TASK DEFINITION: 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.
PROBLEM: 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.

SOLUTION: Is the Amyloid Precursor Protein rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid?

PROBLEM: To investigate the inhibitory effects of adenovirus-mediated NDRG2 on the proliferation of human renal cell carcinoma cell line OS-RC-2 in vitro.', 'NDRG2 was harvested by RT-PCR, confirmed by DNA sequencing, and then cloned into the eukaryotic expression vector pIRES2-EGFP, which encodes green fluorescent protein (GFP), to construct pIRES2-EGFP-NDRG2 plasmid. OS-RC-2 cells with NDRG2 negative expression were transfected with pIRES2-EGFP-NDRG2 plasmid. The growth of transfected OS-RC-2 cells was observed under light and fluorescence microscopes. After colony-forming cell assays, cell proliferation detection and MTT assays, the growth curves of cells in each group were plotted to investigate the inhibitory effects of adenovirus-mediated NDRG2 on the proliferation of OS-RC-2 cells. Cell cycle was determined by flow cytometry. Confocal laser scanning microscopy showed that NDRG2 protein was specifically located on subcellular organelle.', 'A eukaryotic expression vector pIRES2-EGFP-NDRG2 was successfully constructed. After NDRG2 transfection, the growth of OS-RC-2 cells was inhibited. Flow cytometry showed that cells were arrested in S phase but the peak of cell apoptosis was not present, and confocal laser scanning microscopy showed that NDRG2 protein was located in mitochondrion.

SOLUTION: Does adenovirus-mediated NDRG2 inhibit the proliferation of human renal cell carcinoma cell line OS-RC-2 in vitro?

PROBLEM: Certain circulating cells have been shown to predict the clinical outcome of several cancers. The objective of this study was to identify clinical, hematological and immunological predictors of prognosis in non-small cell lung cancer (NSCLC) patients.', 'A retrospective study on a prevalent cohort of 225 NSCLC patients hospitalized at the Zhejiang Province Cancer Hospital (ZPCH) was conducted from August 1, 2006 to April 15, 2008. Circulating lymphocytes were measured by flow cytometry. WBC count and classification in peripheral blood were measured with a Coulter counter. We calculated the proportion of patients surviving after first hospital admission and hazard ratios (HR) using the Cox proportional hazards model.', 'Elevated levels of preoperative circulating CD44(+) lymphocytes, WBCs and neutrophils indicated low cumulative survival. Clinical stage (HR: 2.292; 95% confidence interval (CI): 1.34-3.91, P=0.002), neutrophils (HR: 1.877; 95% CI: 1.34-2.62, P<0.001) and CD44(+) lymphocytes (HR: 1.018; 95% CI: 1.00-1.03, P=0.002) are independent predictors of survival in NSCLC patients, respectively. Elevated levels of CD44(+) lymphocytes and neutrophils correlated with distant metastasis and prognosis in NSCLC patients with stage III/IV, respectively.

SOLUTION:
Do elevated levels of preoperative circulating CD44 lymphocytes and neutrophils predict poor survival for non-small cell lung cancer patients?