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.

[Q]: 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.
[A]: Does the dual S1PR1/S1PR5 drug BAF312 ( Siponimod ) attenuate demyelination in organotypic slice cultures?


[Q]: Context: Invasive species can have devastating effects on native ecosystems and therefore impose a significant threat to human welfare. The introduction rate of invasive species has accelerated dramatically in recent times due to human activity (anthropogenic effects), with a steadily growing pool of widespread tramp species. We present an in-depth analysis of four pantropical species of Xyleborus ambrosia beetles (Xyleborus volvulus, Xyleborus perforans, Xyleborus ferrugineus, and Xyleborus affinis) with similar ecology (fungus cultivation in dead wood), reproductive biology (permanent inbreeding) and genetic system (haplodiploidy). The unique combination of reproductive traits and broad host plant usage pre-adapts these beetles for colonizing of new areas.', 'We found that all four species were broadly distributed long before human-assisted dispersal became common, and that the impact of anthropogenic effects varied among the species. For X. volvulus, X. perforans, and X. affinis there was evidence of ancient establishment in numerous regions, but also of abundant recent introductions into previously colonized areas. For X. ferrugineus, we found clear biogeographical structuring of old clades, but little evidence for recent successful introductions.
Answer: Our results indicate that current human-aided transoceanic dispersal has strongly affected the genetic makeup of three of the species in this study. However, current biogeographical patterns of all four species are equally, if not more strongly, influenced by ancient establishment on different continents.
[A]: Do globally distributed Xyleborus species reveal recurrent intercontinental dispersal in a landscape of ancient worldwide distributions?


[Q]: Context: The safety of silicone breast implants recently has been questioned. Increasing numbers of women have reported a variety of health problems that they attribute to their implants. The purpose of this descriptive study was to explicate the phenomenon of silicone-related illness as reported by women who have had breast implants.', 'A qualitative design was grounded in the theoretical framework proposed by McBride and McBride (1981), the core of which is the first-person, lived experiences of women as interpreted and explained by the women themselves.', 'Participants were recruited through Command Trust Network, an international support group for women with breast implant problems. The sample consisted of 55 women from 19 states and Canada who experienced health problems they attributed to their implants. Eighteen percent labeled themselves as disabled.', 'Themes emerging from responses to 10 questions are discussed in terms of circumstances leading to initial implantation, understanding risks and benefits, health problems and symptoms, physician response, choices made about implant removal, and psychosocial and emotional consequences.
Answer: Findings included dissatisfaction with implants, similarity of health problems, and recurrent surgical and nonsurgical procedures. Dominant themes included lack of informed consent, physician denial of health problems, and the decision to remove implants. Further research should be directed at recipients of implants who report silicone-related illness to determine the number of women affected and the nature of their problems.
[A]:
Do women 's reports of breast implant problems and silicone-related illness?