TASK DEFINITION: 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.
PROBLEM: Context: Glial cell line-derived neurotrophic factor (GDNF) and N-cadherin interact to transduce intracellular signals. However, the specific molecular mechanisms of this interaction are unclear. This study attempted to detect changes in GDNF-induced -catenin phosphorylation and nuclear translocation in C6 glioma cells.', 'C6 glioma cells were treated with GDNF (70 ng/mL) and membrane and cytoplasmic proteins were extracted. A N-cadherin antibody was used for co-immunoprecipitation (co-IP). Western blot analysis using the co-IP protein was completed using antibodies for -catenin, Src and -actin. Immunocytochemistry was conducted with the same antibodies. To determine if Src induced phosphorylation of -catenin Tyr-654, Western blot analysis was also performed on nuclear proteins from C6 cells treated with tyrosine kinase inhibitor PP2 using then p- -catenin antibody.', 'After induced by GDNF, C6 cell membrane -catenin was phosphorylated at Tyr-654 and subsequently separated from the N-cadherin/-catenin complex. Further study confirmed that the induction by GDNF significantly increased cytoplasmic and nuclear expression of phospho--catenin (Tyr-654) in C6 glioma cells. There was also an increase in the binding of non-receptor protein kinase Src with N-cadherin on the inner cell membrane surface. Src induced phosphorylation of -catenin Tyr-654 induced by GDNF decreased significantly.\Question: Does glial cell line-derived neurotrophic factor promote -catenin phosphorylation and nuclear translocation in glioma cells?

SOLUTION: The results of our study demonstrate that GDNF increases the intracellular phosphorylation level of -catenin through N-cadherin/Src signaling, which subsequently stimulates the nuclear translocation of -catenin. This study provides a theoretical basis for us to reveal the role of biological mechanisms on glioma cell by GDNF.

PROBLEM: Context: During reactive hyperemia, the brachial artery in some individuals constricts prior to dilation. Our aim was to describe the frequency of high-flow-mediated constriction (H-FMC) in adults, and its relationship to body composition and biomarkers of cardiovascular and metabolic risk.', 'Two hundred forty-six adults (124 male, 122 female; 367 years old) were assessed for H-FMC via sonographic imaging of the brachial artery. Blood pressure, glucose, insulin, lipids, and body composition assessed via dual energy X-ray absorptiometry were collected. H-FMC was characterized as a 10-second average of maximal postocclusion constriction. Independent t test was used to compare H-FMC versus non-H-FMC individuals.', 'H-FMC was observed in approximately 69% of adult participants (54 obese, 57 overweight, and 59 normal weight). Total body mass (82.317.5 versus 76.316.3 kg, p=0.012), fat mass (27.711.5 versus 23.810.5 kg, p=0.012), body mass index (27.74.9 versus 26.15.0 kg/m\Question: Is high-flow-mediated constriction in adults influenced by biomarkers of cardiovascular and metabolic risk?

SOLUTION: Increased body mass, fat mass, and body mass index were associated with a greater H-FMC. When H-FMC was present, the FMD response to reactive hyperemia was significantly lower. Because H-FMC has been observed to negatively affect FMD response to reactive hyperemia, we suggest that H-FMC should be noted when analyzing and interpreting FMD data. H-FMC may be an ancillary measure of endothelial health. ©️ 2016 Wiley Periodicals, Inc. J Clin Ultrasound, 2016.

PROBLEM: Context: SCF (Skp1-Cullin-F-box) complexes are a major class of E3 ligases that are required to selectively target substrates for ubiquitin-dependent degradation by the 26S proteasome. Conjugation of the ubiquitin-like protein Nedd8 to the cullin subunit (neddylation) positively regulates activity of SCF complexes, most likely by increasing their affinity for the E2 conjugated to ubiquitin. The Nedd8 conjugation pathway is required in C. elegans embryos for the ubiquitin-mediated degradation of the microtubule-severing protein MEI-1/Katanin at the meiosis-to-mitosis transition. Genetic experiments suggest that this pathway controls the activity of a CUL-3-based E3 ligase. Counteracting the Nedd8 pathway, the COP9/signalosome has been shown to promote deneddylation of the cullin subunit. However, little is known about the role of neddylation and deneddylation for E3 ligase activity in vivo.', 'Here, we identified and characterized the COP9/signalosome in C. elegans and showed that it promotes deneddylation of CUL-3, a critical target of the Nedd8 conjugation pathway. As in other species, the C. elegans signalosome is a macromolecular complex containing at least six subunits that localizes in the nucleus and the cytoplasm. Reducing COP9/signalosome function by RNAi results in a failure to degrade MEI-1, leading to severe defects in microtubule-dependent processes during the first mitotic division. Intriguingly, reducing COP9/signalosome function suppresses a partial defect in the neddylation pathway; this suppression suggests that deneddylation and neddylation antagonize each other.\Question: Is neddylation and deneddylation of CUL-3 required to target MEI-1/Katanin for degradation at the meiosis-to-mitosis transition in C. elegans?

SOLUTION:
We conclude that both neddylation and deneddylation of CUL-3 is required for MEI-1 degradation and propose that cycles of CUL-3 neddylation and deneddylation are necessary for its ligase activity in vivo.