instruction:
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.
question:
Context: Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein function until the local cellular redox environment has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the Forkhead Box O4 (FOXO4) transcription factor.', 'In this study, we sought to investigate whether redox signaling differentially controls the human FOXO3 and FOXO4 paralogs.', 'We present evidence that FOXO3 and FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution. Using a proteome-wide screen, we identified previously unknown redox-dependent FOXO3 interaction partners. The nuclear import receptors Importin-7 (IPO7) and Importin-8 (IPO8) form a disulfide-dependent heterodimer with FOXO3, which is required for its reactive oxygen species-induced nuclear translocation. FOXO4 does not interact with IPO7 or IPO8.
Answer: IPO7 and IPO8 control the nuclear import of FOXO3, but not FOXO4, in a redox-sensitive and disulfide-dependent manner. Our findings suggest that evolutionary acquisition of cysteines has contributed to regulatory divergence of FOXO paralogs, and that phylogenetic analysis can aid in the identification of cysteines involved in redox signaling.
answer:
Does evolutionary acquisition of cysteines determine FOXO paralog-specific redox signaling?


question:
Context: To simultaneously study the effect of a selective cyclooxygenase-2 (COX-2) inhibitor and that of a classic non-steroidal anti-inflammatory drug (NSAID) on the expression of pro-inflammatory genes in the cartilage of patients with severe knee osteoarthritis (OA) and in cultured human OA chondrocytes.', 'A 3-month clinical trial was carried out on 30 patients with severe knee OA scheduled for knee replacement surgery. Patients were randomized into two groups: patients treated with celecoxib (CBX) and patients treated with aceclofenac (ACF). OA patients who did not want to be treated served as the control group. After surgery, cartilage was processed for molecular biology studies. We also employed cultured chondrocytes from different OA patients to examine NSAID effects on pro-inflammatory gene expression in cells stimulated with interleukin (IL)-1beta.', 'Both CBX and ACF inhibited COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and inducible nitric oxide synthase (iNOS) synthesis in the articular cartilage of OA patients. In cultured chondrocytes, both NSAID decreased COX-2 and mPGES-1 synthesis and prostaglandin E2 (PGE2) release induced by IL-1beta, while no effect was observed on nitric oxide or iNOS synthesis. In OA patients, only CBX decreased tumor necrosis factor alpha and IL-1beta expression in the cartilage, while both NSAID diminished IL-1beta induced cytokine synthesis in cultured OA chondrocytes.
Answer: Both NSAID diminished PGE2 release and induced a decrease in COX-2 and mPGES-1 synthesis in the cartilage from OA patients and in OA chondrocytes. These data suggest that prolonged therapy with PGE2 blocking agents decreases PGE2 production not only by direct inhibition of COX-2 activity, but also by down-regulating COX-2 and mPGES-1 synthesis in the cartilage. However, CBX and ACF seem to have a different anti-inflammatory profile in controlling pro-inflammatory gene expression in the cartilage.
answer:
Does long-term NSAID treatment directly decrease COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis?


question:
Context: To map and compare the right atrium in patients with AF to those with atrioventricular nodal reentrant tachycardias (AVNRT, as control group) and to investigate the anatomical and electrophysiological abnormality of the right atrium in AF.', 'The anatomy and electrophysiology of right atrium and cavotricuspid isthmus were evaluated in 20 patients with AF (16 M/4 F, mean age 55.9 +/- 10.68 years) and 26 patients with AVNRT (9 M/17 F, mean age 47.50 +/- 19.56 years) during coronary sinus pacing at 600 ms prior to ablation with electro-anatomical mapping system. Right atrial volume (RAV), the length and width of cavotricuspid isthmus (IsL, IsW), unipolar and bipolar voltage in the right atrium (UniV-RA, BiV-RA) were measured and compared between patients with AF and those with AVNRT.', 'RAV, IsL, IsW, UniV-RA, and BiV-RA were 143.22 +/- 40.72 vs 104.35 +/- 21.06 ml, 39.31 +/- 8.10 vs 32.42 +/- 9.77 mm, 30.54 +/- 7.48 vs 23.15 +/- 6.61 mm, 1.96 +/- 1.24 vs 1.53 +/- 0.91 mv and 1.47 +/- 1.47 vs 1.29 +/- 1.12 mv in AF and AVNRT respectively.
Answer: The right atrial volume is larger; both the length and width of cavotricuspid isthmus are greater. Unipolar and bipolar voltages in the right atrium are higher in AF than in AVNRT, suggesting that the enlarged right atrium, increased length and width of cavotricuspid isthmus, and concomitant atrial hypertrophy are important substrates for initiation and perpetuation of typical AF.
answer:

Is electro-anatomic mapping of the right atrium : anatomic abnormality an important substrate?