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

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small vessel disease of the brain caused by mutations in the NOTCH3 gene. CADASIL progresses, in some cases, to subcortical dementia with a particular cognitive impairment. Different diseases in the dementia spectrum share a central cholinergic and sensorimotor plasticity alteration. We aimed to study different intracortical circuits and sensorimotor plasticity in CADASIL patients using transcranial magnetic stimulation protocols, and to determine whether these characteristics correlated with the results of clinical neuropsychological evaluation. Ten CADASIL patients and 10 healthy subjects were included in the study. All subjects underwent a transcranial magnetic stimulation study examining different intracortical circuits. Sensorimotor plasticity was also assessed using a paired associative stimulation and extensive neuropsychological tests. CADASIL patients showed a lack of intracortical facilitation, short latency afferent inhibition and sensorimotor plasticity when compared with control subjects. CADASIL patients also showed an altered neuropsychological profile. Correlation between sensorimotor plasticity and neuropsychological alterations was observed in CADASIL patients. These results suggest that acetylcholine and glutamate could be involved in the dementia process in CADASIL and that abnormal sensorimotor plasticity correlates with the neuropsychological profile in CADASIL patients.
Which gene is involved in CADASIL?

BEIJING - Astronomers have defended against rumors that the terrible earthquake and the following tsunami in Japan were closely related to or even caused by the "supermoon" that will appear in the sky on Saturday. The word "supermoon" was introduced in a report by the British newspaper Daily Mail on March 9, which said amateur scientists were warning that such an astronomical phenomenon could disturb the Earth's climate patterns and may even cause earthquakes and volcanic activity. The moon will be 356,577 kilometers from the Earth on Saturday, the closest in 19 years, and the closest point in its oval orbit coincides with a full moon, the report said. However, Saturday's moon is not actually the closest to Earth in 19 years, Tang Haiming, an astronomer with Shanghai Astronomical Observatory under the Chinese Academy of Sciences, told Xinhua News Agency. A shorter distance of 356,570 km between the two bodies was reached in January 2005, and a distance of 356,566 km was seen in December 2008. Yet some people suggest that previous supermoons have occurred prior to extreme weather events. In 1974 the phenomenon was followed by Cyclone Tracy in Darwin, Australia, and in 2005 it occurred shortly before a deadly tsunami in Indonesia. Coincidentally, two fresh disasters happened in Asia right before Saturday's supermoon. The public's concern about their connection with the moon boomed after Japan's terrible earthquake and tsunami and an earthquake in Southwest China's Yunnan province that killed 25 people on March 10. But astronomers are trying to _ people that such rumors are merely unreasonable. "A supermoon could cause high tides but has no direct relation with natural disasters such as earthquakes," Liu Jie, a researcher with the China Earthquake Network Center, told China Daily on Tuesday. "We can't find any necessary connection between previous supermoons and earthquakes. And the quake in Japan occurred because the Earth's inner energy had accumulated to some extent, and it's not related to the moon. " he said. James Garvin, chief scientist at the Goddard Space Flight Center under NASA, said in an article on NASA's website that "the effects on Earth from a supermoon are minor.""The combination of the moon being at its closest to Earth in its orbit, and being in its 'full moon' configuration ( to the Earth and sun), should not affect the inner energy balance of the Earth, since there are lunar tides every day. " Zhu Jin, curator of the Beijing Planetarium, said"the moon moves around the earth in a certain path, so each orbit has a perigee - its closest approach, and an apogee - its furthest distance.""A lunar perigee occurs once a month and there are very small differences in distances between perigees,"he said."Those tiny differences are far from enough to cause earthquakes or eruption of a volcano,"he added.
What's the real reason for the quake in Japan?

As Tsushima had suffered greatly from its loss of trade with Korea as a result of the invasions, Yoshitoshi of the So family, then dominant in Tsushima, undertook the lead in the peace negotiations by Japan. He sent four peace missions to Joseon in 1599 to normalize relations. The first three were captured and sent directly to Beijing by Chinese troops, but the fourth one, in 1601, successfully obtained from the Joseon court the promise of a normalizing of relations upon the return of remaining Joseon captives. As Ming troops continued to be present in Korea following the withdrawal of Japanese forces, the major incentive for Joseon for the normalization of relations with Japan was the withdrawal of the Chinese soldiers from their territory. The Ming Chinese themselves were causing as much havoc as the Japanese had during the actual conflict, and their presence continued to strain Joseon's national economy and infrastructure. In response to the Joseon request, Yoshitoshi promptly released several Joseon prisoners and between 1603 and 1604 helped the Joseon envoys to repatriate a further 3,000 by organizing negotiations at Kyoto with Tokugawa Ieyasu, by then the Shogun of Japan. In the continuation of the diplomatic talks toward peaceful relations, Joseon in 1606 expanded its conditions and demanded that the Shogun write a formal letter requesting peace, and to extradite the Japanese soldiers who had defiled the Joseon Royal Tombs near Hanseong . Realizing that the Shogunate would never agree to such a request, Yoshitoshi sent a forged letter and a group of criminals instead; the great need to expel the Ming soldiers pushed Joseon into accepting and to send an emissary in 1608. The end result was a return of Joseon prisoners and the restoration of diplomatic and trade relations between the two countries.

Who sent four peace missions to Joseon in 1599?