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.

Ex Input:
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 β-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 β-catenin, Src and β-actin. Immunocytochemistry was conducted with the same antibodies. To determine if Src induced phosphorylation of β-catenin Tyr-654, Western blot analysis was also performed on nuclear proteins from C6 cells treated with tyrosine kinase inhibitor PP2 using then p- β-catenin antibody.', 'After induced by GDNF, C6 cell membrane β-catenin was phosphorylated at Tyr-654 and subsequently separated from the N-cadherin/β-catenin complex. Further study confirmed that the induction by GDNF significantly increased cytoplasmic and nuclear expression of phospho-β-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 β-catenin Tyr-654 induced by GDNF decreased significantly.\Question: Does glial cell line-derived neurotrophic factor promote β-catenin phosphorylation and nuclear translocation in glioma cells?

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


Ex Input:
Context: Most melanomas harbor oncogenic BRAF(V600) mutations, which constitutively activate the MAPK pathway. Although MAPK pathway inhibitors show clinical benefit in BRAF(V600)-mutant melanoma, it remains incompletely understood why 10% to 20% of patients fail to respond. Here, we show that RAF inhibitor-sensitive and inhibitor-resistant BRAF(V600)-mutant melanomas display distinct transcriptional profiles. Whereas most drug-sensitive cell lines and patient biopsies showed high expression and activity of the melanocytic lineage transcription factor MITF, intrinsically resistant cell lines and biopsies displayed low MITF expression but higher levels of NF-κB signaling and the receptor tyrosine kinase AXL. In vitro, these MITF-low/NF-κB-high melanomas were resistant to inhibition of RAF and MEK, singly or in combination, and ERK. Moreover, in cell lines, NF-κB activation antagonized MITF expression and induced both resistance marker genes and drug resistance. Thus, distinct cell states characterized by MITF or NF-κB activity may influence intrinsic resistance to MAPK pathway inhibitors in BRAF(V600)-mutant melanoma.\Question: Does a melanoma cell state distinction influence sensitivity to MAPK pathway inhibitors?

Ex Output:
Although most BRAF(V600)-mutant melanomas are sensitive to RAF and/or MEK inhibitors, a subset fails to respond to such treatment. This study characterizes a transcriptional cell state distinction linked to MITF and NF-κB that may modulate intrinsic sensitivity of melanomas to MAPK pathway inhibitors.


Ex Input:
Context: Trauma is the leading cause of injury and death for individuals aged 1-44 years. Up to 8% of the US population participates in winter sports, and although vascular injuries are uncommon in these activities, little is published in this area. We sought to identify the incidence, injury patterns, and outcomes of vascular injuries resulting from winter sports trauma.', 'Patients with winter sports trauma and the subset with vascular injuries were identified by accessing the National Trauma Data Bank querying years 2007-2010. Patients with and without vascular injuries were then compared. Admission variables included transport time, emergency department hypotension (systolic blood pressure < 90), Glasgow Coma Scale ≤ 8, Injury Severity Score ≥ 25, fractures, solid organ injury, and vascular injury. Outcomes were analyzed and associations with vascular injuries were determined.', 'A total of 2,298 patients were identified with winter sports-related trauma and 28 (1.2%) had associated vascular injuries. Overall, the top 3 injuries were head trauma (16.7%), thoracic vertebral fractures (5.5%), and lumbar vertebral fractures (5.1%). The most common associated vascular injures were to the popliteal artery (17.7%), splenic artery (14.7%), and brachial blood vessels (14.7%). In the entire cohort, 1 patient (0.04%) suffered an amputation and 15 patients (0.7%) died. There were no amputations in the vascular injury group. Mortality was 0.6% in patients without a vascular injury compared with 7.1% of those with a vascular injury (P = 0.01).\Question: Is vascular injury associated with increased mortality in winter sports trauma?

Ex Output:

Although vascular injury is an uncommon associated finding in winter sports trauma, it is associated with a significant increase in mortality. These findings highlight the need for rapid identification of traumatic vascular injuries, which predicts worse overall outcomes in this patient population.