instruction:
Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
question:
Alzheimer's disease (AD) is characterized by cerebral deposition of -amyloid peptide (A). A is produced by sequential cleavage of the Amyloid Precursor Protein (APP) by - and -secretases. Many studies have demonstrated that the internalization of APP from the cell surface can regulate A production, although the exact organelle in which A is produced remains contentious. A number of recent studies suggest that intracellular trafficking also plays a role in regulating A production, but these pathways are relatively under-studied. The goal of this study was to elucidate the intracellular trafficking of APP, and to examine the site of intracellular APP processing.", 'We have tagged APP on its C-terminal cytoplasmic tail with photoactivatable Green Fluorescent Protein (paGFP). By photoactivating APP-paGFP in the Golgi, using the Golgi marker Galactosyltranferase fused to Cyan Fluorescent Protein (GalT-CFP) as a target, we are able to follow a population of nascent APP molecules from the Golgi to downstream compartments identified with compartment markers tagged with red fluorescent protein (mRFP or mCherry); including rab5 (early endosomes) rab9 (late endosomes) and LAMP1 (lysosomes). Because -cleavage of APP releases the cytoplasmic tail of APP including the photoactivated GFP, resulting in loss of fluorescence, we are able to visualize the cleavage of APP in these compartments. Using APP-paGFP, we show that APP is rapidly trafficked from the Golgi apparatus to the lysosome; where it is rapidly cleared. Chloroquine and the highly selective -secretase inhibitor, L685, 458, cause the accumulation of APP in lysosomes implying that APP is being cleaved by secretases in the lysosome. The Swedish mutation dramatically increases the rate of lysosomal APP processing, which is also inhibited by chloroquine and L685, 458. By knocking down adaptor protein 3 (AP-3; a heterotetrameric protein complex required for trafficking many proteins to the lysosome) using siRNA, we are able to reduce this lysosomal transport. Blocking lysosomal transport of APP reduces A production by more than a third.
answer:
Is the Amyloid Precursor Protein rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid?

question:
Visceral obesity is shown to be a predictor of morbidity and mortality. We evaluated the association of measurements of generalized adiposity and visceral fat area (VFA), with abnormalities of metabolic syndrome (MS).', 'Seventy-six women (47.9 +/- 9.2 years) with BMI of 38.7 +/- 5.4 kg/m(2) underwent anthropometric measurements, laboratory procedures, bioeletrical impedance, and abdominal computed tomography (CT) scan. Diagnosis of MS was based on the presence of abdominal obesity and at least two of the following components: hypertension, dyslipidemia, and glucose intolerance and/or hyperinsulinemia.', 'BMI was correlated with both components of adipose tissue--subcutaneous (r = 0.66, P < 0.01) and VFA (r = 0.33, P < 0.02)--and leptin levels (r = 0.38, P < 0.01). In contrast, VFA was correlated with 2-h glucose and insulin levels (r = 0.32 and 0.35, P < 0.05, respectively), triglyceride, HDL cholesterol, and uric acid (r = 0.33, -0.34 and 0.24, P < 0.05, respectively). Subjects with high VFA, matched for BMI, showed greater plasma glucose area under the curve (621 +/- 127 vs. 558 +/- 129 mg x h(-1) x dl(-1), P < 0.05), 2-h insulin (804 +/- 599 vs. 579 +/- 347 pmol/l, P < 0.05), and uric acid levels (0.33 +/- 0.07 vs. 0.26 +/- 0.06 mmol/l, P < 0.05) than subjects with low VFA. In logistic regression analysis, waist circumference, VFA, and 2-h insulin were identified as independent predictors of MS. Receiver operating characteristic curve analysis pointed out the values of 104 cm for waist circumference (58.1% specificity, 84.1% sensitivity), 158.5 cm(2) for VFA (78.1% specificity, 52.3% sensitivity), and 559.8 pmol/l for 2-h insulin (71.9% specificity, 69.8% sensitivity); the presence of at least two of the three variables resulted in a degree of concordance of 76%.
answer:
Does two-hour insulin determination improve the ability of abdominal fat measurement to identify risk for the metabolic syndrome?

question:
The general view on the pathogenesis of drug-induced idiosyncratic liver injury (DILI) is that parent compounds are rendered hepatotoxic by metabolism, mainly by cytochrome (CYP) 450, although other metabolic pathways can contribute. Anecdotal reports suggest a role of CYP 450 polymorphisms in DILI. We aimed to assess in a series of Spanish DILI patients the prevalence of important allelic variants of CYP2C9 and CYP2C19, known to be involved in the metabolism of several hepatotoxic drugs.', 'Genotyping of CYP2C9 ((*)2, (*)3) and CYP2C19 ((*)2 and (*)3), was carried out in a total of 28 and 32 patients with a well established diagnosis of DILI. CYP2C9 and CYP2C19 variants were analysed in genomic DNA by means of PCR-FRET and compared with previous findings in other Caucasian populations.', 'CYP2C9 and CYP2C19 allele and genotype frequencies were in agreement with Hardy-Weinberg equilibrium. Fourteen patients (50%) were heterozygous and 1(4%) found to be compound heterozygous for the CYP2C9 allele. Seven (22%) were found to carry one and 1(3%) carried two CYP2C19 mutated alleles. No patients were homozygous for (*)3 allele. The distribution of both CYP2C9 and CYP2C19 allelic variants in DILI patients were similar to those in other Caucasian populations. Patients with variant and those with wild-type alleles did not differ in regard to clinical presentation of DILI, type of injury and outcome.
answer:
Are genetic polymorphisms of CYP2C9 and CYP2C19 related to drug-induced idiosyncratic liver injury ( DILI )?