instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Animal data show that low protein intake in pregnancy programs higher offspring blood pressure, but similar data in humans are limited. We examined the associations of first and second trimester maternal protein intake with offspring blood pressure (BP) at the age of six months.', 'In a prospective US cohort study, called Project Viva, pregnant women completed validated semi-quantitative food-frequency questionnaires (FFQ) to measure gestational protein intake. Among 947 mother-offspring pairs with first trimester dietary data and 910 pairs with second trimester data, we measured systolic blood pressure (SBP) up to five times with an automated device in the offspring at the age of six months. Controlling for blood pressure measurement conditions, maternal and infant characteristics, we examined the effect of energy-adjusted maternal protein intake on infant SBP using multivariable mixed effects models.', 'Mean daily second trimester maternal protein intake was 17.6% of energy (mean 2111 kcal/day). First trimester nutrient intakes were similar. Mean SBP at age 6 months was 90.0 mm Hg (SD 12.9). Consistent with prior reports, adjusted SBP was 1.94 mm Hg lower [95% confidence interval (CI) -3.45 to -0.42] for each kg increase in birth weight. However, we did not find an association between maternal protein intake and infant SBP. After adjusting for covariates, the effect estimates were 0.14 mm Hg (95% CI 20.12 to 20.40) for a 1% increase in energy from protein during the second trimester, and 20.01 mm Hg (95% CI 20.24 to -0.23) for a 1% increase in energy from protein in the first trimester.\Question: Is maternal protein intake associated with infant blood pressure?
answer:
Variation in maternal total protein intake during pregnancy does not appear to program offspring blood pressure.


question:
Context: The PINK1-Parkin pathway is known to play important roles in regulating mitochondria dynamics, motility, and quality control. Activation of this pathway can be triggered by a variety of cellular stress signals that cause mitochondrial damage. How this pathway senses different levels of mitochondrial damage and mediates cell fate decisions accordingly is incompletely understood.', 'Here, we present evidence that PINK1-Parkin has both cytoprotective and proapoptotic functions. PINK1-Parkin operates as a molecular switch to dictate cell fate decisions in response to different cellular stressors. Cells exposed to severe and irreparable mitochondrial damage agents such as valinomycin can undergo PINK1-Parkin-dependent apoptosis. The proapoptotic response elicited by valinomycin is associated with the degradation of Mcl-1. PINK1 directly phosphorylates Parkin at Ser65 of its Ubl domain and triggers activation of its E3 ligase activity through an autocatalytic mechanism that amplifies its E3 ligase activity toward Mcl-1.\Question: Does pINK1 trigger autocatalytic activation of Parkin to specify cell fate decisions?
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Autocatalytic activation of Parkin bolsters its accumulation on mitochondria and apoptotic response to valinomycin. Our results suggest that PINK1-Parkin constitutes a damage-gated molecular switch that governs cellular-context-specific cell fate decisions in response to variable stress stimuli.


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Context: Epidermal growth factor receptors (EGFR) are required for tumor promotion by Western diet. The metalloprotease, ADAM17 activates EGFR by releasing pro-EGFR ligands. ADAM17 is regulated by G-protein-coupled receptors, including CXCR4. Here we investigated CXCR4-ADAM17 crosstalk and examined the role of ADAM17 in tumorigenesis.', 'We used CXCR4 inhibitor, AMD3100 and ADAM17 inhibitor, BMS566394 to assess CXCR4-ADAM17 crosstalk in colon cancer cells. We compared the expression of CXCR4 ligand, CXCL2, and ADAM17 in mice fed Western diet versus standard diet. Separately, mice were treated with marimastat, a broad-spectrum ADAM17 inhibitor, or AMD3100 to assess EGFR activation by ADAM17 and CXCR4. Using Apc-mutant Min mice, we investigated the effects of ADAM17/10 inhibitor INCB3619 on tumorigenesis. To assess the effects of colonocyte ADAM17, mice with ADAM17 conditional deletion were treated with azoxymethane (AOM). ADAM17 expression was also compared in colonocytes from primary human colon cancers and adjacent mucosa.', 'CXCL12 treatment activated colon cancer cell EGFR signals, and CXCR4 or ADAM17 blockade reduced this activation. In vivo, Western diet increased CXCL12 in stromal cells and TGFα in colonocytes. Marimastat or AMD3100 caused >50% reduction in EGFR signals (P < 0.05). In Min mice, INCB3619 reduced EGFR signals in adenomas and inhibited intestinal tumor multiplicity (P < 0.05). In the AOM model, colonocyte ADAM17 deletion reduced EGFR signals and colonic tumor development (P < 0.05). Finally, ADAM17 was upregulated >2.5-fold in human malignant colonocytes.\Question: Is aDAM17 a Tumor Promoter and Therapeutic Target in Western Diet-associated Colon Cancer?
answer:

ADAM17 is a Western diet-inducible enzyme activated by CXCL12-CXCR4 signaling, suggesting the pathway: Western diet→CXCL12→CXCR4→ADAM17→TGFα→EGFR. ADAM17 might serve as a druggable target in chemoprevention strategies. Clin Cancer Res; 1-13. ©2016 AACR.