Given a passage with a context and an answer, 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.
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Question: Context: Diabetic cardiomyopathy (DCM) is associated with suppressed autophagy and augmented apoptosis in the heart although the interplay between the two remains elusive. The ability of mammalian sterile 20-like kinase 1 to regulate both autophagy and apoptosis prompted us to investigate it as a possible candidate in the progression of DCM.', 'Wild-type, Mst1 (also known as Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to induce experimental diabetes. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulated diabetes to probe mechanisms.', 'Mst1 knockout alleviated while Mst1 overexpression aggravated cardiac dysfunction in diabetes. Diabetic Mst1 transgenic mice exhibited decreased LC3 expression and enhanced protein aggregation. In contrast, typical autophagosomes were observed in diabetic Mst1-knockout mice with increased LC3 expression and reduced protein aggregation. Mst1 downregulation promoted autophagic flux as demonstrated by increased LC3-II and decreased p62 expression in the presence of bafilomycin A1. Furthermore, Mst1 overexpression increased, while Mst1 knockout decreased, cardiomyocyte apoptosis both in vivo and in vitro. Co-immunoprecipitation assays showed that Mst1 overexpression promoted Beclin1 binding to B cell lymphoma 2 (Bcl-2) and induced dissociation of Bcl-2 from Bax in diabetic mice. Conversely, Mst1 knockout disrupted the Beclin1-Bcl-2 complex and enhanced the interaction between Bcl-2 and Bax.
Answer: Mst1 knockout restores autophagy and protects against apoptosis in cardiomyocytes, en route to the rescue against DCM.

Answer: Does mST1 coordinately regulate autophagy and apoptosis in diabetic cardiomyopathy in mice?


Question: Context: Cigarette smoke disrupts the protective barrier established by the airway epithelium through direct damage to the epithelial cells, leading to cell death. Since the morphology of the airway epithelium of smokers does not typically demonstrate necrosis, the most likely mechanism for epithelial cell death in response to cigarette smoke is apoptosis. We hypothesized that cigarette smoke directly up-regulates expression of apoptotic genes, which could play a role in airway epithelial apoptosis.', 'Microarray analysis of airway epithelium obtained by bronchoscopy on matched cohorts of 13 phenotypically normal smokers and 9 non-smokers was used to identify specific genes modulated by smoking that were associated with apoptosis. Among the up-regulated apoptotic genes was pirin (3.1-fold, p < 0.002), an iron-binding nuclear protein and transcription cofactor. In vitro studies using human bronchial cells exposed to cigarette smoke extract (CSE) and an adenovirus vector encoding the pirin cDNA (AdPirin) were performed to test the direct effect of cigarette smoke on pirin expression and the effect of pirin expression on apoptosis.', 'Quantitative TaqMan RT-PCR confirmed a 2-fold increase in pirin expression in the airway epithelium of smokers compared to non-smokers (p < 0.02). CSE applied to primary human bronchial epithelial cell cultures demonstrated that pirin mRNA levels increase in a time-and concentration-dependent manner (p < 0.03, all conditions compared to controls). Overexpression of pirin, using the vector AdPirin, in human bronchial epithelial cells was associated with an increase in the number of apoptotic cells assessed by both TUNEL assay (5-fold, p < 0.01) and ELISA for cytoplasmic nucleosomes (19.3-fold, p < 0.01) compared to control adenovirus vector.
Answer: These observations suggest that up-regulation of pirin may represent one mechanism by which cigarette smoke induces apoptosis in the airway epithelium, an observation that has implications for the pathogenesis of cigarette smoke-induced diseases.

Answer: Is upregulation of pirin expression by chronic cigarette smoking associated with bronchial epithelial cell apoptosis?


Question: Context: Various surgical techniques to treat posterolateral knee instability have been described. To date, the recommended treatment is an anatomic form of reconstruction in which the 3 key structures of the posterolateral corner (PLC) are addressed: the popliteofibular ligament, the popliteus tendon, and the lateral collateral ligament.', 'The purpose of this study was to identify the role of each key structure of the PLC in kinematics of the knee and to biomechanically analyze a single-graft, fibular-based reconstruction that replicates the femoral insertions of the lateral collateral ligament and popliteus to repair the PLC. The hypothesis was that knee kinematics can be reasonably restored using a single graft with a 2-strand "modified Larson" technique.', 'Descriptive laboratory study.', 'Eight fresh-frozen cadaveric knees were used in this study. We conducted sequential sectioning of the popliteofibular ligament (PFL) and then subsequently the popliteal tendon (PT), the lateral collateral ligament (LCL), and the anterior cruciate ligament (ACL). We then reconstructed the ACL first and then the posterolateral corner using the modified Larson technique. A surgical navigation system was used to measure varus laxity and external rotation at 0°, 30°, 60°, and 90° with a 9.8-N·m varus stress and 5-N·m external rotation force applied to the tibia.', 'In extension, varus laxity increased only after the sectioning of the lateral collateral ligament. At 30° of flexion, external rotation in varus and translation of the lateral tibial plateau increased after the isolated popliteofibular ligament section. From 60° to 90° of flexion, translation and mobility of the lateral plateau section increased after sectioning of the PFL. After reconstruction, we observed a restoration of external varus rotation in extension and translation of the lateral tibial plateau at 90° of flexion. This technique provided kinematics similar to the normal knee.
Answer: The PFL has a key role between 30° and 90° of flexion, and the lateral collateral ligament plays a role in extension. Reconstruction with the modified Larson technique restores these 2 complementary stabilizers of the knee.

Answer:
Does reconstruction of the Posterolateral Corner After Sequential Sectioning restore Knee Kinematics?