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.

Input: Consider Input: Context: BAF312 (Siponimod) is a dual agonist at the sphingosine-1 phosphate receptors, S1PR1 and S1PR5. This drug is currently undergoing clinical trials for the treatment of secondary progressive multiple sclerosis (MS). Here, we investigated the effects of BAF312 on isolated astrocyte and microglia cultures as well as in slice culture models of demyelination.', 'Mouse and human astrocytes were treated with S1PR modulators and changes in the levels of pERK, pAkt, and calcium signalling as well as S1PR1 internalization and cytokine levels was investigated using Western blotting, immunochemistry, ELISA and confocal microscopy. Organotypic slice cultures were prepared from the cerebellum of 10-day-old mice and treated with lysophosphatidylcholine (LPC), psychosine and/or S1PR modulators, and changes in myelination states were measured by fluorescence of myelin basic protein and neurofilament H.', 'BAF312 treatment of human and mouse astrocytes activated pERK, pAKT and Ca(2+) signalling as well as inducing S1PR1 internalization. Notably, activation of S1PR1 increased pERK and pAKT in mouse astrocytes while both S1PR1 and S1PR3 equally increased pERK and pAKT in human astrocytes, suggesting that the coupling of S1PR1 and S1PR3 to pERK and pAKT differ in mouse and human astrocytes. We also observed that BAF312 moderately attenuated lipopolysaccharide (LPS)- or TNFα/IL17-induced levels of IL6 in both astrocyte and microglia cell cultures. In organotypic slice cultures, BAF312 reduced LPC-induced levels of IL6 and attenuated LPC-mediated demyelination. We have shown previously that the toxic lipid metabolite psychosine induces demyelination in organotypic slice cultures, without altering the levels of cytokines, such as IL6. Importantly, psychosine-induced demyelination was also attenuated by BAF312.
Answer: Overall, this study suggests that BAF312 can modulate glial cell function and attenuate demyelination, highlighting this drug as a further potential therapy in demyelinating disorders, beyond MS.

Output: Does the dual S1PR1/S1PR5 drug BAF312 ( Siponimod ) attenuate demyelination in organotypic slice cultures?


Input: Consider Input: Context: Alloreactive NK cells play a role in tumor eradication after allogeneic HLA mismatched stem cell transplantation (SCT). The effect of NK alloreactivity in HLA identical SCT is still under debate and in particular in transplantation for chronic myeloid leukemia (CML) the data are very limited and with conflicting outcome. The aim of our study was to evaluate the effect of KIR genes and KIR ligands on leukemia free survival (LFS) and relapse rate in a well-defined, homogeneous group of CML patients phase upon HLA identical sibling SCT.', 'We retrospectively analyzed the effect of KIRs and KIR ligands (C1 and C2) on LFS and relapse in 70 CML patients in 1st chronic phase, who had received an HLA identical sibling graft. For KIR typing we used a single PCR based KIR typing protocol that also included primers allowing for the identification of the KIR binding site on HLA-Cw (AA 77 and 80).', 'The data show clear differences in transplant outcome between patients having both ligands (C1 and C2) as compared to patients having only one ligand (C1 or C2). In the latter group, the stimulatory KIR2DS5 gene was associated with improved leukemia free survival (p=0.007; hazard ratio 4.3; 95% confidence interval 1.3-6.7) and lower relapse rates (p=0.028; HR 4.3, 95% CI 1.1-9.1). In contrast, in patients carrying both ligands, KIR2DS5 was associated with reduced LFS (p=0.0056; HR 0.3; 95% CI 0.1-0.7) and higher relapse rate (p=0.02; HR 0.35, 95% CI 0.1-0.8).
Answer: Our data indicate a role for an NK mediated anti-CML response after HLA identical sibling SCT that is influenced by KIR ligands and, more importantly, by stimulatory KIRs present in the donor.

Output: Is kIR2DS5 associated with leukemia free survival after HLA identical stem cell transplantation in chronic myeloid leukemia patients?


Input: Consider Input: Context: Visfatin is an insulin-mimicking adipokine. Visfatin is elevated in obesity and type 2 diabetes. However, its role in glucose and lipid metabolism in healthy humans is unclear.', 'The objective was to investigate the correlations of visfatin with phenotypes of glucose, lipids, and body composition and the responses of visfatin to short-term overfeeding in healthy young men.', 'Sixty-one healthy young men were recruited from the Newfoundland population. Serum visfatin, interleukin 6, glucose, insulin, total cholesterol, HDL cholesterol, LDL cholesterol, and triacylglycerol concentrations were measured with an autoanalyzer, and percentage body fat (%BF) and percentage trunk fat (%TF) were measured with dual-energy X-ray absorptiometry. Insulin resistance and beta cell function were assessed with the homeostasis model. All measurements were completed at baseline and after a 7-d overfeeding protocol exceeding the baseline requirement by 70%. Subjects were classified on the basis of %BF as lean (<21%), overweight (21-25.9%), or obese (>or=26%).', 'Multiple regression analysis showed that triacylglycerols correlated with fasting serum visfatin (P < 0.001). Moreover, serum visfatin decreased 19% overall-23% in lean, 9% in overweight, and 18% in obese subjects (P < 0.0001)-after the overfeeding protocol. None of the variables measured, including interleukin 6, were associated with the reduction in visfatin. In contrast with the findings in mice, visfatin concentrations before and after overfeeding did not correlate with glucose, insulin, insulin resistance, beta cell function, %BF, or %TF.
Answer: Visfatin is down-regulated by overfeeding. Under physiologic conditions, visfatin does not appear to control glucose metabolism but may play a regulatory role in lipid metabolism.


Output: Are serum visfatin concentrations positively correlated with serum triacylglycerols and down-regulated by overfeeding in healthy young men?