instruction:
Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
question:
It is unanimously accepted that there is an unmet need for pain medications that are both effective and safe. Unfortunately, no really novel analgesics have been approved over the past three decades. In view of both experimental and clinical evidence of a major role for nerve growth factor (NGF) in the generation and maintenance of a wide range of pain states, drug discovery efforts focusing on the development of anti-NGF agents have aroused particular interest. Several humanized anti-NGF monoclonal antibodies (mAbs) have entered clinical trials as potential analgesics. In this respect, tanezumab is at an advanced stage of clinical development while fulranumab, fasinumab and ABT-110, previously known as PG110, are in early phases of clinical development. This Current Opinion article aims at describing the rationale for targeting NGF for pain, reviewing the analgesic efficacy and safety of anti-NGF agents based on data from fully published studies, conference abstracts, and the US Food and Drug Administration (FDA) website, and discussing the possible future of these agents in managing chronic pain. Anti-NGF mAbs produced significant pain relief and functional improvement in patients with osteoarthritis of the knee and/or hip. Conversely, studies in non-specific lower back pain generated mixed results; overall, this condition appeared to be less responsive to anti-NGF agents than osteoarthritis. Finally, there was no conclusive evidence of the effectiveness of anti-NGF mAbs in some types of chronic visceral or neuropathic pain. Furthermore, these studies raised safety concerns about anti-NGF mAbs. As a class, these drugs may cause or worsen peripheral neuropathies. But the most problematic issue-which prompted the FDA to place studies of these compounds on clinical hold in 2010-was rapid joint destruction leading to joint replacement surgery. The aetiologies of these side effects have been much debated and their pathophysiology is poorly understood. After an Arthritis Advisory Committee meeting held in March 2012, pharmaceutical companies negotiated with the FDA on the conditions for restarting clinical studies. Although the FDA lifted its clinical hold, there remain many unresolved issues about the long-term efficacy and safety of anti-NGF mAbs. While acknowledging that the future of these drugs is unforeseeable, it appears that they may not be the safe and effective painkillers that have been awaited for decades.
answer:
What is the target of tanezumab?


question:
Ponds are small bodies of fresh water that usually have no outlet; ponds are often are fed by underground springs. Like lakes, ponds are bordered by hills or low rises so the water is blocked from flowing directly downhill. Lakes are larger bodies of water. Lakes are usually fresh water, although the Great Salt Lake in Utah is just one exception. Water usually drains out of a lake through a river or a stream and all lakes lose water to evaporation. Lakes form in a variety of different ways: in depressions carved by glaciers, in calderas (Figure 1.1), and along tectonic faults, to name a few. Subglacial lakes are even found below a frozen ice cap. As a result of geologic history and the arrangement of land masses, most lakes are in the Northern Hemisphere. In fact, more than 60% of all the worlds lakes are in Canada most of these lakes were formed by the glaciers that covered most of Canada in the last Ice Age (Figure 1.2). Lakes are not permanent features of a landscape. Some come and go with the seasons, as water levels rise and fall. Over a longer time, lakes disappear when they fill with sediments, if the springs or streams that fill them diminish, (a) Crater Lake in Oregon is in a volcanic caldera. Lakes can also form in volcanic craters and impact craters. (b) The Great Lakes fill depressions eroded as glaciers scraped rock out from the landscape. (c) Lake Baikal, ice coated in winter in this image, formed as water filled up a tectonic faults. Lakes near Yellowknife were carved by glaciers during the last Ice Age. or if their outlets grow because of erosion. When the climate of an area changes, lakes can either expand or shrink (Figure 1.3). Lakes may disappear if precipitation significantly diminishes. Large lakes have tidal systems and currents, and can even affect weather patterns. The Great Lakes in the United States contain 22% of the worlds fresh surface water (Figure 1.1). The largest them, Lake Superior, has a tide that rises and falls several centimeters each day. The Great Lakes are large enough to alter the weather system in Northeastern United States by the lake effect, which is an increase in snow downwind of the relatively warm lakes. The Great Lakes are home to countless species of fish and wildlife. Many lakes are not natural, but are human-made. People dam a stream in a suitable spot and then let the water back up behind it, creating a lake. These lakes are called "reservoirs." Click image to the left or use the URL below. URL:
answer:
which of these is not full of fresh water?


question:
Two forms of neurofibromatosis, type 1 (NF1) and type 2 (NF2) are connected with genes localized on chromosomes 17 and 22, respectively. The genes that are inactivated in neurofibromatosis code for the proteins neurofibromine and merline, respectively. Since inactivation leads to neoplasia, they are called tumour suppressor genes. Neurofibromine shows resemblances to proteins that serve to inactivate oncogenes. Merline has a relationship with proteins that connect the cytoskeleton and the cell membrane. The precise function of the proteins is still unknown. The NF1 gene is characterized by extraordinarily high sensitivity to mutation; half the NF1 patients have not inherited the disease. In the familial form of neurofibromatosis, a mutated gene is inherited and the normal allele in the tumour is inactivated, making tumour growth possible. In the sporadic form of neurofibromatosis, both normal alleles are inactivated locally in the tissue so that a tumour develops in that place.
answer:

Which is the gene mutated in type 1 neurofibromatosis?