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

We describe the clinical characteristics and epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in children with cystic fibrosis (CF) from the U.S. CF center with the highest MRSA prevalence. Medical records of children with CF were retrospectively reviewed from 1997-2009. MRSA clinical isolates from 2007-2009 were analyzed by polymerase chain reaction and pulsed field gel electrophoresis. The prevalence of MRSA was 1% in 1997 and 49% in 2009. Fifty-five children (26%) had persistent MRSA infection. Sixty-eight percent of MRSA isolates were hospital-associated (HA) MRSA, of which 52% were pulsed-field type USA 100. Ninety-three percent of HA MRSA isolates were clindamycin resistant. Twelve children acquired MRSA before 1 year of age, 83% of whom were hospitalized prior to acquisition of MRSA. Ten of 11 sibling pairs carried indistinguishable MRSA strains. Children with persistent MRSA were hospitalized more often (P=.01), required inhaled medications more frequently (P=.01), and had higher rates of Pseudomonas aeruginosa coinfection (P<.001). MRSA prevalence in children with CF is increasing, and most children are infected with HA MRSA. Exposure to health care facilities and gastrointestinal surgeries may facilitate early acquisition of MRSA. Siblings carry indistinguishable MRSA strains, indicating household transmission of MRSA. Children with persistent MRSA had worse pulmonary morbidity. Coinfection with MRSA and P aeruginosa is likely associated with further increased pulmonary morbidity.
What is MRSA?

Throughout 1476, supporters of Joanna from the nobility continued to submit to Isabella and Ferdinand, particularly those from the Pacheco-Giron lineage: Juan Tellez-Giron and his brother Rodrigo; Luis de Portocarrero; and, in September, the Marquis of Villena. In November 1476, Isabella's troops captured the castle of Toro. In the following months, they took control of the last bordering localities controlled by the Portuguese and dealt with their adversaries in Extremadura. In July 1477, Isabella arrived in Seville, the most populous city of Castile, with the objective of asserting her power over the nobility of Andalusia. In April 1476, Isabella and Ferdinand gave their first exculpation to the Marquis of Cadiz. He had been regaining power while his rival, the Duke of Medina Sidonia, initially the main Isabella supporter in Andalusia, had been falling into dishonour. Through skilful negotiations, the Queen managed to take control of the main strongholds of Seville occupied by the Marquis and the Duke and, instead of returning them to their legitimate owners, named others as their heads. She prohibited both nobles from entering the city of Seville, under the pretext that their simultaneous presence there would risk violent conflicts. In this way the Duke's political dominance over Seville disappeared, and the city passed into the control of the Crown. One of the few nobles that refused to submit to the monarchs was Marshall Fernan Arias de Saavedra. Isabella's troops laid siege to his fortress at Utrera, and conquered it by assault in March 1478. The defeated suffered harsh repression. The first son of the monarchs, John of Aragon and Castile, was born in Seville on June 30, 1478, which opened new possibilities for dynastic stability of the Isabellian side.
What event happened first, Isabella arriving in Seville or Isabella and Ferdinand giving their first exculpation to the Marquis of Cadiz?

A central feature of Alzheimer's disease is the cleavage of the amyloid precursor protein (APP) to form beta-amyloid peptide (Abeta) by the beta-secretase and gamma-secretase enzymes. Although this has been shown to occur after endocytosis of APP from the cell surface, the exact compartments of APP processing are not well defined. We have previously demonstrated that APP and gamma-secretase proteins and activity are highly enriched in purified rat liver lysosomes. In order to examine the lysosomal distribution and trafficking of APP in cultured cells, we generated constructs containing APP fused to a C-terminal fluorescent protein tag and N-terminal HA-epitope tag. These were co-transfected with a panel of fluorescent-protein tagged compartment markers. Here we demonstrate using laser-scanning confocal microscopy that although APP is present throughout the endosomal/lysosomal system in transfected Cos7 and neuronal SN56 cell lines as well as in immunostained cultured mouse neurons, it is enriched in the lysosome. We also show that the Swedish and London mutations reduce the amount of APP in the lysosome. Surprisingly, in addition to its expected trafficking from the cell surface to the early and then late endosomes, we find that cell-surface labelled APP is transported rapidly and directly from the cell surface to lysosomes in both Cos7 and SN56 cells. This rapid transit to the lysosome is blocked by the presence of either the London or Swedish mutations. These results demonstrate the presence of a novel, rapid and specific transport pathway from the cell surface to the lysosomes. This suggests that regulation of lysosomal traffic could regulate APP processing and that the lysosome could play a central role in the pathophysiology of Alzheimer's disease.
Which disease the London mutation involved in?