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

Ex Input:
Schimke immuno-osseous dysplasia (OMIM 242900) is an uncommon autosomal-recessive multisystem disease caused by mutations in SMARCAL1 (swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), a gene encoding a putative chromatin remodeling protein. Neurologic manifestations identified to date relate to enhanced atherosclerosis and cerebrovascular disease. Based on a clinical survey, we determined that half of Schimke immuno-osseous dysplasia patients have a small head circumference, and 15% have social, language, motor, or cognitive abnormalities. Postmortem examination of 2 Schimke immuno-osseous dysplasia patients showed low brain weights and subtle brain histologic abnormalities suggestive of perturbed neuron-glial migration such as heterotopia, irregular cortical thickness, incomplete gyral formation, and poor definition of cortical layers. We found that SMARCAL1 is highly expressed in the developing and adult mouse and human brain, including neural precursors and neuronal lineage cells. These observations suggest that SMARCAL1 deficiency may influence brain development and function in addition to its previously recognized effect on cerebral circulation.

Ex Output:
Mutations in which gene cause Schimke immune-osseous dysplasia?


Ex Input:
Bone, as well as the lung and liver, is among the sites of predilection for cancer metastasis. The bone stores large amounts of growth factors such as insulin-like growth factors and transforming growth factor-b, and provides fertile soil for metastatic cancer cells by continuously releasing these bone-stored growth factors, which are a consequence of osteoclastic bone resorption. Metastatic cancer cells in turn produce osteoclast-stimulating cytokines such as parathyroid hormone-related protein( PTH-rP), prostaglandin E2.(PGE2), and various interleukins(ILs). These cancer-produced osteoclast-stimulating cytokines bind to their cognitive receptors and promote the expression of ligands for the receptor activators of nuclear factor kB (RANKL)in osteoblasts. RANKL then binds to its receptor RANK, expressed in pre-osteoclasts, stimulates mature osteoclast formation, and subsequently, osteoclastic bone resorption. This vicious cycle between metastatic cancer cells and osteoclasts is critical to the development and progression of bone metastases. In addition, it is likely that metastatic cancer cells are influenced by bone environments(or niche)and acquire additional capacities such as an epithelial-mesenchymal transition(EMT), allowing them to be resistant to chemotherapy or apoptosis, to survive in a dormant state, or to aggressively spread to distant organs including lung and liver. Thus, the bone can serve as transit port. Disrupting this cycle by inhibiting osteoclastic bone resorption, antagonizing bone-derived growth factors, and neutralizing RANKL or PTH-rP, should be a promising therapeutic intervention for bone metastases. Bisphosphonates(BP)are specific inhibitors of osteoclasts, and have been shown to significantly reduce skeletal-related events(SRE)associated with bone metastasis. Denosumab is a neutralizing monoclonal antibody to RANKL and has recently been found to inhibit SRE more effectively than BP. Further understanding of the crosstalk communication between metastatic cancer cells and bone at the molecular level should lead us to design novel, more effective and specific treatments for cancer patients with bone metastases.

Ex Output:
To the ligand of which receptors does Denosumab (Prolia) bind?


Ex Input:
The film opens where the previous film ended, set a few years later, where Rafiki (Robert Guillaume) gathers the animals of the Pride Lands together for the presentation of Simba (Matthew Broderick) and Nalas (Moira Kelly) new daughter Kiara. Mufasa's spirit (James Earl Jones) watches over the ceremony. Later, Simba becomes very overprotective of an older Kiara (Michelle Horn), assigning Timon and Pumbaa (Nathan Lane and Ernie Sabella) to watch her. One day as Kiara was playing, she fell into a small pond as Timon and Pumbba got her back onto land. Kiara tells them only half of her is a princess. Pumbba asks, "Well, who's the other half?" While they wait for her to answer, they start having a snack. Then they started arguing about slimy and crunchy grubs. While they were arguing, Kiara sneaks into the "Outlands" where she meets a young cub named Kovu (Ryan O'Donohue). After escaping a river filled with nile crocodiles, the two become friendly, unaware they are being watched by Kovu's mother, Zira (Suzanne Pleshette). Simba arrives and confronts Zira, who reminds Simba that he exiled the Outsiders, and that if he wants to punish them, Kovu is Scar's hand-chosen successor. Unwilling to harm the cub, Simba orders them to leave. Later Simba scolds Kiara for endangering herself. In the Outlands, Zira's eldest son, Nuka (Andy Dick), complains to his younger sister Vitani (Lacey Chabert) about Kovu's status as "the Chosen One" the cub chosen by Scar to lead the pride after his death. ("I should've been the "Chosen One". I'm the strongest, I'm the smartest, I'm the oldest, etc.") At that moment, Zira returns and scolds both of her sons, but Kovu accidentally gives her the idea to use Kovu's new friendship with Kiara as a means of exacting her revenge on Simba for Scar's death. Now an adult, Kiara (Neve Campbell) heads out from home for her first solo hunt, however Simba again sends Timon and Pumbaa to follow and watch her progress after he promised to let Kiara hunt on her own. Furious to find out her father still insists on maintaining surveillance, Kiara goes further from home to hunt, though is still unsuccessful in her efforts. Meanwhile, Zira's plan to implant Kovu in Simba's pride has been set in motion; Nuka and Vitani (Jennifer Lien) set fire to the plains where Kiara is hunting, causing her to faint and giving Kovu (Jason Marsden) the chance to rescue her. Drawn by the smoke, Simba finds them together and reluctantly accepts Kovu's request to come to Pride Rock in return for saving Kiara's life, though he forces Kovu to sleep outside. That same night, Simba has a nightmare about his father's death, where Scar suddenly morphs into Kovu and Simba takes his father's place falling off the cliff. The next morning, he goes outside to a watering hole where Kovu contemplates attacking him, but Kiara interrupts and they go off together so Kovu can help her learn how to hunt. Kiara kept on failing. During the lesson, Kovu was setting an example for Kiara, thinking Timon was just an ordinary meerkat. They run into Timon and Pumbaa struggling with some birds, so the two lions help them chase the birds off. Together, they have fun playing, something Kovu notes he has never experienced before. That night, Kovu tells Kiara that he is not Scar's real son, but "was a part of him". Simba watches from above, seeking guidance from the "Great Kings" and Nala advises him to give Kovu a chance, because he is not his father. Kovu decides to leave after he almost confesses his real intentions to Kiara, but Rafiki stops him and invites the young lions to experience "Upendi" love. After a musical journey through the jungle, the two fall in love. In the morning, Simba invites Kovu for a walk and tells him the true story of

Ex Output:

Who did Kiara meet at the Outlands?