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 β-amyloid peptide (Aβ). Aβ is produced by sequential cleavage of the Amyloid Precursor Protein (APP) by β- and γ-secretases. Many studies have demonstrated that the internalization of APP from the cell surface can regulate Aβ production, although the exact organelle in which Aβ is produced remains contentious. A number of recent studies suggest that intracellular trafficking also plays a role in regulating Aβ 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 γ-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 γ-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 Aβ 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: Prostasomes are small (40-500 nm), granule-like bodies, found in normal epithelial cells of the prostate and secreted into the prostate duct system. Also poorly differentiated prostate cancer cells are producing prostasomes, since we could isolate and purify prostasomes from vertebral metastases with biochemical methods. To find out whether these prostasomes are secreted into extracellular sites of the metastases, we used electron microscopy.', 'Small biopsies from vertebral metastases of prostate cancer, taken directly from the operating field at surgery, were immediately fixated, embedded in plastic and processed for electron microscopy.', 'We found that prostasomes could be identified extracellularly in the interstitial tissues as well as in the cytoplasm of the metastatic cells.

SOLUTION: Are prostasomes secreted from poorly differentiated cells of prostate cancer metastases?

PROBLEM: The objective of this study was to determine if delivery of wound care instruction pre-Mohs micrographic surgery versus the typical, post-Mohs surgery would allow for greater patient retention.', 'A non-blinded, randomized, controlled trial receiving institutional review board exemption from Michigan State University was conducted over a three-month period. Patients scheduled for Mohs surgery on 13 selected days were randomized into pre- versus post-procedure groups to receive wound care education.', 'This study was conducted at a dermatology practice in Saint Joseph, Michigan.', 'Fifty cognitive and literate patients greater than 18 years of age were evaluated in this study.', "PARTICIPANTS' ability to recall instructions delivered by a Mohs surgeon in the form of digital media was assessed by a 10-question, multiple-choice exam. Additional analyses were conducted on patient's disposition around medical professionals, past experience with Mohs surgery, preference for digital media versus human instruction, and desire for home access.", 'Pre- (n=24; score=77±14%) versus post-(n=26; 83±11%) procedure education displayed no significant difference (p=0.13) in overall questionnaire performance. Seventy-four percent of participants preferred video delivery as opposed to provider instruction. Thirty-four percent reported being intimidated by healthcare workers. Participant performance showed no significant change (p=0.78) with previous exposure (79±19%) to Mohs surgery versus a first-time encounter (80±11%).

SOLUTION:
Does video education provide effective wound care instruction pre- or post-mohs micrographic surgery?