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.
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Question: Context: Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients.', 'The effects of allogeneic umbilical cord-derived MSCs (UC-MSCs) on inhibition of T cell proliferation were determined. MSC functional molecules were stimulated with peripheral blood mononuclear cells from healthy controls and SLE patients and examined by real-time polymerase chain reaction. CD4+ and CD8+ T cells were purified using microbeads to stimulate MSCs in order to determine cytokine expression by MSCs and to further determine which cell subset(s) or which molecule(s) is involved in inhibition of MSC-mediated T cell proliferation. The related signaling pathways were assessed. We determined levels of serum cytokines in lupus patients before and after UC-MSC transplantation.', 'Allogeneic UC-MSCs suppressed T cell proliferation in lupus patients by secreting large amounts of indoleamine 2,3-dioxygenase (IDO). We further found that interferon-γ (IFNγ), which is produced predominantly by lupus CD8+ T cells, is the key factor that enhances IDO activity in allogeneic MSCs and that it is associated with IFNGR1/JAK-2/STAT signaling pathways. Intriguingly, bone marrow-derived MSCs from patients with active lupus demonstrated defective IDO production in response to IFNγ and allogeneic CD8+ T cell stimulation. After allogeneic UC-MSC transplantation, serum IDO activity increased in lupus patients.\Question: Is a CD8 T cell/indoleamine 2,3-dioxygenase axis required for mesenchymal stem cell suppression of human systemic lupus erythematosus?

Answer: We found a previously unrecognized CD8+ T cell/IFNγ/IDO axis that mediates the therapeutic effects of allogeneic MSCs in lupus patients.


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.\Question: Does evolutionary acquisition of cysteines determine FOXO paralog-specific redox signaling?

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.


Question: Context: We previously showed that the cardioversion threshold (CVT) for ventricular tachycardia (VT) is phase dependent when a single monophasic shock (1MP) is used.', 'The purpose of this study was to extend these findings to a biphasic shock (1BP) and to compare the efficacy of phase-independent multiple monophasic (5MP) and biphasic shocks (5BP).', 'Panoramic optical mapping with blebbistatin (5 microM) was performed in postmyocardial infarction rabbit hearts (n = 8). Flecainide (1.64 +/- 0.68 microM) was administered to promote sustained arrhythmias. 5MP and 5BP were applied within one VT cycle length (CL). Results were compared to 1BP and antitachycardia pacing.', 'We observed monomorphic VT with CL = 149.6 +/- 18.0 ms. Similar to 1MP, CVTs of 1BP were found to be phase dependent, and the maximum versus minimum CVT was 8.6 +/- 1.7 V/cm versus 3.7 +/- 1.9 V/cm, respectively (P = .0013). Efficacy of 5MP was higher than that of 1BP and 5BP. CVT was 3.2 +/- 1.4 V/cm for 5MP versus 5.3 +/- 1.9 V/cm for 5BP (P = .00027). 5MP versus averaged 1BP CVT was 3.6 +/- 2.1 V/cm versus. 6.8 +/- 1.5 V/cm, respectively (P = .00024). Antitachycardia pacing was found to be completely ineffective in this model.\Question: Do multiple monophasic shocks improve electrotherapy of ventricular tachycardia in a rabbit model of chronic infarction?

Answer:
Maintenance of shock-induced virtual electrode polarization by multiple monophasic shocks over a VT cycle is responsible for unpinning of reentry leading to self-termination. Elimination of virtual electrode polarization by shock polarity reversal during multiple biphasic shocks proved ineffective. A significant reduction in CVT can be achieved by applying multiple monophasic shocks within one VT CL or one single shock at the proper coupling interval.