear matrix, an ill-defined super-structure of the nucleus proposed to anchor and regulate many nuclear functions, including DNA replication, transcription, or epigenetic silencing.[38] The PML protein is the key organizer of these domains that recruits an ever-growing number of proteins, whose only common known feature to date is their ability to be SUMOylated. Yet, pml-/- mice (which have their PML gene deleted) cannot assemble nuclear bodies, develop normally and live well, demonstrating that PML bodies are dispensable for most basic biological functions.[38]

text: Splicing speckles

text: Speckles are subnuclear structures that are enriched in pre-messenger RNA splicing factors and are located in the interchromatin regions of the nucleoplasm of mammalian cells. At the fluorescence-microscope level they appear as irregular, punctate structures, which vary in size and shape, and when examined by electron microscopy they are seen as clusters of interchromatin granules. Speckles are dynamic structures, and both their protein and RNA-protein components can cycle continuously between speckles and other nuclear locations, including active transcription sites. Studies on the composition, structure and behaviour of speckles have provided a model for understanding the functional compartmentalization of the nucleus and the organization of the gene-expression machinery[39] splicing snRNPs[40][41] and other splicing proteins necessary for pre-mRNA processing.[42] Because of a cell's changing requirements, the composition and location of these bodies changes according to mRNA transcription and regulation via phosphorylation of specific proteins.[43] The splicing speckles are also known as nuclear speckles (nuclear specks), splicing factor compartments (SF compartments), interchromatin granule clusters (IGCs), B snurposomes.[44] B snurposomes are found in the amphibian oocyte nuclei and in Drosophila melanogaster embryos. B snurposomes appear alone or attached to the Cajal bodies in the electron micrographs of the amphibian nuclei.[45] IGCs function as storage sites for the splicing factors.[46]

text: Paraspeckles

text: Discovered by Fox et al. in 2002, paraspeckles are irregularly shaped compartments in the nucleus' interchromatin space.[47] First documented in HeLa cells, where there are generally 10–30 per nucleus,[48] paraspeckles are now known to also exist in all human primary cells, transformed cell lines, and tissue sections.[49] Their name is derived from their distribution in the nucleus; the "para" is short for parallel and the "speckles" refers to the splicing speckles to which they are always in close proximity.[48]

text: Paraspeckles are dynamic structures that are altered in response to changes in cellular metabolic activity. They are transcription dependent[47] and in the absence of RNA Pol II transcription, the paraspeckle disappears and all of its associated protein components (PSP1, p54nrb, PSP2, CFI(m)68, and PSF) form a crescent shaped perinucleolar cap in the nucleolus. This phenomenon is demonstrated during the cell cycle. In the cell cycle, paraspeckles are present during interphase and during all of mitosis except for telophase. During telophase, when the two daughter nuclei are formed, there is no RNA Pol II transcription so the protein components instead form a perinucleolar cap.[49]

text: Perichromatin fibrils

text: Perichromatin fibrils are visible only under electron microscope. They are located next to the transcriptionally active chromatin and are hypothesized to be the sites of active pre-mRNA processing.[46]

text: Clastosome

text: Clastosomes are small nuclear bodies (0.2-0.5 µm) described as donut-shaped due to the peripheral capsule around these bodies.[28] This name is derived from the Greek klastos, broken and soma, body.[28] Clastosomes are not typically present in normal cells, making them hard to detect. They form under high proteolysis conditions within the nucleus and degrade once there is a decrease in activity or if cells are treated with proteasome inhibitors.[28][50] The scarcity of clastosomes in cells indicates that they are not required for proteasome function.[51] Osmotic stress has also been shown to cause the formation of clastosomes.[52] These nuclear bodies contain catalytic and regulatory sub-units of the proteasome and its substrates, indicating that clastosomes are sites for degrading proteins.[51]

text: The Clastosome would be an important addition to the ‘Cell Nucleus’ Wiki page because it plays a role in cell function. With further research, we may discover that this nuclear body has a more influential job in cell function than what is already known.[28]

text: Function

text: The nucleus provides a site for genetic transcription that is segregated from the location of translation in the cytoplasm, allowing levels of gene regulation that are not available to prokaryotes. The main function of the cell nucleus is to control gene expression and mediate the replication of DNA during the cell cycle.

text: The nucleus is an organelle found in eukaryotic cells. Inside its fully enclosed nuclear membrane, it contains the majority of the cell's genetic material. This material is organized as DNA molecules, along with a variety of proteins, to form chromosomes.

text: Cell compartmentalization

text: The nuclear envelope allows the nucleus to control its contents, and separate them from the rest of the cytoplasm where necessary. This is important for controlling processes on either side of the nuclear membrane. In most cases where a cytoplasmic process needs to be restricted, a key participant is removed to the nucleus, where it interacts with transcription factors to downregulate the production of certain enzymes in the pathway. This regulatory mechanism occurs in the case of glycolysis, a cellular pathway for breaking down glucose to produce energy. Hexokinase is an enzyme responsible for the first the step of glycolysis, forming glucose-6-phosphate from glucose. At high concentrations of fructose-6-phosphate, a molecule made later from glucose-6-phosphate, a regulator protein removes hexokinase to the nucleus,[53] where it forms a transcriptional repressor complex with nuclear proteins to reduce the expression of genes involved in glycolysis.[54]

text: In order to control which genes are being transcribed, the cell separates some transcription factor proteins responsible for regulating gene expression from physical access to the DNA until they are activated by other signaling pathways. This prevents even low levels of inappropriate gene expression. For example, in the case of NF-κB-controlled genes, which are involved in most inflammatory responses, transcription is induced in response to a signal pathway such as that initiated by the signaling molecule TNF-α, binds to a cell membrane receptor, resulting in the recruitment of signalling proteins, and eventually activating the transcription factor NF-κB. A nuclear localisation signal on the NF-κB protein allows it to be transported through the nuclear pore and into the nucleus, where it stimulates the transcription of the target genes.[6]

text: The compartmentalization allows the cell to prevent translation of unspliced mRNA.[55] Eukaryotic mRNA contains introns that must be removed before being translated to produce functional proteins. The splicing is done inside the nucleus before the mRNA can be accessed by ribosomes for translation. Without the nucleus, ribosomes would translate newly transcribed (unprocessed) mRNA, resulting in malformed and nonfunctional proteins.

text: Gene expression

text: Gene expression first involves transcription, in which DNA is used as a template to produce RNA. In the case of genes encoding proteins, that RNA produced from this process is messenger RNA (mRNA), which then needs to be translated by ribosomes to form a protein. As ribosomes are located outside the nucleus, mRNA produced needs to be exported.[56]

text: Since the nucleus is the site of transcription, it also contains a variety of proteins that either directly mediate transcription or are involved in regulating the process. These proteins include helicases, which unwind the double-stranded DNA molecule to facilitate access to it, RNA polymerases, which bind to the DNA promoter to synthesize the growing RNA molecule, topoisomerases, which change the amount of supercoiling in DNA, helping it wind and unwind, as well as a large variety of transcription factors that regulate expression.[57]

text: Processing of pre-mRNA

text: Newly synthesized mRNA molecules are known as primary transcripts or pre-mRNA. They must undergo post-transcriptional modification in the nucleus before being exported to the cytoplasm; mRNA that appears in the cytoplasm without these modifications is degraded rather than used for protein translation. The three main modifications are 5' capping, 3' polyadenylation, and RNA splicing. While in the nucleus, pre-mRNA is associated with a variety of proteins in complexes known as heterogeneous ribonucleoprotein particles (hnRNPs). Addition of the 5' cap occurs co-transcriptionally and is the first step in post-transcriptional modification. The 3' poly-adenine tail is only added after transcription is complete.

text: RNA splicing, carried out by a complex called the spliceosome, is the process by which introns, or regions of DNA that do not code for protein, are removed from the pre-mRNA and the remaining exons connected to re-form a single continuous molecule. This process normally occurs after 5' capping and 3' polyadenylation but can begin before synthesis is complete in transcripts with many exons.[5] Many pre-mRNAs, including those encoding antibodies, can be spliced in multiple ways to produce different mature mRNAs that encode different protein sequences. This process is known as alternative splicing, and allows production of a large variety of proteins from a limited amount of DNA.

text: Dynamics and regulation

text: Nuclear transport

text: The entry and exit of large molecules from the nucleus is tightly controlled by the nuclear pore complexes. Although small molecules can enter the nucleus without regulation,[58] macromolecules such as RNA and proteins require association karyopherins called importins to enter the nucleus and exportins to exit. "Cargo" proteins that must be translocated from the cytoplasm to the nucleus contain short amino acid sequences known as nuclear localization signals, which are bound by importins, while those transported from the nucleus to the cytoplasm carry nuclear export signals bound by exportins. The ability of importins and exportins to transport their cargo is regulated by GTPases, enzymes that hydrolyze the molecule guanosine triphosphate to release energy. The key GTPase in nuclear transport is Ran, which can bind either GTP or GDP (guanosine diphosphate), depending on whether it is located in the nucleus or the cytoplasm. Whereas importins depend on RanGTP to dissociate from their cargo, exportins require RanGTP in order to bind to their cargo.[11]

text: Nuclear import depends on the importin binding its cargo in the cytoplasm and carrying it through the nuclear pore into the nucleus. Inside the nucleus, RanGTP acts to separate the cargo from the importin, allowing the importin to exit the nucleus and be reused. Nuclear export is similar, as the exportin binds the cargo inside the nucleus in a process facilitated by RanGTP, exits through the nuclear pore, and separates from its cargo in the cytoplasm.

text: Specialized export proteins exist for translocation of mature mRNA and tRNA to the cytoplasm after post-transcriptional modification is complete. This quality-control mechanism is important due to these molecules' central role in protein translation. Mis-expression of a protein due to incomplete excision of exons or mis-incorporation of amino acids could have negative consequences for the cell; thus, incompletely modified RNA that reaches the cytoplasm is degraded rather than used in translation.[5]

text: Assembly and disassembly

text: During its lifetime, a nucleus may be broken down or destroyed, either in the process of cell division or as a consequence of apoptosis (the process of programmed cell death). During these events, the structural components of the nucleus — the envelope and lamina — can be systematically degraded. In most cells, the disassembly of the nuclear envelope marks the end of the prophase of mitosis. However, this disassembly of the nucleus is not a universal feature of mitosis and does not occur in all cells. Some unicellular eukaryotes (e.g., yeasts) undergo so-called closed mitosis, in which the nuclear envelope remains intact. In closed mitosis, the daughter chromosomes migrate to opposite poles of the nucleus, which then divides in two. The cells of higher eukaryotes, however, usually undergo open mitosis, which is characterized by breakdown of the nuclear envelope. The daughter chromosomes then migrate to opposite poles of the mitotic spindle, and new nuclei reassemble around them.

text: At a certain point during the cell cycle in open mitosis, the cell divides to form two cells. In order for this process to be possible, each of the new daughter cells must have a full set of genes, a process requiring replication of the chromosomes as well as segregation of the separate sets. This occurs by the replicated chromosomes, the sister chromatids, attaching to microtubules, which in turn are attached to different centrosomes. The sister chromatids can then be pulled to separate locations in the cell. In many cells, the centrosome is located in the cytoplasm, outside the nucleus; the microtubules would be unable to attach to the chromatids in the presence of the nuclear envelope.[59] Therefore, the early stages in the cell cycle, beginning in prophase and until around prometaphase, the nuclear membrane is dismantled.[14] Likewise, during the same period, the nuclear lamina is also disassembled, a process regulated by phosphorylation of the lamins by protein kinases such as the CDC2 protein kinase.[60] Towards the end of the cell cycle, the nuclear membrane is reformed, and around the same time, the nuclear lamina are reassembled by dephosphorylating the lamins.[60]

text: However, in dinoflagellates, the nuclear envelope remains intact, the centrosomes are located in the cytoplasm, and the microtubules come in contact with chromosomes, whose centromeric regions are incorporated into the nuclear envelope (the so-called closed mitosis with extranuclear spindle). In many other protists (e.g., ciliates, sporozoans) and fungi, the centrosomes are intranuclear, and their nuclear envelope also does not disassemble during cell division.

text: Apoptosis is a controlled process in which the cell's structural components are destroyed, resulting in death of the cell. Changes associated with apoptosis directly affect the nucleus and its contents, for example, in the condensation of chromatin and the disintegration of the nuclear envelope and lamina. The destruction of the lamin networks is controlled by specialized apoptotic proteases called caspases, which cleave the lamin proteins and, thus, degrade the nucleus' structural integrity. Lamin cleavage is sometimes used as a laboratory indicator of caspase activity in assays for early apoptotic activity.[14] Cells that express mutant caspase-resistant lamins are deficient in nuclear changes related to apoptosis, suggesting that lamins play a role in initiating the events that lead to apoptotic degradation of the nucleus.[14] Inhibition of lamin assembly itself is an inducer of apoptosis.[61]

text: The nuclear envelope acts as a barrier that prevents both DNA and RNA viruses from entering the nucleus. Some viruses require access to proteins inside the nucleus in order to replicate and/or assemble. DNA viruses, such as herpesvirus replicate and assemble in the cell nucleus, and exit by budding through the inner nuclear membrane. This process is accompanied by disassembly of the lamina on the nuclear face of the inner membrane.[14]

text: Disease-related dynamics

text: Initially, it has been suspected that immunoglobulins in general and autoantibodies in particular do not enter the nucleus. Now there is a body of evidence that under pathological conditions (e.g. lupus erythematosus) IgG can enter the nucleus.[62]

text: Nuclei per cell

text: Most eukaryotic cell types usually have a single nucleus, but some have no nuclei, while others have several. This can result from normal development, as in the maturation of mammalian red blood cells, or from faulty cell division.

text: Anucleated cells

text: An anucleated cell contains no nucleus and is, therefore, incapable of dividing to produce daughter cells. The best-known anucleated cell is the mammalian red blood cell, or erythrocyte, which also lacks other organelles such as mitochondria, and serves primarily as a transport vessel to ferry oxygen from the lungs to the body's tissues. Erythrocytes mature through erythropoiesis in the bone marrow, where they lose their nuclei, organelles, and ribosomes. The nucleus is expelled during the process of differentiation from an erythroblast to a reticulocyte, which is the immediate precursor of the mature erythrocyte.[63] The presence of mutagens may induce the release of some immature "micronucleated" erythrocytes into the bloodstream.[64][65] Anucleated cells can also arise from flawed cell division in which one daughter lacks a nucleus and the other has two nuclei.

text: In flowering plants, this condition occurs in sieve tube elements.

text: Multinucleated cells

text: Multinucleated cells contain multiple nuclei. Most acantharean species of protozoa[66] and some fungi in mycorrhizae[67] have naturally multinucleated cells. Other examples include the intestinal parasites in the genus Giardia, which have two nuclei per cell.[68] In humans, skeletal muscle cells, called myocytes and syncytium, become multinucleated during development; the resulting arrangement of nuclei near the periphery of the cells allows maximal intracellular space for myofibrils.[5] Multinucleated and binucleated cells can also be abnormal in humans; for example, cells arising from the fusion of monocytes and macrophages, known as giant multinucleated cells, sometimes accompany inflammation[69] and are also implicated in tumor formation.[70]

text: A number of dinoflagellates are known to have two nuclei.[71] Unlike other multinucleated cells these nuclei contain two distinct lineages of DNA: one from the dinoflagellate and the other from a symbiotic diatom. The mitochondria and the plastids of the diatom somehow remain functional.

text: Evolution

text: As the major defining characteristic of the eukaryotic cell, the nucleus' evolutionary origin has been the subject of much speculation. Four major hypotheses have been proposed to explain the existence of the nucleus, although none have yet earned widespread support.[72]

text: The first model known as the "syntrophic model" proposes that a symbiotic relationship between the archaea and bacteria created the nucleus-containing eukaryotic cell. (Organisms of the Archaea and Bacteria domain have no cell nucleus.[73]) It is hypothesized that the symbiosis originated when ancient archaea, similar to modern methanogenic archaea, invaded and lived within bacteria similar to modern myxobacteria, eventually forming the early nucleus. This theory is analogous to the accepted theory for the origin of eukaryotic mitochondria and chloroplasts, which are thought to have developed from a similar endosymbiotic relationship between proto-eukaryotes and aerobic bacteria.[74] The archaeal origin of the nucleus is supported by observations that archaea and eukarya have similar genes for certain proteins, including histones. Observations that myxobacteria are motile, can form multicellular complexes, and possess kinases and G proteins similar to eukarya, support a bacterial origin for the eukaryotic cell.[75]

text: A second model proposes that proto-eukaryotic cells evolved from bacteria without an endosymbiotic stage. This model is based on the existence of modern planctomycetes bacteria that possess a nuclear structure with primitive pores and other compartmentalized membrane structures.[76] A similar proposal states that a eukaryote-like cell, the chronocyte, evolved first and phagocytosed archaea and bacteria to generate the nucleus and the eukaryotic cell.[77]

text: The most controversial model, known as viral eukaryogenesis, posits that the membrane-bound nucleus, along with other eukaryotic features, originated from the infection of a prokaryote by a virus. The suggestion is based on similarities between eukaryotes and viruses such as linear DNA strands, mRNA capping, and tight binding to proteins (analogizing histones to viral envelopes). One version of the proposal suggests that the nucleus evolved in concert with phagocytosis to form an early cellular "predator".[78] Another variant proposes that eukaryotes originated from early archaea infected by poxviruses, on the basis of observed similarity between the DNA polymerases in modern poxviruses and eukaryotes.[79][80] It has been suggested that the unresolved question of the evolution of sex could be related to the viral eukaryogenesis hypothesis.[81]

text: A more recent proposal, the exomembrane hypothesis, suggests that the nucleus instead originated from a single ancestral cell that evolved a second exterior cell membrane; the interior membrane enclosing the original cell then became the nuclear membrane and evolved increasingly elaborate pore structures for passage of internally synthesized cellular components such as ribosomal subunits.[82]