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: 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.

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


Question: Context: Only 2\xa0% of the human genome code for proteins. Among the remaining 98\xa0%, transposable elements (TEs) represent millions of sequences. TEs have an impact on genome evolution by promoting mutations. Especially, TEs possess their own regulatory sequences and can alter the expression pattern of neighboring genes. Since they can potentially be harmful, TE activity is regulated by epigenetic mechanisms. These mechanisms participate in the modulation of gene expression and can be associated with some human diseases resulting from gene expression deregulation. The fact that the TE silencing can be removed in cancer could explain a part of the changes in gene expression. Indeed, epigenetic modifications associated locally with TE sequences could impact neighboring genes since these modifications can spread to adjacent sequences.', 'We compared the histone enrichment, TE neighborhood, and expression divergence of human genes between a normal and a cancer conditions. We show that the presence of TEs near genes is associated with greater changes in histone enrichment and that differentially expressed genes harbor larger histone enrichment variation related to the presence of particular TEs.
Answer: Taken together, these results suggest that the presence of TEs near genes could favor important variation in gene expression when the cell environment is modified.

Answer: Is the transposable element environment of human genes associated with histone and expression changes in cancer?


Question: Context: Exclusion of macroprolactinaemia, a well-recognised interference, as the cause of hyperprolactinaemia is essential to avoid potential misdiagnosis and mismanagement of patients. We have derived gender-specific serum total and post-polyethylene glycol (PEG) precipitation monomeric reference ranges for the recently re-standardised Abbott Architect prolactin assay.', "Prolactin was measured in serum samples obtained from males (n=49) and females (n=52) using the current Abbott Architect immunoassay pre- and post-PEG precipitation. Gender-specific reference ranges were derived for total and monomeric (post-PEG) prolactin. Routine patients' samples (n=175) with a serum total prolactin >700 mIU/L were screened for macroprolactinaemia to assess classification compared with our previous post-PEG precipitation percentage recovery-based approach.", "Reference ranges for serum total prolactin were 58-419 mIU/L (male) and 63-561 mIU/L (female). Male and female monomeric prolactin reference ranges were 32-309 mIU/L and 39-422 mIU/L, respectively. Mean (SD) post-PEG percentage recovery of the IS 84/500 prolactin standard was 80 (2.3)%. Of 175 patients' samples screened for macroprolactinaemia, 149 had monomeric prolactin concentrations (median monomeric prolactin=1035 mIU/L; median recovery=83%) above the gender-specific reference range. Monomeric prolactin concentrations (median monomeric prolactin=162 mIU/L; median recovery=20%) in the remaining 26 were within the reference ranges. One patient classified as macroprolactin positive and another classified as macroprolactin negative would not have been identified as such using the previous recovery-based approach.
Answer: The use of post-PEG monomeric reference ranges not only identifies hyperprolactinaemia due solely to macroprolactinaemia but has the added advantage of identifying patients who have simultaneous true monomeric hyperprolactinaemia and elevated concentrations of macroprolactin.

Answer:
Does reference range for serum total and monomeric prolactin for the current generation Abbott Architect assay?