Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.

Q: Polycomb gene silencing requires histone methyltransferase activity of Polycomb repressive complex 2 (PRC2), which methylates lysine 27 of histone H3. Information on how PRC2 works is limited by lack of structural data on the catalytic subunit, Enhancer of zeste (E(Z)), and the paucity of E(z) mutant alleles that alter its SET domain. Here we analyze missense alleles of Drosophila E(z), selected for molecular study because of their dominant genetic effects. Four missense alleles identify key E(Z) SET domain residues, and a fifth is located in the adjacent CXC domain. Analysis of mutant PRC2 complexes in vitro, and H3-K27 methylation in vivo, shows that each SET domain mutation disrupts PRC2 histone methyltransferase. Based on known SET domain structures, the mutations likely affect either the lysine-substrate binding pocket, the binding site for the adenosylmethionine methyl donor, or a critical tyrosine predicted to interact with the substrate lysine epsilon-amino group. In contrast, the CXC mutant retains catalytic activity, Lys-27 specificity, and trimethylation capacity. Deletion analysis also reveals a functional requirement for a conserved E(Z) domain N-terminal to CXC and SET. These results identify critical SET domain residues needed for PRC2 enzyme function, and they also emphasize functional inputs from outside the SET domain.

A: What is the characteristic domain of histone methyltransferases?
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Q: Patients with multiple myeloma (MM) experience pathologic fractures, bone pain, hypercalcemia, neurologic symptoms, and renal insufficiency with substantial morbidity and mortality. Bisphosphonates have been used successfully for the management of MM-related bone disease. Increased incidence of osteonecrosis of the jaw has been observed in patients with cancer receiving bisphosphonate therapy. Recent advances in the pathobiology of MM-related bone disease and other cancer-related bone metastases have led to the identification of novel therapeutic targets, such as receptor activator of nuclear factor-kappaB (RANK); its ligand (RANKL); and a decoy receptor, osteoprotegerin, for the development of potential targeted agents. Initials studies have demonstrated that targeting RANK/ RANKL signaling with the fully human monoclonal antibody denosumab prevented skeletal complications in patients with MM and other cancers with bone metastases. Ongoing studies evaluating the clinical utility of denosumab in cancer- related bone destruction have been discussed. In addition, several potential targets, such as macrophage inflammatory protein-1alpha, chemokine receptors 1 and 5, interleukin-3, and Wnt signaling, are b riefly described.

A: To the ligand of which receptors does Denosumab (Prolia) bind?
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Q: Newspaper columnist John Klein (Richard Gere) and his wife Mary (Debra Messing) are involved in an accident when Mary swerves to avoid a black, flying figure. John survives the crash unscathed, but Mary is hospitalized. After Mary dies of an unrelated brain tumor, John discovers mysterious drawings of the creature that she had created prior to the night of the accident. Two years later, John becomes lost in West Virginia and inexplicably finds himself in Point Pleasant, hundreds of miles off his route. Driving in the middle of the night, his car breaks down; and he walks to a nearby house to get help. The owner, Gordon Smallwood (Will Patton), reacts violently to John's appearance and holds him at gunpoint. Local police officer Connie Mills (Laura Linney) defuses the situation while Gordon explains that this is the third consecutive night John has knocked on his door asking to use a phone, much to John's confusion. John stays at a local motel and considers how he ended up so far from his original destination. Officer Mills mentions to John that many strange things have been occurring in the past few weeks and that people report seeing a large winged creature like a giant moth with red eyes. She also tells John about a strange dream she had, in which the words "Wake up, Number 37" were spoken to her. While conversing with Gordon one day, it is revealed to John that he had heard voices from his sink telling him that, in Denver, "99 will die". While discussing the day's events at a local diner, John notices that the news is showing a story on an airplane crash in Denver that killed all 99 passengers aboard. The next night, Gordon frantically explains that he had met the voices in his head, a being named Indrid Cold Later that night, Gordon calls John and says that he is standing with a character named Indrid Cold. While John keeps Cold on the line, Officer Mills checks on Gordon. Cold answers John's questions, convincing him that he is a supernatural being. This episode starts a string of supernatural calls to John's motel room. One tells him that there will be a great tragedy on the Ohio River. Later, John receives a call from Gordon and rushes to his home to check on him. He finds Gordon outside, dead from exposure. John becomes obsessed with the being, dubbed Mothman. He meets an expert on the subject, Alexander Leek (Alan Bates), who explains its nature and discourages John from becoming further involved. However, when John learns the governor (Murphy Dunne) plans to tour a chemical plant located on the Ohio River the following day, he becomes convinced the tragedy will occur there. Officer Mills and the governor ignore his warnings, and nothing happens during the tour. Soon afterwards, John receives a mysterious message that instructs him to await a call from his deceased wife Mary back in Georgetown, and he returns home. On Christmas Eve, Officer Mills calls and convinces him to ignore the phone call from "Mary", return to Point Pleasant, and join her. Though anguished, John agrees. As John reaches the Silver Bridge, a malfunctioning traffic light causes traffic congestion. As John walks onto the bridge to investigate, the bolts and supports of the bridge strain. The bridge comes apart, and John realizes that the prophesied tragedy on the Ohio River was about the bridge. As the bridge collapses, Officer Mills's car falls into the water. John jumps in after her and pulls her from the river and up to safety. As the two sit on the back of an ambulance, they see that 36 people have been killed, making Connie the "number 37" from her dream. The epilogue displays a series of graphics that state the cause of the bridge collapse was never fully determined. It also states that, although the Mothman has been sighted in other parts of the world, it was never seen again in Point Pleasant.

A:
Who is John's wife?
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